Adenocarcinoma of the prostate is now the most common tumor in males. The use of the digital rectal examination, prostate-specific antigen (PSA), and transrectal ultrasound of the prostate with biopsies has improved the detection of prostate cancer and has increased the percentage of patients with organ-confined disease who are treated with radical prostatectomy. It is critical for the practicing urologic and medical oncologist to have accurate and precise pathologic information in order to counsel patients for appropriate therapy. Ideal biopsy and clinical predictive criteria for tumor volume in prostates are not readily available in the literature.

The ideal evaluation should probably separate patients whose tumors are too small to be clinically significant from those requiring surgery or other curative or palliative treatment. The percentage of tumor in biopsy specimens, ultrasound findings, and PSA density have all been used to stratify patients. However, Dr. Epstein summarizes studies that conclude, in general, that there is no strict correlation between tumor size and extent of biopsy involvement, necessitating expert consultation in those cases for which a convincing diagnosis of carcinoma cannot be reached. Since follow-up biopsies may be negative in such patients, there is a risk of underdiagnosis, especially given that many pathologists are uncomfortable making a diagnosis of cancer based on one or two atypical glands.

Generally Accepted Prognostic Factors

In general, Dr. Epstein provides a thorough discussion of the generally accepted prognostic factors that may be obtained and reported by the pathologist. The histologic recognition of high-grade prostatic intraepithelial neoplasia (PIN) is important because of the high degree of association with carcinoma. It is incumbent upon both the pathologist and oncologist to have a clear understanding of the definition and significance of high-grade PIN. Patients with high-grade neoplasia need to have a repeat biopsy and very careful follow-up. Previous studies have found carcinoma on repeat biopsies in 30% to 50% of patients with high-grade PIN [1,2].

The most important of the prognostic factors is the Gleason sum, which, in some cases, may be underestimated due to limited tumor or failure to recognize a higher-grade pattern. The author makes an excellent point about the need to distinguish between the Gleason sum and Gleason pattern. The pathologist should assign both a primary and secondary pattern to avoid any confusion.

Evaluation of tumor ploidy is somewhat controversial and may not be an independent predictor of tumor behavior. However, in the face of limited disease, an aneuploid tumor may indicate a worse prognosis and may suggest the need for more aggressive treatment.

In assessing the extent of tumor in radical prostatectomy specimens, pathologists need only approximate tumor volumes, as well as assess capsular and seminal vesicle invasion. These staging parameters derived from whole-mount or quadrant sections are important features that will assist the urologic and medical oncologist in making decisions about the need for postoperative radiation to the prostatic bed vs close observation with serial PSA values.

New Markers on the Horizon

There is an urgent need to identify new markers to predict the biologic behavior of prostate cancer. Exciting laboratory work is being conducted looking at the extent of angiogenesis, the degree of neuroendocrine expression, c-erB-2 (HER-2/neu), E-cadherin, and p53. These new markers and the pathologic criteria defined by Dr. Epstein will allow us to counsel our patients more appropriately regarding the various treatment options for prostate cancer.