Adjuvant radiation therapy, androgen deprivation, and docetaxel for high-risk prostate cancer postprostatectomy: Results of NRG Oncology/RTOG study 0621.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania.
Mark D
MD
Hurwitz
NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania.
Jonathan
J
Harris
Tulane University Cancer Center, New Orleans, Louisiana.
Oliver
O
Sartor
Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania.
Ying
Y
Xiao
Department of Urology, McMaster University, Hamilton, Ontario, Canada.
Bobby
B
Shayegan
Gamma Knife Center, University of Minnesota Medical Center, Minneapolis, Minnesota.|Minneapolis Radiation Oncology, Minneapolis, Minnesota.
Paul W
PW
Sperduto
Department of Radiation Oncology, Virginia Mason Medical Center, Seattle, Washington.
Kasra R
KR
Badiozamani
Department of Radiation Oncology, Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin.
Colleen A F
CAF
Lawton
Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
Eric M
EM
Horwitz
Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri.
Jeff M
JM
Michalski
Southeast Radiation Oncology, Charlotte, North Carolina.
Kevin
K
Roof
Arizona Oncology Services, Phoenix, Arizona.
David C
DC
Beyer
NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania.
Qiang
Q
Zhang
Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, California.
Howard M
HM
Sandler
D000230:Adenocarcinoma / Q000097:blood / Q000473:pathology / Q000628:therapy*; D000328:Adult; D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use*; D000813:Anilides / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D059186:Chemoradiotherapy, Adjuvant / Q000379:methods*; D018572:Disease-Free Survival; D000077143:Docetaxel; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists; D006801:Humans; D007610:Kallikreins / Q000097:blood; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009570:Nitriles / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000097:blood / Q000473:pathology / Q000628:therapy*; D020266:Radiotherapy, Conformal; D050397:Radiotherapy, Intensity-Modulated; D043823:Taxoids / Q000627:therapeutic use*; D014105:Tosyl Compounds / Q000627:therapeutic use*
D000726:Androgen Antagonists; D000813:Anilides; D000970:Antineoplastic Agents; D009570:Nitriles; D043823:Taxoids; D014105:Tosyl Compounds; D000077143:Docetaxel; D007987:Gonadotropin-Releasing Hormone; C053541:bicalutamide; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen
androgen deprivation; chemotherapy; docetaxel; high risk; postprostatectomy; radiation