The effect of secondary cytoreductive surgery on survival in recurrent epithelial ovarian cancer

Background: The purpose of this research was to determine the key factors that can predict the outcomes of secondary cytoreductive surgery and the criteria for selecting patients that would result in improved survival rates. Methods: The retrospective study analyzed a cohort of 97 individuals who were diagnosed with platinum-sensitive epithelial ovarian cancer at the Gynecologic Oncology Unit from 1990 to 2012, and who had undergone surgery for recurrence following initial treatment, which included primary surgery and adjuvant chemotherapy. Surgical intervention was recommended for patients who had a median disease-free interval (DFI) of at least 6 months from their initial treatment to the recurrence, and who exhibited an Eastern Cooperative Gynecologic Oncology Group performance status of 2 or lower. All patients were treated with platinum-based chemotherapy or other chemotherapy regimens in the postoperative period. Results: The DFI was 24.5 months (95% confidence interval (CI): 18.2–30.7). Optimal secondary cytoreduction was achieved in 63 (64.9%) patients, with a significant increase in survival compared to patient groups with suboptimal cytoreduction (142.9 months vs. 42.2 months and 33.7 months) (p < 0.001). Survival was significantly increased in patients with a DFI >14 months (p = 0.002). Multivariate analysis revealed that disease-free interval (DFI) and the presence of residual disease following secondary surgery emerged as pivotal independent predictors of survival. Conclusions: Secondary cytoreductive surgery stands out as a secure and efficient therapeutic approach for recurrent epithelial ovarian cancer, leading to a decrease in complication rates. Employing maximal surgical interventions notably extends patients’ survival times.

Recurrent epithelial ovarian cancer; Secondary cytoreductive surgery; Disease-free interval (DFI); Overall survival (OS); Residual tumour; Complete cytoreduction; Optimal cytoreduction

[1] Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians. 2021; 71: 209–249.

[2] Peres LC, Cushing-Haugen KL, Köbel M, Harris HR, Berchuck A, Rossing MA, et al. Invasive epithelial ovarian cancer survival by histotype and disease stage. Journal of the National Cancer Institute. 2019; 111: 60–68.

[3] Colombo N, Sessa C, du Bois A, Ledermann J, McCluggage WG, McNeish I, et al.; ESMO-ESGO Ovarian Cancer Consensus Conference Working Group. ESMO-ESGO consensus conference recommendations on ovarian cancer: pathology and molecular biology, early and advanced stages, borderline tumours and recurrent disease†. Annals of Oncology. 2019; 30: 672–705.

[4] Torre LA, Trabert B, DeSantis CE, Miller KD, Samimi G, Runowicz CD, et al. Ovarian cancer statistics, 2018. CA: A Cancer Journal for Clinicians. 2018; 68: 284–296.

[5] Suh DH, Kim HS, Chang S, Bristow RE. Surgical management of recurrent ovarian cancer. Gynecologic Oncology. 2016; 142: 357–367.

[6] Ushijima K. Treatment for recurrent ovarian cancer—at first relapse. Journal of Oncology. 2010; 2010: 497429.

[7] Garzon S, Laganà AS, Casarin J, Raffaelli R, Cromi A, Franchi M, et al. Secondary and tertiary ovarian cancer recurrence: what is the best management? Gland Surgery. 2020; 9: 1118–1129.

[8] Berek JS, Hacker NF, Lagasse LD, Nieberg RK, Elashoff RM. Survival of patients following secondary cytoreductive surgery in ovarian cancer. Obstetrics and Gynecology. 1983; 61: 189–193.

[9] Sehouli J, Richter R, Braicu EI, Bühling KJ, Bahra M, Neuhaus P, et al. Role of secondary cytoreductive surgery in ovarian cancer relapse: who will benefit? A systematic analysis of 240 consecutive patients. Journal of Surgical Oncology. 2010; 102: 656–662.

[10] Chi DS, McCaughty K, Diaz JP, Huh J, Schwabenbauer S, Hummer AJ, et al. Guidelines and selection criteria for secondary cytoreductive surgery in patients with recurrent, platinum‐sensitive epithelial ovarian carcinoma. Cancer. 2006; 106: 1933–1939.

[11] Onda T, Yoshikawa H, Yasugi T, Yamada M, Matsumoto K, Taketani Y. Secondary cytoreductive surgery for recurrent epithelial ovarian carcinoma: proposal for patients selection. British Journal of Cancer. 2005; 92: 1026–1032.

[12] Ledermann JA, Matias-Guiu X, Amant F, Concin N, Davidson B, Fotopoulou C, et al. ESGO–ESMO–ESP consensus conference recommendations on ovarian cancer: pathology and molecular biology and early, advanced and recurrent disease. Annals of Oncology. 2024; 35: 248–266.

