{"paper_id":"b7240220-0a75-4380-9572-294f65c880bf","body_text":"J Women Health Care and Issues                                                                                                                                                                                Copy rights@ Chul Jung Kim \n \n \nAuctores Publishing – Volume 4(3)-052 www.auctoresonline.org  \nISSN: 2642-9756   Page 6 of 6 \n \n \nThe Clinical Characteristics and Treatment Results  \nJung Kim \nDepartment of Obstetrics & Gynecology,Konyang University Hospital.158,Gwanjeodong-ro, Seo-gu, Daejeon, 35365, Rep. of KOREA \nCorresponding author: Jung Kim, Department of Obstetrics & Gynecology,Konyang University Hospital.158,Gwanjeodong-ro, Seo-gu, \nDaejeon, 35365, Rep. of KOREA. \nReceived date: April 07, 2021; Accepted date: April 26, 2021; published Date: May 21, 2021 \nCitation: Chul Jung Kim (2021) The Clinical Characteristics and Treatment Results in the Patients with Clear Cell Carcinoma of the Ovary.  J. \nWomen Health Care and Issues. 4(4); DOI:10.31579/2642-9756/052 \nCopyright: © 2021 Chul Jung Kim , This is an open access article distributed under the Creative Commons Attribution License, which permits \nunrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. \nAbstract \nBackground: It is well known that clear cell carcinoma of the ovary (CCC) demonstrates different clinical behaviors \nfrom other epithelial ovarian cancer and has strong association with endometriosis, thromboembolic complication, \nhypercalcemia, and large pelvic mass. The introduction of cisplatin -based chemotherapy significantly changed the \npostoperative management of ovarian cancer patients. Different studies showed a better response rate of CCC to \nchemotherapy with paclitaxel plus carboplatin regime than with the conventional platinum-based regimens. \nAim: The purpose of this study was to evaluate the patients’ clinical characteristics and treatment results for clear cell \ncarcinoma (CCC) of the ovary treated in paclitaxel -platinum chemotherapy in comparison with those treated in \nconventional platinum-based chemotherapy after primary surgery \nMethods: We retrospectively reviewed the medical records of 40 patients with CCC who received treatment in the \ndepartment of obstetrics and gynecology, Samsung Medical Center from Ma rch, 1996 to April 2006. The clinical \ncharacteristics, treatment results and follow-up data were collected from medical records and/or telephone surveys. \nResults: Mean age was 47 years (range 30 –72 years). Patients with age less than 50years were 62.5%. Tumors were \n15% (6/40) stage IA, 2.5% (1/40) stage IB, 37.5% (15/40) stage IC, 5% (2/40) stage II, 32.5% (13/40) stage III, and \n7.5% (3/40) stage IV. Patients with CCC were more likely to have FIGO stage I & II disease than FIGO stage III & IV \n(60% vs. 40%). Five -year progression-free survival and overall survival were 91% and 80% in stage I & II, 36% and \n55% in stage III & IV, respectively (5-yr PFS; P<0.01, 5-yr OS; P=0.03). With a median follow-up of 45 months (2-112 \nmonths), 75% (18/24) of stage I/II patients are alive, while 19% (3/16) of stage III/IV patients are alive. 37.5% (15/40) \nof the patients presented with endometriosis. Except for one patient who was re ferred by a local clinic, all patients \nunderwent cytoreductive surgery. The rate of optimal debulking (≤ 1cm residual tumor diameter) was 90% (36/40). \nOverall, for women treated with platinum -based chemotherapy, 75% (27/36) had clinically complete response s to \nadjuvant chemotherapy. But there was no survival benefit according to chemotherapeutic differences in the patients who \nreceived cytoreductive surgery followed between conventional platinum -based chemotherapy (CAP or CP) and by \npaclitaxel and platinum -based chemotherapy (P=0.40). Univariate analysis showed that stage was the only favorable \nprognostic factor for women with clear cell carcinoma of the ovary (P=0.04). \nConclusions: Our results suggest that CCC has a distinct clinical behavior, similar to previous studies, that frequently \npresents at early- stages and is associated with endometriosis. In addition, there was a close correlation between the level \nof CA-125 and survival, and there was no survival benefit according to chemotherapeutic differences. 