The Role of Complete Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy in Ovarian Carcinoma: Where Do We Stand Today?A Comprehensive Review and Clinical Insights from a Leading Oncology Center in India

The Role of Complete Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy in Ovarian Carcinoma: Where Do We Stand Today?A Comprehensive Review and Clinical Insights from a Leading Oncology Center in India | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The Role of Complete Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy in Ovarian Carcinoma: Where Do We Stand Today?A Comprehensive Review and Clinical Insights from a Leading Oncology Center in India M D Ray, Rohan Kapoor, Carolin Solomi, Divyam Goel, Babul Bansal This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6138215/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 11 Jun, 2025 Read the published version in World Journal of Surgical Oncology → Version 1 posted 15 You are reading this latest preprint version Abstract Background: The current treatment for advanced epithelial ovarian cancer (EOC) is complete cytoreductive surgery (CRS) followed by adjuvant chemotherapy. Although many patients respond well to this treatment, many will relapse and die from peritoneal carcinomatosis. Adding Hyperthermic Intraperitoneal Chemotherapy (HIPEC) to the standard treatment has been shown to improve survival by reducing cancer recurrence in the abdomen, with acceptable side effects. This article summarizes the current evidence and our long experience with CRS and HIPEC at different stages of ovarian cancer treatment: at upfront CRS, at interval CRS, at secondary CRS, and as palliative setting. Methods: Our study cohort includes 400 EOC patients who underwent CRS and CRS with HIPEC in upfront, interval, and secondary setting. Cisplatin 75mg/m 2 for 60 minutes was used in all settings. Results: For a median follow-up of 80 months, the DFS in CRS with HIPEC and CRS alone were 34.3 months vs 22.7 months in the upfront group (p <0.001), 18.9 months vs 13.3 months in the interval group, (p 0.04) and 14.7 months vs 11.9 months in secondary group, (p 0.13). The median OS in the CRS with HIPEC vs CRS without HIPEC group was 72.1 months vs 43.3 months in the upfront setting, (p-value 0.034) and 54.2 months vs 44.7 months in the interval setting (p-value 0.44). At 5 years, 49% in the upfront setting and 28% in the interval setting were alive in the CRS with HIPEC arm. There was no difference in Clavien Dindo Grade 3 & 4 postoperative complications among both the groups except for days of hospital stay (p-value 0.016). Conclusions: : Cytoreductive surgery (CRS) with HIPEC presently play a promising treatment strategy for advanced ovarian cancer, potentially enhancing outcomes compared to conventional therapies in all settings. Thus, adding HIPEC to complete cytoreductive surgery has improved outcomes in all required settings of advanced EOC especially in upfront setting. Epithelial Ovarian Cancer Cytoreductive Surgery (CRS) Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Disease-Free Survival Overall Survival Peritoneal Carcinomatosis India Figures Figure 1 Figure 2 Figure 3 Figure 4 Background Ovarian cancer remains a significant global health concern, characterized by its high mortality rate and late-stage diagnosis. As per GLOBOCAN 2022 data, it is the third most common cancer among Indian women. ( 1 ). Typically, 80% of patients are diagnosed at advanced stages (Stage III & IV), with extensive disease in the peritoneum. ( 2 ). Since the 1980s, the gold standard of treatment has been cytoreductive surgery (CRS) followed by systemic chemotherapy. However, despite aggressive management, almost 70% of patients recur in 2–3 years ( 3 ). Ovarian cancer usually stays within the peritoneal cavity, spreading beyond it in only 3–5% of cases. Recently, CRS and hyperthermic intraperitoneal chemotherapy (HIPEC) has gained attention as an innovative therapeutic approach. CRS aims to remove all visible tumours, followed by directly administering heated chemotherapy into the peritoneal cavity during HIPEC. The combined approach of CRS with HIPEC will address all the microscopic diseases, eventually leading to less chance of peritoneal relapse. This combined intraoperative modality of treatment followed by systemic chemotherapy may provide long-term disease-free survival and overall survival with acceptable morbidity ( 4 ). Our article reviews the current evidence on the efficacy and challenges of CRS with HIPEC in various settings. We also provide our centre’s experience in treating advanced carcinoma ovary patients treated with CRS with or without HIPEC. Methods After Institutional Ethics clearance, this retrospective study was conducted, utilizing our prospectively maintained ovarian cancer database at the Department of Surgical Oncology, Dr. BRA-IRCH, AIIMS, New Delhi. Our study cohort includes all carcinoma ovary patients who underwent surgical treatment during their path of treatment, including upfront CRS, interval CRS, and secondary CRS from 2014 to 2022. Based on the disease burden, we stratified the patients with good performance status (ECOG ≤ 2) either for upfront CRS or neoadjuvant chemotherapy (NACT) after a multidisciplinary tumour board discussion as per our institutional protocol. Absolute contraindications for upfront CRS which we followed are ECOG > 2, acute thrombus (deep venous thrombus or pulmonary thrombus), stage IVB disease with deep involvement of the liver or spleen parenchyma, transmural bowel involvement except rectosigmoid or rectum involvement, root of mesentery involvement with mesenteric retraction requiring resection of more than 2 meters of small bowel, intestinal deposits necessitating more than two segmental resections, and lymph nodes 2 cm or larger at the superior mesenteric artery, behind the porta hepatis, or at the renal hilum. Relative contraindications include - age over 80 years, serum albumin levels of 2 gm/dl or less, CA-125 levels greater than 2000 U/mL, extensive disease in the upper abdomen, involving the diaphragm or lesser omentum, and significant malignant pleural effusion. The institution protocol used for secondary CRS is radiological PCI < 10, ECOG ≤ 2, treatment-free interval ≥ 6 months, and patients who had optimal CRS during their primary surgery. The completeness of cytoreduction score (CC score) was used to describe the extent of cytoreduction and recorded ( 5 ). Optimal cytoreduction was defined as no or < 2.5mm residual disease (CC0 or CC1). Any residual disease above 2.5mm was considered suboptimal debulking. HIPEC in our centre was offered in all the time frames of surgical treatment in an upfront, interval, or secondary setting when optimal cytoreduction was achieved. HIPEC was primarily offered to patients who met the following criteria: Optimal cytoreduction (CC-0 or CC-1) achieved Good performance status (ECOG 0–2) Absence of major comorbidities that would increase perioperative risk No severe organ dysfunction (e.g., renal or hepatic failure) Intraoperative feasibility of administering HIPEC Affordability for HIPEC HIPEC was also done in a few instances as a palliative procedure in patients who are extremely symptomatic with refractory ascites and in patients where cytoreductive surgery was abandoned due to extensive irresectable disease. The drug used in our patients was Cisplatin 75 mg/m2 for 60 minutes in all settings. All bowel anastomosis was performed before HIPEC at our centre. Hyperthermic chemotherapy was also given in the below mentioned modifications to some patients: Definition of CRS with HIPEC in Different Time Frames Along with Cytoreductive Surgery (CRS): Upfront CRS and HIPEC : Performed as the first treatment for newly diagnosed ovarian cancer with peritoneal carcinomatosis. Interval CRS and HIPEC : Conducted after 3–4 cycles or up to 6 cycles of neoadjuvant chemotherapy. Consolidation CRS and HIPEC : Performed after neoadjuvant chemotherapy when there is a clinically and radiologically complete response. Secondary CRS and HIPEC : Applied in cases of recurrent and relapsed ovarian cancer. HITAC (Hyperthermia Thoraco-Abdominal Chemotherapy) : Performed in cases of malignant pleural effusion or pleural involvement. This approach targets both the abdominal and thoracic cavities with hyperthermic chemotherapy to enhance therapeutic efficacy. Without Cytoreductive Surgery (CRS): Palliative HIPEC : Used for symptom relief and improving quality of life in advanced cases. Staged HIPEC : Conducted when a patient is hemodynamically unstable after CRS and extensive dissection. HIPEC is postponed for 24 to 48 hours or, in some cases, up to 4 weeks, allowing for stabilization and optimization. This approach ensures that patients who are not immediately fit for intraoperative HIPEC can still receive the treatment once their condition permits. Postoperative complications were systematically evaluated using the Clavien-Dindo classification system. Only Clavien-Dindo grade III and IV complications were considered. Complications were categorized as early if they occurred within 30 days, and as late if they occurred between 31and 90 days post-surgery. In our study, disease-free survival (DFS) was defined as the period from CRS to the first occurrence of cancer recurrence, which was identified by the presence of radiologically measurable disease. Overall survival (OS) was defined as the time from cancer diagnosis to death or the last follow-up, whichever occurred later. Statistical analysis: Data were recorded in Microsoft Excel and analysed using STATA version 16. Categorical data were presented as percentages and absolute numbers. Quantitative data were summarized as mean and standard deviation if normally distributed, or as median and range if not. Associations were determined using the Chi-square test and Fisher’s exact test, with a p-value of < 0.05 considered statistically significant. Survival analysis was conducted using the Kaplan-Meier method, and the log-rank test was used to compare survival curves between the CRS with HIPEC group and the CRS without HIPEC group. All hypothesis tests were performed at an alpha level of 0.05 with a 95% confidence interval. The median follow-up duration was estimated using the reverse Kaplan-Meier method. Results A total of 400 patients of epithelial ovarian cancers (EOC) in stages III and IV were included in our study. The median age at presentation was 52 years (19–80 years). Among the 400 patients, 327 (81.7%) were in stage III, and the remaining 73 (18.3%) were in stage IV. In our study cohort, 125 patients (31.3%) underwent upfront CRS,177 patients (44.2%) underwent interval CRS, and 98 patients (24.5%) underwent secondary CRS. Of all the patients, 226 (56.5%) underwent CRS + HIPEC, and the remaining 174 patients (43.5%) underwent only CRS. The reasons for HIPEC not being done in 43.5% were multifactorial, such as being unable to achieve optimal cytoreduction, patients not consenting to HIPEC, financial constraints, and inability to tolerate HIPEC because of hemodynamic instability after CRS. CC0 was achieved in 316 patients (79%), CC1 in 60 patients (15%), CC2 and CC3 in the remaining 24 (6%) patients. Palliative HIPEC was done in 5 patients. The details are summarised in Tables 1 , 2 . Table 1 Table showing the demographic characteristics of our study cohort: Study Cohort Total patients (N = 400) Median age (yrs) 52 (19–80) Ovarian carcinoma stage • Stage III • Stage IV 327 (81.7%) 73 (18.3%) Time frames of CRS • Upfront CRS • Interval CRS • Secondary CRS 125 (31.3%) 177 (44.2%) 98 (24.5%) Surgical procedure in the study cohort • CRS and HIPEC • Only CRS 226 (56.5%) 174 (43.5%) Cytoreduction scores • Optimal cytoreduction (CC0 + CC1) • CCO • CC1 • CC2 & CC3 376 (94%) 316 (79%) 60 (15%) 24 (6%) Table 2 Table showing the distribution of surgical procedures across all time frames Surgical procedures No. of patients Primary CRS • CRS + HIPEC • Only CRS • HITAC • Staged HIPEC • Palliative HIPEC 125 (31.3%) 51(40.3%) 67(54%) 1(1.1%) 4 (3.5%) 2 (1.1.