Introduction: There are five rare histological variants of prostate adenocarcinoma (PCa), namely, ductal, mucinous, signet ring cell (SRC), adenosquamous (ASC) and neuroendocrine (NEC). Although ductal, SRC, ASC and NEC display poorer survival outcomes when compared to nonvariant PCa, they have also been shown to present more frequently with metastases. Hence, we sought to describe overall survival (OS) in men with nonmetastatic rare variant PCa.
Methods: We included a total of 947,579 patients with nonmetastatic PCa (cN0M0) diagnosed between 2004 and 2015, within the National Cancer Database (NCDB). We estimated 5-year OS for all rare variants and compared them to nonvariant PCa. Kaplan-Meier estimates were used to visualize the impact of histological subtype on survival. Cox regression analyses tested the effect of variant on OS, after adjusting for all available covariates.
Results: Only 2555 (0.27%) men presented with nonmetastatic rare variant PCa. Specifically, 19 presented with ASC, 132 with SRC, 277 with NEC, 757 with mucinous, 1370 with ductal, and 945,024 with nonvariant PCa. Median (IQR) follow up period was 5.0 (4.8-5.3) years. Estimated 5-year OS was highest in mucinous (92.4%) followed by nonvariant (90.0%), ductal (84.2%), SRC (76.0%), ASC (37.3%), and NEC (35.2%). Compared to nonvariant, NEC, ASC, SRC and ductal were found to have lower OS at 5 years (all p<0.01), whereas mucinous was found to have higher OS (p=0.003). Kaplan-Meier curves displaying the effect of subtype on survival are represented in the associated figure. After adjusting for covariates, regression analyses confirmed histological subtype to be an independent predictor of survival. Compared to nonvariant, mortality was found to be greatest in ASC (HR: 8.49, 95% CI: 4.42-16.32) and NEC (HR: 5.73, 95% CI: 4.91-6.69) and was lowest in mucinous (HR: 1.02, 95% CI: 0.79-1.32).
Conclusions: Unlike nonvariant PCa, NEC, ASC and SRC have compromised outcomes, even when presenting at a nonmetastatic stage. Our findings are of importance in counselling patients and setting realistic expectations. Moreover, considering the unfavorable survival, it may be reasonable to consider early systemic treatment in these men, before systemic progression. This warrants further investigation. Source of