〔CAP (CP) VS \nTP(TC)〕 \nKey Words: clear cell carcinoma; ovary; platinum-based chemotherapy \nIntroduction \nClear cell carcinoma has been recognized as a distinct histological entity \nin the World Health Organization classification of ovarian tumors since \n1973. The precise incidence of this tumor is unknown but estimated to be \n5–10% of all epithelial ovarian canc ers diagnosed [1]. Clear cell \ncarcinoma of the ovary (CCC) is a distinctive subtype of epithelial ovarian \ncancer that demonstrates different clinical behaviors from other epithelial \novarian cancer [2-5]. Several studies have reported that CCC has a high \nincidence rate of endometriosis, thromboembolic complication, \nhypercalcemia, and large pelvic mass. CCC tends to present at earlier \nstages, with 59~71% of all patients presenting with stage I and II disease. \nAlthough half of the patients have stage I disease at the diagnosis, they \nhave poorer prognoses than do those with other epithelial ovarian cancer \n[2, 6-8]. A significant proportion of women (20 –50%) with stage I clear \ncell ovarian carcinoma have recurrences and die of their malignancies[2]. \nThe introduction of cisplatin -based chemotherapy in the late 1970s \n  Open Access  \n    Research Article \n .     Journal of Women Health Care and Issues \n                                                                                                                  Chul Jung Kim*                                                                                                                                                        \nAUCTORES \nGlobalize your   Research \n\nJ Women Health Care and Issues                                                                                                                                                                                Copy rights@ Chul Jung Kim \n \n \nAuctores Publishing – Volume 4(3)-052 www.auctoresonline.org  \nISSN: 2642-9756   Page 6 of 6 \nmarkedly changed the postoperative management of ovarian cancer \npatients. Nonetheless, the results and value of these newer efforts and \ntherapies applied to clear cell carcinoma are yet und etermined [2, 9, 10]. \nThe most distinctive characteristic is that CCC has a low response rate to \nchemotherapy [7, 11 -15]. The response rate of c hemotherapy for CCC \nwas 11.1% with platinum -based regimens [11] and 22 -56% with \npaclitaxel 64 plus carboplatin [16]. In the study by Goff et al, overall, 70% \nof the 23 evaluable patients with stage III OCCA showed progression of \ndisease while on platinum -based chemotherapy, which is significantly \ndifferent from the 29% rate of progressive disease observed in patients \nwith papillary serous carcinoma [9]. \nWe conducted the retrospective study to evaluate the clinical \ncharacteristics of the patients with CCC of the ovary and to compare \ntreatment results of paclitaxel-platinum chemotherapy with those treated \nin conventional platinum-based chemotherapy after primary surgery. \nMaterials and Methods \nWe retrospectively reviewed the medical records of 40 patients with CCC \nwho received treatment in obstetrics and gynecology department, \nSamsung Medical Center from March 1996 to April 2006. Data were \ncollected from medical records and telephone surveys. All pathological \nspecimens (3outside specimens) from primary surgery were reviewed by \npathologists worked at Samsung Medical Center. Two of the 4 0 patients \nhad mixed – type (papillary, sarcomatous type) CCC. \n34patients underwent surgical staging including total hysterectomy, \nbilateral salpingooophorectomy, omentectomy, intraperitoneal cytology, \nwith/without pelvic and/or para -aortic lymphadenectomy . The other 6 \npatients underwent total hysterectomy, bilateral salpingooophorectomy. \nThirty-eight of the 40 patients with CCC (95%) received platinum -based \nchemotherapy after the initial surgery. among 38patients who received \nchemotherapy, one of 2 patient s received only one cycle of TP and the \nother received one cycle of TC, and then they did not receive any more \nchemotherapy. So, they were excluded from the evaluation of the \nresponse to chemotherapy. 