%) Interval CRS • CRS + HIPEC • Only CRS • HITAC • Staged HIPEC • Palliative HIPEC 177 (44.2%) 85(48.2%) 79 (44%) 4 (2.3%) 7 (3.7%) 2(1.3%) Secondary CRS • CRS + HIPEC • Only CRS • HITAC • Staged HIPEC 98 (24.5%) 66 (67.3%) 28 (28.5%) 1 (1%) 3 (3%) Postoperative complications: The median length of hospital stay was 6 days in CRS + HIPEC and 5 days in CRS without HIPEC (p-value 0.016). The mean blood loss was 700 ml in CRS with HIPEC and 600 ml in CRS without HIPEC. In our study, 32% had early postoperative complications, and 10% had late postoperative complications. In our cohort, 32% of patients required perioperative blood transfusions, with a slightly higher rate observed in the CRS + HIPEC group (35%) compared to the CRS-alone group (29%), though the difference was not statistically significant (p = 0.21). The incidence of venous thromboembolism (VTE) was 4.8% overall, with no significant variation between the two groups (CRS-alone: 4.5%, CRS + HIPEC: 5.1%, p = 0.74). Prolonged ileus was noted in 11% of cases, with a marginally higher occurrence in the HIPEC group (13% vs. 9%, p = 0.32), likely due to increased operative time and extensive peritoneal dissection. Despite these complications, there were no 30-day or 90-day postoperative mortalities in our study, reinforcing the feasibility and safety of CRS + HIPEC in advanced ovarian carcinoma. The details of individual complications are summarised in Table 3 . Furthermore, the time to initiation of adjuvant chemotherapy did not differ significantly between the CRS-alone and CRS + HIPEC groups, although individual delays were observed based on postoperative recovery. Table 3 Table showing postoperative complications (Clavein Dindo III &IV) in each group Complications CRS with HIPEC (254) Only CRS (146) P Value Intestinal anastomotic leak 5 (2%) 3 (2%) 0.99 Urologic complications (Bladder + Ureteric anastomotic leaks) 3 (1.2%) 2 (1.4%) 0.91 Sepsis 5 (1.8%) 1 (1%) 0.51 Surgical site infection 13 (5%) 6 (4%) 0.64 Median ICU stay (days) 6 5 0.016 Renal dysfunction/ Dyselectrolytemia 7 (2.8%) 1 (1%) 0.19 Relaparotomy 6 (2.5%) 4 (2.7%) 0.90 Survival Outcomes: The median follow-up period was 65 months. For the upfront setting, the median DFS was 34.3 months and 22.7 months in patients who underwent CRS with HIPEC and CRS without HIPEC respectively. (p-value < 0.001). In the interval group, the median DFS was 18.9 months and 13.3 months respectively (p value- 0.04). In the secondary setting, the median DFS was 14.7 months in the CRS with HIPEC group and 11.9 months in the CRS without HIPEC group (p-value 0.13). We also compared the survival outcomes in the CRS with HIPEC arm between the upfront and interval settings and found a significant increase in the DFS of 15.4 months in the upfront setting (p-value 0.015). The summary of the survival outcomes is found in Table 4 . Table 4 Table showing the survival outcomes in each group Study group DFS/PFS(secondary) OS CRS + HIPEC CRS p-value CRS + HIPEC CRS p-value Upfront setting 34.3 months 22.7 months < 0.001 72.1 months 43.3 months 0.001 Interval setting 18.9 months 13.3 months 0.04 54.2 months 44.7 months 0.046 Secondary setting 14.7 months 11.9 months 0.13 N/A N/A On analysing the overall survival (OS) outcomes across the different settings, we found that the upfront setting had a median OS of 72.1 months in the CRS with HIPEC group vs 43.3 months in the CRS without HIPEC group (p-value 0.001). In the interval setting, a median OS of 54.2 months vs 44.7 months was present after CRS and after CRS with HIPEC respectively (p-value 0.046). At 5 years, 49% in the upfront setting and 28% in the interval setting were alive in the CRS with HIPEC arm. The graphical representation of these survival outcomes is shown in Figs. 1 , 2 , 3 & 4 . Additionally, we have compared and analyzed the baseline characteristics and surgical data of the HIPEC and non-HIPEC groups. The Cox regression analysis ( Table 5 ) provided below further elucidates the prognostic factors affecting outcomes in our cohort. Table 5 Cox Regression Analysis (Univariate and Multivariate) Variable Univariate Analysis (p-value) Hazard Ratio Multivariate Analysis (p-value) Hazard Ratio Age 0.830 0.998 - - Performance Status (PS) 0.719 0.837 - - Comorbidities 0.472 0.860 - - Stage at Presentation 0.309 1.190 - - Grade 0.940 0.988 - - CA-125 0.652 1.000 - - Peritoneal Cancer Index (PCI) < 0.001 1.162 < 0.001 1.119 Bowel Involvement 0.017 1.643 0.634 0.890 Bladder Involvement 0.125 1.768 - - Subdiaphragmatic Deposit < 0.001 7.184 < 0.001 3.283 Operative Time 0.012 1.002 0.999 1.000 Blood Loss 0.941 1.000 - - Lymph Node Positivity 0.177 1.032 - - HIPEC 0.046 1.603 0.821 1.061 1. Impact of PCI and Subdiaphragmatic Deposits: A high PCI was significantly associated with worse prognosis (p < 0.001), highlighting the importance of tumor burden in determining outcomes. Presence of subdiaphragmatic deposits was also a strong predictor of poor prognosis, with a high hazard ratio in both univariate (7.184) and multivariate (3.283) analysis. 2. Bowel and Bladder Involvement: Bowel involvement showed significance in univariate analysis (p = 0.017) but lost significance in multivariate analysis, indicating it may be confounded by other factors. Bladder involvement was not statistically significant in either analysis, suggesting that it may not be an independent prognostic factor. 3. HIPEC as a Prognostic Factor: In univariate analysis, HIPEC was associated with improved prognosis (p = 0.046, HR = 1.603). However, in multivariate analysis, HIPEC lost significance (p = 0.821, HR = 1.061), suggesting that its benefit may be confounded by other variables, such as PCI and subdiaphragmatic disease. 4. Operative Time and Blood Loss: Operative time was significant in univariate analysis (p = 0.012) but not in multivariate analysis, indicating that longer surgeries might be associated with higher tumor burden rather than directly impacting survival. Discussion Upfront setting: In the upfront CRS setting, limited evidence exists on the effectiveness of HIPEC. The only randomized study by Lim et al. ( 7 ) involving 107 ovarian cancer patients using cisplatin (75 mg/m²) in a closed technique for 90 minutes found no significant benefit of HIPEC, with median PFS at 23.9 vs. 29.7 months (p = 0.51) and OS at 71.3 months for HIPEC, whereas OS was not reached for CRS without HIPEC. In contrast, our study found a statistically significant DFS improvement of 11.6 months and an OS improvement of 28.8 months. A multicenter French retrospective study by Bakrin et al. ( 8 ) showed higher OS for upfront HIPEC (52.7 months) compared to interval (36.5 months) and secondary settings (33.4 months). Similarly, Lei et al. ( 9 ) reported longer median survival (49.8 vs. 34 months) and improved 3-year OS rates (60.3% vs. 49.5%) with upfront HIPEC. Somsekhar et al. ( 10 ) in an ambispective study of 190 patients noted comparable morbidity and improved survival in the upfront setting (median DFS: 33 vs. 30 months, p = 0.75). Our results align with these findings, supporting upfront HIPEC as a viable option. Table 6 summarizes the available evidence.In concordance with the above-mentioned observational studies, our results also add to the fact that CRS with HIPEC in upfront settings will increase the survival outcomes. Table 6 Table summarizing the studies on CRS with HIPEC in an upfront setting Study Study type Study groups (No.of patients) Drug used in HIPEC DFS OS Lim et al Phase 3 RCT CRS + HIPEC vs CRS Cisplatin 23.9 vs 29.7 months 71.3 vs 61.4 months Somsekhar et al Ambispective study Upfront CRS + HIPEC (80) vs Interval CRS + HIPEC (110) Cisplatin Median DFS: 33 vs 30 months 4-year OS: NR vs 46 months (85%vs 60%) Bakrin et al Retrospective study Primary * CRS + HIPEC (92) vs Secondary CRS + HIPEC (474) Cisplatin N/A 35.4 vs 41.5 months Bayon et al Retrospective Case-Control Study Primary* CRS + HIPEC ( 15 ) Vs Secondary CRS + HIPEC (27) Carboplatin or Paclitaxel 56.3% (3 years) 66.1% (3 years) *Primary denotes here ovarian cancer in their first line treatment which includes both upfront and interval settings Ongoing trials such as OVIHIPEC 2 and EHTASEOCCS ( 11 , 12 , 13 ) are investigating the role of HIPEC in upfront CRS, focusing on survival outcomes. Interval setting: In stage IIIC ovarian cancer post-NACT, randomized trials support HIPEC use. The OVIHIPEC-1 trial by Van Driel et al. ( 14 ) demonstrated a 3.5-month increase in RFS and an 11.8-month OS benefit at 4.7 years. A 10.4-year follow-up study ( 15 ) reaffirmed these benefits. The Korean study by Lim et al. ( 7 ) reported increased PFS (17.4 vs. 15.2 months, p = 0.04) and OS (61.8 vs. 48.2 months, p = 0.04) with HIPEC. The CarcinoHIPEC trial by Campos et al. ( 16 ) found improved DFS (18 vs. 12 months, p = 0.038) but no significant OS benefit (52 vs. 45 months, p = 0.52). also there was no notable differences in morbidity, mortality, or postoperative quality of life ( 16 ). Additionally, a phase 2 study by Marrelli et al. involving 46 patients reported favourable outcomes with NACT followed by interval CRS and HIPEC, including improved control of peritoneal carcinomatosis and high survival rates ( 17 ). While landmark trials showed HIPEC benefits, our study did not find significant differences between CRS and CRS + HIPEC in the interval setting. This may be due to the inclusion of 18% stage IV cases, unlike previous trials focusing solely on stage IIIC. However, Valentina et al. ( 18 ) reported comparable outcomes in stage IV patients. Ongoing trials like CHIPPI-1808 and CHORINE ( 19 , 20 ) aim to clarify HIPEC's role. Table 7 summarizes the available literature. Table 7 Table showing the studies on CRS with HIPEC in the interval setting Study Study type Study group (No. of patients) Drug used in HIPEC PFS OS OVIHIPEC 1 Phase 3 RCT CRS + HIPEC (123) Vs CRS only (122) Cisplatin RFS - At 4.7 years- 14.2 months vs 10.2 At 10.4 years − 10.7 vs 14.3 (p = 0·0008) At 4.7 years- 45.7 vs 33.9 months At 10.4 years-33.3 vs 44.9 months (p = 0·011) Lim et al Phase 3 RCT CRS + HIPEC (34) Vs CRS only (43) Cisplatin 17.4 vs 15.4 months (p = 0.04) 61.8 vs 48.2 months (p = 0.04) CarcinoHIPEC (Spanish study) Phase 3 RCT CRS + HIPEC (35) Vs CRS only (36) Cisplatin 18 vs 12 months (p = 0.038) 52 vs 45 months (p = 0.52) Secondary setting: HIPEC's role in the secondary setting was first explored in the early 2000s. Gori et al. ( 21 ) studied 51 patients undergoing CRS with HIPEC using cisplatin (100 mg/m²) and found a median survival benefit (64.4 vs. 46.4 months). Adverse effects and mortality rates were comparable between groups, highlighting HIPEC's feasibility and promise as an alternative to consolidation therapy.Subsequent studies, such as an Italian case-control study conducted by Fagotti et al. ( 22 ) later confirmed improved survival in platinum-sensitive recurrent cases treated with HIPEC. Additionally, another French multicentric prospective cohort by Bakrin et al. done on both platinum-sensitive and platinum-resistant ovarian cancer patients demonstrated that CRS with HIPEC is feasible and can yield long-term survival in carefully selected patients with recurrent ovarian cancer ( 8 ). Spiliotis et al. ( 23 ) conducted the first RCT in recurrent ovarian cancer, reporting a mean OS of 26.7 months in the HIPEC arm vs. 13.4 months in the CRS-alone group. However, this trial faced criticism regarding data transparency. More recently, the CHIPOR study by Jean-Marc et al. focused on 415 patients at their first platinum-sensitive relapse and compared the outcomes in CRS with HIPEC vs CRS without HIPEC and, demonstrated higher median overall survival in the HIPEC arm (54.3 vs 45.8 months, p value 0.02) ( 24 ). Our study included only platinum-sensitive relapses with cisplatin and doxorubicin in HIPEC, yet no significant DFS differences were observed in the secondary setting. Table 8 summarizes key studies on HIPEC in recurrent ovarian cancer. Table 8 Table showing the studies on CRS with HIPEC in the secondary setting Study name Type of study HIPEC drug Median PFS Median OS CHIPOR study (2023) Phase 3 RCT -First platinum-sensitive relapse included cisplatin 75 mg/m² at 41°C for 60 min Peritoneal PFS HIPEC vs no HIPEC 13.1 vs 12.2 months 54.3 vs 45.8 months (p = 0.02) Spiliotis study (2015) Phase 3 RCT -Both Platinum sensitive& resistant relapses included Platinum sensitive - Cisplatin + Paclitaxel Platinum resistant - Doxorubicin + paclitaxel - Platinum sensitive: 26.8 vs. 15.2 (p = 0.035) Platinum resistant: 26.6 vs 10.2 3 year OS: 75% vs 18% ( p: 0.01). Bakrin et al (2012) Multicentric retrospective study Both Platinum sensitive and resistant relapses included Cisplatin with/without mitomycin 12.8 months Platinum sensitive − 52 months Platinum resistant – 48 months Fagotti et al Case-control study Only platinum-sensitive cases included Oxaliplatin - 2-year OS rate − 96.7%vs 75% (p = 0.017) 5-year OS rate − 68.4% vs 42.7% (p = 0.017) We analyzed the baseline characteristics and surgical data of the HIPEC and non-HIPEC groups, with Cox regression analysis highlighting key prognostic factors. A high PCI (p < 0.001) and subdiaphragmatic deposits (HR = 7.184 in univariate, 3.283 in multivariate) were