BACKGROUND A significant number of prostate adenocarcinoma patients undergoing radical prostatectomy are found to have microscopic extraprostatic disease extension. A majority of these patients have focal extraprostatic extension limited to one or both sides of the prostate. In addition, positive surgical margins are a common pathologic finding in this patient subgroup. In the current study, the authors evaluated the impact of positive surgical margins as an independent predictive factor for prostate specific antigen (PSA) progression in patients with pT3a/b N0M0 carcinoma. METHODS The Mayo Clinic prostate cancer registry list provided 1202 patients with pT3a/b NO prostate carcinoma (no seminal vesicle or regional lymph node involvement) who underwent a radical prostatectomy between 1987–1995. To reduce confounding variables, patients who received preoperative therapy or adjuvant therapy were excluded, resulting in 842 patients who were eligible for analysis. RESULTS A total of 354 patients (42%) had ≥ 1 positive surgical margins whereas 488 patients (58%) demonstrated no margin involvement. The sites of margin positivity were as follows: apex (n = 163), base (n = 47), posterior prostate (n = 227), and anterior prostate (n = 11). A total of 111 patients had ≥ 2 positive surgical margins. The 5‐year survival free of clinical recurrence and/or biochemical failure (postoperative PSA level > 0.2 ng/mL) for patients with no positive surgical margins was 76% and was 65% for patients with 1 positive surgical margin (P = 0.0001). There was no significant difference in biochemical disease progression between patients with 1 versus those with ≥ 2 surgical margins (65% vs. 62%). Multivariate analysis revealed that positive surgical margins were a significant predictor (P = 0.0017) of clinical disease recurrence and biochemical failure (relative risk, 1.55; 95% confidence interval, 1.18–2.04) after controlling for preoperative PSA, Gleason score, and DNA ploidy. CONCLUSIONS In the current study, positive surgical margins were found to be a significant predictor of disease recurrence in patients with pT3a/b NO prostate carcinoma, a finding that is independent of PSA, Gleason score, and DNA ploidy. The benefit of adjuvant therapy in optimizing recurrence‐free survival remains to be tested. Cancer 2002;95:1215–9. © 2002 American Cancer Society. DOI 10.1002/cncr.10871

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BACKGROUND Dedifferentiation is a distinctive feature of cancer progression. Detailed histologic analysis of primary prostate carcinoma and synchronous lymph node metastases may improve our understanding of the complex process of cancer progression and metastasis. METHODS The authors studied 242 regional lymph node positive prostate carcinoma patients who underwent radical prostatectomy and bilateral lymphadenectomy between 1987 and 1992 at the Mayo Clinic. Patients ranged in age from 47–79 years (median, 66 years). The median follow‐up was 6.1 years. Gleason scores of lymph node metastases and primary tumors were compared and correlated with systemic disease progression. Histologic dedifferentiation was defined as a higher Gleason grade in the lymph node metastases than in the primary tumor. Systemic disease progression was defined as the presence of distant metastases documented by biopsies, abdominal computed tomography, plain radiograph, or bone scan. RESULTS The 5‐year systemic progression free survival (PFS) rate was 90%. The Gleason score in the lymph node metastases was higher than in the primary tumor in 45% of patients, lower in 12% of patients, and matched exactly in 43% of patients. The 5‐year PFS was significantly different between patients with histologic dedifferentiation (88% ± 3) and those without dedifferentiation (94% ± 2) (P = 0.04). Adjusting for the Gleason grade of the primary tumor and total lymph node tumor volume, the relative risk for disease progression associated with dedifferentiation was 1.8 (95% confidence interval, 0.7–4.7; P = 0.25). CONCLUSIONS The findings of the current study demonstrate the morphologic heterogeneity of metastases from prostate carcinoma. There is a trend toward histologic dedifferentiation when prostate carcinoma metastasizes to regional lymph nodes. This dedifferentiation, although univariately significant, was not associated with disease progression when adjusted for lymph node tumor volume. Cancer 1999;86:657–63. © 1999 American Cancer Society.