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

Urol Oncol. 2025 Jun;43(6):397.e9-397.e16. doi: 10.1016/j.urolonc.2025.01.001. Epub 2025 Jan 24.

Abstract

Objective: 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.

Materials and 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.

Conclusion: Frailty and specific comorbidities significantly influence cancer-control outcomes in mHSPC, as well as mCRPC patients, even after controlling for adverse tumor characteristics.

Keywords: ECOG; Prostate cancer; Secondary malignancy; mCRPC, Cardiovascular; mHSPC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Comorbidity
  • Frailty* / complications
  • Frailty* / epidemiology
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Prostatic Neoplasms, Castration-Resistant* / drug therapy
  • Prostatic Neoplasms, Castration-Resistant* / epidemiology
  • Prostatic Neoplasms, Castration-Resistant* / mortality
  • Prostatic Neoplasms, Castration-Resistant* / pathology
  • Retrospective Studies