Oncological Outcomes of Primary Prostate Cancer Patients Treated with Focal Cryotherapy. Does Gleason Impact Results?

Oncological Outcomes of Primary Prostate Cancer Patients Treated with Focal Cryotherapy. 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Does Gleason Impact Results? Kinga Mate, Pedro de Pablos-Rodríguez, Marta Burbano Herraiz, and 11 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6285402/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose Focal cryotherapy is a minimally invasive treatment for localized prostate cancer (PCa), but its medium-term oncological outcomes, particularly in relation to baseline Gleason Grade Group (GG), remain understudied. This study evaluates its efficacy and the impact of baseline Gleason score on recurrence-free survival. Methods A retrospective analysis included 111 patients with localized PCa treated with focal cryotherapy between 2014 and January 2025. Patients with prior treatments or follow-up < 12 months were excluded. All patients underwent MRI and transperineal biopsy, with cryotherapy performed using the Visual ICE Cryoablation System. Confirmatory biopsies were recommended at 12–24 months post-treatment. Recurrence was classified as in-field (treated or adjacent areas) or out-field (non-adjacent areas). Any recurrence-free survival was defined as the absence of positive biopsy or additional treatment, while radical treatment-free survival was defined as the absence of whole-gland treatment (e.g., radical prostatectomy, radiotherapy), androgen deprivation therapy, metastasis, or death. Outcomes were compared between patients with baseline GG 1 and GG > 1. Results Median follow-up was 35 months (IQR 24–49). Confirmatory biopsies were performed in 78% of patients (n = 87), revealing in-field recurrence in 14% and out-field recurrence in 23%. No significant differences in recurrence rates were observed between GG 1 and GG > 1 patients (p = 0.9 for in-field; p = 0.8 for out-field). The 3-year any recurrence-free and radical treatment-free survival rates were 63% and 85%, respectively, with no significant variation by baseline GG. Conclusion Focal cryotherapy demonstrates favorable medium-term oncological outcomes for localized PCa, with no significant differences in recurrence-free survival based on baseline Gleason score. These findings support its role as a viable treatment option for patients seeking to minimize treatment-related morbidity. Prostate cancer focal cryotherapy recurrence rate in-field out-field Figures Figure 1 Figure 2 Figure 3 INTRODUCTION Prostate cancer (PCa) is one of the most commonly diagnosed malignancies in men worldwide. In Europe, it is the most frequently diagnosed cancer in men and ranks as the third leading cause of cancer-related mortality [ ]. The standard treatment options for localized PCa patients are active surveillance (AS), radical prostatectomy (RP) or radiotherapy (RT). However, RP and RT are associated with significant morbidity, including urinary incontinence, erectile dysfunction, all of which can adversely impact quality of life [ ]. Additionally, active surveillance requires regular follow-up consisting of PSA testing, clinical examination, MRI imaging and repeated prostate biopsies. More than one-third of patients are reclassified during follow-up, with the majority undergoing curative treatment for disease progression [ ]. To enhance the benefit-to-risk ratio, alternative therapies have emerged that aim to minimize adverse effects while maintaining positive oncological outcomes. Focal cryotherapy, also known as cryoablation or cryosurgery, is a promising alternative for localized PCa. It enables targeted destruction of tumor tissue while preserving surrounding healthy structures. This technique induces apoptosis by application of cryo-needles into the targeted area, leading to cell death via coagulative necrosis [ ]. The ideal candidate for focal cryotherapy remains uncertain. Patients with intermediate D Amico risk with visible lesion in the MRI appear to be the primary candidates [ ]. Additionally, patients with low-risk disease but MRI-visible lesions have been reported to have worse oncological outcomes compared to those with non-visible lesions when initiating an active surveillance protocol [ ]. Furthermore, there is a lack of data comparing oncological outcomes based on patient’s Grade Group (GG) Gleason score following focal therapy (FT). Several studies have highlighted the favorable functional outcomes of cryoablation particularly, when compared to standard treatments (RP or RT) [ , , ]. However, oncological outcomes remain a critical area of investigation to determine the safety of this approach in managing localized PCa. Current guidelines from the NCCN [ ] and EAU [ ] recommend performing cryotherapy within prospective registries or clinical trials. To date, only a few centers have reported oncological outcomes following cryotherapy, and none have specifically evaluated its relationship with baseline GG disease. In this study, we present our experience with medium-term follow-up of patients treated with focal cryotherapy, focusing on the influence of baseline Gleason score. MATERIALS AND METHODS Retrospective study of consecutive patients with primary PCa who underwent cryotherapy between 2014 and January 2025 at out institution. Patients with prior treatments or a follow-up shorter than 12 months after cryotherapy were excluded. Eligibility for cryotherapy was determined based on the physician criteria. Data were collected from a PCa registry (CAPROSIVO), which was approved by the local ethics committee. All patients underwent preoperative MRI, with or without regions of interest (ROI), followed by transperineal biopsy. Most MRIs were performed at Valencian Institute of Oncology using the General Electric Signa Artist 1.5 Tesla model. The images were interpreted by three experienced radiologists using the PI-RADS 2.0 or 2.1 version. For each ROI, 3–5 cores targeted biopsy cores were obtained, and systematic sextant biopsies (20 to 30 cores) were performed following a modified version of Dickinson scheme, as previously described [ ]. Biopsies were conducted using the Hitachi V70 ultrasound system, with Biopsee software (Medcom) employed for fusion when required. Cryotherapy was performed by the same experienced urologist (J.C.R) using Visual ICE Cryoablation System (Boston Scientific). Patients were treated under general anesthesia with 2–4 IceSeed needles and were discharged the following day with a bladder catheter. The first visit was made 7–10 days after surgery, when the bladder catheter was removed. No adjuvant deprivation therapy (ADT) was used. Patients were advised to undergo a unique confirmatory biopsy at 12–24 months after cryotherapy, unless recurrence was suspected earlier. Regarding oncological outcomes, in-field recurrence was defined as any cancer foci within the previously treated area or directly adjacent regions. Adjacency was determined based on the transverse or craniocaudal sextants, excluding oblique or other sextants. Out-field recurrence referred to the detection of any cancer in non-adjacent areas of the prostate. Any recurrence-free survival was defined as the absence of a positive biopsy or any additional treatment at any time during follow-up. Radical treatment-free survival was considered as the absence of whole-gland treatment (brachytherapy, RT, RP), ADT, metastasis or death. At last, a comparison was made between patients with baseline GG 1 vs GG > 1. Statistical analysis Differences in categorical variables were assessed using chi-square tests, while differences in continuous variables were evaluated with t-test or Mann-Whitney U tests, as appropriate. The Log-Rank test and Kaplan-Meier curves were used to compare any recurrence and radical treatment-free survival between the GG 1 and GG > 1 cohorts. All statistical analyses were performed using Python 3.13.0 software, with a significance level set at p < 0.05. RESULTS A total of 111 patients with localized PCa treated by focal cryotherapy were included. The median follow-up was 35 months (IQR 24–49). The median age at the time of cryotherapy was 70 years (IQR 64–74) and the median PSA