30 patients received adjuvant chemotherapy \ncombining pa clitaxel 135mg/m2 and cisplatin 75mg/m2 (20cases), or \npaclitaxel 175mg/m2 and carboplatin (AUC=5) (10cases) at every 3 \nweeks . 6 patients received combination therapy of cyclophosphamide \n500mg/m2, Adriamycin 50mg/m2 and cisplatin 50mg/m2 (CAP) (1case) \nor cisplatin 50mg/m2 and cyclophosphamide 750mg/m2 (CP)(5cases) at \nevery 3 weeks. \nResponse to chemotherapy was evaluated with CT or MRI for patients \nwith clinically measurable disease, according to RECIST criteria or \nassessed in patients with non -measurable disease, according to the level \nof CA-125 combined with CT/MRI. By definition of RECIST criteria, a \ncomplete response (CR) was defined as the complete disappearance of all \ndetectable disease for at least 4 weeks. A partial response (PR) was \ndefined as a ≥ 30 % decrease in tumor size for at least 4 weeks. Stable \ndisease (SD) was defined as the absence of any significant change in \nmeasurable lesions for at least 4 weeks. Progressive disease (PD) was \ndefined as the appearance of a new lesion or a ≥20% increase in  tumor \nsize. According to the level of CA125, PD was defined as the elevation of \nCA125 to ≥2 x UNL or ≥2 x nadir value. \nThe time to progression was defined as the interval from the date of \nprimary surgery until the date of documented recurrence or tumor \nprogression (PD). The Survival duration was determined as the time from \nthe date of primary surgery until death or the date of last follow -up \ncontact. \nStatistical Methods \nPatient survival distribution was calculated using the Kaplan –Meier \nmethod. The significance of the survival distribution in each group was \ntested by the log rank test. The hazard ratios with 95% confidence \nintervals (95%CIs) were estimated by using a Cox’s proportional hazard \nmodel to evaluate prognostic factors for survival. A P- value of 0.05 was \nconsidered statistically significant. \nResult \nThe characteristics of Patients are summarized in Table 1.  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\nJ Women Health Care and Issues                                                                                                                                                                                Copy rights@ Chul Jung Kim \n \n \nAuctores Publishing – Volume 4(3)-052 www.auctoresonline.org  \nISSN: 2642-9756   Page 6 of 6 \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \nTable.1. the characteristics of patients with clear cell carcinoma of the ovary \nThe median age of the 40 patients was 47 years (range 30~72years). The \nMedian duration  \nOf follow–up was 45months (range 4~112months). Patients with age less \nthan 50years were 62.5% and those more than 50years were 37.5%. \nAccording to the classification of the International Federation of \nObstetrics and Gynecology (FIGO), Tumors were 15% (6/40) stage Ia, \n2.5% (1/40) stage Ib, 37.5% (15/40)  stage Ic, 5% (2/40) stage II, 32.5% \n(13/40) stage III, and 7.5% (3/40) stage IV, respectively. Of the 40 \npatients with CCC, the level of Preoperative CA -125 was more than 100 \nU/ml in 18patients (45%), less than <100U/ml in 22patients (55%). 