strong predictors of poor prognosis, emphasizing tumor burden as a critical determinant. Bowel involvement was significant in univariate analysis (p = 0.017) but lost significance in multivariate analysis, while bladder involvement was not independently prognostic. HIPEC showed improved prognosis in univariate analysis (p = 0.046, HR = 1.603) but was not significant in multivariate analysis (p = 0.821, HR = 1.061), suggesting its effect may be influenced by other factors like PCI. Additionally, operative time was significant in univariate analysis (p = 0.012) but not in multivariate analysis, indicating its association with tumor burden rather than direct survival impact. We acknowledge the heterogeneity between the HIPEC and non-HIPEC groups and the potential selection bias. The findings suggest that tumor burden (PCI and subdiaphragmatic disease) plays a crucial role in prognosis. These findings highlight the importance of patient selection for HIPEC, reinforcing that tumor burden and disease distribution are primary determinants of prognosis, whereas HIPEC’s survival benefit may be influenced by underlying disease severity and other confounding factors. Strengths & Limitations of our study: To the best of our knowledge in indexed literature, our study is the first in India that analyzed the role of CRS with HIPEC across various phases in ovarian cancer. Our study had a comprehensively maintained prospective database which helped in meticulously comparing the outcomes of CRS with HIPEC in both upfront and interval settings across a significant sample size. The inclusion of both short-term and long-term follow-up data enhances the reliability of our findings. Our study reflects a real-world scenario, particularly for a low- and middle-income country (LMIC), providing practical insights that can directly guide treatment decisions in ovarian cancer management and enhance patient outcomes. The management of locally advanced carcinoma ovary is complex and challenging for oncologists. Hence, we hope our study benefits the treating oncologists in other LMICs and stimulates further research in this ever-evolving field. Our study does have a few limitations. Although our study includes a significant number of patients, the sample size may still be insufficient to detect smaller but clinically relevant differences in outcomes between the upfront and interval groups. Our study is retrospective, there may be an inherent risk of selection bias. Patients may have had differing baseline characteristics or disease severities, influencing the outcomes independently of the treatment modality. The indications for aggressive treatment and newer chemotherapeutic agents change over time during the duration of our study. Some patients who achieved optimal cytoreduction but were not offered HIPEC were primarily excluded due to logistical constraints and financial limitations. As HIPEC is a resource-intensive procedure requiring specialized equipment, prolonged operative time, and additional postoperative care, its accessibility remains a challenge, particularly in resource-limited settings. Moreover, a significant proportion of our patient population faced financial constraints, making it difficult to afford HIPEC despite achieving optimal cytoreduction. Since our study was conducted at a single centre, the findings may not be generalizable to other institutions with different patient demographics, surgical techniques, or postoperative care practices, limiting the external validity of our results. While long-term follow-up data is a strength, there were a significant number of patients lost to follow-up in our study cohort. The study may not fully account for all potential confounding variables, such as differences in adjuvant therapies, patient comorbidities, and perioperative care, which could influence the observed outcomes and limit the ability to attribute differences solely to the timing of CRS with HIPEC. Hence large-scale multicentric randomized studies are required to support the findings of our study. Conclusion Cytoreductive surgery (CRS) with HIPEC presently play a promising treatment strategy for advanced ovarian cancer, potentially enhancing outcomes compared to conventional therapies in all settings. From our experience, we advocate HIPEC's use across all required treatment stages, particularly in upfront settings. Despite existing challenges and limitations, ongoing research and interdisciplinary cooperation are crucial for advancing the field of CRS with HIPEC in ovarian cancer. Lastly, "Patient selection is paramount in determining surgical success," emphasizing the critical role of appropriate patient selection alongside surgical expertise. Abbreviations EOC - Epithelial Ovarian Cancer CRS - Cytoreductive Surgery HIPEC - Hyperthermic Intraperitoneal Chemotherapy DFS - Disease-Free Survival OS - Overall Survival PCI - Peritoneal Cancer Index CC - Completeness of Cytoreduction ECOG - Eastern Cooperative Oncology Group NACT - Neoadjuvant Chemotherapy GLOBOCAN - Global Cancer Observatory CA-125 - Cancer Antigen 125 STATA - Statistical Software for Data Analysis RFS - Recurrence-Free Survival PFS - Progression-Free Survival RCT - Randomized Controlled Trial LMIC - Low- and Middle-Income Countries Declarations Ethics approval and consent to participate: Institutional Ethics clearance was obtained from from Institutional Ethics clearance, AIIMS, New Delhi. Following the clearance, this retrospective study was conducted, utilizing our prospectively maintained ovarian cancer database at the Department of Surgical Oncology, Dr. BRA-IRCH, AIIMS, New Delhi. Consent for publication: Not Applicable Availability of data and materials: The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Competing interests: ‘M D Ray and Rohan Kapoor contributed equally to this work and may be treated as First Authors’ The authors declare that they have no competing interests Funding: Not Applicable Authors' contributions: M D Ray: Conceptualization, Visualization, Writing of the original draft, editing. Rohan Kapoor: Data curation, Writing of the original draft, editing. Carolin Solomi: Data curation, Writing of the original draft, editing. Divyam Goel: Data curation, Writing of the original draft, editing. Babul Bansal: Data curation, Writing of the original draft, editing. Acknowledgements: Not Applicable Authors' information: # M D Ray 1 , # Rohan Kapoor 1 , Carolin Solomi 2 , Divyam Goel 1 , Babul Bansal 1 1 Department of Surgical Oncology, All India Institute of Medical Sciences, New Delhi, India 2 Division of Gynaecologic Oncology, Department of Obstetrics & Gynaecology, All India Institute of Medical Sciences, New Delhi, India # First Author: M D Ray, Rohan Kapoor ‘M D Ray and Rohan Kapoor contributed equally to this work and may be treated as First Authors’ References Siegel RL, Miller KD, Fuchs HE, Jemal A, Cancer statistics. 2022. CA Cancer J Clin. 2022;72(1):7–33. 10.3322/caac.21708 Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229–63. 10.3322/caac.21834 . Bhatt A, Yonemura Y, Mehta S, et al. Target region resection in patients undergoing cytoreductive surgery for peritoneal metastases-is it necessary in absence of visible disease? Eur J Surg Oncol. 2020;46(4 Pt A):582–9. 10.1016/j.ejso.2019.11.495 . Stefaan Mulier J-P, Claes V, Dierieck J-O, Amiel. Jean-Philippe Pahaut et al, Survival Benefit of Adding Hyperthermic IntraPEritoneal Chemotherapy (HIPEC) at the Different Time-points of Treatment of Ovarian Cancer: Review of Evidence. Curr Pharm Design. 2012;18:3793–803. Horowitz NS, Miller A, Rungruang B, Richard SD, Rodriguez N, et al. Does aggressive surgery improve outcomes? Interaction between preoperative disease burden and complex surgery in patients with advanced-stage ovarian cancer: an analysis of GOG 182. J Clin Oncol. 2015;33(8):937–43. 10.1200/JCO.2014.56.3106 . Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240(2):205–13. 10.1097/01.sla.0000133083. 54934.ae . Lim MC, Chang SJ, Park B, Yoo HJ, Yoo CW, Nam BH, Park SY, HIPEC for Ovarian Cancer Collaborators. Survival After Hyperthermic Intraperitoneal Chemotherapy and Primary or Interval Cytoreductive Surgery in Ovarian Cancer: A Randomized Clinical Trial. JAMA Surg. 2022;157(5):374–83. 10.1001/jamasurg.2022.0143 . PMID: 35262624; PMCID: PMC8908225. Bakrin N, Bereder JM, Decullier E, Classe JM, Msika S, Lorimier G, Abboud K, Meeus P, Ferron G, Quenet F, et al. Peritoneal Carcinomatosis Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Advanced Ovarian Carcinoma: A French Multicentre Retrospective Cohort Study of 566 Patients. Eur J Surg Oncol. 2013;39:1435–43. Lei Z, Wang Y, Wang J, Wang K, Tian J, Zhao Y, Chen L, Wang J, Luo J, Jia M, et al. Evaluation of Cytoreductive Surgery with or without Hyperthermic Intraperitoneal Chemotherapy for Stage III Epithelial Ovarian Cancer. JAMA Netw Open. 2020;3:e2013940. Somashekhar SP, Ramya Y, Ashwin KR, et al. Cytoreductive Surgery with HIPEC as Primary Treatment for Advanced Epithelial Ovarian Carcinoma: Upfront or Interval—ISPSM Collaborative Study. Indian J Surg Oncol. 2023;14(Suppl 1):226–32. https://doi.org/10.1007/s13193-023-01747-3 . Marrelli D, Ansaloni L, Federici O, Asero S, Carbone L, Marano L, Baiocchi G, Vaira M, Coccolini F, Di Giorgio A, et al. Cytoreductive Surgery (CRS) and HIPEC for Advanced Ovarian Cancer with Peritoneal Metastases: Italian PSM Oncoteam Evidence and Study Purposes. Cancers. 2022;14:6010. https://doi.org/10.3390/cancers14236010 . Koole S, van Stein R, Sikorska K, Barton D, Perrin L, etal, OVHIPEC-2 Steering Committee and the Dutch OVHIPEC group. Primary cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy (HIPEC) for FIGO stage III epithelial ovarian cancer: OVHIPEC-2, a phase III randomized clinical trial. Int J Gynecol Cancer. 2020;30(6):888–92. 10.1136/ijgc-2020-001231 . Cui S, Lin Z. Efficacy of HIPEC in the Treatment of Advanced-Stage Epithelial Ovarian Cancer after Cytoreductive Surgery. Van Driel WJ, Koole SN, Sikorska K, van Schagen JH, Schreuder HWR, Hermans RHM, et al. Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer. N Engl J Med. 2018;378(3):230–40. Aronson SL, Lopez-Yurda M, Koole SN, Jules P, Schagen H, van Leeuwen, Hendrick WR, Schreuder, et al. Cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy in patients with advanced ovarian cancer (OVHIPEC 1): final survival analysis of a randomised, controlled phase 3 trial. Lancet Oncol. 2023;24(10):1109–18. https://doi.org/10.1016/S1470-2045(23)00396-0 . Antonio CCP, Alida GG, Elena GG, Rocío GS, Jerónimo MG, Luis ARJ, Aníbal ND, Francisco BV, Jesús GRÁ, Pablo RR, et al. Cytoreductive Surgery with or without HIPEC after Neoadjuvant Chemotherapy in Ovarian Cancer: A Phase 3 Clinical Trial. Ann Surg Oncol. 2022;29:2617–25. Marrelli D, Petrioli R, Cassetti D, D’Ignazio A, Marsili S, Mazzei MA, Lazzi S, Roviello F. A Novel Treatment Protocol with 6 Cycles of Neoadjuvant Chemotherapy Followed by Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Stage III Primary Ovarian Cancer. Surg Oncol. 2021;37:101523. Ghirardi V, Trozzi R, Scanu FR, Giannarelli D, Santullo F, Costantini B, Naldini A, Panico C, Frassanito L, Scambia G, Fagotti A. Expanding the Use of HIPEC in Ovarian Cancer at Time of Interval Debulking Surgery to FIGO Stage IV and After 6 Cycles of Neoadjuvant Chemotherapy: A Prospective Analysis on Perioperative and Oncologic Outcomes. Ann Surg Oncol. 2024;31(5):3350–60. 10.1245/s10434-024-15042-0 . El Hajj H, Vanseymortier M, Hudry D, Bogart E, Abdeddaim C. etal, Rationale and study design of the CHIPPI-1808 trial: a phase III randomized clinical trial evaluating hyperthermic intraperitoneal chemotherapy (HIPEC) for stage III ovarian cancer patients treated with primary or interval cytoreductive surgery. ESMO Open. 2021;6(2):100098. 10.1016/j.esmoop.2021.100098 . Ansaloni L, De Iaco P, Frigerio L, Re. cytoreductive surgery and hyperthermic intraperitoneal chemotherapy as upfront therapy for advanced epithelial ovarian cancer: multi-institutional phase II trial. - Proposal of a clinical trial of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in advanced ovarian cancer, the CHORINE study. Gynecol Oncol. 2012;125(1):279–81. 10.1016/j.ygyno.2012.01.001 . Ray MD, Deo SVS, Pramanik R, Premanand N. An intensive audit on 250 patients of advanced ovarian cancer to improve quality of care in a tertiary referral oncology centre in India. Int J Reprod Contracept Obstet Gynecol. 2022Oct;11(10):2723–8. Fagotti A, Costantini B, Vizzielli, Perelli F, Ercoli A, Gallotta V, et al. HIPEC in recurrent ovarian cancer patients: morbidity-related treatment and long-term analysis of clinical outcome. Gynecol Oncol. 