was 6.3 ng/ml (IQR 4.6–8.6). As shown in Table 1 , the majority of patients had non-palpable disease (91%) but visible lesions on MRI (80%). Table 1 Baseline patient characteristics Total of patients (N 111) GG 1 (N 40) GG > 1 (N 71) P value Age, median (IQR), years 70 (64–74) 66 (63–71) 72 (66–74) 0.003 PSA, median (IQR), ng/ml 6.3 (4.6–8.6) 6 (4.7–7.5) 6.6 (4.6–8.7) 0.29 Clinical stage, n (%) 0.39 cT1c 101 (91) 39 (98) 63 (89) cT2 10 (9) 2 (3) 8 (11) Prostate volume, median (IQR), cc 48 (36–65) 53 (34–79) 47 (37–61) 0.39 MRI visible lesion, n (%) 88 (80) 26 (65) 62 (87) < 0.05 Grade Group, n (%) - Grade Group 1 40 (36) 40 (100) - Grade Group 2 55 (50) - 55 (77) Grade Group 3 13 (12) - 13 (18) Grade Group 4–5 3 (2) - 3 (5) Positive cores at initial biopsy, median (IQR) 3 (2–4) 3 (2–4) 3 (2–4) 0.36 Positive millimeters at initial biopsy, median (IQR) 11 ( 7–20) 10 (6–16) 12 (7–20) 0.27 At the end of the analysis, 87 patients (78%) agreed to undergo a confirmatory biopsy with a median time to biopsy of 18 months (IQR 14–19). The results of the confirmatory biopsy are shown in Fig. 1 . In-field recurrence was found in 14% of patients, while out-field recurrence was found in 23% of patients. There were no statistically significant differences in the in-field or the out-field recurrence rates between patients with baseline GG 1 vs GG > 1 disease (p = 0.9; p = 0.8, respectively). Patients who declined confirmatory biopsy had no clinical suspicion of recurrence, with a median PSA of 2 ng/ml (0.9–4.9) and negative MRI findings during follow-up. Twenty (20%) out of the 111 patients required secondary treatments, including brachytherapy (5 patients), second cryotherapy (7 patients), RT (2 patients), PT (2 patients), lymphadenectomy (1 patient) and ADT (3 patients). At 3 years, 65% of patients were free from any recurrence and 88% were free from radical treatment. As shown in Figs. 2 and 3, no significant differences were observed between the initial GG 1 and GG > 1 groups regarding any-recurrence free survival or radical treatment free survival. DISCUSSION Focal cryotherapy has demonstrated excellent functional outcomes, but its oncological efficacy remains under investigation due to limited data on cancer control. In this study we found that, three years following cryoablation, seven out of eight patients remained free of radical treatment and two out of three were free of any recurrence. Notably, we observed no significant difference in prognosis between patients with GG 1 disease and those with a higher GG at the diagnosis. The impact of FT on urinary and sexual function has been well-documented, with severe complications reported in less than 3% and 6% of patients, respectively. In contrast, RP and RT are associated with 13% and 4% rates of urinary incontinence and 76% and 72% of erectile dysfunction, respectively [ , ]. Given that FT has already shown superior functional outcomes compared to conventional treatments, our study focused on its primary challenge: oncological outcomes. Follow-up protocols after focal therapy vary widely across studies, affecting the interpretation of oncological results. Heterogeneity exists in biopsy approaches (e.g., number of cores, transrectal vs. transperineal, targeted vs. systematic) and triggers for biopsy (e.g., protocolized vs. based on clinical suspicion such as rising PSA or MRI findings). Recent expert consensus recommends performing an MRI and control biopsy within 6–12 months post-treatment [ , ]. In our protocol, an initial MRI was conducted within six weeks to detect complications, followed by a second MRI at 12 months to assess potential recurrences before performing a confirmatory biopsy. The median time to biopsy in our study was 18 months, compared to 6, 12, and 24 months in other series [ , , ]. In our cohort, 24 patients (22%) declined confirmatory biopsy, consistent with refusal rates of 16–23% reported in other studies [17, ]. The primary reason for refusal was low suspicion of recurrence based on stable PSA levels and negative MRI findings. If these patients had undergone biopsy, the positivity rate might have been lower. Our overall positive biopsy rate of 32% is slightly lower than rates reported by Baskin, Esaú, and Marra but significantly higher than the 7% reported by Wysock et al. [17,18,19,20]. This data is summarized in Table 2 , which includes cryotherapy cohorts that consider Group Grade 1 disease as a positive finding and used MRI from baseline. These discrepancies may stem from differences in patient selection criteria, biopsy protocols, and timing. Notably, despite expert MRI interpretation and extensive pre-treatment biopsies, 23% of patients developed new out-field cancer focis. However, the clinical significance of these findings remains unclear. Table 2 Comparison of biopsy findings between MRI-guided cryotherapy cohorts. *GG. Grade Group. *NR: Not Reported N Baseline GG 1, n (%) Time to biopsy, months Systematic biopsy, nº cores GG ≥ 1 at biopsy, n (%) In – Field, n (%) Out – Field, n (%) Wysock, 2020 70 9 (11) 6 12 5 (7) 4 (6) 1 (1) Baskin, 2022 75 4 (5) 24 14 37 (49) 20 (26) 17 (23) Esaú, 2022 50 25 (50) NA NR 23 (46) 10 (20) 13 (26) Marra, 2022 117 92 (76) 12 NR, Saturation 52 (43) -- -- Casanova, 2024 87 30 (34) 18 20–30 30 (32) 9 (14) 21 (23) We performed cryotherapy in 34% of patients with GG1 disease, 65% of whom had MRI-visible lesions. While active surveillance (AS) is the standard for GG1 disease, patients with MRI-visible lesions have a higher risk of AS discontinuation at five years (63% vs. 48% for those with negative MRI) [6]. Although intermediate-risk patients are often considered the primary candidates for FT, this recommendation is based largely on expert opinion [5]. Our findings suggest that oncological outcomes are similar between patients with baseline GG1 and GG > 1 disease, challenging the notion that GG should limit FT eligibility. Beyond biopsy findings, biochemical recurrence (BCR) and the need for secondary treatments have been proposed as early oncological endpoints for FT. A recent systematic review identified Phoenix criteria for BCR, salvage focal re-treatment, and salvage radical treatment as the most commonly used endpoints [ ]. We did not analyze BCR due to its variable definitions and unproven correlation with more robust endpoints (e.g., biopsy findings, clinical recurrence, metastasis) in the FT setting. At three years, 65% of our patients remained free from recurrence. Unlike previous studies that excluded biopsy findings from their recurrence definitions, we propose that any recurrence—encompassing positive biopsies and secondary treatments—provides a more comprehensive measure of treatment failure. Additionally, 88% of our patients avoided radical treatment at three years. This aligns with findings from Baskin, Shah, and Marra, who reported 96%, 91%, and 88% radical treatment-free survival rates at two, three, and five years, respectively. While small sample sizes and varying baseline characteristics (e.g., 76% GG1 in Marra’s study vs. 5% in Baskin’s) may influence these rates, the consistency across studies suggests that FT offers reliable oncological control across diverse patient populations. In our study, no significant differences were observed between GG1 and GG > 1 groups in recurrence-free survival (HR 1.2, 95% CI 0.6–2.5) or radical treatment-free survival (HR 1.1, 95% CI 0.35–3.2). In summary, we present medium-term oncological outcomes for cohort primary PCa patients treated with focal cryotherapy at a single institution. Our findings demonstrate adequate cancer control with this technique at 3 years of follow-up, with no significant differences in outcomes based on baseline Gleason score. However, the study is limited by the retrospective design and relatively small sample size, which may limit the ability to detect differences between Gleason subgroups. Larger studies are needed to validate these findings and determine whether Gleason score should influence the indication for cryotherapy. CONCLUSION Focal cryotherapy provides effective medium-term cancer control for localized prostate cancer, with the majority of patients remaining free from recurrence and radical treatment at