Cytoreduction status and platinum sensitivity in women with recurrent ovarian cancer

Abstract

<h3>Objectives:</h3> Neoadjuvant chemotherapy (NACT) and interval cytoreduction (IDS) is an increasingly used treatment modality for women with advanced ovarian cancer not amenable to primary cytoreduction. Clinical trials have demonstrated decreased perioperative morbidity and mortality with similar overall survival (OS) with NACT-IDS. However, controversy regarding initial management is ongoing. This study aims to determine the association between cytoreduction status and time to second recurrence (TTSR) in women with ovarian cancer treated with NACT-IDS; and explore associations between platinum sensitivity, <i>BRCA1/2</i> status, homologous recombination deficiency (HRD), and TTSR. <h3>Methods:</h3> Women diagnosed with advanced ovarian, tubal, and peritoneal cancer who received NACT-IDS from 2000-2020 were included. Patients were enrolled in a prospective NACT database from 9/2013. Demographics and cancer-specific data, including germline/somatic <i>BRCA1/2</i> status; HRD status defined based on genomic instability scoring; platinum sensitivity (sensitive [PS]/resistant [PR]) at first and second recurrences; TTSR, and survival were abstracted from medical records. Residual disease after cytoreduction was classified as optimal (<1cm residual) or suboptimal (>1 cm) as R0 was not consistently reported. Kaplan Meier (KM) curves and log-rank tests were used to estimate TTSR based on cytoreduction status and platinum sensitivity. Patients achieving complete remission were included in the PS cohort. <h3>Results:</h3> 187 women were included in the study, the majority had optimal cytoreductive surgery (81.8%). Overall, 39.6% (74/187) of patients did not have germline/somatic testing. Of those tested, 30.9% (35/113) had ≥1 positive test (18 germline <i>BRCA,</i> 8 somatic <i>BRCA,</i> 9 HRD). Women with optimal cytoreduction experienced a longer median TTSR or death compared to those who underwent suboptimal debulking (24.2 vs 15.6 months; p<0.001). Though not statistically significant, median TTSR or death in women with suboptimal cytoreduction and PS disease at first recurrence was 26.7 months vs 16.5 months for those with optimal cytoreduction and PR disease at first recurrence (p=0.055). Women with <i>BRCA1/2</i> mutation or HRD had no difference in odds of optimal debulking (p=0.34) or TTSR (p=0.07) compared to those without <i>BRCA</i> mutations or HRD, though sample size was limited by patients with incomplete or no <i>BRCA</i> testing. There was a significant difference in survival and TTSR by cytoreductive status and platinum sensitivity (p<0.001). In pairwise tests, the difference between OC+PS vs OC+PR (p<0.0001), OC+PS vs SC+PR (p<0.0001), SC+PS vs SC+PR (p=0.02) were significant. <h3>Conclusions:</h3> Platinum sensitivity at first recurrence may have a greater association with survival than cytoreductive status for women receiving NACT for advanced ovarian cancer. Cytoreductive status is associated with TTSR. Genetic evaluation has evolved into critical knowledge in the care of these patients; further analysis is warranted to define the association between genetic mutational burden, TTSR, and OS to individualize adjuvant therapy.