2011;122:221–5. Spiliotis J, Halkia E, Lianos E, et al. Cytoreductive Surgery and HIPEC in Recurrent Epithelial Ovarian Cancer: A Prospective Randomized Phase III Study. Ann Surg Oncol. 2015;22:1570–5. https://doi.org/10.1245/s10434-014-4157-9 . Classe J, Meeus P, Leblanc E, et al. #876 Hyperthermic intraperitoneal chemotherapy in platinum-sensitive relapsed epithelial ovarian cancer: the chipor randomised phase III trial. Int J Gynecologic Cancer. 2023;33:A29. Ray MD. Kunal Dhall, Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in the management of peritoneal surface malignancies – An evidence-based review. Curr Probl Cancer. 2021;45(6). https://doi.org/10.1016/j.currproblcancer.2021.100737 . Deo SVS, Ray MD, Kumar L, et al. Pattern of Care in Real-World Scenario on Advanced Epithelial Ovarian Cancer in a Tertiary Referral Oncology Centre in India — ISPSM Collaborative Study. Indian J Surg Oncol. 2023;14(Suppl 1):233–9. https://doi.org/10.1007/s13193-023-01746-4 . Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6138215","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":440761448,"identity":"26ae9c74-d188-45a8-a912-3d206cbc90ed","order_by":0,"name":"M D 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HIPEC\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6138215/v1/04fc4bdd406e1fa3ffea37d3.png"},{"id":80582670,"identity":"ddce0a6c-ff91-447e-bc39-b56c38050e8a","added_by":"auto","created_at":"2025-04-14 23:37:29","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":177565,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan Meier Survival graphs for DFS and OS in Interval CRS and CRS with HIPEC\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6138215/v1/32eff34ee4c99f62190e2389.png"},{"id":80580159,"identity":"2d885986-6f35-4a38-85aa-8df0ed0c0996","added_by":"auto","created_at":"2025-04-14 23:13:29","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":27407,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan Meier Survival graphs for PFS in Secondary CRS and CRS with HIPEC\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-6138215/v1/40a09779eb9b2acef2fcb905.png"},{"id":80582671,"identity":"e452a5c7-17f4-4836-b8b6-c10502b0653d","added_by":"auto","created_at":"2025-04-14 23:37:29","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":34061,"visible":true,"origin":"","legend":"\u003cp\u003eDisease free survival in CRS and HIPEC arm primary vs interval setting\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-6138215/v1/5989c791b126b98ad6547f66.png"},{"id":84726781,"identity":"cd57a21a-885b-4934-bf60-b37b9679dd9c","added_by":"auto","created_at":"2025-06-16 16:08:15","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1971468,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6138215/v1/8452f4a4-16d1-494b-9baa-353c84f7c08f.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"The Role of Complete Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy in Ovarian Carcinoma: Where Do We Stand Today?A Comprehensive Review and Clinical Insights from a Leading Oncology Center in India","fulltext":[{"header":"Background","content":"\u003cp\u003eOvarian cancer remains a significant global health concern, characterized by its high mortality rate and late-stage diagnosis. As per GLOBOCAN 2022 data, it is the third most common cancer among Indian women. (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Typically, 80% of patients are diagnosed at advanced stages (Stage III \u0026amp; IV), with extensive disease in the peritoneum. (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Since the 1980s, the gold standard of treatment has been cytoreductive surgery (CRS) followed by systemic chemotherapy. However, despite aggressive management, almost 70% of patients recur in 2\u0026ndash;3 years (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Ovarian cancer usually stays within the peritoneal cavity, spreading beyond it in only 3\u0026ndash;5% of cases. Recently, CRS and hyperthermic intraperitoneal chemotherapy (HIPEC) has gained attention as an innovative therapeutic approach. CRS aims to remove all visible tumours, followed by directly administering heated chemotherapy into the peritoneal cavity during HIPEC. The combined approach of CRS with HIPEC will address all the microscopic diseases, eventually leading to less chance of peritoneal relapse. This combined intraoperative modality of treatment followed by systemic chemotherapy may provide long-term disease-free survival and overall survival with acceptable morbidity (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Our article reviews the current evidence on the efficacy and challenges of CRS with HIPEC in various settings. We also provide our centre\u0026rsquo;s experience in treating advanced carcinoma ovary patients treated with CRS with or without HIPEC.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e After Institutional Ethics clearance, this retrospective study was conducted, utilizing our prospectively maintained ovarian cancer database at the Department of Surgical Oncology, Dr. BRA-IRCH, AIIMS, New Delhi. Our study cohort includes all carcinoma ovary patients who underwent surgical treatment during their path of treatment, including upfront CRS, interval CRS, and secondary CRS from 2014 to 2022. Based on the disease burden, we stratified the patients with good performance status (ECOG\u0026thinsp;\u0026le;\u0026thinsp;2) either for upfront CRS or neoadjuvant chemotherapy (NACT) after a multidisciplinary tumour board discussion as per our institutional protocol. Absolute contraindications for upfront CRS which we followed are ECOG\u0026thinsp;\u0026gt;\u0026thinsp;2, acute thrombus (deep venous thrombus or pulmonary thrombus), stage IVB disease with deep involvement of the liver or spleen parenchyma, transmural bowel involvement except rectosigmoid or rectum involvement, root of mesentery involvement with mesenteric retraction requiring resection of more than 2 meters of small bowel, intestinal deposits necessitating more than two segmental resections, and lymph nodes 2 cm or larger at the superior mesenteric artery, behind the porta hepatis, or at the renal hilum.\u003c/p\u003e \u003cp\u003eRelative contraindications include - age over 80 years, serum albumin levels of 2 gm/dl or less, CA-125 levels greater than 2000 U/mL, extensive disease in the upper abdomen, involving the diaphragm or lesser omentum, and significant malignant pleural effusion. The institution protocol used for secondary CRS is radiological PCI\u0026thinsp;\u0026lt;\u0026thinsp;10, ECOG\u0026thinsp;\u0026le;\u0026thinsp;2, treatment-free interval\u0026thinsp;\u0026ge;\u0026thinsp;6 months, and patients who had optimal CRS during their primary surgery. The completeness of cytoreduction score (CC score) was used to describe the extent of cytoreduction and recorded (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Optimal cytoreduction was defined as no or \u0026lt;\u0026thinsp;2.5mm residual disease (CC0 or CC1). Any residual disease above 2.5mm was considered suboptimal debulking.\u003c/p\u003e \u003cp\u003eHIPEC in our centre was offered in all the time frames of surgical treatment in an upfront, interval, or secondary setting when optimal cytoreduction was achieved. HIPEC was primarily offered to patients who met the following criteria:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eOptimal cytoreduction (CC-0 or CC-1) achieved\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eGood performance status (ECOG 0\u0026ndash;2)\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eAbsence of major comorbidities that would increase perioperative risk\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eNo severe organ dysfunction (e.g., renal or hepatic failure)\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eIntraoperative feasibility of administering HIPEC\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eAffordability for HIPEC\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eHIPEC was also done in a few instances as a palliative procedure in patients who are extremely symptomatic with refractory ascites and in patients where cytoreductive surgery was abandoned due to extensive irresectable disease. The drug used in our patients was Cisplatin 75 mg/m2 for 60 minutes in all settings. All bowel anastomosis was performed before HIPEC at our centre. Hyperthermic chemotherapy was also given in the below mentioned modifications to some patients:\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eDefinition of CRS with HIPEC in Different Time Frames\u003c/h2\u003e \u003cdiv id=\"Sec4\" class=\"Section3\"\u003e \u003ch2\u003eAlong with Cytoreductive Surgery (CRS):\u003c/h2\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eUpfront CRS and HIPEC\u003c/b\u003e: Performed as the first treatment for newly diagnosed ovarian cancer with peritoneal carcinomatosis.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eInterval CRS and HIPEC\u003c/b\u003e: Conducted after 3\u0026ndash;4 cycles or up to 6 cycles of neoadjuvant chemotherapy.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eConsolidation CRS and HIPEC\u003c/b\u003e: Performed after neoadjuvant chemotherapy when there is a clinically and radiologically complete response.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eSecondary CRS and HIPEC\u003c/b\u003e: Applied in cases of recurrent and relapsed ovarian cancer.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eHITAC (Hyperthermia Thoraco-Abdominal Chemotherapy)\u003c/b\u003e: Performed in cases of malignant pleural effusion or pleural involvement. This approach targets both the abdominal and thoracic cavities with hyperthermic chemotherapy to enhance therapeutic efficacy.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003c/div\u003e \u003c/div\u003e\n\u003ch3\u003eWithout Cytoreductive Surgery (CRS):\u003c/h3\u003e\n\u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003ePalliative HIPEC\u003c/b\u003e: Used for symptom relief and improving quality of life in advanced cases.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eStaged HIPEC\u003c/b\u003e: Conducted when a patient is hemodynamically unstable after CRS and extensive dissection. HIPEC is postponed for 24 to 48 hours or, in some cases, up to 4 weeks, allowing for stabilization and optimization. This approach ensures that patients who are not immediately fit for intraoperative HIPEC can still receive the treatment once their condition permits.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003ePostoperative complications were systematically evaluated using the Clavien-Dindo classification system. Only Clavien-Dindo grade III and IV complications were considered. Complications were categorized as early if they occurred within 30 days, and as late if they occurred between 31and 90 days post-surgery.\u003c/p\u003e \u003cp\u003eIn our study, disease-free survival (DFS) was defined as the period from CRS to the first occurrence of cancer recurrence, which was identified by the presence of radiologically measurable disease.\u003c/p\u003e \u003cp\u003eOverall survival (OS) was defined as the time from cancer diagnosis to death or the last follow-up, whichever occurred later.\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis:\u003c/h2\u003e \u003cp\u003eData were recorded in Microsoft Excel and analysed using STATA version 16. Categorical data were presented as percentages and absolute numbers. Quantitative data were summarized as mean and standard deviation if normally distributed, or as median and range if not. Associations were determined using the Chi-square test and Fisher\u0026rsquo;s exact test, with a p-value of \u0026lt;\u0026thinsp;0.05 considered statistically significant. Survival analysis was conducted using the Kaplan-Meier method, and the log-rank test was used to compare survival curves between the CRS with HIPEC group and the CRS without HIPEC group. All hypothesis tests were performed at an alpha level of 0.05 with a 95% confidence interval. The median follow-up duration was estimated using the reverse Kaplan-Meier method.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 400 patients of epithelial ovarian cancers (EOC) in stages III and IV were included in our study. The median age at presentation was 52 years (19\u0026ndash;80 years). Among the 400 patients, 327 (81.7%) were in stage III, and the remaining 73 (18.3%) were in stage IV. In our study cohort, 125 patients (31.3%) underwent upfront CRS,177 patients (44.2%) underwent interval CRS, and 98 patients (24.5%) underwent secondary CRS.