Timing of cytoreductive surgery does not impact overall survival in ovarian cancer

Primary cytoreductive surgery (PCS) in participants with advanced, resectable ovarian cancer offers no significant improvement in overall survival (OS) compared with interval cytoreductive surgery (ICS). However, in selected participants from the phase 3 TRUST study, PCS was associated with improved progression-free survival (PFS).

The goal of surgery in advanced ovarian cancer is to prolong remission, improve OS, and maintain quality-of-life. Complete gross tumour resection is consistently associated with a favourable prognosis [1]. PCS followed by systemic therapy has been considered the standard-of-care for decades. However, neoadjuvant chemotherapy followed by ICS and then systemic therapy has emerged as an alternative strategy [2,3]. The optimal timing of surgery in resectable advanced ovarian cancer remains uncertain.

“The phase 3 TRUST study (NCT02828618) evaluated the optimal timing of maximal effort cytoreductive surgery in participants with advanced ovarian cancer,” introduced Prof. Sven Mahner (LMU University Hospital Munich, Germany) [4]. In total, 796 participants were randomised 1:1 to receive PCS or ICS, performed in centres with high surgical quality (e.g., ≥50% complete resection rate in upfront surgery for FIGO IIIB–IVB participants and ≥36 debulking surgeries per year). The primary endpoint was OS; key secondary endpoints included PFS, complete resection rate, and quality-of-life.

TRUST did not meet its primary endpoint with a median OS of 54.3 months in the PCS arm versus 48.3 months in the ICS arm (HR 0.89; 95% CI 0.74–1.08; P=0.24). However, PCS resulted in a statistically significant improvement in median PFS, reaching 22.1 months compared to 19.7 months in the ICS arm (HR 0.80; 95% CI 0.66–0.96; P=0.018). “The PFS benefit of PCS was most evident in participants with FIGO stage III disease and those who achieved complete gross resection,” elaborated Prof. Mahner.

Surgical morbidity was low in both groups, with complications reported in 18% and 12% of participants in the PCS and ICS arms, respectively. No significant differences in quality-of-life scores were observed at any time point.

“TRUST is the first randomised phase 3 trial to demonstrate a PFS benefit of primary over interval cytoreductive surgery, without compromising short- or long-term quality-of-life,” concluded Prof. Mahner.

1. Bristow RE, et al. J Clin Oncol 2023;41(25):4065–4076.
2. Fagotti A, et al. Int J Gynaecol Cancer. 2020;30(11):1657–1664.
3. Onda T, et al. Eur J Cancer. 2020;130:114–125.
4. Mahner S, et al. TRUST. Trial of Radical Upfront Surgical ^Therapy in advanced ovarian cancer. Abstract LBA5500, ASCO Annual Meeting 2025, May 30–June 3, Chicago, IL, USA.

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Posted on 30 July 2025