Phase 3 trials have demonstrated a benefit from adjuvant radiation therapy (ART) for men who have adverse factors at radical prostatectomy (RP). However, some patients have a high risk of progression despite ART. The role of systemic therapy with ART in this high-risk group remains to be defined.
Patients who had either a post-RP prostate-specific antigen (PSA) nadir > 0.2 ng/mL and a Gleason score ≥7 or a PSA nadir ≤0.2 ng/mL, a Gleason score ≥8, and a pathologic tumor (pT) classification ≥ pT3 received 6 months of androgen-deprivation therapy (ADT) plus radiotherapy and 6 cycles of docetaxel. The primary objective was to assess whether the addition of ADT and docetaxel to ART resulted in a freedom from progression (FFP) rate ≥ 70% compared with an expected rate of 50%. Multivariate logistic and Cox regression analyses were used to model associations between factors and outcomes.
In total, 74 patients were enrolled. The median follow-up was 4.4 years. The pathologic tumor classification was pT2 in 4% of patients, pT3 in 95%, and pT4 in 1%. The Gleason score was 7 in 18% of patients and ≥8 in 82%. Post-RP PSA levels were ≤0.2 ng/mL in 53% of patients and >0.2 ng/mL in 47%. The 3-year FFP rate was 73% (95% confidence interval, 61%-83%), and the 3-year cumulative incidence of biochemical, distant, and local failure was 26%, 7%, and 0%, respectively. In multivariate models, postprostatectomy PSA nadir was associated with 3-year FFP, Gleason score, and PSA with biochemical failure. Grade 3 and 4 neutropenia was common; however, only 3 episodes of febrile neutropenia occurred. Late toxicities were not impacted by the addition of systemic therapy.
Combined ADT, docetaxel, and ART for men with high-risk prostate cancer after prostatectomy exceeded the prespecified study endpoint of 70% 3-year FFP. Phase 3 trials assessing combined local and systemic therapies for these high-risk patients are warranted. Cancer 2017;123:2489-96. © 2017 American Cancer Society.
Cancer. 2017 Mar 21 [Epub]
Mark D Hurwitz, Jonathan Harris, Oliver Sartor, Ying Xiao, Bobby Shayegan, Paul W Sperduto, Kasra R Badiozamani, Colleen A F Lawton, Eric M Horwitz, Jeff M Michalski, Kevin Roof, David C Beyer, Qiang Zhang, Howard M Sandler
Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania., NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania., Tulane University Cancer Center, New Orleans, Louisiana., Department of Urology, McMaster University, Hamilton, Ontario, Canada., Gamma Knife Center, University of Minnesota Medical Center, Minneapolis, Minnesota., Department of Radiation Oncology, Virginia Mason Medical Center, Seattle, Washington., Department of Radiation Oncology, Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin., Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania., Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri., Southeast Radiation Oncology, Charlotte, North Carolina., Arizona Oncology Services, Phoenix, Arizona., Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, California.