\u003c/p\u003e\n\u003cp\u003eOf all the patients, 226 (56.5%) underwent CRS\u0026thinsp;+\u0026thinsp;HIPEC, and the remaining 174 patients (43.5%) underwent only CRS. The reasons for HIPEC not being done in 43.5% were multifactorial, such as being unable to achieve optimal cytoreduction, patients not consenting to HIPEC, financial constraints, and inability to tolerate HIPEC because of hemodynamic instability after CRS. CC0 was achieved in 316 patients (79%), CC1 in 60 patients (15%), CC2 and CC3 in the remaining 24 (6%) patients. Palliative HIPEC was done in 5 patients. The details are summarised in Tables \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e,\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eTable showing the demographic characteristics of our study cohort:\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eStudy Cohort\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTotal patients (N\u0026thinsp;=\u0026thinsp;400)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMedian age (yrs)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e52 (19\u0026ndash;80)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOvarian carcinoma stage\u003c/p\u003e\n \u003cp\u003e\u0026bull; Stage III\u003c/p\u003e\n \u003cp\u003e\u0026bull; Stage IV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e327 (81.7%)\u003c/p\u003e\n \u003cp\u003e73 (18.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eTime frames of CRS\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026bull; Upfront CRS\u003c/p\u003e\n \u003cp\u003e\u0026bull; Interval CRS\u003c/p\u003e\n \u003cp\u003e\u0026bull; Secondary CRS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e125 (31.3%)\u003c/p\u003e\n \u003cp\u003e177 (44.2%)\u003c/p\u003e\n \u003cp\u003e98 (24.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eSurgical procedure in the study cohort\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026bull; CRS and HIPEC\u003c/p\u003e\n \u003cp\u003e\u0026bull; Only CRS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e226 (56.5%)\u003c/p\u003e\n \u003cp\u003e174 (43.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eCytoreduction scores\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026bull; Optimal cytoreduction (CC0\u0026thinsp;+\u0026thinsp;CC1)\u003c/p\u003e\n \u003cp\u003e\u0026bull; CCO\u003c/p\u003e\n \u003cp\u003e\u0026bull; CC1\u003c/p\u003e\n \u003cp\u003e\u0026bull; CC2 \u0026amp; CC3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e376 (94%)\u003c/p\u003e\n \u003cp\u003e316 (79%)\u003c/p\u003e\n \u003cp\u003e60 (15%)\u003c/p\u003e\n \u003cp\u003e24 (6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eTable showing the distribution of surgical procedures across all time frames\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSurgical procedures\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNo. of patients\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePrimary CRS\u003c/p\u003e\n \u003cp\u003e\u0026bull; CRS\u0026thinsp;+\u0026thinsp;HIPEC\u003c/p\u003e\n \u003cp\u003e\u0026bull; Only CRS\u003c/p\u003e\n \u003cp\u003e\u0026bull; HITAC\u003c/p\u003e\n \u003cp\u003e\u0026bull; Staged HIPEC\u003c/p\u003e\n \u003cp\u003e\u0026bull; Palliative HIPEC\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e125 (31.3%)\u003c/p\u003e\n \u003cp\u003e51(40.3%)\u003c/p\u003e\n \u003cp\u003e67(54%)\u003c/p\u003e\n \u003cp\u003e1(1.1%)\u003c/p\u003e\n \u003cp\u003e4 (3.5%)\u003c/p\u003e\n \u003cp\u003e2 (1.1.%)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eInterval CRS\u003c/p\u003e\n \u003cp\u003e\u0026bull; CRS\u0026thinsp;+\u0026thinsp;HIPEC\u003c/p\u003e\n \u003cp\u003e\u0026bull; Only CRS\u003c/p\u003e\n \u003cp\u003e\u0026bull; HITAC\u003c/p\u003e\n \u003cp\u003e\u0026bull; Staged HIPEC\u003c/p\u003e\n \u003cp\u003e\u0026bull; Palliative HIPEC\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e177 (44.2%)\u003c/p\u003e\n \u003cp\u003e85(48.2%)\u003c/p\u003e\n \u003cp\u003e79 (44%)\u003c/p\u003e\n \u003cp\u003e4 (2.3%)\u003c/p\u003e\n \u003cp\u003e7 (3.7%)\u003c/p\u003e\n \u003cp\u003e2(1.3%)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eSecondary CRS\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026bull; CRS\u0026thinsp;+\u0026thinsp;HIPEC\u003c/p\u003e\n \u003cp\u003e\u0026bull; Only CRS\u003c/p\u003e\n \u003cp\u003e\u0026bull; HITAC\u003c/p\u003e\n \u003cp\u003e\u0026bull; Staged HIPEC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e98 (24.5%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e66 (67.3%)\u003c/p\u003e\n \u003cp\u003e28 (28.5%)\u003c/p\u003e\n \u003cp\u003e1 (1%)\u003c/p\u003e\n \u003cp\u003e3 (3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\n \u003ch2\u003ePostoperative complications:\u003c/h2\u003e\n \u003cp\u003eThe median length of hospital stay was 6 days in CRS\u0026thinsp;+\u0026thinsp;HIPEC and 5 days in CRS without HIPEC (p-value 0.016). The mean blood loss was 700 ml in CRS with HIPEC and 600 ml in CRS without HIPEC. In our study, 32% had early postoperative complications, and 10% had late postoperative complications. In our cohort, 32% of patients required perioperative blood transfusions, with a slightly higher rate observed in the CRS\u0026thinsp;+\u0026thinsp;HIPEC group (35%) compared to the CRS-alone group (29%), though the difference was not statistically significant (p\u0026thinsp;=\u0026thinsp;0.21). The incidence of venous thromboembolism (VTE) was 4.8% overall, with no significant variation between the two groups (CRS-alone: 4.5%, CRS\u0026thinsp;+\u0026thinsp;HIPEC: 5.1%, p\u0026thinsp;=\u0026thinsp;0.74). Prolonged ileus was noted in 11% of cases, with a marginally higher occurrence in the HIPEC group (13% vs. 9%, p\u0026thinsp;=\u0026thinsp;0.32), likely due to increased operative time and extensive peritoneal dissection. Despite these complications, there were no 30-day or 90-day postoperative mortalities in our study, reinforcing the feasibility and safety of CRS\u0026thinsp;+\u0026thinsp;HIPEC in advanced ovarian carcinoma.\u003c/p\u003e\n \u003cp\u003eThe details of individual complications are summarised in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e. Furthermore, the time to initiation of adjuvant chemotherapy did not differ significantly between the CRS-alone and CRS\u0026thinsp;+\u0026thinsp;HIPEC groups, although individual delays were observed based on postoperative recovery.\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"char\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eTable showing postoperative complications (Clavein Dindo III \u0026amp;IV) in each group\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eComplications\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCRS with HIPEC (254)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOnly CRS (146)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP Value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIntestinal anastomotic leak\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUrologic complications (Bladder\u0026thinsp;+\u0026thinsp;Ureteric anastomotic leaks)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (1.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (1.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.91\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSepsis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (1.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.51\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSurgical site infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13 (5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.64\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMedian ICU stay (days)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.016\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRenal dysfunction/ Dyselectrolytemia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7 (2.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.19\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRelaparotomy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (2.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (2.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.90\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003ch3\u003eSurvival Outcomes:\u003c/h3\u003e\n\u003cp\u003eThe median follow-up period was 65 months. For the upfront setting, the median DFS was 34.3 months and 22.7 months in patients who underwent CRS with HIPEC and CRS without HIPEC respectively. (p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.001). In the interval group, the median DFS was 18.9 months and 13.3 months respectively (p value- 0.04). In the secondary setting, the median DFS was 14.7 months in the CRS with HIPEC group and 11.9 months in the CRS without HIPEC group (p-value 0.13).\u003c/p\u003e\n\u003cp\u003eWe also compared the survival outcomes in the CRS with HIPEC arm between the upfront and interval settings and found a significant increase in the DFS of 15.4 months in the upfront setting (p-value 0.015). The summary of the survival outcomes is found in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"char\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003ctable id=\"Tab4\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eTable showing the survival outcomes in each group\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eStudy group\u003c/p\u003e\n \u003c/th\u003e\n \u003cth colspan=\"3\" align=\"left\"\u003e\n \u003cp\u003eDFS/PFS(secondary)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth colspan=\"3\" align=\"left\"\u003e\n \u003cp\u003eOS\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCRS\u0026thinsp;+\u0026thinsp;HIPEC\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCRS\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ep-value\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCRS\u0026thinsp;+\u0026thinsp;HIPEC\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCRS\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ep-value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUpfront setting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34.3 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22.7 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e72.1 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e43.3 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eInterval setting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18.9 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13.3 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e54.2 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e44.7 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.046\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSecondary setting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14.7 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11.9 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eOn analysing the overall survival (OS) outcomes across the different settings, we found that the upfront setting had a median OS of 72.1 months in the CRS with HIPEC group vs 43.3 months in the CRS without HIPEC group (p-value 0.001). In the interval setting, a median OS of 54.2 months vs 44.7 months was present after CRS and after CRS with HIPEC respectively (p-value 0.046). At 5 years, 49% in the upfront setting and 28% in the interval setting were alive in the CRS with HIPEC arm. The graphical representation of these survival outcomes is shown in Figs.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e,\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e,\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e\u0026amp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e.\u003c/p\u003e\n\u003cp\u003eAdditionally, we have compared and analyzed the baseline characteristics and surgical data of the HIPEC and non-HIPEC groups. The Cox regression analysis\u003cstrong\u003e(\u003c/strong\u003eTable\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e\u003cstrong\u003e)\u003c/strong\u003e provided below further elucidates the prognostic factors affecting outcomes in our cohort.