Society of Urologic Oncology (SUO) 21st Annual Meeting

SUO 2020: Resetting the Active Surveillance Clock: Apalutamide in Lower Risk Prostate Cancer

( In a session of the Best Prostate Cancer Poster Presentations at this year's Society of Urologic Oncology (SUO) virtual annual meeting, Dr. Michael Schweizer presented there worked examining the role of apalutamide in lower-risk prostate cancer.

Active surveillance has, over the past twenty years, become the standard of care for patients with low-risk prostate cancer. With this approach, patients delay, and many often completely avoid active intervention. However, progression to active treatment, often as a result of pathologic reclassification due to increased tumor volume or grade, remains common.


Previous studies, including the REDEEM trial, Dutasteride in localised prostate cancer management: the REDEEM randomised, double-blind, placebo-controlled trial (REDEEM), examining dutasteride, have examined the use of secondary prevention for men on active surveillance, demonstrating increased rates of higher negative biopsy.

In the past few years, at the other end of the disease spectrum, novel androgen receptor signaling inhibitors including apalutamide, enzalutamide, and darolutamide, have demonstrated improved survival for patients with non-metastatic castration-resistant prostate cancer, metastatic castration sensitive prostate cancer, and metastatic castration-resistant prostate cancer. These authors postulated that the use of apalutamide would reduce rates of pathologic reclassification.

To do so, they performed an open-label, phase II trial of apalutamide (240mg PO daily) for 90 days followed by active surveillance. Patients were included if they had no more than clinical T1c prostate cancer, prostate-specific antigen (PSA) <15 ng/mL, Gleason 3+4 in no more than 50% of one core, and Gleason 3+3 in all other cores. Patients did not receive medical or surgical castration.

The primary objective was to determine the proportion of patients with a negative biopsy immediately following the 90-day treatment course, with secondary objectives including long-term clinical outcomes, quality of life, safety, and exploratory biomarker analysis.

Of 23 enrolled patients, 22 completed 3-months of apalutamide followed by a biopsy. 15 patients had GS6 disease while the remaining 7 had GS3+4 disease and 3 (13%) had NCCN very low-risk disease. Median patient age was 67 years and 3 (14%) had very low-risk disease, 11 (50%) had low-risk disease, and 8 (36%) had favorable intermediate-risk disease.

13 of 22 evaluable patients (59%) had no evidence of residual cancer on repeat biopsy immediately following apalutamide therapy. Repeat biopsy was performed 1 year following enrollment in 20 patients of whom 7 (35%) had no evidence of residual cancer. Notably, of the patients who had a negative biopsy at 90 days, 6 of 11 (55%) had a persistently negative biopsy at 1 year. All four patients who had a repeat biopsy at 2 years had evidence of disease at this time point. All patients experienced a >50% decrease in PSA while on therapy.

Following the cessation of therapy, PSA levels returned to approximately baseline levels by 1 year following the index. As expected based on the mechanism of apalutamide, a rise in testosterone was observed.

Further, apalutamide monotherapy was well tolerated and resolved following cessation of therapy. Two grade 3 events included hypertension and rash which were managed with dose reduction.

The authors concluded that apalutamide was safe in an active surveillance population and was associated with high rates of negative biopsy. They postulate that this approach warrants assessment in randomized trials. Further correlative studies are ongoing.

Presented by: Michael Schweizer, MD, Assistant Professor, Division of Medical Oncology, University of Washington School of Medicine

Written by: Christopher J.D. Wallis, MD, Ph.D., Instructor in Urology, Vanderbilt University Medical Center, Nashville, Tennessee @WallisCJD on Twitter at the 2020 Society of Urologic Oncology Annual Meeting – December 2-5, 2020 – Washington, DC