[13] Gao B, Li X, Li S, Wang S, Wu J, Li J. Pan-cancer analysis identifies RNA helicase DDX1 as a prognostic marker. Phenomics. 2022; 2: 33–49.

[14] Younes M, Loubnane G, Sleiman C, Rizk S. Tocotrienol isoforms: the molecular mechanisms underlying their effects in cancer therapy and their implementation in clinical trials. Journal of Integrative Medicine. 2024; 22: 1–11.

[15] Krause D, Richardson DL. Is there a role for secondary debulking in ovarian cancer? A review of the current literature. Current Opinion in Obstetrics & Gynecology. 2023; 35: 1–5.

[16] Classe J, Meeus P, Hudry D, Wernert R, Quenet F, Marchal F, et al. Hyperthermic intraperitoneal chemotherapy for recurrent ovarian cancer (CHIPOR): a randomised, open-label, phase 3 trial. The Lancet Oncology. 2024; 25: 1551–1562.

[17] Bristow RE, Tomacruz RS, Armstrong DK, Trimble EL, Montz FJ. Survival effect of maximal cytoreductive surgery for advanced ovarian carcinoma during the platinum era: a meta-analysis. Journal of Clinical Oncology. 2023; 41: 4065–4076.

[18] Eisenkop SM, Friedman RL, Spirtos NM. The role of secondary cytoreductive surgery in the treatment of patients with recurrent epithelial ovarian carcinoma. Cancer. 2000; 88: 144–153.

[19] Tian WJ, Jiang R, Cheng X, Tang J, Xing Y, Zang RY. Surgery in recurrent epithelial ovarian cancer: benefits on Survival for patients with residual disease of 0.1–1 cm after secondary cytoreduction. Journal of Surgical Oncology. 2010; 101: 244–250.

[20] Salani R, Santillan A, Zahurak ML, Giuntoli RL II, Gardner GJ, Armstrong DK, et al. Secondary cytoreductive surgery for localized, recurrent epithelial ovarian cancer: analysis of prognostic factors and survival outcome. Cancer. 2007; 109: 685–691.

[21] Bristow RE, Puri I, Chi DS. Cytoreductive surgery for recurrent ovarian cancer: a meta-analysis. Gynecologic Oncology. 2009; 112: 265–274.

[22] Harter P, du Bois A, Hahmann M, Hasenburg A, Burges A, Loibl S, et al; Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Committee; AGO Ovarian Cancer Study Group. Surgery in recurrent ovarian cancer: the Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) DESKTOP OVAR trial. Annals of Surgical Oncology. 2006; 13: 1702–1710.

[23] Berek JS, Bertelsen K, du Bois A, Brady MF, Carmichael J, Eisenhauer EA, et al. Advanced epithelial ovarian cancer: 1998 consensus statements. Annals of Oncology. 1999; 10: S87–S92.

[24] Harter P, Sehouli J, Reuss A, Hasenburg A, Scambia G, Cibula D, et al. Prospective validation study of a predictive score for operability of recurrent ovarian cancer: the Multicenter Intergroup Study DESKTOP II. A project of the AGO Kommission OVAR, AGO Study Group, NOGGO, AGO-Austria, and MITO. International Journal of Gynecological Cancer. 2011; 21: 289–295.

[25] Coleman RL, Brady MF, Herzog TJ, Sabbatini P, Armstrong DK, Walker JL, et al. Bevacizumab and paclitaxel-carboplatin chemotherapy and secondary cytoreduction in recurrent, platinum-sensitive ovarian cancer (NRG Oncology/Gynecologic Oncology Group study GOG-0213): a multicentre, open-label, randomised, phase 3 trial. The Lancet Oncology. 2017; 18: 779–791.

[26] Harter P, Sehouli J, Vergote I, Ferron G, Reuss A, Meier W, et al.; DESKTOP III Investigators. Randomized trial of cytoreductive surgery for relapsed ovarian cancer. The New England Journal of Medicine. 2022; 386: 704.

[27] Shi T, Zhu J, Feng Y, Tu D, Zhang Y, Zhang P, et al. Secondary cytoreduction followed by chemotherapy versus chemotherapy alone in platinum-sensitive relapsed ovarian cancer (SOC-1): a multicentre, open-label, randomised, phase 3 trial. The Lancet Oncology. 2021; 22: 439–449.

[28] National Comprehensive Cancer Network. NCCN clinical practice guidelines: ovarian cancer including fallopian tube cancer and primary peritoneal cancer (ver. 2.2023). 2023. Available at: https://www.nccn.org (Accessed: 11 August 2024).