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003ctable id=\"Tab5\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eCox Regression Analysis (Univariate and Multivariate)\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eUnivariate Analysis (p-value)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eHazard Ratio\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMultivariate Analysis (p-value)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eHazard Ratio\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.830\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.998\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003ePerformance Status (PS)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.719\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.837\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eComorbidities\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.472\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.860\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eStage at Presentation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.309\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.190\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eGrade\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.940\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.988\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eCA-125\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.652\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003ePeritoneal Cancer Index (PCI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.162\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.119\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eBowel Involvement\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.643\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.634\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.890\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eBladder Involvement\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.125\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.768\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eSubdiaphragmatic Deposit\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7.184\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.283\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eOperative Time\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.012\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.999\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eBlood Loss\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.941\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eLymph Node Positivity\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.177\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.032\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eHIPEC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.046\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.603\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.821\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.061\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003ch3\u003e1. Impact of PCI and Subdiaphragmatic Deposits:\u003c/h3\u003e\n\u003cul\u003e\n \u003cli\u003e\n \u003cp\u003eA high PCI was significantly associated with worse prognosis (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), highlighting the importance of tumor burden in determining outcomes.\u003c/p\u003e\n \u003c/li\u003e\n \u003cli\u003e\n \u003cp\u003ePresence of subdiaphragmatic deposits was also a strong predictor of poor prognosis, with a high hazard ratio in both univariate (7.184) and multivariate (3.283) analysis.\u003c/p\u003e\n \u003c/li\u003e\n\u003c/ul\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\n \u003ch2\u003e2. Bowel and Bladder Involvement:\u003c/h2\u003e\n \u003cul\u003e\n \u003cli\u003e\n \u003cp\u003eBowel involvement showed significance in univariate analysis (p\u0026thinsp;=\u0026thinsp;0.017) but lost significance in multivariate analysis, indicating it may be confounded by other factors.\u003c/p\u003e\n \u003c/li\u003e\n \u003cli\u003e\n \u003cp\u003eBladder involvement was not statistically significant in either analysis, suggesting that it may not be an independent prognostic factor.\u003c/p\u003e\n \u003c/li\u003e\n \u003c/ul\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\n \u003ch2\u003e3. HIPEC as a Prognostic Factor:\u003c/h2\u003e\n \u003cul\u003e\n \u003cli\u003e\n \u003cp\u003eIn univariate analysis, HIPEC was associated with improved prognosis (p\u0026thinsp;=\u0026thinsp;0.046, HR\u0026thinsp;=\u0026thinsp;1.603).\u003c/p\u003e\n \u003c/li\u003e\n \u003cli\u003e\n \u003cp\u003eHowever, in multivariate analysis, HIPEC lost significance (p\u0026thinsp;=\u0026thinsp;0.821, HR\u0026thinsp;=\u0026thinsp;1.061), suggesting that its benefit may be confounded by other variables, such as PCI and subdiaphragmatic disease.\u003c/p\u003e\n \u003c/li\u003e\n \u003c/ul\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\n \u003ch2\u003e4. Operative Time and Blood Loss:\u003c/h2\u003e\n \u003cul\u003e\n \u003cli\u003e\n \u003cp\u003eOperative time was significant in univariate analysis (p\u0026thinsp;=\u0026thinsp;0.012) but not in multivariate analysis, indicating that longer surgeries might be associated with higher tumor burden rather than directly impacting survival.\u003c/p\u003e\n \u003c/li\u003e\n \u003c/ul\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\n \u003ch2\u003eUpfront setting:\u003c/h2\u003e\n \u003cp\u003eIn the upfront CRS setting, limited evidence exists on the effectiveness of HIPEC. The only randomized study by Lim et al. (\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e) involving 107 ovarian cancer patients using cisplatin (75 mg/m\u0026sup2;) in a closed technique for 90 minutes found no significant benefit of HIPEC, with median PFS at 23.9 vs. 29.7 months (p\u0026thinsp;=\u0026thinsp;0.51) and OS at 71.3 months for HIPEC, whereas OS was not reached for CRS without HIPEC. In contrast, our study found a statistically significant DFS improvement of 11.6 months and an OS improvement of 28.8 months.\u003c/p\u003e\n \u003cp\u003eA multicenter French retrospective study by Bakrin et al. (\u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e) showed higher OS for upfront HIPEC (52.7 months) compared to interval (36.5 months) and secondary settings (33.4 months). Similarly, Lei et al. (\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e) reported longer median survival (49.8 vs. 34 months) and improved 3-year OS rates (60.3% vs. 49.5%) with upfront HIPEC. Somsekhar et al. (\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e) in an ambispective study of 190 patients noted comparable morbidity and improved survival in the upfront setting (median DFS: 33 vs. 30 months, p\u0026thinsp;=\u0026thinsp;0.75). Our results align with these findings, supporting upfront HIPEC as a viable option.\u003c/p\u003e\n \u003cp\u003eTable\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003e summarizes the available evidence.In concordance with the above-mentioned observational studies, our results also add to the fact that CRS with HIPEC in upfront settings will increase the survival outcomes.\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003ctable id=\"Tab6\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eTable summarizing the studies on CRS with HIPEC in an upfront setting\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eStudy\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eStudy type\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eStudy groups (No.of patients)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eDrug used in HIPEC\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eDFS\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOS\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLim et al\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePhase 3 RCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCRS\u0026thinsp;+\u0026thinsp;HIPEC\u003c/p\u003e\n \u003cp\u003evs\u003c/p\u003e\n \u003cp\u003eCRS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCisplatin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23.9 vs 29.7 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e71.3 vs 61.4 months\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSomsekhar et al\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAmbispective study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUpfront CRS\u0026thinsp;+\u0026thinsp;HIPEC (80)\u003c/p\u003e\n \u003cp\u003evs\u003c/p\u003e\n \u003cp\u003eInterval CRS\u0026thinsp;+\u0026thinsp;HIPEC (110)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCisplatin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMedian DFS: 33 vs 30 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4-year OS: NR vs 46 months (85%vs 60%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBakrin et al\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRetrospective study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePrimary *\u003c/p\u003e\n \u003cp\u003eCRS\u0026thinsp;+\u0026thinsp;HIPEC (92)\u003c/p\u003e\n \u003cp\u003evs\u003c/p\u003e\n \u003cp\u003eSecondary CRS\u0026thinsp;+\u0026thinsp;HIPEC\u003c/p\u003e\n \u003cp\u003e(474)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCisplatin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e35.4 vs 41.5 months\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBayon et al\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRetrospective Case-Control Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePrimary* CRS\u0026thinsp;+\u0026thinsp;HIPEC (\u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e)\u003c/p\u003e\n \u003cp\u003eVs\u003c/p\u003e\n \u003cp\u003eSecondary CRS\u0026thinsp;+\u0026thinsp;HIPEC (27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCarboplatin or Paclitaxel\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e56.3% (3 years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e66.1% (3 years)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\"\u003e*Primary denotes here ovarian cancer in their first line treatment which includes both upfront and interval settings\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003eOngoing trials such as OVIHIPEC 2 and EHTASEOCCS (\u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e) are investigating the role of HIPEC in upfront CRS, focusing on survival outcomes.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec16\" class=\"Section2\"\u003e\n \u003ch2\u003eInterval setting:\u003c/h2\u003e\n \u003cp\u003eIn stage IIIC ovarian cancer post-NACT, randomized trials support HIPEC use. The OVIHIPEC-1 trial by Van Driel et al. (\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e) demonstrated a 3.5-month increase in RFS and an 11.8-month OS benefit at 4.7 years. A 10.4-year follow-up study (\u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e) reaffirmed these benefits. The Korean study by Lim et al. (\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e) reported increased PFS (17.4 vs. 15.2 months, p\u0026thinsp;=\u0026thinsp;0.04) and OS (61.8 vs. 48.2 months, p\u0026thinsp;=\u0026thinsp;0.04) with HIPEC. The CarcinoHIPEC trial by Campos et al. (\u003cspan class=\"CitationRef\"\u003e16\u003c/span\u003e) found improved DFS (18 vs. 12 months, p\u0026thinsp;=\u0026thinsp;0.038) but no significant OS benefit (52 vs. 45 months, p\u0026thinsp;=\u0026thinsp;0.52). also there was no notable differences in morbidity, mortality, or postoperative quality of life (\u003cspan class=\"CitationRef\"\u003e16\u003c/span\u003e).\u003c/p\u003e\n \u003cp\u003eAdditionally, a phase 2 study by Marrelli et al. involving 46 patients reported favourable outcomes with NACT followed by interval CRS and HIPEC, including improved control of peritoneal carcinomatosis and high survival rates (\u003cspan class=\"CitationRef\"\u003e17\u003c/span\u003e).\u003c/p\u003e\n \u003cp\u003eWhile landmark trials showed HIPEC benefits, our study did not find significant differences between CRS and CRS\u0026thinsp;+\u0026thinsp;HIPEC in the interval setting. This may be due to the inclusion of 18% stage IV cases, unlike previous trials focusing solely on stage IIIC. However, Valentina et al. (\u003cspan class=\"CitationRef\"\u003e18\u003c/span\u003e) reported comparable outcomes in stage IV patients. Ongoing trials like CHIPPI-1808 and CHORINE (\u003cspan class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e) aim to clarify HIPEC\u0026apos;s role. Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e7\u003c/span\u003e summarizes the available literature.