Key Takeaways in mCSPC: Combination Therapy and Germline Testing Is the New Standard of Care

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The treatment landscape for mCSPC has fundamentally shifted away from ADT monotherapy. Leading oncologists emphasize that ADT alone is no longer acceptable for most patients, with rare exceptions only for extremely frail patients with significant comorbidities and limited life expectancy. The new standard mandates ADT plus an AR pathway inhibitor (ARPI) or ADT plus chemotherapy, with treatment selection guided by patient functional status, preferences, comorbidities, and cancer-related factors.

Universal germline testing has emerged as a critical component of mCSPC management, extending beyond current guidelines to include high-risk localized disease and cases with significant family history. This comprehensive genetic evaluation benefits the patient’s treatment selection and enables cascade testing for cancer prevention across tumor types in male and female family members. The low utilization of germline testing in the urologic community represents a significant gap that must be addressed to provide state-of-the-art care.

Modern mCSPC care requires integrating various genomic testing approaches, including tumor somatic testing for treatment-relevant alterations like PARP inhibitor targets, and germline testing for hereditary cancer predisposition. The complexity of current treatment options, described as an “embarrassment of riches,” necessitates multidisciplinary care teams including medical oncologists, radiation oncologists, urological oncologists, nutritionists, geneticists, and palliative care specialists. This patient-centered approach ensures optimal treatment selection while addressing the comprehensive needs of patients facing an advanced prostate cancer diagnosis.