three years. Importantly, outcomes were similar regardless of baseline Gleason score, suggesting that cryotherapy is a viable option for a broad range of patients. The study’s retrospective design and limited sample size highlight the need for larger studies to confirm these findings and further refine patient selection criteria. Declarations Conflict of Interest Statement: Juan Luis Casanova Ramón Borja has a proctorship contract with Boston Scientific; however, no financial funding was received from the company for conducting this study. Authors’ Contribution All authors contributed to the study conception and design. All authors read and approved the final manuscript. K Mate : Project development, data collection, and manuscript writing and editing P. de Pablos Rodriguez : Project development, data collection, data analysis and manuscript writing and editing M Burbano Herraiz : Project development M Hassi Román : Data collection, data analysis P Pelechano Gómez : Project development and analyzing MRIs A Calatrava Fons : Project development and prostate biopsies analysis M I Martín García : Project development and analyzing MRIs J Patiño Aliaga : Project development and prostate biopsies analysis M Beamud Cortés : Data collection Á Gómez-Ferrer Lozano : Manuscript writing and editing J L Dominguez Escrig : Data collection C Gutierrez Castañé : Manuscript editing V Rodríguez Part : Data analysis J L Casanova Ramón Borja : Realization of cryotherapies, data collection, manuscript editing References Union, E. PCa burden in EU-27. 2021 Resnick MJ, Koyama T, Fan KH, Albertsen PC, Goodman M, Hamilton AS, et al. Long-term functional outcomes after treatment for localized PCa. N Engl J Med. 2013;368:436–45. EAU Guidelines. Edn. presented at the EAU Annual Congress Milan 2023. ISBN 978-94-92671-19-6 Gage AA, Baust J. Mechanisms of tissue injury in cryosurgery. Cryobiology. 1998;37:171–86. Tay KJ, Scheltema MJ, Ahmed HU, Barret E, Coleman JA, Dominguez-Escrig J, Ghai S, Huang J, Jones JS, Klotz LH, Robertson CN, Sanchez-Salas R, Scionti S, Sivaraman A, de la Rosette J, Polascik TJ. Patient selection for prostate focal therapy in the era of active surveillance: an International Delphi Consensus Project. Prostate Cancer Prostatic Dis. 2017 Sep;20(3):294-299. doi: 10.1038/pcan.2017.8. Epub 2017 Mar 28. PMID: 28349978. Olivier J, Li W, Nieboer D, Helleman J, Roobol M, Gnanapragasam V, Frydenberg M, Sugimoto M, Carroll P, Morgan TM, Valdagni R, Rubio-Briones J, Robert G, Stricker P, Hayen A, Schoots I, Haider M, Moore CM, Denton B, Villers A; Movember Foundation's Global Action Plan Prostate Cancer Active Surveillance GAP3 Consortium. Prostate Cancer Patients Under Active Surveillance with a Suspicious Magnetic Resonance Imaging Finding Are at Increased Risk of Needing Treatment: Results of the Movember Foundation's Global Action Plan Prostate Cancer Active Surveillance (GAP3) Consortium. Eur Urol Open Sci. 2022 Jan 3;35:59-67. doi: 10.1016/j.euros.2021.11.006. PMID: 35024633; PMCID: PMC8738894. Shah TT, Ahmed H, Kanthabalan A, Lau B, Ghei M, Maraj B, Arya M. Focal cryotherapy of localized PCa: a sys­tematic review of the literature. Expert Rev Anticancer Ther 2014;14(11):1337–1347. Shah TT, Peters M, Eldred-Evans D, Miah S, Yap T, Faure- Walker NA, Hosking-Jervis F, Thomas B, Dudderidge T, Hindley RG et al. Early-Medium-Term Outcomes of Primary Focal Cryo­therapy to Treat Nonmetastatic Clinically Significant PCa from a Prospective Multicentre Registry. Eur Urol 2019; 76(1):98–105. Basseri, S., Perlis, N. & Ghai, S. Focal therapy for PCa. Abdom Radiol (2024). https://doi.org/10.1007/s00261-024-04482-7 Schaeffer EM, Srinivas S, Adra N, An Y, Barocas D, Bitting R, Bryce A, Chapin B, Cheng HH, D'Amico AV, Desai N, Dorff T, Eastham JA, Farrington TA, Gao X, Gupta S, Guzzo T, Ippolito JE, Kuettel MR, Lang JM, Lotan T, McKay RR, Morgan T, Netto G, Pow-Sang JM, Reiter R, Roach M, Robin T, Rosenfeld S, Shabsigh A, Spratt D, Teply BA, Tward J, Valicenti R, Wong JK, Shead DA, Snedeker J, Freedman-Cass DA. PCa, Version 4.2023, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2023 Oct;21(10):1067-1096. doi: 10.6004/jnccn.2023.0050. PMID: 37856213. Cornford P, van den Bergh RCN, Briers E, Van den Broeck T, Brunckhorst O, Darraugh J, Eberli D, De Meerleer G, De Santis M, Farolfi A, Gandaglia G, Gillessen S, Grivas N, Henry AM, Lardas M, van Leenders GJLH, Liew M, Linares Espinos E, Oldenburg J, van Oort IM, Oprea-Lager DE, Ploussard G, Roberts MJ, Rouvière O, Schoots IG, Schouten N, Smith EJ, Stranne J, Wiegel T, Willemse PM, Tilki D. EAU-EANM-ESTRO-ESUR-ISUP-SIOG Guidelines on PCa-2024 Update. Part I: Screening, Diagnosis, and Local Treatment with Curative Intent. Eur Urol. 2024 Aug;86(2):148-163. doi: 10.1016/j.eururo.2024.03.027. Epub 2024 Apr 13. PMID: 38614820. Diez, N.G., de Pablos-Rodríguez, P., Sánchez-Mateos Manzaneque, D. et al. Correction: Can we rely on magnetic resonance imaging for prostate cancer detection and surgical planning? Comprehensive analysis of a large cohort of patients undergoing transperineal mapped biopsies. World J Urol 43, 164 (2025). https://doi.org/10.1007/s00345-025-05534-3 Tay KJ, Fong KY, Stabile A, Dominguez-Escrig JL, Ukimura O, Rodriguez-Sanchez L, Blana A, Becher E, Laguna MP. Established focal therapy-HIFU, IRE, or cryotherapy-where are we now?-a systematic review and meta-analysis. Prostate Cancer Prostatic Dis. 2024 Oct 28. doi: 10.1038/s41391-024-00911-2. Epub ahead of print. PMID: 39468217. Resnick MJ, Koyama T, Fan KH, Albertsen PC, Goodman M, Hamilton AS, Hoffman RM, Potosky AL, Stanford JL, Stroup AM et al. Long-term functional outcomes after treatment for localized prostate cancer. N Engl J Med 2013; 368(5):436–445. Lebastchi AH, George AK, Polascik TJ, Coleman J, de la Rosette J, Turkbey B, Wood BJ, Gorin MA, Sidana A, Ghai S, Tay KJ, Ward JF, Sanchez-Salas R, Muller BG, Malavaud B, Mozer P, Crouzet S, Choyke PL, Ukimura O, Rastinehad AR, Pinto PA. Standardized Nomenclature and Surveillance Methodologies After Focal Therapy and Partial Gland Ablation for Localized Prostate Cancer: An International Multidisciplinary Consensus. Eur Urol. 2020 Sep;78(3):371-378. doi: 10.1016/j.eururo.2020.05.018. Epub 2020 Jun 10. PMID: 32532513; PMCID: PMC8966411. Light A, Mayor N, Cullen E, Kirkham A, Padhani AR, Arya M, Bomers JGR, Dudderidge T, Ehdaie B, Freeman A, Guillaumier S, Hindley R, Lakhani A, Pendse D, Punwani S, Rastinehad AR, Rouvière O, Sanchez-Salas R, Schoots IG, Sokhi HK, Tam H, Tempany CM, Valerio M, Verma S, Villeirs G, van der Meulen J, Ahmed HU, Shah TT. The Transatlantic Recommendations for Prostate Gland Evaluation with Magnetic Resonance Imaging After Focal Therapy (TARGET): A Systematic Review and International Consensus Recommendations. Eur Urol. 2024 May;85(5):466-482. doi: 10.1016/j.eururo.2024.02.001. Epub 2024 Mar 21. PMID: 38519280. Wysock, J.S., Becher, E., Gogaj, R. et al. Early oncological control following partial gland cryo-ablation: a prospective experience specifying reflex MRI guided biopsy of the ablation zone. Prostate Cancer Prostatic Dis 24, 114–119 (2021). https://doi.org/10.1038/s41391-020-0244-0 Marra G, Soeterik T, Oreggia D, Tourinho-Barbosa R, Moschini M, Filippini C, van Melick HHE, van den Bergh RCN, Gontero P, Cathala N, Macek P, Sanchez-Salas R, Cathelineau X. Long-term Outcomes of Focal Cryotherapy for Low- to Intermediate-risk Prostate Cancer: Results and Matched Pair Analysis with Active Surveillance. Eur Urol Focus. 2022 May;8(3):701-709. doi: 10.1016/j.euf.2021.04.008. Epub 2021 Apr 27. PMID: 33926838. Baskin A, Charondo LB, Balakrishnan A, Cowan JE, Cooperberg MR, Carroll PR, Nguyen H, Shinohara K. Medium Term Outcomes of Focal Cryoablation for Intermediate and High Risk Prostate Cancer: MRI and PSA are Not Predictive of Residual or Recurrent Disease. Urol Oncol. 