Pathologic classification of prostate carcinoma: the impact of margin status

A proposed pathologic (pTNM) classification system for prostate carcinoma was analyzed for its impact on survival outcome in the prostate specific antigen (PSA) era. The impact of margin status on the survival outcome of patients with otherwise organ-confined disease (i.e., without extraprostatic extension or seminal vesicle involvement) was assessed.

Among 5467 patients, the original pathologic classification was T2 in 2094 patients; those with evidence of positive margins, extraprostatic extension, or seminal vesicle involvement were initially classified as having pT3 disease (2920 patients) or pT4 residual disease (211 patients). According to the proposed pTNM system, 1512 patients for whom margin status was considered independent of T classification were reclassified.

After reclassification, 803 specimens had been down-classified to pT2, resulting in 2932 (54%) with pT2N0 organ-confined disease and a margin positivity rate of 27%; originally, only 38% of patients had been classified as pT2N0. When the old and new classifications were compared, 5-year progression free survival to the combined endpoint of clinical and/or PSA progression (< or = 0.2 ng/mL) was 86% versus 84% and 70% versus 67% for disease classified as pT2N0 and pT3N0, respectively. Multivariate analysis assessed the effect of margin status on 2334 pT2N0 patients (classified according to the proposed pTNM system) who did not receive adjuvant therapy; adjustments were made for Gleason grade, preoperative PSA, and DNA ploidy. In this analysis, the relative risk (with 95% confidence interval) associated with positive margins was 1.65 (1.24-2.18); this was significant for the combined endpoint of clinical/PSA progression. The 5-year survival, free of clinical/PSA progression, was 86% for those without versus 75% for those with positive margins.

This analysis supports the adoption of the proposed pTNM system, which will allow for uniform reporting of pathologic data on prostate carcinoma. For patients with organ-confined disease, positive margins are associated with higher rates of PSA progression. Accordingly, patients should be stratified based on margin positivity in addition to pT classification.