37.5% \n(15/40) of the patients with CCC presented with endometriosis. The rate \nof optimal debulking (≤ 1cm residual tumor diameter) was 90% (36/40 ). \n(Table1).38patients (95%) with CCC received platinum -based \nchemotherapy after initial surgery. among 38patients who receiv ed \nchemotherapy, one of 2patients received only one cycle of TP and the \nother received one cycle of TC. They did not any more chemotherapy. \nOne of two patients died of disease (DOD), the other did not receive \nfollow-up. So, those 2patients were therefore e xcluded from the analysis \nfor response of adjuvant chemotherapy. Among 2patients without \nreceiving chemotherapy, one has been NED status; the other developed \nrecurrence and died of renal failure. 30patients received adjuvant \nchemotherapy combining paclitax el 135mg/m2 and cisplatin75mg/m2 \n(20cases), or paclitaxel 175mg/m2 and carboplatin (AUC=5) (10cases) at \nevery 3weeks. 6patients received combination therapy of \ncyclophosphamide 500mg/m2, adriamycin 50mg/m2 and cisplatin \n50mg/m2 (CAP) (1case) or cisplatin 5 0mg/m2 and cyclophophamide \n750mg/m2 (CP)(5cases) at every 3 weeks. For women treated with \nplatinum-based chemotherapy, the overall clinical response rate was 89%, \nincluding a CR in 75% (27/36) and a PR in 14% (5/36), to adjuvant \nchemotherapy. SD was 8% (3/ 36) and PD was 3% (1/36) ( Table2).  \nCurrent status of patients at last f/u was NED in 20(50%) cases, AWD \n  CAP(CP) Paclitaxel+ cisplatin(carboplatin) Chemo(-) Total (%) \nCharacteristics No of patients (%) \nAll case 40 \nAge(years)  \nMean age 47(30~72) \n<50 25(62.5) \n≥50 15(37.5) \nFIGO Stage  \nI 22(55) \nIA 6(15) \nIB 1(2.5) \nIC 15(37.5) \nII 2(5.0) \nIIA 0(0) \nIIB 0(0) \nIIC 2(5) \nIII 13(32.5) \nIIIA 0(0) \nIIIB 4(7.5) \nIIIC 9(22.5) \nIV 3(7.5) \nPresence of endometriosis  \nYes 15(37.5) \nNo 25(62.5) \nPreoperative CA-125 level  \nMean(range) \n<100 U/ml \n>100 U/ml \n793(4.8~14640) \n22(55) \n18(45) \nResidual tumor diameter  \n<1cm 36(90) \n>1cm 4(10) \nPostoperative chemotherapy  \nCAP(CP) 6(15) \nPaclitaxel + cisplatin(carboplatin) 32(80) \nNone 2( 5) \n\nJ Women Health Care and Issues                                                                                                                                                                                Copy rights@ Chul Jung Kim \n \n \nAuctores Publishing – Volume 4(3)-052 www.auctoresonline.org  \nISSN: 2642-9756   Page 6 of 6 \nResponse CR 6(100) 21(70)  27(75) \n PR 0 5(17)  5(14) \n SD 0 3(10)  3( 8) \n PD 0 1(3)  1( 3) \n Total 6 30  36 \nCurrent status \nat last F/U \nNED 4(67) 15(50) 1(25) 20(50) \nAWD 0 5(17) 0 5(13) \nDOD 2(33) 10(33) 2(50) 14(35) \n F/U loss   1(25) 1( 2) \n Total 6 30 4 40 \nTable 2.Response of adjuvant-chemotherapy and current status at last F/U \nBut there was no survival benefit according to chemotherapeutic differences in the patients who received cytoreductive surger y followed by \nconventional platinum-based chemotherapy (CAP or CP) or paclitaxel and platinum-based chemotherapy (P=0.82 & P=0.40). (Table3). \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \nCox`sregression analysis (Table 3). \nTable 3: Univariate and multivariate Cox`s regression analysis of clinical variables affecting overall survival for patients with CCC \nCox`s regression analysis in patients with CCC revealed that the level of \npreoperative CA -125 was not a significant difference but had a \nremarkable correlation with overall survival in patients with CCC \n(P=0.051). The results from the univariate analysis showed that stage was \nthe only prognostic factor for affecting overall survival in patients with \nCCC. But multivariate analysis showed stage was not an independent \nprognostic factor. Other covariates (age, parity, pre -op CA -125, ES, \nascites, residual tumor, chemotherapy regimen) were not significant \nprognostic factors according to univariates and multivariate. \nThe differences in PFS and OS of between the subgroups (residual tumor \ndiameter <1cm group vs. >1cm group) were not statistically significant in \npatients with stage I & II (P=0.53, P=0.47, respectively) and with stage \nIII & IV (P=0.39, P=0.20, respectively) (Figure was not shown in this \narticle). But, the patients with stage I & II had significant ly better PFS \nand OS than those with stage