2022 Oct;40(10):451.e15-451.e20. doi: 10.1016/j.urolonc.2022.06.010. Epub 2022 Jul 15. PMID: 35851186. Fernández-Pascual, E., Manfredi, C., Martín, C., Martínez-Ballesteros, C., Balmori, C., Lledó-García, E., Quintana, L. M., Curvo, R., Carballido-Rodríguez, J., Bianco, F. J., Jr., & Martínez-Salamanca, J. I. (2022). mpMRI-US Fusion-Guided Targeted Cryotherapy in Patients with Primary Localized Prostate Cancer: A Prospective Analysis of Oncological and Functional Outcomes. Cancers , 14 (12), 2988. https://doi.org/10.3390/cancers14122988 Nicoletti R, Alberti A, Castellani D, Yee CH, Zhang K, Poon DMC, Chiu PK, Campi R, Resta GR, Dibilio E, Pirola GM, Chiacchio G, Fuligni D, Brocca C, Giulioni C, De Stefano V, Serni S, Gauhar V, Ng CF, Gacci M, Teoh JYC. Oncological results and cancer control definition in focal therapy for PCa: a systematic review. PCa Prostatic Dis. 2024 Dec;27(4):623-634. doi: 10.1038/s41391-023-00699-7. Epub 2023 Jul 28. PMID: 37507479. Additional Declarations Competing interest reported. Conflict of Interest Statement: Juan Luis Casanova Ramón Borja has a proctorship contract with Boston Scientific; however, no financial funding was received from the company for conducting this study. It does not affect the results and/or the discussion outlined in this paper. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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Oncologia","correspondingAuthor":false,"prefix":"","firstName":"Ana","middleName":"Calatrava","lastName":"Fons","suffix":""},{"id":449462883,"identity":"b3b8c8a6-c481-4848-a1bc-f672c2227bbb","order_by":6,"name":"Maria Isabel Martín García","email":"","orcid":"","institution":"Fundacion Instituto Valenciano de Oncologia","correspondingAuthor":false,"prefix":"","firstName":"Maria","middleName":"Isabel Martín","lastName":"García","suffix":""},{"id":449462884,"identity":"cdbbf65c-0532-496c-817d-709645809a48","order_by":7,"name":"Jessica Patiño Aliaga","email":"","orcid":"","institution":"Fundacion Instituto Valenciano de Oncologia","correspondingAuthor":false,"prefix":"","firstName":"Jessica","middleName":"Patiño","lastName":"Aliaga","suffix":""},{"id":449462885,"identity":"07c6179d-b26f-483d-be15-39cfa8de16c6","order_by":8,"name":"Manel Beamud Cortés","email":"","orcid":"","institution":"Fundacion Instituto Valenciano de Oncologia","correspondingAuthor":false,"prefix":"","firstName":"Manel","middleName":"Beamud","lastName":"Cortés","suffix":""},{"id":449462886,"identity":"30d15ae8-37cf-4f03-a48a-5fd59d6bba0e","order_by":9,"name":"Álvaro Gómez-Ferrer Lozano","email":"","orcid":"","institution":"Fundacion Instituto Valenciano de Oncologia","correspondingAuthor":false,"prefix":"","firstName":"Álvaro","middleName":"Gómez-Ferrer","lastName":"Lozano","suffix":""},{"id":449462887,"identity":"2eed2a02-3452-49e4-906b-ea566e7bc3e7","order_by":10,"name":"Jose Luis Dominguez Escrig","email":"","orcid":"","institution":"Fundacion Instituto Valenciano de Oncologia","correspondingAuthor":false,"prefix":"","firstName":"Jose","middleName":"Luis Dominguez","lastName":"Escrig","suffix":""},{"id":449462888,"identity":"cf2e5d82-a78d-48e6-83c9-1f2dac119c89","order_by":11,"name":"Cristina Gutierrez Castañé","email":"","orcid":"","institution":"Fundación Instituto Valenciano de Oncologia","correspondingAuthor":false,"prefix":"","firstName":"Cristina","middleName":"Gutierrez","lastName":"Castañé","suffix":""},{"id":449462889,"identity":"1f90c2e6-5c45-49ea-b304-9626aa3dd196","order_by":12,"name":"Victor Rodríguez Part","email":"","orcid":"","institution":"Fundacion Instituto Valenciano de Oncologia","correspondingAuthor":false,"prefix":"","firstName":"Victor","middleName":"Rodríguez","lastName":"Part","suffix":""},{"id":449462890,"identity":"ea64e124-5ed0-4e59-9c40-ffc62e4e0f76","order_by":13,"name":"Juan Luis Casanova Ramón Borja","email":"","orcid":"","institution":"Fundación Instituto Valenciano de Oncologia","correspondingAuthor":false,"prefix":"","firstName":"Juan","middleName":"Luis Casanova Ramón","lastName":"Borja","suffix":""}],"badges":[],"createdAt":"2025-03-22 20:38:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6285402/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6285402/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":82162094,"identity":"aa698c9e-4843-41aa-b78c-385146827edb","added_by":"auto","created_at":"2025-05-07 08:41:25","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":42222,"visible":true,"origin":"","legend":"\u003cp\u003eResults of confirmatory biopsies.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6285402/v1/2130d64fb2094c8789e1a050.png"},{"id":82162093,"identity":"af308514-632c-4637-a80e-539acfb76d26","added_by":"auto","created_at":"2025-05-07 08:41:25","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":41807,"visible":true,"origin":"","legend":"\u003cp\u003eAny recurrence-free survival in patients with baseline GG1 vs patients with GG \u0026gt; 1.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6285402/v1/dd15630a9d15dd02ed29ec04.png"},{"id":82162095,"identity":"73083f4a-0185-4c75-82d3-5a81294497cb","added_by":"auto","created_at":"2025-05-07 08:41:25","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":33438,"visible":true,"origin":"","legend":"\u003cp\u003eRadical treatment-free survival in patients with baseline GG1 vs patients with GG \u0026gt; 1.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-6285402/v1/16d0eb25492b836154698e1c.png"},{"id":83180091,"identity":"4bde496e-e67d-4c9e-a5bf-0f576e89ee60","added_by":"auto","created_at":"2025-05-20 21:46:24","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":851321,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6285402/v1/9272920d-23e3-4042-92c1-567eec7303ea.pdf"}],"financialInterests":"Competing interest reported. Conflict of Interest Statement: Juan Luis Casanova Ramón Borja has a proctorship contract with Boston Scientific; however, no financial funding was received from the company for conducting this study. It does not affect the results and/or the discussion outlined in this paper.","formattedTitle":"\u003cp\u003e\u003cstrong\u003eOncological Outcomes of Primary Prostate Cancer Patients Treated with Focal Cryotherapy. Does Gleason Impact Results?\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eProstate cancer (PCa) is one of the most commonly diagnosed malignancies in men worldwide. In Europe, it is the most frequently diagnosed cancer in men and ranks as the third leading cause of cancer-related mortality [\u003ca class=\"FNLink\" href=\"#Fn1\" id=\"#FNLinkFn1\"\u003e\u003c/a\u003e]. The standard treatment options for localized PCa patients are active surveillance (AS), radical prostatectomy (RP) or radiotherapy (RT). However, RP and RT are associated with significant morbidity, including urinary incontinence, erectile dysfunction, all of which can adversely impact quality of life [\u003ca class=\"FNLink\" href=\"#Fn2\" id=\"#FNLinkFn2\"\u003e\u003c/a\u003e]. Additionally, active surveillance requires regular follow-up consisting of PSA testing, clinical examination, MRI imaging and repeated prostate biopsies. More than one-third of patients are reclassified during follow-up, with the majority undergoing curative treatment for disease progression [\u003ca class=\"FNLink\" href=\"#Fn3\" id=\"#FNLinkFn3\"\u003e\u003c/a\u003e]. To enhance the benefit-to-risk ratio, alternative therapies have emerged that aim to minimize adverse effects while maintaining positive oncological outcomes.\u003c/p\u003e \u003cp\u003eFocal cryotherapy, also known as cryoablation or cryosurgery, is a promising alternative for localized PCa. It enables targeted destruction of tumor tissue while preserving surrounding healthy structures. This technique induces apoptosis by application of cryo-needles into the targeted area, leading to cell death via coagulative necrosis [\u003ca class=\"FNLink\" href=\"#Fn4\" id=\"#FNLinkFn4\"\u003e\u003c/a\u003e]. The ideal candidate for focal cryotherapy remains uncertain. Patients with intermediate D Amico risk with visible lesion in the MRI appear to be the primary candidates [\u003ca class=\"FNLink\" href=\"#Fn5\" id=\"#FNLinkFn5\"\u003e\u003c/a\u003e]. Additionally, patients with low-risk disease but MRI-visible lesions have been reported to have worse oncological outcomes compared to those with non-visible lesions when initiating an active surveillance protocol [\u003ca class=\"FNLink\" href=\"#Fn6\" id=\"#FNLinkFn6\"\u003e\u003c/a\u003e]. Furthermore, there is a lack of data comparing oncological outcomes based on patient\u0026rsquo;s Grade Group (GG) Gleason score following focal therapy (FT).