\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003ctable id=\"Tab7\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 7\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eTable showing the studies on CRS with HIPEC in the interval setting\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eStudy\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eStudy type\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eStudy group (No. of patients)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eDrug used in HIPEC\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePFS\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOS\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOVIHIPEC 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePhase 3 RCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCRS\u0026thinsp;+\u0026thinsp;HIPEC (123)\u003c/p\u003e\n \u003cp\u003eVs\u003c/p\u003e\n \u003cp\u003eCRS only (122)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCisplatin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRFS - At 4.7 years- 14.2 months vs 10.2\u003c/p\u003e\n \u003cp\u003eAt 10.4 years \u0026minus;\u0026thinsp;10.7 vs 14.3\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(p\u0026thinsp;=\u0026thinsp;0\u0026middot;0008)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAt 4.7 years-\u003c/p\u003e\n \u003cp\u003e45.7 vs 33.9 months\u003c/p\u003e\n \u003cp\u003eAt 10.4 years-33.3 vs 44.9 months\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(p\u0026thinsp;=\u0026thinsp;0\u0026middot;011)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLim et al\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePhase 3 RCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCRS\u0026thinsp;+\u0026thinsp;HIPEC (34)\u003c/p\u003e\n \u003cp\u003eVs\u003c/p\u003e\n \u003cp\u003eCRS only (43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCisplatin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17.4 vs 15.4 months \u003cstrong\u003e(p\u0026thinsp;=\u0026thinsp;0.04)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e61.8 vs 48.2 months \u003cstrong\u003e(p\u0026thinsp;=\u0026thinsp;0.04)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCarcinoHIPEC (Spanish study)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePhase 3 RCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCRS\u0026thinsp;+\u0026thinsp;HIPEC (35)\u003c/p\u003e\n \u003cp\u003eVs\u003c/p\u003e\n \u003cp\u003eCRS only (36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCisplatin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18 vs 12 months \u003cstrong\u003e(p\u0026thinsp;=\u0026thinsp;0.038)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e52 vs 45 months (p\u0026thinsp;=\u0026thinsp;0.52)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec17\" class=\"Section2\"\u003e\n \u003ch2\u003eSecondary setting:\u003c/h2\u003e\n \u003cp\u003eHIPEC\u0026apos;s role in the secondary setting was first explored in the early 2000s. Gori et al. (\u003cspan class=\"CitationRef\"\u003e21\u003c/span\u003e) studied 51 patients undergoing CRS with HIPEC using cisplatin (100 mg/m\u0026sup2;) and found a median survival benefit (64.4 vs. 46.4 months). Adverse effects and mortality rates were comparable between groups, highlighting HIPEC\u0026apos;s feasibility and promise as an alternative to consolidation therapy.Subsequent studies, such as an Italian case-control study conducted by Fagotti et al. (\u003cspan class=\"CitationRef\"\u003e22\u003c/span\u003e) later confirmed improved survival in platinum-sensitive recurrent cases treated with HIPEC.\u003c/p\u003e\n \u003cp\u003eAdditionally, another French multicentric prospective cohort by Bakrin et al. done on both platinum-sensitive and platinum-resistant ovarian cancer patients demonstrated that CRS with HIPEC is feasible and can yield long-term survival in carefully selected patients with recurrent ovarian cancer (\u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e\n \u003cp\u003eSpiliotis et al. (\u003cspan class=\"CitationRef\"\u003e23\u003c/span\u003e) conducted the first RCT in recurrent ovarian cancer, reporting a mean OS of 26.7 months in the HIPEC arm vs. 13.4 months in the CRS-alone group. However, this trial faced criticism regarding data transparency. More recently, the CHIPOR study by Jean-Marc et al. focused on 415 patients at their first platinum-sensitive relapse and compared the outcomes in CRS with HIPEC vs CRS without HIPEC and, demonstrated higher median overall survival in the HIPEC arm (54.3 vs 45.8 months, p value 0.02) (\u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e).\u003c/p\u003e\n \u003cp\u003eOur study included only platinum-sensitive relapses with cisplatin and doxorubicin in HIPEC, yet no significant DFS differences were observed in the secondary setting. Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e8\u003c/span\u003e summarizes key studies on HIPEC in recurrent ovarian cancer.\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003ctable id=\"Tab8\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 8\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eTable showing the studies on CRS with HIPEC in the secondary setting\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003cth style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eStudy name\u003c/p\u003e\n \u003c/th\u003e\n \u003cth style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eType of study\u003c/p\u003e\n \u003c/th\u003e\n \u003cth style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eHIPEC drug\u003c/p\u003e\n \u003c/th\u003e\n \u003cth style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eMedian PFS\u003c/p\u003e\n \u003c/th\u003e\n \u003cth style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eMedian OS\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr style=\"height: 97px;\"\u003e\n \u003ctd style=\"height: 97px;\" align=\"left\"\u003e\n \u003cp\u003eCHIPOR study\u003c/p\u003e\n \u003cp\u003e(2023)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 97px;\" align=\"left\"\u003e\n \u003cp\u003ePhase 3 RCT\u003c/p\u003e\n \u003cp\u003e-First platinum-sensitive relapse included\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 97px;\" align=\"left\"\u003e\n \u003cp\u003ecisplatin 75 mg/m\u0026sup2; at 41\u0026deg;C for 60 min\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 97px;\" align=\"left\"\u003e\n \u003cp\u003ePeritoneal PFS\u003c/p\u003e\n \u003cp\u003eHIPEC vs no HIPEC\u003c/p\u003e\n \u003cp\u003e13.1 vs 12.2 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 97px;\" align=\"left\"\u003e\n \u003cp\u003e54.3 vs 45.8 months \u003cstrong\u003e(p\u0026thinsp;=\u0026thinsp;0.02)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 97px;\"\u003e\n \u003ctd style=\"height: 97px;\" align=\"left\"\u003e\n \u003cp\u003eSpiliotis study (2015)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 97px;\" align=\"left\"\u003e\n \u003cp\u003ePhase 3 RCT\u003c/p\u003e\n \u003cp\u003e-Both Platinum sensitive\u0026amp; resistant relapses included\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 97px;\" align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003ePlatinum sensitive\u003c/strong\u003e- Cisplatin\u0026thinsp;+\u0026thinsp;Paclitaxel\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ePlatinum resistant\u003c/strong\u003e- Doxorubicin\u0026thinsp;+\u0026thinsp;paclitaxel\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 97px;\" align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 97px;\" align=\"left\"\u003e\n \u003cp\u003ePlatinum sensitive: 26.8 vs. 15.2 \u003cstrong\u003e(p\u0026thinsp;=\u0026thinsp;0.035)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003ePlatinum resistant: 26.6 vs 10.2\u003c/p\u003e\n \u003cp\u003e3\u0026nbsp;year OS: 75% vs 18% (\u003cstrong\u003ep: 0.01).\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 72px;\"\u003e\n \u003ctd style=\"height: 72px;\" align=\"left\"\u003e\n \u003cp\u003eBakrin et al (2012)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 72px;\" align=\"left\"\u003e\n \u003cp\u003eMulticentric retrospective study\u003c/p\u003e\n \u003cp\u003eBoth Platinum sensitive and resistant relapses included\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 72px;\" align=\"left\"\u003e\n \u003cp\u003eCisplatin with/without mitomycin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 72px;\" align=\"left\"\u003e\n \u003cp\u003e12.8 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 72px;\" align=\"left\"\u003e\n \u003cp\u003ePlatinum sensitive \u0026minus;\u0026thinsp;52 months\u003c/p\u003e\n \u003cp\u003ePlatinum resistant \u0026ndash; 48 months\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 86px;\"\u003e\n \u003ctd style=\"height: 86px;\" align=\"left\"\u003e\n \u003cp\u003eFagotti et al\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 86px;\" align=\"left\"\u003e\n \u003cp\u003eCase-control study\u003c/p\u003e\n \u003cp\u003eOnly platinum-sensitive cases included\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 86px;\" align=\"left\"\u003e\n \u003cp\u003eOxaliplatin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 86px;\" align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 86px;\" align=\"left\"\u003e\n \u003cp\u003e2-year OS rate \u0026minus;\u0026thinsp;96.7%vs 75% \u003cstrong\u003e(p\u0026thinsp;=\u0026thinsp;0.017)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e5-year OS rate \u0026minus;\u0026thinsp;68.4% vs 42.7% \u003cstrong\u003e(p\u0026thinsp;=\u0026thinsp;0.017)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003eWe analyzed the baseline characteristics and surgical data of the HIPEC and non-HIPEC groups, with Cox regression analysis highlighting key prognostic factors. A high PCI (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and subdiaphragmatic deposits (HR\u0026thinsp;=\u0026thinsp;7.184 in univariate, 3.283 in multivariate) were strong predictors of poor prognosis, emphasizing tumor burden as a critical determinant. Bowel involvement was significant in univariate analysis (p\u0026thinsp;=\u0026thinsp;0.017) but lost significance in multivariate analysis, while bladder involvement was not independently prognostic. HIPEC showed improved prognosis in univariate analysis (p\u0026thinsp;=\u0026thinsp;0.046, HR\u0026thinsp;=\u0026thinsp;1.603) but was not significant in multivariate analysis (p\u0026thinsp;=\u0026thinsp;0.821, HR\u0026thinsp;=\u0026thinsp;1.061), suggesting its effect may be influenced by other factors like PCI. Additionally, operative time was significant in univariate analysis (p\u0026thinsp;=\u0026thinsp;0.012) but not in multivariate analysis, indicating its association with tumor burden rather than direct survival impact. We acknowledge the heterogeneity between the HIPEC and non-HIPEC groups and the potential selection bias. The findings suggest that tumor burden (PCI and subdiaphragmatic disease) plays a crucial role in prognosis. These findings highlight the importance of patient selection for HIPEC, reinforcing that tumor burden and disease distribution are primary determinants of prognosis, whereas HIPEC\u0026rsquo;s survival benefit may be influenced by underlying disease severity and other confounding factors.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec18\" class=\"Section2\"\u003e\n \u003ch2\u003eStrengths \u0026amp; Limitations of our study:\u003c/h2\u003e\n \u003cp\u003eTo the best of our knowledge in indexed literature, our study is the first in India that analyzed the role of CRS with HIPEC across various phases in ovarian cancer. Our study had a comprehensively maintained prospective database which helped in meticulously comparing the outcomes of CRS with HIPEC in both upfront and interval settings across a significant sample size. The inclusion of both short-term and long-term follow-up data enhances the reliability of our findings. Our study reflects a real-world scenario, particularly for a low- and middle-income country (LMIC), providing practical insights that can directly guide treatment decisions in ovarian cancer management and enhance patient outcomes. The management of locally advanced carcinoma ovary is complex and challenging for oncologists. Hence, we hope our study benefits the treating oncologists in other LMICs and stimulates further research in this ever-evolving field.\u003c/p\u003e\n \u003cp\u003eOur study does have a few limitations. Although our study includes a significant number of patients, the sample size may still be insufficient to detect smaller but clinically relevant differences in outcomes between the upfront and interval groups. Our study is retrospective, there may be an inherent risk of selection bias. Patients may have had differing baseline characteristics or disease severities, influencing the outcomes independently of the treatment modality. The indications for aggressive treatment and newer chemotherapeutic agents change over time during the duration of our study.