III & IV. (P<0.01. P=0.03, respectively). \nEstimated 5-year PFS and OS were 91% and 80% in stage I & II, 36% \nand 55% in stage III & IV, respectively. Median PFS was 22months, and \nHazard ratio \n \nVariables \n \nNo \n \nUnivariate \n(95%CI) \np- value \n \nMultivariate \n(95%CI) \np-value \nAge   0.63  0.93 \n≤50 27 1  1  \n>50 13 1.31(0.43-4.02)  0.93(0.20-4.32)  \nParity   0.11  0.22 \nNulliparous 5 1  1  \nParous 35 0.33(0.08-1.29)  0.41(0.09-1.73)  \nPreopCA-125   0.05  0.26 \n<100 22 1  1  \n>100 18 3.10(0.99-9.65)  2.09(0.57-7.26)  \nES   0.25  0.78 \nNo 25 1  1  \nYes 15 0.49(0.14-1.66)  0.81(0.18-3.62)  \nAscite   0.40  0.50 \nNo 27 1  1  \nYes 13 1.61(0.53-4.94)  1.56(0.42-5.68)  \nResudual tumor   0.27  0.28 \n>1cm 6 1  1  \n<1cm 34 0.48(0.13-1.76)  0.40(0.08-2.10)  \n      \nFIGO stage   0.04  0.36 \nI,II 24 1  1  \nIII,IV 16 3.27(1.05-10.13)  1.89(0.48-7.44)  \nChemotherapy   0.82  0.40 \nCP(CAP) 6 1  1  \nPaclitaxel \n+platinum \n32 1.30(0.28-5.96)  0.39(0.04-3.24)  \nNone 2 2.19(0.19-24.8)  2.19(0.09-51.5)  \n\nJ Women Health Care and Issues                                                                                                                                                                                Copy rights@ Chul Jung Kim \n \n \nAuctores Publishing – Volume 4(3)-052 www.auctoresonline.org  \nISSN: 2642-9756   Page 6 of 6 \nmedian OS was 69months in stages III & IV (Figure 1 & 2). \n \nFigure 1: kaplan- meier estimated progression free survival. \n \nFigure 2: Kaplan- Meier estimated overall survival. \n \n\nJ Women Health Care and Issues                                                                                                                                                                                Copy rights@ Chul Jung Kim \n \n \nAuctores Publishing – Volume 4(3)-052 www.auctoresonline.org  \nISSN: 2642-9756   Page 6 of 6 \nDiscussion \nCCC has been reported to be an interesting histology type classified as a \nsubgroup of epithelial ovarian cancer with unique clinical characteristics \n[8, 10, 11] . Several studies suggest that CCC of the ovary tended to \npresent at earlier stages. The proportion of stage I/II tumors ranged from \n59 to 71% [2, 8, 11, 17] . Our study also supported those reports [stage I \n& II disease vs. stage III & IV (60% vs. 40%)] especially, among patients \nwith stage I CCC, the majority has stage IC (15/22 in stage I). The present \nstudy compared with other reports had a similar finding that CCC was \naccompanied with endometriosis (37.5%). The association between \nendometriosis and clear cell or endometrioid ovarian cancer is well \ndocumented [18, 19] . Sampson was the first author who described a \npossible association between ovarian cancer  and endometriosis. Since \nthen, several studies have reported a potential malignant transformation \nof endometriosis in the ovary. The frequency of coexistent endometriosis \nin patients with CCC ranged from 5~54% [18-22]. \nThe reasons for early -stage detection of CCC may be explained by the \nslow gr owing behavior and frequent presentation as relatively large \nmasses and by the fact that endometriosis may be symptomatic, which \nmay lead to an earlier diagnosis of this otherwise silent disease in early \nstages [23]. In our study of patients with CCC, endometriosis was \nassociated with 37.5% of the clear cell ovarian cancer. Some studies \nreported that patients having ovarian clear cell carcinoma with  pelvic \nendometriosis exhibited a better prognosis than those without \nendometriosis  [24]. On the contrary, other studies suggested that there \nare no statistical differences concerning the recurrence or survival [23]. \nThere was no statistical difference regarding overall survival in our study \n(P=0.25). However, careful attention is required to interpret this result  \nbecause of the small sample size in the current study. \nMore than 80% of epithelial ovarian cancers are found in postmenopausal \nwomen. The peak