Impact of surgical margin status on prostate-cancer-specific mortality

Study Type--Diagnostic (exploratory cohort) Level of Evidence 2b. What's known on the subject? and What does the study add? Surgical margin status at radical prostatectomy (RP) has been shown to be a predictor of disease progression and the strongest predictor of benefit from adjuvant therapy, but the impact of a positive surgical margin (PSM) on long-term prostate-cancer-specific survival is unknown. The PSM rate is dependent on the pathological stage of the cancer. In a recent multicentre nomogram for 15-year prostate-cancer-specific mortality (PCSM) after RP, PSM was not significantly associated with PCSM, while Gleason score and pathological stage were the only significant predictors. This has not been validated in a single centre, and PSM has been shown to vary greatly with surgical technique. This is the first study on the impact of PSM on PCSM in a single surgeon's cohort. In other centres, the decision to administer adjuvant therapy may be influenced by surgical margin status. In this cohort, men routinely did not receive adjuvant therapy, affording the unique opportunity to study the long-term implications of a PSM.

• To examine the relative impact of a positive surgical margin (PSM) and other clinicopathological variables on prostate-cancer-specific mortality (PCSM) in a large retrospective cohort of patients undergoing radical prostatectomy (RP).

• Between 1982 and 2011, 4569 men underwent RP performed by a single surgeon. • Of the patient population, 4461 (97.6%) met all the inclusion criteria. • The median (range) age was 58 (33-75) years and the median prostate-specific antigen (PSA) was 5.4 ng/mL; RP Gleason score was ≤ 6 in 2834 (63.7%), 7 in 1351 (30.3%), and 8-10 in 260 (6.0%) patients; PSMs were found in 462 (10.4%) patients. • Cox proportional hazards models were used to determine the impact of a PSM on PCSM.

• At a median (range) follow-up of 10 years (1-29), 187 men (4.3%) had died from prostate cancer. • The 20-year prostate-cancer-specific survival rate was 75% for those with a PSM and 93% for those without. • Compared with those with a negative surgical margin, men with a PSM were more likely to be older (median age 60 vs 58 years) and to have undergone RP in the pre-PSA era (36.6% vs 11.8%). Additionally, they were more likely to have a higher PSA level (median 7.6 vs 5.2 ng/mL), a Gleason score of ≥ 7 (58.7% vs 33.7%), and a non-organ-confined tumour (90.9% vs 30.6% [P < 0.001 for all]). • In a univariate model for PCSM, PSM was highly significant (hazard ratio [HR] 5.0, 95% confidence interval [CI] 3.7-6.7, P < 0.001). • In a multivariable model, adjusting for pathological variables and RP year, PSM remained an independent predictor of PCSM (HR 1.4, 95% CI 1.0-1.9, P = 0.036) with a modest effect relative to RP Gleason score (HR 5.7-12.6) and pathological stage (HR 2.2-11.0 [P < 0.001]).

• Although a PSM has a statistically significant adverse effect on prostate-cancer-specific survival in multivariable analysis, Gleason grade and pathological stage were stronger predictors.