Metastatic Castration-Sensitive Prostate Cancer: Evolving Management With New Data from ASCO 2025

Panelists discuss how clinical factors, including disease characteristics (Gleason score, volume, metastatic sites), patient factors (performance status, comorbidities, symptoms), and emerging genomic biomarkers, guide treatment intensification decisions in metastatic castration-sensitive prostate cancer.

Panelists discuss how medical comorbidities, physiologic vs chronologic age, drug interactions, and performance status influence the choice between doublet and triplet therapy regimens.

Panelists discuss how the ARASENSE and PEACE-1 phase 3 trials demonstrated the efficacy of triplet therapy combining androgen deprivation therapy (ADT), docetaxel, and novel antiandrogens, while addressing the ongoing underutilization of intensified treatment approaches.

Panelists discuss how emerging trials like AMPLITUDE (PARP inhibitors for BRCA mutations), PSMA-ADDITION (radioligand therapy), and CAPITELLO (AKT inhibitors for PTEN deficiency) are moving the field toward increasingly complex, biomarker-driven treatment selection.

Panelists discuss how the ARANOTE trial’s quality-of-life data and the ARCHES trial’s 5-year follow-up demonstrate sustained benefits of doublet therapy, with enzalutamide plus ADT showing a 3-year overall survival improvement in high-volume patients.

Panelists discuss how the ARANOTE trial’s progression-free survival benefits with darolutamide inform treatment selection between doublet and triplet approaches, emphasizing personalized decision-making based on tumor burden, patient performance status, and the “first shot, best shot” treatment philosophy.

Panelists discuss how the ARANOTE trial’s subgroup analysis of 65 Black patients (primarily from Brazil and South Africa) demonstrated consistent treatment benefits and highlights the importance of diversity in clinical trials to address health care disparities and potential biological differences across populations.

Panelists discuss how androgen deprivation therapy (ADT) monotherapy is no longer acceptable for metastatic castration-sensitive prostate cancer (mCSPC), emphasizing that combination therapy with androgen receptor (AR) pathway inhibitors or chemotherapy plus universal germline testing should be the new standard of care.

Panelists discuss how prostate-specific antigen (PSA) nadir serves as a crucial prognostic marker in metastatic castration-sensitive prostate cancer (mCSPC), with faster drops to lower levels (particularly below 0.2) correlating with better outcomes, whereas imaging frequency should be customized based on clinical status and PSA kinetics.

Panelists discuss how data from the International Registry for Men with Advanced Prostate Cancer (IRONMAN) demonstrates that achieving a prostate-specific antigen (PSA) threshold below 0.2 ng/mL at 6 to 12 months is associated with improved progression-free survival and overall survival regardless of treatment regimen.

Panelists discuss how managing patients with suboptimal prostate-specific antigen (PSA) response or rising PSA requires careful consideration of PSA kinetics, doubling time, duration of prior response, and imaging findings to determine whether to continue monitoring, add therapy, or transition to castration-resistant treatment approaches.

Panelists discuss how quality-of-life considerations are paramount in treatment selection for patients with metastatic castration-sensitive prostate cancer (mCSPC), with data showing that achieving ultralow prostate-specific antigen (PSA) levels correlates with better quality-of-life outcomes and that tolerability profiles, particularly regarding fatigue and drug-drug interactions, significantly impact daily patient experience.

Panelists discuss how successful metastatic castration-sensitive prostate cancer (mCSPC) management requires balancing cancer control with quality-of-life preservation, emphasizing the need for better tools to measure patient-reported outcomes, comprehensive survivorship care addressing cardiovascular and bone health, and personalized approaches that help patients understand their prognosis while maintaining their ability to thrive during treatment.