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.