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.
To delineate patients who may benefit from salvage radiotherapy for
prostate cancer recurrence by identifying variables associated with a durable
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.
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.
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.