incidence of epithelial ovarian cancer is 56 to 60 years \nof age [25]. However, the incidence age of CCC ranges from 30 to 72 \nyears of age in the current study. This cancer is relatively common in \nwomen younger than age 50(62.5%). Especially, there were 8(20%) \npatients in the fourth decade and 17(42.5%) patients in the fifth decade in \nour study. \nInterestingly, there was a close correlation between the level of CA -125 \nand survival in the present study, although there was no statistical \nsignificance (p=0.051). The serum level of CA-125 is commonly used as \nthe most available diagnostic marker for ovarian cancer. But, the level is \nrelatively low in CCC. Meyer et al reported that 50% of patients with \nCCA did not show abnormal CA -125 levels [26]. Thus  CA-125 \nmeasurements cannot often contribute to the detection of ovarian cancer, \nespecially CCC, in the clinic, and this failure may lead to difficulties in \nproviding a proper therapy. Therefore, to achieve a more successful \nclinical treatment of ovarian cancer, new markers are needed that improve \nspecificity and early detection of CCC. Recently, Morita et al reported \nthat they discovered clinically useful candidates by a proteomic approach \n[27]. But, there have yet been no reliable biomarker for diagnosis and \ntarget therapy. \nThe rate of optimal debulking (≤ 1cm residual tumor diameter) in the \npresent study was 90% (36/40). But, there was no difference in survival \nbetween patients who received optimal and suboptimal cytoreduction \n(P=0.27 & 0.28 univariate & multivariate analysis, respectively). In \ngeneral, optimal cytoreduction is a well-known prognostic factor in other \nsubtypes of epithelial ovarian cancers [6, 7]. However, due to the small \nnumber of cases (10%, 4/40) in the suboptimal group, we considered that \nour study showed no significant difference in survival. Therefore, there \nwas a little bit of pitfall for Statistical analysis. \nThe results from univariate analysis showed that stage was the only \nprognostic factor for affecting overall survival in patients with CCC. But \nmultivariate analysis showed that stage was not an independent \nprognostic factor. Such results may be considered due to the high \nproportion of optimal cytoreduction (≤ 1cm residual tumor diameter) in \nour study [90 % (36/40)]. Other covari ates (age, parity, pre -op CA-125, \nES, ascites, residual tumor, chemotherapy regimen) were not significant \nprognostic factors according to univariates and multivariate Cox`s \nregression analysis. \nFor women treated with platinum -based chemotherapy, the overal l \nclinical response rate was 89%, including a CR in 75% (27/36) and a PR \nin 14% (5/36), to adjuvant chemotherapy. Our study showed a very higher \nresponse rate (89%) with platinum-based chemotherapy in CCCs than do \nthe show in other histologic types of epit helial ovarian cancer.it may be \ndue to a relatively large proportion of patients with early stage than other \nhistologic types of epithelial ovarian cancer and a higher rate of optimal \ndebulking surgery (90%). But, there was no survival benefit according to \nthe chemotherapeutic regimen in the patients who received cytoreductive \nsurgery followed in between by conventional platinum -based \nchemotherapy (CAP or CP) and by paclitaxel and platinum -based \nchemotherapy (P=0.40). Among patients receiving CP (CAP) \nchemotherapy in the current study, four patients with stage IA, one patient \nwith stage IB, and another one patient with stage IC. Among Other \npatients receiving TP (TC) chemotherapy, all patients except one with \nstage IA were more than stage IC. Combination chemotherapy consisting \nof a platinum analog and paclitaxel after debulking -surgery is the \nestablished standard therapy for advanced ovarian cancer. But, the \noptimal chemotherapeutic regimen for CCC is still being debated. Clear \ncell carcinoma is treated in t he same manner as other epithelial ovarian \ncarcinomas at our