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Abstract
Importance:
Prostate cancer with adverse pathological features (ie, pT3 and/or positive margins) after prostatectomy may be managed with adjuvant radiotherapy (ART) or surveillance followed by early-salvage radiotherapy (ESRT) for biochemical recurrence. The optimal timing of postoperative radiotherapy is unclear.

Objective:
To compare the clinical outcomes of postoperative ART and ESRT administered to patients with prostate cancer with adverse pathological features.

Design, Setting, and Participants:
This multi-institutional, propensity score-matched cohort study involved 1566 consecutive patients who underwent postprostatectomy ART or ESRT at 10 US academic medical centers between January 1, 1987, and December 31, 2013. Propensity score 1-to-1 matching was used to account for covariates potentially associated with treatment selection. Data were collected from January 1 to September 30, 2016. Data analysis was conducted from October 1, 2016, to October 21, 2017.

Main Outcomes and Measures:
Freedom from postirradiation biochemical failure, freedom from distant metastases, and overall survival. All outcomes were measured from date of surgery to address lead-time bias.

Results:
Of 1566 patients, 1195 with prostate-specific antigen levels of 0.1 to 0.5 ng/mL received ESRT and 371 patients with prostate-specific antigen levels lower than 0.1 ng/mL received ART. The median age (interquartile range) was 60 (55-65) years. After propensity score matching, the median (interquartile range) follow-up after surgery was similar between the ESRT and ART groups (73.3 [44.9-106.6] months vs 65.8 [40-107] months; P = .22). Adjuvant RT, compared with ESRT, was associated with higher freedom from biochemical failure (12-year actuarial rates: 69% [95% CI, 60%-76%] vs 43% [95% CI, 35%-51%]; effect size, 26%), freedom from distant metastases (95% [95% CI, 90%-97%] vs 85% [95% CI, 76%-90%]; effect size, 10%), and overall survival (91% [95% CI, 84%-95%] vs 79% [95% CI, 69%-86%]; effect size, 12%). Adjuvant RT, lower Gleason score and T stage, nodal irradiation, and postoperative androgen deprivation therapy were favorable prognostic features on multivariate analysis for biochemical failure. Sensitivity analysis demonstrated that the decreased risk of biochemical failure associated with ART remained significant unless more than 56% of patients in the ART group were cured by surgery alone. This threshold is greater than the estimated 12-year freedom from biochemical failure rate of 33% to 52% after radical prostatectomy alone, as determined by a contemporary dynamic nomogram.

Conclusions and Relevance:
Adjuvant RT, compared with ESRT, was associated with reduced biochemical recurrence, distant metastases, and death for high-risk patients, pending prospective validation. These findings suggest that a greater proportion of patients with prostate cancer who have adverse pathological features may benefit from postprostatectomy ART rather than surveillance followed by ESRT.

Author information

Hwang WL1, Tendulkar RD2, Niemierko A1, Agrawal S3, Stephans KL2, Spratt DE4, Hearn JW4, Koontz BF5, Lee WR5, Michalski JM6, Pisansky TM7, Liauw SL8, Abramowitz MC9, Pollack A9, Moghanaki D10, Anscher MS11, Den RB12, Zietman AL1, Stephenson AJ2, Efstathiou JA1.
1
Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
2
Departments of Radiation Oncology and Urology, Cleveland Clinic, Cleveland, Ohio.
3
Department of Radiation Oncology, Case Western Reserve University School of Medicine, Cleveland, Ohio.
4
Department of Radiation Oncology, University of Michigan, Ann Arbor.
5
Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina.
6
Department of Radiation Oncology, Washington University School of Medicine, St Louis, Missouri.
7
Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota.
8
Department of Radiation Oncology, University of Chicago, Chicago, Illinois.
9
Department of Radiation Oncology, University of Miami, Miami, Florida.
10
Department of Radiation Oncology, Hunter Holmes McGuire Veterans Affairs Medical Center, Richmond, Virginia.
11
Department of Radiation Oncology, Virginia Commonwealth University Medical Center, Richmond.
12
Department of Radiation Oncology, Sidney Kimmel Cancer Center at Thomas Jefferson University, Philadelphia, Pennsylvania.