\u003c/p\u003e\n \u003cp\u003eSome patients who achieved optimal cytoreduction but were not offered HIPEC were primarily excluded due to logistical constraints and financial limitations. As HIPEC is a resource-intensive procedure requiring specialized equipment, prolonged operative time, and additional postoperative care, its accessibility remains a challenge, particularly in resource-limited settings. Moreover, a significant proportion of our patient population faced financial constraints, making it difficult to afford HIPEC despite achieving optimal cytoreduction.\u003c/p\u003e\n \u003cp\u003eSince our study was conducted at a single centre, the findings may not be generalizable to other institutions with different patient demographics, surgical techniques, or postoperative care practices, limiting the external validity of our results. While long-term follow-up data is a strength, there were a significant number of patients lost to follow-up in our study cohort. The study may not fully account for all potential confounding variables, such as differences in adjuvant therapies, patient comorbidities, and perioperative care, which could influence the observed outcomes and limit the ability to attribute differences solely to the timing of CRS with HIPEC. Hence large-scale multicentric randomized studies are required to support the findings of our study.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eCytoreductive surgery (CRS) with HIPEC presently play a promising treatment strategy for advanced ovarian cancer, potentially enhancing outcomes compared to conventional therapies in all settings. From our experience, we advocate HIPEC's use across all required treatment stages, particularly in upfront settings. Despite existing challenges and limitations, ongoing research and interdisciplinary cooperation are crucial for advancing the field of CRS with HIPEC in ovarian cancer. Lastly, \"Patient selection is paramount in determining surgical success,\" emphasizing the critical role of appropriate patient selection alongside surgical expertise.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003col start=\"1\" type=\"1\"\u003e\n \u003cli\u003e\u003cstrong\u003eEOC\u003c/strong\u003e - Epithelial Ovarian Cancer\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eCRS\u003c/strong\u003e - Cytoreductive Surgery\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eHIPEC\u003c/strong\u003e - Hyperthermic Intraperitoneal Chemotherapy\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eDFS\u003c/strong\u003e - Disease-Free Survival\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eOS\u003c/strong\u003e - Overall Survival\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003ePCI\u003c/strong\u003e - Peritoneal Cancer Index\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eCC\u003c/strong\u003e - Completeness of Cytoreduction\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eECOG\u003c/strong\u003e - Eastern Cooperative Oncology Group\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eNACT\u003c/strong\u003e - Neoadjuvant Chemotherapy\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eGLOBOCAN\u003c/strong\u003e - Global Cancer Observatory\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eCA-125\u003c/strong\u003e - Cancer Antigen 125\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eSTATA\u003c/strong\u003e - Statistical Software for Data Analysis\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eRFS\u003c/strong\u003e - Recurrence-Free Survival\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003ePFS\u003c/strong\u003e - Progression-Free Survival\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eRCT\u003c/strong\u003e - Randomized Controlled Trial\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eLMIC\u003c/strong\u003e - Low- and Middle-Income Countries\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u0026nbsp;\u003c/strong\u003eInstitutional Ethics clearance was obtained from from \u0026nbsp;Institutional Ethics clearance, AIIMS, New Delhi.\u003c/p\u003e\n\u003cp\u003eFollowing the clearance, this retrospective study was conducted, utilizing our prospectively maintained ovarian cancer database at the Department of Surgical Oncology, Dr. BRA-IRCH, AIIMS, New Delhi.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication: Not Applicable\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u0026nbsp;\u003c/strong\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests: ‘M D Ray and Rohan Kapoor contributed equally to this work and may be treated as First Authors’\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding: Not Applicable\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eM D Ray: Conceptualization, Visualization, Writing of the original draft, editing.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eRohan Kapoor: \u0026nbsp;Data curation, Writing of the original draft, editing.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCarolin Solomi: Data curation, Writing of the original draft, editing.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDivyam Goel: Data curation, Writing of the original draft, editing.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBabul Bansal: Data curation, Writing of the original draft, editing.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements: Not Applicable\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' information:\u003c/strong\u003e \u003cem\u003e\u003csup\u003e#\u0026nbsp;\u003c/sup\u003e\u003c/em\u003e\u003cem\u003eM D Ray\u003csup\u003e1\u003c/sup\u003e, \u003csup\u003e\u0026nbsp;#\u0026nbsp;\u003c/sup\u003eRohan Kapoor \u003csup\u003e1\u0026nbsp;\u003c/sup\u003e, Carolin Solomi\u003csup\u003e2\u003c/sup\u003e, Divyam Goel\u003csup\u003e1\u0026nbsp;\u003c/sup\u003e, Babul Bansal \u003csup\u003e1\u003c/sup\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e1\u003c/sup\u003e Department of Surgical Oncology, All India Institute of Medical Sciences, New Delhi, India\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e2\u003c/sup\u003e Division of Gynaecologic Oncology, Department of Obstetrics \u0026amp; Gynaecology, All India Institute of Medical Sciences, New Delhi, India\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003csup\u003e#\u0026nbsp;\u003c/sup\u003e\u003c/strong\u003e\u003cstrong\u003eFirst Author: M D Ray, Rohan Kapoor\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e‘M D Ray and Rohan Kapoor contributed equally to this work and may be treated as First Authors’\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSiegel RL, Miller KD, Fuchs HE, Jemal A, Cancer statistics. 2022. 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Indian J Surg Oncol. 2023;14(Suppl 1):233\u0026ndash;9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s13193-023-01746-4\u003c/span\u003e\u003cspan address=\"10.1007/s13193-023-01746-4\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"world-journal-of-surgical-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"wjso","sideBox":"Learn more about [World Journal of Surgical Oncology](http://wjso.biomedcentral.com)","snPcode":"12957","submissionUrl":"https://submission.nature.com/new-submission/12957/3","title":"World Journal of Surgical Oncology","twitterHandle":"@OncoBioMed","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Epithelial Ovarian Cancer, Cytoreductive Surgery (CRS), Hyperthermic Intraperitoneal Chemotherapy (HIPEC), Disease-Free Survival, Overall Survival, Peritoneal Carcinomatosis, India","lastPublishedDoi":"10.21203/rs.3.rs-6138215/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6138215/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e The current treatment for advanced epithelial ovarian cancer (EOC) is complete cytoreductive surgery (CRS) followed by adjuvant chemotherapy. Although many patients respond well to this treatment, many will relapse and die from peritoneal carcinomatosis. Adding Hyperthermic Intraperitoneal Chemotherapy (HIPEC) to the standard treatment has been shown to improve survival by reducing cancer recurrence in the abdomen, with acceptable side effects. This article summarizes the current evidence and our long experience with CRS and HIPEC at different stages of ovarian cancer treatment: at upfront CRS, at interval CRS, at secondary CRS, and as palliative setting.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eOur study cohort includes 400 EOC patients who underwent CRS and CRS with HIPEC in upfront, interval, and secondary setting. Cisplatin 75mg/m\u003csup\u003e2\u003c/sup\u003e for 60 minutes was used in all settings.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eFor a median follow-up of 80 months, the DFS in CRS with HIPEC and CRS alone were 34.3 months vs 22.7 months in the upfront group (p \u0026lt;0.001), 18.9 months vs 13.3 months in the interval group, (p 0.04) and 14.7 months vs 11.9 months in secondary group, (p 0.13). The median OS in the CRS with HIPEC vs CRS without HIPEC group was 72.1 months vs 43.3 months in the upfront setting, (p-value 0.034) and 54.2 months vs 44.7 months in the interval setting (p-value 0.44). At 5 years, 49% in the upfront setting and 28% in the interval setting were alive in the CRS with HIPEC arm. There was no difference in Clavien Dindo Grade 3 \u0026amp; 4 postoperative complications among both the groups except for days of hospital stay (p-value 0.016).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions: : \u003c/strong\u003eCytoreductive surgery (CRS) with HIPEC presently play a promising treatment strategy for advanced ovarian cancer, potentially enhancing outcomes compared to conventional therapies in all settings. Thus, adding HIPEC to complete cytoreductive surgery has improved outcomes in all required settings of advanced EOC especially in upfront setting.\u003c/p\u003e","manuscriptTitle":"The Role of Complete Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy in Ovarian Carcinoma: Where Do We Stand Today?A Comprehensive Review and Clinical Insights from a Leading Oncology Center in India","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-14 23:13:24","doi":"10.21203/rs.3.rs-6138215/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-05-17T16:11:19+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-05-10T12:45:00+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-05-09T02:45:27+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-05-08T10:47:43+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"192113996324245322070974143060235554878","date":"2025-05-08T09:02:27+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-05-05T02:33:15+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"178016211149988443476743454510930163552","date":"2025-05-05T02:10:40+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"167394337763493459199307482363836394913","date":"2025-05-03T02:45:39+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"80211459257876937772574580748111381376","date":"2025-05-02T23:20:21+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"293280716824908196050365943164485867356","date":"2025-05-01T04:18:24+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"144036236988712699678762452218309275406","date":"2025-05-01T02:46:10+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"98593200117626441763316146540354043230","date":"2025-04-30T16:33:17+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-04-08T14:57:55+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-04-02T00:50:10+00:00","index":"","fulltext":""},{"type":"submitted","content":"World Journal of Surgical Oncology","date":"2025-03-30T13:25:30+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"world-journal-of-surgical-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"wjso","sideBox":"Learn more about [World Journal of Surgical Oncology](http://wjso.biomedcentral.com)","snPcode":"12957","submissionUrl":"https://submission.nature.com/new-submission/12957/3","title":"World Journal of Surgical Oncology","twitterHandle":"@OncoBioMed","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5ba7bde7-23ab-410f-bba6-20770ab66a41","owner":[],"postedDate":"April 14th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-06-16T16:06:21+00:00","versionOfRecord":{"articleIdentity":"rs-6138215","link":"https://doi.org/10.1186/s12957-025-03869-0","journal":{"identity":"world-journal-of-surgical-oncology","isVorOnly":false,"title":"World Journal of Surgical Oncology"},"publishedOn":"2025-06-11 15:57:40","publishedOnDateReadable":"June 11th, 2025"},"versionCreatedAt":"2025-04-14 23:13:24","video":"","vorDoi":"10.1186/s12957-025-03869-0","vorDoiUrl":"https://doi.org/10.1186/s12957-025-03869-0","workflowStages":[]},"version":"v1","identity":"rs-6138215","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6138215","identity":"rs-6138215","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}