Add on Apalutamide to ADT Improves Outcomes after Prostate Cancer Surgery: NEJM

A new study published in The New England Journal of Medicine showed that when compared to androgen deprivation therapy (ADT) plus placebo, perioperative treatment with ADT plus apalutamide improved oncologic outcomes following radical prostatectomy in patients with high-risk localized or locally progressed prostate cancer.

Radical prostatectomy is possibly curative in individuals with high-risk localized or locally progressed prostate cancer; nevertheless, up to half of patients recur within 5 years. Thus, this research was set to evaluate perioperative apalutamide in high-risk localized prostate cancer.

Patients with recently diagnosed high-risk localized or locally advanced prostate cancer were randomly assigned in a 1:1 ratio to receive ADT plus apalutamide (240 mg daily) or ADT plus placebo for six cycles (28 days each) prior to and following radical prostatectomy with pelvic lymph node dissection in this study.

A composite of pathological complete response or minimal residual disease (defined as a pathological stage of ypT2 or lower, with a tumor size of ≤5 mm in the greatest dimension) and metastasis-free survival, as determined by conventional imaging or prostate-specific membrane antigen positron-emission tomography, served as the dual primary end points. Event-free survival, the first subsequent therapy, distant metastases (measured in time-to-event analyses), and safety were secondary end objectives.

A total of 2109 individuals were randomized, with 1052 receiving ADT with a placebo and 1057 receiving ADT plus apalutamide. 61.7 months was the median follow-up.

Both the percentage of patients with metastasis-free survival (probability of metastasis-free survival at 5 years, 78.2% vs. 73.5%; hazard ratio for distant metastasis or death, 0.80; 95% CI, 0.67 to 0.96; P=0.02) and the percentage of patients with a pathological complete response or minimal residual disease (8.9% vs. 1.0%; odds ratio, 10.17; 95% CI, 5.27 to 19.64; P<0.001).

ADT with apalutamide substantially outperformed ADT plus placebo in terms of event-free survival, time to first subsequent treatment, and time to distant metastases (P<0.001 for all between-group comparisons).

39.6% of patients in the apalutamide group and 31.0% of patients in the placebo group experienced grade 3 or 4 adverse events; the apalutamide group's greater incidence of rash was the main cause of the group difference.

Overall, in individuals who have high-risk localized or locally progressed prostate cancer, perioperative therapy with ADT with apalutamide resulted in better oncologic outcomes following radical prostatectomy than ADT plus placebo. 

Source:

Taplin, M.-E., Gleave, M., Shore, N. D., Lopez-Gitlitz, A., Kretschmer, A., Efstathiou, E., Nguyen, P. L., Damião, R., Kamoto, T., Ross, A., Briganti, A., Hadaschik, B. A., Heidenreich, A., Juárez Soto, Á., Ye, H., Gotto, G., Rooney, B., Tian, S. K., Wetherhold, L., … PROTEUS Investigators. (2026). Perioperative apalutamide in high-risk localized prostate cancer. The New England Journal of Medicine, NEJMoa2603878. https://doi.org/10.1056/NEJMoa2603878