For the treatment of sensitive recurrent ovarian cancer, platinum-containing chemotherapy is widely recognized, however, as for the feasibility of SCS, there are still obvious controversies as mentioned before. Currently, there are at least two ongoing clinical trials exploring the advantages of SCS in sensitive recurrent ovarian cancer, including DESKTOP-III (ClinicalTrials.gov, NCT01166737) and SOCceR (Netherlands Trial Register number, NL3137) .The previous study of DESKTOP-III confirmed the scoring model for predicting complete resection of lesions, and it was verified by the clinical trial of DESKTOP-II(16), so this scoring model was also adopted in this retrospective analysis. In our study, the complete removal rates of BRCAmut and BRCAwt patients were comparable (77.4% vs 68.4%, p = 0.51), suggesting that the DESKTOP Trial Score model was not affected by the mutation status of BRCA1/2. To the best of our knowledge, this is the first study to adopt DESKTOP Trial Score model to discuss the effect of BRCA1/2 mutation status on secondary cytoreductive surgery.
Our study found that BRCAmut patients had a better prognosis, regardless of whether SCS was performed. Even though there was a significant prolongation of median PFS in patients receiving SCS, the overall survival benefit was comparable (77.5 vs 76.8 months, p = 0.827). However, it was worth noting that our study confirmed the effectiveness of SCS in BRCAwt patients. SCS could prolong the median FPS of BRCAwt patients by 4.3 months, and the median OS was extended by 17.4 months. Therefore, we only recommend SCS for BRCAwt patients. Further analysis revealed that complete resection was an independent risk factor affecting overall survival of patients underwent SCS, which was consistent with the reports in the literature(4, 17–21). Therefore, complete resection of the tumor should be achieved, which is inseparable from adequate preoperative evaluation.
In previous literature reports, the mutation rate of BRCA1/2 in Chinese ovarian cancer patients was between 16.7–28.5%(11, 22, 23), while in our study, the proportion of patients with BRCA1/2 mutation was as high as 42.0%. In addition, BRCAmut patients have a lower age of onset and a higher proportion of fully sensitive patients (PFI > 12 months). This could be explained by that patients with BRCA1/2 mutations have a longer relapse interval and higher platinum sensitivity(22, 24, 25). There was no detection of somatic BRCA1/2 mutation in the study, which might lead to some deviation in the results, however, the clinical characteristics of the SCS group and the chemotherapy group were similar, which could avoid the bias of the study to some extent and make the conclusion more scientific and reliable.
Among the BRCAmut patients, the median OS of the SCS group and the chemotherapy group was up to 77.5 and 76.8 months, respectively, which was significantly higher than previous literature reports(4, 7, 18). There were several possible reasons. First of all, the patients included in the study were all patients with platinum sensitive recurrence with a better prognosis than platinum-resistant patients. Secondly, 56.2% of the BRCAmut patients were treated with PARP inhibitors, which could improve the therapeutic effect of BRCAmut patients by synthetic lethality(26, 27). In recent years, a large number of studies have confirmed the significant survival benefit of BRCAmut patients with PARP inhibitors(28–31), therefore, the use of PARP inhibitors might conceal he benefit of SCS. In addition, the benefit of PARP inhibitors in BRCAwt patients was relatively limited(28, 32), so the benefit of SCS was still remained. The occurrence of this situation was similar to the GOG-0213(8). Compared with chemotherapy alone, the PFS and OS of GOG-0213 patients underwent SCS were not significantly improved. As the authors discussed, more than 80% of patients in the study received bevacizumab combined therapy, but it was not possible to assess the effect of bevacizumab. In our study, due to the limited number of patients and the inconsistency of the medication regimen for PARP inhibitors, the subgroup analysis was not conducted. In general, the survival benefits of secondary cytoreductive surgery may be concealed by certain effective therapeutic measures.
In conclusion, secondary surgical cytoreduction in platinum-sensitive recurrent HGSOC patients with BRCAwt could result in longer overall survival than no surgery. In contrast, patients with BRCAmut had no obvious survival benefit. We recommend that BRCA testing in all HGSOC patients for individualized treatment.