Salvage Settings, Duration, and Next Steps in Very High-Risk Prostate Cancer

Tamim Niazi, MDCM, begins by separating DASL-HiCaP's (NCT04136353) post-prostatectomy cohort from EMBARK (NCT02319837). EMBARK enrolled patients who were not eligible for salvage curative treatment or had already received it, he explains, whereas DASL-HiCaP enrolled patients still eligible for cure, who received 24 months of androgen deprivation therapy (ADT) and locoregional radiation therapy with or without darolutamide (Nubeqa). Although event numbers in the salvage setting are small, he reports an HR of about 0.1 in favor of darolutamide and expects it to remain below 0.5 as data mature.

On choosing primary treatment, Niazi describes close discussion between urology and radiation oncology at his center. For favorable high-risk disease, he says outcomes with surgery and radiation are nearly identical and patients decide. For very high-risk disease, his team uses the CAPRA nomogram, favoring radiation and long-term ADT when the score indicates a higher risk of relapse after prostatectomy.

Niazi notes that STAMPEDE (NCT00268476) used 36 months of ADT, whereas DASL-HiCaP used 24 months of ADT and study treatment to reflect the current standard. He adds that some lower-tier high-risk patients may need less hormone therapy, citing a Canadian trial randomly assigning favorable high-risk patients to 24 vs 12 months of ADT.

Looking ahead, Niazi says the key task is identifying which patients benefit most from intensification and which can be spared its adverse events or receive shorter therapy, with gene-expression signatures and multimodal artificial intelligence tools as potential aids. His single request for urologists: If prostate-specific antigen persists or rises above 0.1 ng/mL within 12 months of surgery, refer the patient for staging rather than waiting for 0.2 ng/mL.