Small prostate size and high grade disease--biology or artifact?

PURPOSE: Prior radical prostatectomy series have shown an inverse association between prostate size and high grade cancer. It has been suggested that smaller size prostates arise in a low androgen environment, enabling development of more aggressive cancer. We propose that this observation is the result of ascertainment bias driven by prostate specific antigen performance. MATERIALS AND METHODS: We identified 1,404 patients from the Stanford Radical Prostatectomy Database with clinical stage T1c (723) and T2 (681) disease who underwent surgery between 1988 and 2002, and underwent detailed morphometric mapping by a single pathologist. Multivariate linear regression was performed to assess for the effects of age, prostate weight and prostate specific antigen on total and high grade (Gleason grade 4/5) cancer volume and percentage of high grade disease. RESULTS: In patients who underwent biopsy due to abnormal prostate specific antigen (stage T1c), prostate weight was negatively associated (p = 0.0002) with total cancer volume, volume of high grade disease and percentage of high grade disease. For patients who underwent biopsy based on abnormal digital rectal examination (stage T2) these associations were not observed. CONCLUSIONS: Improved prostate specific antigen performance for high grade disease results in ascertainment bias in patients with T1c disease. Thus, the association between prostate size and high grade disease may be a consequence of grade dependent performance of prostate specific antigen rather than true tumor biology.

Smoking and adverse outcomes at radical prostatectomy.

BACKGROUND: Multiple large epidemiologic studies have examined the relationship between smoking and prostate cancer incidence and mortality only to arrive at contradictory results. In this series, we studied the effect of smoking on pathologic outcomes and biochemical recurrence in a cohort of men undergoing radical prostatectomy. METHODS: We identified 630 men who underwent radical prostatectomy between 1989 and 2005 who had detailed smoking histories. There were 321 smokers and 309 nonsmokers. Pathologic outcomes included prostate weight, volume of cancer, volume of high grade cancer, margin status, seminal vesicle involvement, extraprostatic extension, perineural invasion, angiolymphatic invasion, and the presence of nodal metastasis. Biochemical recurrence was defined as a postoperative PSA ≥ 0.1 ng/ml. Univariate analysis and multivariate linear and Cox regression were used to study the impact of smoking on these outcomes. RESULTS: The volume of cancer (2.54 vs. 2.16 ml, P = 0.016) and the volume of high grade cancer (0.58 vs. 0.28 ml, P = 0.004) were greater in smokers compared with nonsmokers. Smoking independently predicted greater volumes of cancer and high grade cancer in multivariate analysis. Heavy smokers (≥20 pack-year history) had a greater risk of biochemical recurrence on univariate survival analysis. Smoking also predicted a greater risk of biochemical recurrence on Cox regression, the magnitude of which was approximately 1% per pack-year smoked. CONCLUSIONS: Smoking is associated with adverse pathologic features and a higher risk of biochemical recurrence in men undergoing radical prostatectomy. If confirmed by additional studies, smoking history may need to be included into risk assessment models.

Performance characteristics of prostate-specific antigen in patients undergoing radical prostatectomy.

OBJECTIVE: To assess the performance characteristics of prostate-specific antigen (PSA) for predicting the volume of total or high-grade cancer in men undergoing radical prostatectomy. It is known that the performance characteristics of PSA are improved for predicting the presence of high-grade prostate cancer. METHODS: We identified 1459 patients from the Stanford Radical Prostatectomy Database with clinical Stage T1c (n = 783) and T2 (n = 676) disease who underwent surgery from 1988 to 2003 with detailed morphometric mapping. We generated receiver operating characteristic curves for PSA levels according to the total and high-grade (Gleason score 4 or 5) cancer volume and compared the areas under the curve (AUC) for the various total and high-grade cancer volumes. RESULTS: For patients with Stage T1c disease, the AUC for the PSA ROC curve increased in a stepwise fashion as both the total cancer volume and the high-grade cancer volume increased. Significant differences between the AUCs for low and high volumes of total and high-grade disease were observed. For T2 disease, the AUCs for predicting high-grade cancer volume were generally greater than the corresponding AUCs for T1c disease, although no incremental increase was observed. CONCLUSION: In patients with Stage T1c disease, in whom the PSA level was the driving force for biopsy, the PSA performance improved in a stepwise fashion with greater total and high-grade cancer volumes as evidenced by improved ROC. Previous studies have shown that PSA performs better for detecting the presence of high-grade disease. We have shown that PSA performs better in predicting greater volumes of high-grade disease in radical prostatectomy specimens.