\u003c/p\u003e \u003cp\u003eSeveral studies have highlighted the favorable functional outcomes of cryoablation particularly, when compared to standard treatments (RP or RT) [\u003ca class=\"FNLink\" href=\"#Fn7\" id=\"#FNLinkFn7\"\u003e\u003c/a\u003e,\u003ca class=\"FNLink\" href=\"#Fn8\" id=\"#FNLinkFn8\"\u003e\u003c/a\u003e,\u003ca class=\"FNLink\" href=\"#Fn9\" id=\"#FNLinkFn9\"\u003e\u003c/a\u003e]. However, oncological outcomes remain a critical area of investigation to determine the safety of this approach in managing localized PCa. Current guidelines from the NCCN [\u003ca class=\"FNLink\" href=\"#Fn10\" id=\"#FNLinkFn10\"\u003e\u003c/a\u003e] and EAU [\u003ca class=\"FNLink\" href=\"#Fn11\" id=\"#FNLinkFn11\"\u003e\u003c/a\u003e] recommend performing cryotherapy within prospective registries or clinical trials. To date, only a few centers have reported oncological outcomes following cryotherapy, and none have specifically evaluated its relationship with baseline GG disease. In this study, we present our experience with medium-term follow-up of patients treated with focal cryotherapy, focusing on the influence of baseline Gleason score.\u003c/p\u003e"},{"header":"MATERIALS AND METHODS","content":"\u003cp\u003eRetrospective study of consecutive patients with primary PCa who underwent cryotherapy between 2014 and January 2025 at out institution. Patients with prior treatments or a follow-up shorter than 12 months after cryotherapy were excluded. Eligibility for cryotherapy was determined based on the physician criteria. Data were collected from a PCa registry (CAPROSIVO), which was approved by the local ethics committee.\u003c/p\u003e \u003cp\u003eAll patients underwent preoperative MRI, with or without regions of interest (ROI), followed by transperineal biopsy. Most MRIs were performed at Valencian Institute of Oncology using the General Electric Signa Artist 1.5 Tesla model. The images were interpreted by three experienced radiologists using the PI-RADS 2.0 or 2.1 version. For each ROI, 3\u0026ndash;5 cores targeted biopsy cores were obtained, and systematic sextant biopsies (20 to 30 cores) were performed following a modified version of Dickinson scheme, as previously described [\u003ca class=\"FNLink\" href=\"#Fn12\" id=\"#FNLinkFn12\"\u003e\u003c/a\u003e]. Biopsies were conducted using the Hitachi V70 ultrasound system, with Biopsee software (Medcom) employed for fusion when required.\u003c/p\u003e \u003cp\u003eCryotherapy was performed by the same experienced urologist (J.C.R) using Visual ICE Cryoablation System (Boston Scientific). Patients were treated under general anesthesia with 2\u0026ndash;4 IceSeed needles and were discharged the following day with a bladder catheter. The first visit was made 7\u0026ndash;10 days after surgery, when the bladder catheter was removed. No adjuvant deprivation therapy (ADT) was used. Patients were advised to undergo a unique confirmatory biopsy at 12\u0026ndash;24 months after cryotherapy, unless recurrence was suspected earlier.\u003c/p\u003e \u003cp\u003eRegarding oncological outcomes, in-field recurrence was defined as any cancer foci within the previously treated area or directly adjacent regions. Adjacency was determined based on the transverse or craniocaudal sextants, excluding oblique or other sextants. Out-field recurrence referred to the detection of any cancer in non-adjacent areas of the prostate. Any recurrence-free survival was defined as the absence of a positive biopsy or any additional treatment at any time during follow-up. Radical treatment-free survival was considered as the absence of whole-gland treatment (brachytherapy, RT, RP), ADT, metastasis or death. At last, a comparison was made between patients with baseline GG 1 vs GG\u0026thinsp;\u0026gt;\u0026thinsp;1.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eDifferences in categorical variables were assessed using chi-square tests, while differences in continuous variables were evaluated with t-test or Mann-Whitney U tests, as appropriate. The Log-Rank test and Kaplan-Meier curves were used to compare any recurrence and radical treatment-free survival between the GG 1 and GG\u0026thinsp;\u0026gt;\u0026thinsp;1 cohorts. All statistical analyses were performed using Python 3.13.0 software, with a significance level set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003eA total of 111 patients with localized PCa treated by focal cryotherapy were included. The median follow-up was 35 months (IQR 24\u0026ndash;49). The median age at the time of cryotherapy was 70 years (IQR 64\u0026ndash;74) and the median PSA was 6.3 ng/ml (IQR 4.6\u0026ndash;8.6). As shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, the majority of patients had non-palpable disease (91%) but visible lesions on MRI (80%).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline patient characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal of patients\u003c/p\u003e \u003cp\u003e(N 111)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGG 1\u003c/p\u003e \u003cp\u003e(N 40)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGG\u0026thinsp;\u0026gt;\u0026thinsp;1\u003c/p\u003e \u003cp\u003e(N 71)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge, median (IQR), years\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e70 (64\u0026ndash;74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e66 (63\u0026ndash;71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e72 (66\u0026ndash;74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePSA, median (IQR), ng/ml\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.3 (4.6\u0026ndash;8.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (4.7\u0026ndash;7.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.6 (4.6\u0026ndash;8.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.29\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eClinical stage, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.39\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ecT1c\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e101 (91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39 (98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e63 (89)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ecT2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 (11)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eProstate volume, median (IQR), cc\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e48 (36\u0026ndash;65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e53 (34\u0026ndash;79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e47 (37\u0026ndash;61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.39\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMRI visible lesion, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e88 (80)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26 (65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e62 (87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGrade Group, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGrade Group 1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40 (36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGrade Group 2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e55 (50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e55 (77)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGrade Group 3\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13 (18)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGrade Group 4\u0026ndash;5\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePositive cores at initial biopsy, median (IQR)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (2\u0026ndash;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (2\u0026ndash;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (2\u0026ndash;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.36\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePositive millimeters at initial biopsy, median (IQR)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 ( 7\u0026ndash;20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (6\u0026ndash;16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12 (7\u0026ndash;20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.27\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAt the end of the analysis, 87 patients (78%) agreed to undergo a confirmatory biopsy with a median time to biopsy of 18 months (IQR 14\u0026ndash;19). The results of the confirmatory biopsy are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. In-field recurrence was found in 14% of patients, while out-field recurrence was found in 23% of patients. There were no statistically significant differences in the in-field or the out-field recurrence rates between patients with baseline GG 1 vs GG\u0026thinsp;\u0026gt;\u0026thinsp;1 disease (p\u0026thinsp;=\u0026thinsp;0.9; p\u0026thinsp;=\u0026thinsp;0.8, respectively). Patients who declined confirmatory biopsy had no clinical suspicion of recurrence, with a median PSA of 2 ng/ml (0.9\u0026ndash;4.9) and negative MRI findings during follow-up.