Shachar Eliya, Raz Yael, Rotkop Gilat, Katz Uriel, Laskov Ido, Michan Nadav, Grisaru Dan, Wolf Ido, Safra Tamar
Division of Oncology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Faculty of Medical & Health Sciences, Tel Aviv University, Tel Aviv, Israel; Department of Obstetrics & Gynecology, University of California, Los Angeles, CA, USA.
Faculty of Medical & Health Sciences, Tel Aviv University, Tel Aviv, Israel; Department of Obstetrics & Gynecology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Int J Gynecol Cancer. 2025 Jun;35(6):101809. doi: 10.1016/j.ijgc.2025.101809. Epub 2025 Apr 4.
Guidelines endorse both interval and primary debulking cytoreductive surgeries in the treatment of epithelial ovarian cancer, emphasizing that the treatment strategy should be tailored to the patient's clinical condition and tumor burden. Despite these recommendations, experts have yet to agree on a definitive surgical approach.
A retrospective longitudinal analysis of 929 women diagnosed with advanced-stage (International Federation of Gynecology and Obstetrics stage III-IV) epithelial ovarian cancer between January 2002 and January 2025 was conducted. The effects of interval debulking surgery versus primary debulking surgery on median overall survival and progression-free survival were evaluated. Additionally, we aimed to identify patients who may benefit from a particular surgical approach based on clinical variables, mutation in either of the BRCA1 or BRCA2 genes, and homologous recombination profile.
A total of 929 patients were diagnosed with stage III to IV disease (87.2%) and underwent either primary debulking (n = 389, 41.9%) or interval debulking surgery following neoadjuvant chemotherapy (n = 540, 58.1%). Patients treated with primary debulking had a longer median overall survival than those treated with interval debulking surgery (68.40 months, 95% CI 62.92 to 76.45 vs 52.01 months, 95% CI 47.15 to 57.86, HR 1.2, p = .0004). However, when adjusted for age at diagnosis, stage, histology, BRCA status, and tumor resectability, multivariate analysis demonstrated no significant difference in survival between the two surgical groups (HR 1.15, 95% CI 0.96 to 1.39, p = .12). Younger women (<69 years), stage III, and BRCA-wild-type and/or homologous recombination proficient had longer survival with primary debulking than with interval debulking surgery (74.55 months, 95% CI 65.35 to 93.27 vs 55.98 months, 95% CI 48.10 to 64.79, HR 1.38, p = .03). Patients with a pathogenic BRCA variant or homologous recombination deficient profile had similar survival outcomes with either debulking approach, regardless of age and disease stage (p > .05). Propensity score analysis demonstrated comparable median overall survival with the two surgical timings (64.39 months, 95% CI 58.38 to 71.23 vs 57.69 months, 95% CI 50.66 to 64.79, HR 1.33, p = .27).
Our findings support the use of neoadjuvant chemotherapy followed by interval debulking surgery without compromising survival outcomes, regardless of age and stage, particularly among harder-to-treat patients. We identified a specific subset of patients who may benefit from primary debulking surgery as the optimal intervention. These findings advocate for a personalized treatment approach and the potential for tailored surgical strategies guided by patient clinical variables, homologous recombination, and genetic factors.
指南认可间隔减瘤细胞减灭术和初次减瘤细胞减灭术在治疗上皮性卵巢癌中的应用，并强调治疗策略应根据患者的临床状况和肿瘤负荷进行调整。尽管有这些建议，但专家们尚未就明确的手术方法达成一致。
对2002年1月至2025年1月期间诊断为晚期（国际妇产科联盟III-IV期）上皮性卵巢癌的929名女性进行回顾性纵向分析。评估间隔减瘤手术与初次减瘤手术对中位总生存期和无进展生存期的影响。此外，我们旨在根据临床变量、BRCA1或BRCA2基因中的任何一个突变以及同源重组谱，确定可能从特定手术方法中获益的患者。
共有929例患者被诊断为III至IV期疾病（87.2%），并接受了初次减瘤手术（n = 389，41.9%）或新辅助化疗后的间隔减瘤手术（n = 540，58.1%）。接受初次减瘤手术的患者中位总生存期长于接受间隔减瘤手术的患者（68.40个月，95%CI 62.92至76.45 vs 52.01个月，95%CI 47.15至57.86，HR 1.2，p = .0004）。然而，在调整诊断年龄、分期、组织学、BRCA状态和肿瘤可切除性后，多变量分析显示两个手术组之间的生存率无显著差异（HR 1.15，95%CI 0.96至1.39，p = .12）。年龄小于69岁、III期以及BRCA野生型和/或同源重组 proficient 的年轻女性，初次减瘤手术的生存期长于间隔减瘤手术（74.55个月，95%CI 65.35至93.27 vs 55.98个月，95%CI 48.10至64.79，HR 1.38，p = .03）。无论年龄和疾病分期如何，具有致病性BRCA变异或同源重组缺陷谱的患者，两种减瘤方法的生存结果相似（p > .05）。倾向评分分析显示，两种手术时机的中位总生存期相当（64.39个月，95%CI 58.38至71.23 vs 57.69个月，95%CI 50.66至64.79，HR 1.33，p = .27）。
我们的研究结果支持在不影响生存结果的情况下使用新辅助化疗后进行间隔减瘤手术，无论年龄和分期如何，尤其是在难以治疗的患者中。我们确定了一个特定的患者亚组，他们可能从初次减瘤手术作为最佳干预措施中获益。这些发现主张采用个性化治疗方法，并有可能根据患者的临床变量、同源重组和遗传因素制定量身定制的手术策略。