institute, without any particular consideration because \nof its low rate of incidence among epithelial ovarian carcinoma patients. \nHowever, stage IA and IB patients with CCC were treated by CAP (C P) \nin our institute, because of government `s policy (national health \ninsurance). There have been only a few reports to document the response \nof chemotherapeutic regimen for CCC patients, but each of them included \na relatively small number of cases. The tw o reports suggested that CAP \nregimen showed a low response rate and quite a high incidence of PD in \nCCC patients [6, 11]. Recio et al. demonstrated that platinum -based \nchemotherapy did not appear to improve the survival of patients with clear \ncell carcinoma compared to survival of patients given nonplatinum-based \nchemotherapy. They suggested that platinum -based chemotherapy such \nas cisplatin, Adriamycin, cyclophosphamide (PAC), or cisplatin and \ncyclophosphamide (CP) have generally low lacked sensitivity for  clear \ncell carcinoma of the ovary [13]. In support of this conclusion, Gorai et al \nreported that clear cell carcinoma cells exhibited resistance to cisplatin in \nvitro study [12]. Ho et al suggested a potential benefit of paclitaxel and \ncarboplatin regimen  for stage I clear cell carcinoma in comparison to \nregimen reported in previous studies [28]. Another study by Ho et al \nshowed that paclitaxel plus platinum-based chemotherapy for improving \nsurvival among patients with stage III and IV clear cell carcinoma  [16]. \nBased on their study, they suggested that paclitaxel plus platinum regimen \nhad a higher response rate compared to conventional platinum -based \nchemotherapy [16]. However, the results by Takano et al showed that \nthere was no survival benefit with chem otherapy with paclitaxel and \nplatinum compared with CAP regimen in both early and advanced cases \n[6]. Also, our series showed no survival benefit between paclitaxel and \nplatinum and CAP regimen in patients with CCC. The current series might \nsupport the res ults of ACTION study which no benefit of adjuvant \nchemotherapy was observed in early -stage ovarian cancer with optimal \nsurgical procedures [29], despite CCC or this might be interpreted as like \nthat, due to a very small number of cases in CP (CAP) group. Until now, \nthere is no clinical trial for the treatment of CCC patients of the ovary. \nFurther studies are needed to establish the candidate regimen for CCC of \nthe ovary. \n\nJ Women Health Care and Issues                                                                                                                                                                                Copy rights@ Chul Jung Kim \n \n \nAuctores Publishing – Volume 4(3)-052 www.auctoresonline.org  \nISSN: 2642-9756   Page 6 of 6 \nIn general, many authors have stated that serous epithelial ovarian cancer \nhas a better prognosis at both early stage and advanced stage than CCC. \nOmura et al. suggested that the median time to death was 6.7months for \nthe women with CCC compared to 16.4 months for those with stage III & \nIV serous epithelial ovarian cancer [30]. Also, Goff et  al reported that \nCCC was associated with a poorer outcome, with a median survival of \n12months compared to 22 months for serous carcinoma [9]. In contrast, \nSugiyama et al. reported that the estimated 5-yr OS for patients with CCC \ndid not differ significant ly from that for patients with serous \nadenocarcinoma [52% in CCC vs 44.1% in SAC] [11]. Also, Kennedy et \nal. reported that the overall survival for patients with CCC was identical \nto that for patients with other high-grade epithelial ovarian cancers when \ncontrolled for grade and stage [31]. Ryu et al suggested that CCC of the \novary showed 57% overall 5-year survival rate. In stage I disease, 5-year \nsurvival rate of CCC of the ovary is comparable to that of other epithelial \novarian cancers (82% versus 85%). However, advanced-stage CCC of the \novary showed an