\u003c/p\u003e\u003cp\u003eTwenty (20%) out of the 111 patients required secondary treatments, including brachytherapy (5 patients), second cryotherapy (7 patients), RT (2 patients), PT (2 patients), lymphadenectomy (1 patient) and ADT (3 patients). At 3 years, 65% of patients were free from any recurrence and 88% were free from radical treatment. As shown in Figs.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and 3, no significant differences were observed between the initial GG 1 and GG\u0026thinsp;\u0026gt;\u0026thinsp;1 groups regarding any-recurrence free survival or radical treatment free survival. \u003c/p\u003e "},{"header":"DISCUSSION","content":"\u003cp\u003eFocal cryotherapy has demonstrated excellent functional outcomes, but its oncological efficacy remains under investigation due to limited data on cancer control. In this study we found that, three years following cryoablation, seven out of eight patients remained free of radical treatment and two out of three were free of any recurrence. Notably, we observed no significant difference in prognosis between patients with GG 1 disease and those with a higher GG at the diagnosis.\u003c/p\u003e \u003cp\u003eThe impact of FT on urinary and sexual function has been well-documented, with severe complications reported in less than 3% and 6% of patients, respectively. In contrast, RP and RT are associated with 13% and 4% rates of urinary incontinence and 76% and 72% of erectile dysfunction, respectively [\u003ca class=\"FNLink\" href=\"#Fn13\" id=\"#FNLinkFn13\"\u003e\u003c/a\u003e,\u003ca class=\"FNLink\" href=\"#Fn14\" id=\"#FNLinkFn14\"\u003e\u003c/a\u003e]. Given that FT has already shown superior functional outcomes compared to conventional treatments, our study focused on its primary challenge: oncological outcomes.\u003c/p\u003e \u003cp\u003eFollow-up protocols after focal therapy vary widely across studies, affecting the interpretation of oncological results. Heterogeneity exists in biopsy approaches (e.g., number of cores, transrectal vs. transperineal, targeted vs. systematic) and triggers for biopsy (e.g., protocolized vs. based on clinical suspicion such as rising PSA or MRI findings). Recent expert consensus recommends performing an MRI and control biopsy within 6\u0026ndash;12 months post-treatment [\u003ca class=\"FNLink\" href=\"#Fn15\" id=\"#FNLinkFn15\"\u003e\u003c/a\u003e,\u003ca class=\"FNLink\" href=\"#Fn16\" id=\"#FNLinkFn16\"\u003e\u003c/a\u003e]. In our protocol, an initial MRI was conducted within six weeks to detect complications, followed by a second MRI at 12 months to assess potential recurrences before performing a confirmatory biopsy. The median time to biopsy in our study was 18 months, compared to 6, 12, and 24 months in other series [\u003ca class=\"FNLink\" href=\"#Fn17\" id=\"#FNLinkFn17\"\u003e\u003c/a\u003e, \u003ca class=\"FNLink\" href=\"#Fn18\" id=\"#FNLinkFn18\"\u003e\u003c/a\u003e, \u003ca class=\"FNLink\" href=\"#Fn19\" id=\"#FNLinkFn19\"\u003e\u003c/a\u003e].\u003c/p\u003e \u003cp\u003eIn our cohort, 24 patients (22%) declined confirmatory biopsy, consistent with refusal rates of 16\u0026ndash;23% reported in other studies [17,\u003ca class=\"FNLink\" href=\"#Fn20\" id=\"#FNLinkFn20\"\u003e\u003c/a\u003e]. The primary reason for refusal was low suspicion of recurrence based on stable PSA levels and negative MRI findings. If these patients had undergone biopsy, the positivity rate might have been lower. Our overall positive biopsy rate of 32% is slightly lower than rates reported by Baskin, Esa\u0026uacute;, and Marra but significantly higher than the 7% reported by Wysock et al. [17,18,19,20]. This data is summarized in Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, which includes cryotherapy cohorts that consider Group Grade 1 disease as a positive finding and used MRI from baseline. These discrepancies may stem from differences in patient selection criteria, biopsy protocols, and timing. Notably, despite expert MRI interpretation and extensive pre-treatment biopsies, 23% of patients developed new out-field cancer focis. However, the clinical significance of these findings remains unclear.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of biopsy findings between MRI-guided cryotherapy cohorts. \u003cem\u003e*GG. Grade Group. *NR: Not Reported\u003c/em\u003e\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBaseline GG 1,\u003c/p\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTime to biopsy, months\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSystematic biopsy,\u003c/p\u003e \u003cp\u003en\u0026ordm; cores\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eGG\u0026thinsp;\u0026ge;\u0026thinsp;1 at biopsy,\u003c/p\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eIn \u0026ndash; Field, n (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOut \u0026ndash; Field,\u003c/p\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eWysock, 2020\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5 (7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4 (6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1 (1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBaskin, 2022\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e37 (49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e20 (26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e17 (23)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eEsa\u0026uacute;, 2022\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25 (50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e23 (46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e10 (20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e13 (26)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMarra, 2022\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e117\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e92 (76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNR, Saturation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e52 (43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e--\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e--\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCasanova, 2024\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30 (34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e20\u0026ndash;30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e30 (32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e9 (14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e21 (23)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eWe performed cryotherapy in 34% of patients with GG1 disease, 65% of whom had MRI-visible lesions. While active surveillance (AS) is the standard for GG1 disease, patients with MRI-visible lesions have a higher risk of AS discontinuation at five years (63% vs. 48% for those with negative MRI) [6]. Although intermediate-risk patients are often considered the primary candidates for FT, this recommendation is based largely on expert opinion [5]. Our findings suggest that oncological outcomes are similar between patients with baseline GG1 and GG\u0026thinsp;\u0026gt;\u0026thinsp;1 disease, challenging the notion that GG should limit FT eligibility.