Influence of frailty and specific comorbidities on oncological outcomes in metastatic hormone-sensitive and castration resistant prostate cancer

Abstract

Background: Demographic changes will lead to higher proportions of metastatic hormone-sensitive (mHSPC) and castration resistant metastatic prostate cancer (mCRPC) patients with higher frailty index and multiple comorbidities. Methods: We relied on an institutional tertiary-care database to explore the effect of frailty (Eastern Cooperative Oncology Group [ECOG]), as well as cardiovascular (CVD) and secondary malignancy (SecCa) comorbidities on overall survival (OS) and time to mCRPC in mHSPC and OS in mCRPC patients with Kaplan-Meyer estimates and Cox regression models. Results: Of 802 mHSPC patients, 61% were ECOG0 vs. 32% ECOG1 vs. 6.5% ECOG ≥ 2. Significant differences in baseline patient and baseline mHSPC characteristics were observed for all three groups (all p ≤ 0.05). In time to mCRPC analyses and OS analyses of mHSPC and mCRPC patients, significant disadvantages were observed for ECOG 1/≥2 patients, relative to ECOG0, even after multivariable adjustment. Moreover, 31% of included patients had history/active CVD, which yielded significant median OS differences in mHSPC patients (95 vs. 63 months, multivariable hazard ratio: HR: 1.77, p < 0.01), but not in mCRPC patients (p = 0.085). After stratification according to SecCa, 14% had a SecCa which led to significant median OS differences in mCRPC patients (50 vs. 37 months, p < 0.01) but not in mHSPC patients (76 vs. 64 months, p = 0.089). Patients with higher frailty index and comorbidities showed significant differences in therapy lines. Conclusions: Frailty and specific comorbidities significantly influence cancer-control outcomes in mHSPC, as well as mCRPC patients, even after controlling for adverse tumor characteristics.