extremely poorer prognosis than the other epithelial \novarian cancers (7% versus 25%), with the stage serving as the strongest \nprognostic factor [32]. In the present study, CCC of the ovary showed a \nmore favorable prognosis than expected. In our study showed that 5 -yr \nPFS and 5-yr OS of CCC have similar or better than that of other epithelial \novarian cancer. [91% and 80% in stage I & II, 36% and 55% in stages III \n& IV, respectively in CCC]. Median PFS was 22months, and median OS \nwas 69months in stage III & IV. why there are rather favorable overall \nsurvival rates associated with CCC of the ovary may be explained by the \nrelatively large proportion of early -stage disease [60% (24/40)], high \nproportion of optima l cytoreduction (≤ 1cm residual tumor diameter) \n[90% (36/40)] and the chemotherapy with paclitaxel plus platinum \n(cisplatin or carboplatin) which administered to patients with CCC \n(mainly ≥stage IC) as a main chemotherapy regimen [83%(30/36)]. \nAccording to  many studies, patients with early -stage CCC have a \nrelatively favorable prognosis than expected, but patients with advanced-\nstage CCC have a poorer prognosis than do those with other pathological \ntypes of epithelial ovarian cancer, because of its chemores istance and \nhighly invasive character. Therefore, it may be important for the \nimprovement of survival in patients with CCC that early detection and \noptimal debulking-operation of patients with CCC. Considering the limit \nof CA-125 that 50% of patients with CCC did not show abnormal CA -\n125 levels [26], studies for finding of new markers that improve \nspecificity and early detection of CCC are warranted. \nDue to the very small number of cases in both stage II and stage IV, \nAnalysis was done divided two subgroups . Therefore, further analysis \nshould be conducted, if a larger number of patients with CCC would be \ngathered later. But, to my knowledge, until now, among single research \ninstitution published papers, our study has the largest number of patients \nwith CCC. Therefore, the method of therapies (surgery or chemotherapy) \nwhich was followed at our single institution was more homogeneous than \nthat done at multi -center research so that there may be advantages to \nanalysis and evaluation of the results because of fewe r confounding \nfactors. But, clearer information of the clinical characteristics and \ntreatment results in the patients with CCC, a large -scale, multi -center, \nprospective clinical trial is warranted. \nConclusion \nOur results suggest that CCC has a distinct clinical behavior, similar to \nprevious studies, that frequently presents at early- stages and is \nassociated with endometriosis. In addition, there was a close correlation \nbetween the level of CA-125 and survival, and there was no survival \nbenefit according to chemotherapeutic differences. 〔CAP (CP) VS TP \n(TC)〕 \nReferences: \n1. Russell P, Bannatyne P. Surgical pathology of the ovaries. \nNew-York: Churchill Livingstone, 1989. \n2. 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Ryu SY, Park SI, Nam BH, Kim I, Yoo CW, Nam JH, et al. \nPrognostic significance of histological grade in clear -cell \ncarcinoma of the ovary: a retrospective study of Korean \nGynecologic Oncology Group. Ann Oncol 2009; 20: 1032 -\n1036.\n \n \n \n \n \n \n \n \n This work is licensed under Creative    \n   Commons Attribution 4.0 License \n \n \nTo Submit Your Article Click Here: Submi Manuscript \n \nDOI:10.31579/2642-9756/052\n \n \n \n \nReady to submit your research? Choose Auctores and benefit from:  \n \n fast, convenient online submission \n rigorous peer review by experienced research in your field  \n rapid publication on acceptance  \n authors retain copyrights \n unique DOI for all articles \n immediate, unrestricted online access \n \nAt Auctores, research is always in progress. \n \nLearn more www.auctoresonline.org/journals/women-health-care-and-\nissues","source_license":"CC0","license_restricted":false}