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Salvage Radiotherapy for Recurrent Prostate Cancer After Radical Prostatectomy
Andrew J. Stephenson, MD;
Shahrokh F. Shariat, MD;
Michael J. Zelefsky, MD;
Michael W. Kattan, PhD;
E. Brian Butler, MD;
Bin S. Teh, MD;
Eric A. Klein, MD;
Patrick A. Kupelian, MD;
Claus G. Roehrborn, MD;
David A. Pistenmaa, MD;
Heather D. Pacholke, MD;
Stanley L. Liauw, MD;
Matthew S. Katz, MD;
Steven A. Leibel, MD;
Peter T. Scardino, MD;
Kevin M. Slawin, MD
JAMA. 2004;291:1325-1332.
Context Salvage radiotherapy may potentially cure patients with disease recurrence after radical prostatectomy, but previous evidence has suggested that it is ineffective in patients at the highest risk of metastatic disease progression.
Objective To delineate patients who may benefit from salvage radiotherapy for prostate cancer recurrence by identifying variables associated with a durable response.
Design, Setting, and Patients Retrospective review of a cohort of 501 patients at 5 US academic tertiary referral centers who received salvage radiotherapy between June 1987 and November 2002 for detectable and increasing prostate-specific antigen (PSA) levels after radical prostatectomy.
Main Outcome Measure Disease progression after salvage radiotherapy, defined as a serum PSA value  0.1 ng/mL above the postradiotherapy PSA nadir confirmed by a second PSA measurement that was higher than the first by any amount, by a continued increase in PSA level after treatment, or by the initiation of androgen deprivation therapy after treatment.
Results Over a median follow-up of 45 months, 250 patients (50%) experienced disease progression after treatment, 49 (10%) developed distant metastases, 20 (4%) died from prostate cancer, and 21 (4%) died from other or unknown causes. The 4-year progression-free probability (PFP) was 45% (95% confidence interval [CI], 40%-50%). By multivariable analysis, predictors of progression were Gleason score of 8 to 10 (hazard ratio [HR], 2.6; 95% CI, 1.7-4.1; P<.001), preradiotherapy PSA level greater than 2.0 ng/mL (HR, 2.3; 95% CI, 1.7-3.2; P<.001), negative surgical margins (HR, 1.9; 95% CI, 1.4-2.5; P<.001), PSA doubling time (PSADT) of 10 months or less (HR, 1.7; 95% CI, 1.2-2.2; P = .001), and seminal vesicle invasion (HR, 1.4; 95% CI, 1.1-1.9; P = .02). Patients with no adverse features had a 4-year PFP of 77% (95% CI, 64%-91%). When treatment was given for early recurrence (PSA level  2.0 ng/mL), patients with Gleason scores of 4 to 7 and a rapid PSADT had a 4-year PFP of 64% (95% CI, 51%-76%) and of 22% (95% CI, 6%-38%) when the surgical margins were positive and negative, respectively. Patients with Gleason scores of 8 to 10, positive margins, and receiving early salvage radiotherapy had a 4-year PFP of 81% (95% CI, 57%-100%) when the PSADT was longer than 10 months and of 37% (95% CI, 16%-58%) when the PSADT was 10 months or less.
Conclusions Gleason score, preradiotherapy PSA level, surgical margins, PSADT, and seminal vesicle invasion are prognostic variables for a durable response to salvage radiotherapy. Selected patients with high-grade disease and/or a rapid PSADT who were previously thought to be destined to develop progressive metastatic disease may achieve a durable response to salvage radiotherapy.
Author Affiliations: Department of Urology, Sidney Kimmel Center for Prostate and Urologic Cancers (Drs Stephenson, Kattan, and Scardino) and Departments of Radiation Oncology (Drs Zelefsky, Katz, and Leibel) and Epidemiology and Biostatistics (Dr Kattan), Memorial Sloan-Kettering Cancer Center, New York, NY; Departments of Urology (Drs Shariat and Roehrborn) and Radiation Oncology (Dr Pistenmaa), University of Texas-Southwestern Medical Center, Dallas; Departments of Urology (Dr Klein) and Radiation Oncology (Dr Kupelian), Cleveland Clinic, Cleveland, Ohio; Department of Radiation Oncology (Drs Pacholke and Liauw), University of Florida, Gainesville; Scott Department of Urology (Dr Slawin) and Department of Radiation Oncology (Drs Butler and Teh), Baylor College of Medicine and the Methodist Hospital, Houston, Tex.
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