Matching mCRPC Treatment to Fitness in Older Adults

Key Takeaways:

• In major trials of metastatic castration-resistant prostate cancer (mCRPC), roughly a quarter to more than a third of patients were 75 or older. Age and performance status alone do not show what these patients can tolerate.
• A Geriatric 8 (G8) score of 14 or lower flags patients who need a full geriatric assessment.
• Fit older adults and vulnerable adults whose impairments have been addressed should be considered for the same treatment options as younger patients.

Metastatic castration-resistant prostate cancer (mCRPC) is largely a disease of older men. The CARD trial enrolled patients previously treated with docetaxel and an androgen receptor pathway inhibitor (ARPI). Their median age was 70, and 31 percent were 75 or older.¹ With radioligand therapy (RLT), 27 percent of patients were 75 or older in the VISION trial, as were 37 percent in the PSMAfore trial, which enrolled patients who had not received a taxane.² In the 2025 Prostate Cancer In America survey, 51 percent of respondents with metastatic disease were 70 or older.³

Why age alone misleads

Eastern Cooperative Oncology Group (ECOG) and Karnofsky performance status scores poorly reflect functional impairment in older patients with cancer. Geriatric assessment (GA) detects impairments that routine history and physical examination may miss. It is also able to predict severe treatment-related toxicity risk, overall survival across various cancers, and it can impact decision-making around treatment choice and intensity. The International Society of Geriatric Oncology (SIOG) recommends that a GA cover functional status, comorbidity, cognition, mental health, fatigue, social support, nutrition, and geriatric syndromes.⁴

Screening with the G8

A full GA takes time, so a short screen identifies who needs one. The G8 screening tool combines 7 items from the Mini Nutritional Assessment with age. In 364 patients older than 70 starting first-line chemotherapy, a cutoff G8 value of 14 had 85 percent sensitivity and 65 percent specificity for identifying at-risk patients that may benefit from a full GA.⁵

The 2026 European Association of Urology (EAU) guidelines, developed with SIOG, recommend using a screening tool that has been validated (e.g. the G8 screening tool) for health status screening in older men with prostate cancer. They call for a full specialist geriatric evaluation when the score is 14 or lower.⁶ National Comprehensive Cancer Network (NCCN) guidelines also advise considering GA.⁷ American Society of Clinical Oncology (ASCO) guidance recommends GA for patients 65 and older receiving systemic therapy for cancer, including those receiving chemotherapy or targeted therapy, with subsequent GA-guided patient management.⁸

What the assessment changes

GA findings matter differently across treatment classes. For taxane chemotherapy, cabazitaxel labeling reports higher rates of grade 3 to 4 neutropenia and febrile neutropenia in patients 65 and older than in younger patients. It also reports more deaths from causes other than disease progression in this population within 30 days of the last dose. The recommended dose is 20 mg/m2 every 3 weeks with daily prednisone, with 25 mg/m2 for select patients.⁹ NCCN lists age older than 65 on full-dose-intensity chemotherapy as a febrile neutropenia risk factor.¹⁰ Cabazitaxel labeling recommends primary granulocyte colony-stimulating factor (G-CSF) prophylaxis in patients with high-risk clinical features and advises considering it for all patients receiving 25 mg/m2.⁹ In CARD, with its older population, patients received cabazitaxel at 25 mg/m2 with primary G-CSF prophylaxis from the first cycle.¹

For ARPIs, abiraterone and enzalutamide labeling report no overall differences in safety or effectiveness between older and younger trial patients.^11,12 Enzalutamide labeling also calls for evaluating fall and fracture risk.¹¹

For RLT, serious adverse reactions in VISION, after a taxane, occurred in 41 percent of patients 75 or older versus 35 percent of younger patients. In PSMAfore, before a taxane, they occurred in 20 percent of both groups. Neither trial showed an overall difference in effectiveness by age. Labeling advises frequent renal function monitoring, because mild to moderate renal impairment may raise toxicity risk.²

For poly(ADP-ribose) polymerase (PARP) inhibitors, 24 percent of patients in the PROpel trial of olaparib with abiraterone were 75 or older. Labeling reports no overall differences in safety or effectiveness by age, and it calls for monthly complete blood counts. Eligibility depends on genomic status: olaparib with abiraterone is approved for BRCA-mutated mCRPC, and olaparib alone for homologous recombination repair (HRR) gene-mutated mCRPC after a specified ARPI.¹³

Fit, vulnerable, and frail

EAU guidelines sort older men into 3 groups. Fit patients (G8 above 14) and vulnerable patients whose reversible impairments have been resolved should be considered for receiving the same treatment as younger patients. Frail patients with irreversible impairments should receive adapted treatment. Patients who are too ill for active treatment should receive palliative treatment alone.⁶

A practical sequence follows from these recommendations. Screen with the G8, and refer patients who score 14 or lower for full assessment. Address reversible problems such as poor nutrition, polypharmacy, or limited social support before choosing a regimen.^6,8 Fitness then helps guide which treatment suits the patient, including taxane chemotherapy, an ARPI, RLT, or a PARP inhibitor. For RLT and PARP inhibitors, eligibility is set first by prostate-specific membrane antigen (PSMA) positron emission tomography (PET) and genomic testing, respectively.^2,13