\u003c/p\u003e \u003cp\u003eBeyond biopsy findings, biochemical recurrence (BCR) and the need for secondary treatments have been proposed as early oncological endpoints for FT. A recent systematic review identified Phoenix criteria for BCR, salvage focal re-treatment, and salvage radical treatment as the most commonly used endpoints [\u003ca class=\"FNLink\" href=\"#Fn21\" id=\"#FNLinkFn21\"\u003e\u003c/a\u003e]. We did not analyze BCR due to its variable definitions and unproven correlation with more robust endpoints (e.g., biopsy findings, clinical recurrence, metastasis) in the FT setting. At three years, 65% of our patients remained free from recurrence. Unlike previous studies that excluded biopsy findings from their recurrence definitions, we propose that any recurrence\u0026mdash;encompassing positive biopsies and secondary treatments\u0026mdash;provides a more comprehensive measure of treatment failure.\u003c/p\u003e \u003cp\u003eAdditionally, 88% of our patients avoided radical treatment at three years. This aligns with findings from Baskin, Shah, and Marra, who reported 96%, 91%, and 88% radical treatment-free survival rates at two, three, and five years, respectively. While small sample sizes and varying baseline characteristics (e.g., 76% GG1 in Marra\u0026rsquo;s study vs. 5% in Baskin\u0026rsquo;s) may influence these rates, the consistency across studies suggests that FT offers reliable oncological control across diverse patient populations. In our study, no significant differences were observed between GG1 and GG\u0026thinsp;\u0026gt;\u0026thinsp;1 groups in recurrence-free survival (HR 1.2, 95% CI 0.6\u0026ndash;2.5) or radical treatment-free survival (HR 1.1, 95% CI 0.35\u0026ndash;3.2).\u003c/p\u003e \u003cp\u003eIn summary, we present medium-term oncological outcomes for cohort primary PCa patients treated with focal cryotherapy at a single institution. Our findings demonstrate adequate cancer control with this technique at 3 years of follow-up, with no significant differences in outcomes based on baseline Gleason score. However, the study is limited by the retrospective design and relatively small sample size, which may limit the ability to detect differences between Gleason subgroups. Larger studies are needed to validate these findings and determine whether Gleason score should influence the indication for cryotherapy.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eFocal cryotherapy provides effective medium-term cancer control for localized prostate cancer, with the majority of patients remaining free from recurrence and radical treatment at three years. Importantly, outcomes were similar regardless of baseline Gleason score, suggesting that cryotherapy is a viable option for a broad range of patients. The study\u0026rsquo;s retrospective design and limited sample size highlight the need for larger studies to confirm these findings and further refine patient selection criteria.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConflict of Interest Statement:\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eJuan Luis Casanova Ram\u0026oacute;n Borja has a proctorship contract with Boston Scientific; however, no financial funding was received from the company for conducting this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; Contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors contributed to the study conception and design. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003eK Mate : Project development, data collection, and manuscript writing and editing\u003c/p\u003e\n\u003cp\u003eP. de Pablos Rodriguez\u0026nbsp;: Project development, data collection, data analysis and manuscript writing and editing\u003c/p\u003e\n\u003cp\u003eM Burbano Herraiz\u0026nbsp;: Project development\u003c/p\u003e\n\u003cp\u003eM Hassi Rom\u0026aacute;n : Data collection, data analysis\u003c/p\u003e\n\u003cp\u003eP Pelechano G\u0026oacute;mez\u0026nbsp;: Project development and analyzing MRIs\u003c/p\u003e\n\u003cp\u003eA Calatrava Fons\u0026nbsp;: Project development and prostate biopsies analysis\u003c/p\u003e\n\u003cp\u003eM I Mart\u0026iacute;n Garc\u0026iacute;a\u0026nbsp;: Project development and analyzing MRIs\u003c/p\u003e\n\u003cp\u003eJ Pati\u0026ntilde;o Aliaga : Project development and prostate biopsies analysis\u003c/p\u003e\n\u003cp\u003eM Beamud Cort\u0026eacute;s\u0026nbsp;: Data collection\u003c/p\u003e\n\u003cp\u003e\u0026Aacute; G\u0026oacute;mez-Ferrer Lozano\u0026nbsp;: Manuscript writing and editing\u003c/p\u003e\n\u003cp\u003eJ L Dominguez Escrig\u0026nbsp;: Data collection\u003c/p\u003e\n\u003cp\u003eC Gutierrez Casta\u0026ntilde;\u0026eacute; : Manuscript editing\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eV Rodr\u0026iacute;guez Part : Data analysis\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eJ L Casanova Ram\u0026oacute;n Borja : Realization of cryotherapies, data collection, manuscript editing\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eUnion, E. PCa burden in EU-27. 2021\u003c/li\u003e\n\u003cli\u003eResnick MJ, Koyama T, Fan KH, Albertsen PC, Goodman M, Hamilton AS, et al. Long-term functional outcomes after treatment for localized PCa. N Engl J Med. 2013;368:436\u0026ndash;45.\u003c/li\u003e\n\u003cli\u003eEAU Guidelines. Edn. presented at the EAU Annual Congress Milan 2023. ISBN 978-94-92671-19-6\u003c/li\u003e\n\u003cli\u003eGage AA, Baust J. Mechanisms of tissue injury in cryosurgery. Cryobiology. 1998;37:171\u0026ndash;86.\u003c/li\u003e\n\u003cli\u003eTay KJ, Scheltema MJ, Ahmed HU, Barret E, Coleman JA, Dominguez-Escrig J, Ghai S, Huang J, Jones JS, Klotz LH, Robertson CN, Sanchez-Salas R, Scionti S, Sivaraman A, de la Rosette J, Polascik TJ. Patient selection for prostate focal therapy in the era of active surveillance: an International Delphi Consensus Project. Prostate Cancer Prostatic Dis. 2017 Sep;20(3):294-299. doi: 10.1038/pcan.2017.8. Epub 2017 Mar 28. PMID: 28349978.\u003c/li\u003e\n\u003cli\u003eOlivier J, Li W, Nieboer D, Helleman J, Roobol M, Gnanapragasam V, Frydenberg M, Sugimoto M, Carroll P, Morgan TM, Valdagni R, Rubio-Briones J, Robert G, Stricker P, Hayen A, Schoots I, Haider M, Moore CM, Denton B, Villers A; Movember Foundation\u0026apos;s Global Action Plan Prostate Cancer Active Surveillance GAP3 Consortium. Prostate Cancer Patients Under Active Surveillance with a Suspicious Magnetic Resonance Imaging Finding Are at Increased Risk of Needing Treatment: Results of the Movember Foundation\u0026apos;s Global Action Plan Prostate Cancer Active Surveillance (GAP3) Consortium. Eur Urol Open Sci. 2022 Jan 3;35:59-67. doi: 10.1016/j.euros.2021.11.006. PMID: 35024633; PMCID: PMC8738894.\u003c/li\u003e\n\u003cli\u003eShah TT, Ahmed H, Kanthabalan A, Lau B, Ghei M, Maraj B, Arya M. Focal cryotherapy of localized PCa: a sys\u0026shy;tematic review of the literature. Expert Rev Anticancer Ther 2014;14(11):1337\u0026ndash;1347.\u003c/li\u003e\n\u003cli\u003eShah TT, Peters M, Eldred-Evans D, Miah S, Yap T, Faure- Walker NA, Hosking-Jervis F, Thomas B, Dudderidge T, Hindley RG et al. Early-Medium-Term Outcomes of Primary Focal Cryo\u0026shy;therapy to Treat Nonmetastatic Clinically Significant PCa from a Prospective Multicentre Registry. Eur Urol 2019; 76(1):98\u0026ndash;105.\u003c/li\u003e\n\u003cli\u003eBasseri, S., Perlis, N. \u0026amp; Ghai, S. Focal therapy for PCa. \u003cem\u003eAbdom Radiol\u003c/em\u003e (2024). https://doi.org/10.1007/s00261-024-04482-7\u003c/li\u003e\n\u003cli\u003eSchaeffer EM, Srinivas S, Adra N, An Y, Barocas D, Bitting R, Bryce A, Chapin B, Cheng HH, D\u0026apos;Amico AV, Desai N, Dorff T, Eastham JA, Farrington TA, Gao X, Gupta S, Guzzo T, Ippolito JE, Kuettel MR, Lang JM, Lotan T, McKay RR, Morgan T, Netto G, Pow-Sang JM, Reiter R, Roach M, Robin T, Rosenfeld S, Shabsigh A, Spratt D, Teply BA, Tward J, Valicenti R, Wong JK, Shead DA, Snedeker J, Freedman-Cass DA. PCa, Version 4.2023, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2023 Oct;21(10):1067-1096. doi: 10.6004/jnccn.2023.0050. PMID: 37856213.