To determine the differential effect of the treatment periods on the survival of patients with stage IV serous papillary peritoneal carcinoma (SPPC), fallopian tube cancers, and epithelial ovarian cancers (EOC).
This was an exploratory, population-based observational study of all patients with stage IV SPPC, fallopian tube cancers, and EOC collected from the SEER Research Data 1973–2017. The study period was divided into three time-periods: platinum combinations before the taxane era (1990–1995), platinum plus taxane chemotherapy era (1996–2013), and bevacizumab era (2014–2017).
A total of 9828 patients were eligible for analyses: SPPC (3898 patients; 39.7%), fallopian tube cancers (1290 patients; 13.1%) and EOC (4640 patients, 47.2%). In the 1990–1995 era, the 3-year cause-specific survival was 40% for SPPC, 53% for fallopian tube cancers, and 40% for POC. In the following era 1993–2013, the 3-year cause-specific survival increased to 55% for SPPC, 74% for fallopian tube cancers, and 45% for POC. The last era 2014–2017 showed a 3-year cause-specific survival of 64%, 67%, and 45% for patients with SPPC, fallopian tube cancers, and POC, respectively. The differences in cause-specific survival were statistically significant for patients with SPPC ( p =0.004). Multivariable analysis showed that the treatment eras and age at diagnosis were associated with cause-specific survival.
The results of this study are hypothesis-generating and cannot be considered conclusive given the inherent limitations of registry analysis. Subgroup analyses of the phase III randomized controlled trials, by tumor subset (EOC, fallopian tube cancer, and SPPC) would shed more light on the differential effects of novel therapies.
- • SPPC, fallopian tube cancers and EOC share many features and are treated similarly.
- • The pivotal trials never reported on the outcomes of each entity separately.
- • This study reports on the differential effect of treatment eras over the three entities.
- • The differences in CSS were statistically significant for patients with SPPC, only.
Serous papillary peritoneal cancer (SPPC) is a clinically well-recognized but biologically enigmatic entity that was considered historically a cancer of unknown primary subset . It shares common molecular, histological, and clinical features with epithelial ovarian cancer (EOC), mainly high-grade serous ovarian cancer (HGSOC), which made it reasonable to manage the two entities similarly . The 2014 International Federation of Gynecology and Obstetrics (FIGO) classification combined SPPC and EOC in the same staging depending on the disease extent and localization . However, it did not address the biological behavior of these entities although they present different molecular patterns, which allude to different carcinogenic pathways . The molecular differences between SPPC and EOC were reported in studies with relatively small numbers of cases and the differences in immunohistochemistry patterns were relatively minor compared to the substantial similarities. Thus a debate has emerged between experts as to whether these tumors should be managed similarly to EOC because the clinical experience shows that patients with SPPC had a poorer prognosis at similar stages .
Patients with SPPC are commonly treated in line with the EOC guidelines and have achieved considerable survival benefit . The molecular advances during the last decade yielded two targeted therapies, bevacizumab and poly(ADP-ribose) polymerase (PARP) inhibitors, that were approved by the Food and Drug Administration and the European Medicines Agency based on pivotal trials mainly including EOC . Bevacizumab is a recombinant humanized monoclonal IgG1 antibody that targets vascular endothelial growth factor (VEGF)-A, a validated target that promotes tumor angiogenesis . PARP inhibitors are mainly effective in tumors with defective repair of double-stranded DNA damage by homologous recombination . The corresponding pivotal clinical trials of both bevacizumab and PARP inhibitors have also included patients with SPPC; however, the outcomes in these patients have never been reported specifically. The current study aimed to determine the differential effect of the treatment periods on the survival of patients with stage IV SPPC, fallopian tube cancers, and EOC according to patient information from the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) Program data collected between 1990 and 2017.