Androgen deprivation therapy (ADT) with salvage radiation therapy (RT) improves survival for patients with prostate-specific antigen (PSA) recurrence after radical prostatectomy (RP) for prostate cancer (PC), but many patients suffer further relapse. This study aims to determine the benefit of the combination of ADT, apalutamide, salvage RT, and docetaxel for high-risk PSA recurrent PC.
STARTAR is a multicenter, investigator-initiated phase 2 trial of men with PSA recurrent PC after RP. The key inclusion criteria included M0 by computed tomography/bone scan, Gleason 7 with either T3/positive margin/N1 disease or Gleason 8-10 prostate adenocarcinoma, PSA relapse (0.2-4 ng/ml) <4 yr after RP, and fewer than four positive resected lymph nodes. Patients received ADT with apalutamide for 9 mo, RT starting week 8, and then six cycles of docetaxel. The primary endpoint was 36-mo progression-free survival (PFS) with testosterone recovery and compared against the prior STREAM trial.
We enrolled 39 men, including those with Gleason 8-10 (46%), pN1 (23%); the median PSA was 0.58 ng/ml. The median follow-up was 37 mo. All patients achieved undetectable PSA nadir. At 24 and 36 mo, PFS rates were 84% and 71%, respectively, which improved significantly over 3-yr 47% historic PFS and 54% enzalutamide/ADT/RT (STREAM) PFS rates (p = 0.004 and p = 0.039, respectively). Common any-grade adverse events included 98% hot flashes, 88% fatigue, 77% alopecia, 53% rash (10% G3), and 5% febrile neutropenia.
In this phase 2 trial of ADT, apalutamide, salvage RT, and six cycles of docetaxel for high-risk PSA recurrence, the 3-yr PFS rate improved to 71%, indicating feasible and efficacious treatment intensification, with durable remissions beyond historic data.
Prostate cancer recurrence after surgical removal of the tumor occurs often, and current treatment options to limit recurrence after surgery are only partially effective. In this study, we found that the addition of an androgen receptor inhibitor and docetaxel chemotherapy to standard postsurgery radiation therapy and androgen deprivation therapy significantly improved progression-free survival at 3 yr after treatment. These results suggest that intensification of treatment after surgery can provide long-term benefit to a subset of patients with high-risk prostate cancer.
European urology oncology. 2024 Jul 05 [Epub ahead of print]
Tian Zhang, Lauren Howard, Bridget F Koontz, Scott T Tagawa, Himanshu Nagar, Rhonda L Bitting, Bart A Frizzell, Luke Nordquist, Julia Rasmussen, Colleen Riggan, Marco Reyes, Catrin Davies, Steven R Gray, Carly R Newman, Escarleth Fernandez, Sundhar Ramalingam, Michael R Harrison, Daniel J George, Yuan Wu, Andrew J Armstrong
Duke Cancer Institute Center for Prostate and Urologic Cancers, Duke University, Durham, NC, USA; Division of Hematology and Oncology, Department of Internal Medicine, Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX, USA., Duke Cancer Institute Center for Prostate and Urologic Cancers, Duke University, Durham, NC, USA., Brody School of Medicine, East Carolina University, Greenville, NC, USA., Department of Internal Medicine, Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA., Department of Internal Medicine, Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA; Department of Radiation Oncology, Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA., Duke Cancer Institute Center for Prostate and Urologic Cancers, Duke University, Durham, NC, USA; Wake Forest Baptist Medical Center, Winston-Salem, NC, USA., Wake Forest Baptist Medical Center, Winston-Salem, NC, USA., XCancer, Omaha, NE, USA., Duke Cancer Institute Center for Prostate and Urologic Cancers, Duke University, Durham, NC, USA. Electronic address: .