\u003c/li\u003e\n\u003cli\u003eCornford P, van den Bergh RCN, Briers E, Van den Broeck T, Brunckhorst O, Darraugh J, Eberli D, De Meerleer G, De Santis M, Farolfi A, Gandaglia G, Gillessen S, Grivas N, Henry AM, Lardas M, van Leenders GJLH, Liew M, Linares Espinos E, Oldenburg J, van Oort IM, Oprea-Lager DE, Ploussard G, Roberts MJ, Rouvi\u0026egrave;re O, Schoots IG, Schouten N, Smith EJ, Stranne J, Wiegel T, Willemse PM, Tilki D. EAU-EANM-ESTRO-ESUR-ISUP-SIOG Guidelines on PCa-2024 Update. Part I: Screening, Diagnosis, and Local Treatment with Curative Intent. Eur Urol. 2024 Aug;86(2):148-163. doi: 10.1016/j.eururo.2024.03.027. Epub 2024 Apr 13. PMID: 38614820.\u003c/li\u003e\n\u003cli\u003eDiez, N.G., de Pablos-Rodr\u0026iacute;guez, P., S\u0026aacute;nchez-Mateos Manzaneque, D. \u003cem\u003eet al.\u003c/em\u003e Correction: Can we rely on magnetic resonance imaging for prostate cancer detection and surgical planning? Comprehensive analysis of a large cohort of patients undergoing transperineal mapped biopsies. \u003cem\u003eWorld J Urol\u003c/em\u003e 43, 164 (2025). https://doi.org/10.1007/s00345-025-05534-3\u003c/li\u003e\n\u003cli\u003eTay KJ, Fong KY, Stabile A, Dominguez-Escrig JL, Ukimura O, Rodriguez-Sanchez L, Blana A, Becher E, Laguna MP. Established focal therapy-HIFU, IRE, or cryotherapy-where are we now?-a systematic review and meta-analysis. Prostate Cancer Prostatic Dis. 2024 Oct 28. doi: 10.1038/s41391-024-00911-2. Epub ahead of print. PMID: 39468217.\u003c/li\u003e\n\u003cli\u003eResnick MJ, Koyama T, Fan KH, Albertsen PC, Goodman M, Hamilton AS, Hoffman RM, Potosky AL, Stanford JL, Stroup AM et al. Long-term functional outcomes after treatment for localized prostate cancer. N Engl J Med 2013; 368(5):436\u0026ndash;445.\u003c/li\u003e\n\u003cli\u003eLebastchi AH, George AK, Polascik TJ, Coleman J, de la Rosette J, Turkbey B, Wood BJ, Gorin MA, Sidana A, Ghai S, Tay KJ, Ward JF, Sanchez-Salas R, Muller BG, Malavaud B, Mozer P, Crouzet S, Choyke PL, Ukimura O, Rastinehad AR, Pinto PA. Standardized Nomenclature and Surveillance Methodologies After Focal Therapy and Partial Gland Ablation for Localized Prostate Cancer: An International Multidisciplinary Consensus. Eur Urol. 2020 Sep;78(3):371-378. doi: 10.1016/j.eururo.2020.05.018. Epub 2020 Jun 10. PMID: 32532513; PMCID: PMC8966411.\u003c/li\u003e\n\u003cli\u003eLight A, Mayor N, Cullen E, Kirkham A, Padhani AR, Arya M, Bomers JGR, Dudderidge T, Ehdaie B, Freeman A, Guillaumier S, Hindley R, Lakhani A, Pendse D, Punwani S, Rastinehad AR, Rouvi\u0026egrave;re O, Sanchez-Salas R, Schoots IG, Sokhi HK, Tam H, Tempany CM, Valerio M, Verma S, Villeirs G, van der Meulen J, Ahmed HU, Shah TT. The Transatlantic Recommendations for Prostate Gland Evaluation with Magnetic Resonance Imaging After Focal Therapy (TARGET): A Systematic Review and International Consensus Recommendations. Eur Urol. 2024 May;85(5):466-482. doi: 10.1016/j.eururo.2024.02.001. Epub 2024 Mar 21. PMID: 38519280.\u003c/li\u003e\n\u003cli\u003eWysock, J.S., Becher, E., Gogaj, R. et al. Early oncological control following partial gland cryo-ablation: a prospective experience specifying reflex MRI guided biopsy of the ablation zone. Prostate Cancer Prostatic Dis 24, 114\u0026ndash;119 (2021). https://doi.org/10.1038/s41391-020-0244-0\u003c/li\u003e\n\u003cli\u003eMarra G, Soeterik T, Oreggia D, Tourinho-Barbosa R, Moschini M, Filippini C, van Melick HHE, van den Bergh RCN, Gontero P, Cathala N, Macek P, Sanchez-Salas R, Cathelineau X. Long-term Outcomes of Focal Cryotherapy for Low- to Intermediate-risk Prostate Cancer: Results and Matched Pair Analysis with Active Surveillance. Eur Urol Focus. 2022 May;8(3):701-709. doi: 10.1016/j.euf.2021.04.008. Epub 2021 Apr 27. PMID: 33926838.\u003c/li\u003e\n\u003cli\u003eBaskin A, Charondo LB, Balakrishnan A, Cowan JE, Cooperberg MR, Carroll PR, Nguyen H, Shinohara K. Medium Term Outcomes of Focal Cryoablation for Intermediate and High Risk Prostate Cancer: MRI and PSA are Not Predictive of Residual or Recurrent Disease. Urol Oncol. 2022 Oct;40(10):451.e15-451.e20. doi: 10.1016/j.urolonc.2022.06.010. Epub 2022 Jul 15. PMID: 35851186.\u003c/li\u003e\n\u003cli\u003eFern\u0026aacute;ndez-Pascual, E., Manfredi, C., Mart\u0026iacute;n, C., Mart\u0026iacute;nez-Ballesteros, C., Balmori, C., Lled\u0026oacute;-Garc\u0026iacute;a, E., Quintana, L. M., Curvo, R., Carballido-Rodr\u0026iacute;guez, J., Bianco, F. J., Jr., \u0026amp; Mart\u0026iacute;nez-Salamanca, J. I. (2022). mpMRI-US Fusion-Guided Targeted Cryotherapy in Patients with Primary Localized Prostate Cancer: A Prospective Analysis of Oncological and Functional Outcomes. \u003cem\u003eCancers\u003c/em\u003e, \u003cem\u003e14\u003c/em\u003e(12), 2988. https://doi.org/10.3390/cancers14122988\u003c/li\u003e\n\u003cli\u003eNicoletti R, Alberti A, Castellani D, Yee CH, Zhang K, Poon DMC, Chiu PK, Campi R, Resta GR, Dibilio E, Pirola GM, Chiacchio G, Fuligni D, Brocca C, Giulioni C, De Stefano V, Serni S, Gauhar V, Ng CF, Gacci M, Teoh JYC. Oncological results and cancer control definition in focal therapy for PCa: a systematic review. PCa Prostatic Dis. 2024 Dec;27(4):623-634. doi: 10.1038/s41391-023-00699-7. Epub 2023 Jul 28. PMID: 37507479.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Prostate cancer, focal cryotherapy, recurrence rate, in-field, out-field","lastPublishedDoi":"10.21203/rs.3.rs-6285402/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6285402/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eFocal cryotherapy is a minimally invasive treatment for localized prostate cancer (PCa), but its medium-term oncological outcomes, particularly in relation to baseline Gleason Grade Group (GG), remain understudied. This study evaluates its efficacy and the impact of baseline Gleason score on recurrence-free survival.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003e A retrospective analysis included 111 patients with localized PCa treated with focal cryotherapy between 2014 and January 2025. Patients with prior treatments or follow-up \u0026lt;\u0026thinsp;12 months were excluded. All patients underwent MRI and transperineal biopsy, with cryotherapy performed using the Visual ICE Cryoablation System. Confirmatory biopsies were recommended at 12\u0026ndash;24 months post-treatment. Recurrence was classified as in-field (treated or adjacent areas) or out-field (non-adjacent areas). Any recurrence-free survival was defined as the absence of positive biopsy or additional treatment, while radical treatment-free survival was defined as the absence of whole-gland treatment (e.g., radical prostatectomy, radiotherapy), androgen deprivation therapy, metastasis, or death. Outcomes were compared between patients with baseline GG 1 and GG\u0026thinsp;\u0026gt;\u0026thinsp;1.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eMedian follow-up was 35 months (IQR 24\u0026ndash;49). Confirmatory biopsies were performed in 78% of patients (n\u0026thinsp;=\u0026thinsp;87), revealing in-field recurrence in 14% and out-field recurrence in 23%. No significant differences in recurrence rates were observed between GG 1 and GG\u0026thinsp;\u0026gt;\u0026thinsp;1 patients (p\u0026thinsp;=\u0026thinsp;0.9 for in-field; p\u0026thinsp;=\u0026thinsp;0.8 for out-field). The 3-year any recurrence-free and radical treatment-free survival rates were 63% and 85%, respectively, with no significant variation by baseline GG.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eFocal cryotherapy demonstrates favorable medium-term oncological outcomes for localized PCa, with no significant differences in recurrence-free survival based on baseline Gleason score. These findings support its role as a viable treatment option for patients seeking to minimize treatment-related morbidity.\u003c/p\u003e","manuscriptTitle":"Oncological Outcomes of Primary Prostate Cancer Patients Treated with Focal Cryotherapy. Does Gleason Impact Results?","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-07 08:41:20","doi":"10.21203/rs.3.rs-6285402/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ac2f71ec-3f74-4b4f-b4ec-08c824cebe0a","owner":[],"postedDate":"May 7th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-05-20T21:38:17+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-07 08:41:20","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6285402","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6285402","identity":"rs-6285402","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}