Future handling of patients with localized prostate cancer will undoubtedly depend upon a more sophisticated prognostication then that available today. The basis will continue to be the histopathotogical evaluation of tumor size, grade, localization and distribution within the gland. The aim of this section is to summarize current concepts of the morphological characteristics of localized prostate cancer and their prognostic implications as well as to give guidelines for standardization of the methods involved in morphological evaluation. First, baseline recommendations for the tissue processing procedures are given: Needle core biopsies, taken in a systematic way, potentially contain the information necessary for estimation of grade, size, distribution and extension to seminal vesicles, and could yield material for DNA-measurements, cytogenetic and genetic information. For TUR specimens it is suggested that at least 10 grams should be embedded or 8 to 10 cassettes employed minimally. The prostatectomy specimens should be carefully examined. Material should be frozen both from tumor tissue and from other areas eg by taking 'mapping' biopsies in a standardized way. After fixation (in 10% buffered formalin for at least 24 hours) and appropriate inking of surgical margins, whole mount sections at 2.5 - 5 mm intervals should be cut. The extension of the tumor should be outlined and at least the two largest tumors should be graded. Capsule penetration and extension to surgical margins and seminal vesicles should be indicated. Grading of malignancy should always include the Gleason grade and where possible Gleason score (ie the sum of the dominant and the secondary grade or pattern). The WHO and the Boecking systems combine a grading of glandular architecture with a grading of the nuclear atypia. It is stressed that in core biopsies the amount of cancer is sometimes scanty, which limits the possibility to find dominant and secondary patterns. In such cases, a grading of glandular differentiation and of nuclear grade seems rational. Also, for comparison with cytological grading, the WHO system is suitable, since in both cases both tissue differentiation and nuclear atypia are judged. The future need for objective techniques is recognized. Prostatectomy pathology includes important features with high correlation to postoperative prognosis: eg capsular penetration. The extent of capsular penetration and the extent of involvement of the surgical margins is of importance. Only focal penetration or focal involvement of the margin carry a relatively low risk of progression, The Gleason score and the tumor volume have been claimed to stratify patients with capsular penetration: if margins are negative and grade low, the 5 year progression is rare; if margins are positive or grade high, progression occurs in every other or third case and if margin is positive and grade high, two out of three progress. Seminal vesicle invasion is regarded a significant independent predictor of progression following radical prostatectomy. Thus, the Gleason score is a highly significant predictor of progression and the addition of positive margin enhances prediction. In other studies the tumor volume is claimed to be more important than grade. Hence, the exact relationship between Gleason score and tumor volume, complemented with DNA-ploidy estimates and other objective prognosticators, needs to be investigated further. Preoperative needle core biopsies, taken in a systematic manner from six strategic points, can provide estimates of tumor volume and grade: when one core biopsy out of six is positive, the tumor is likely to be larger than 0.5 cc and less than 3 cc, provided the core cancer length is 3 mm or longer. If two biopsies from the same side are positive, and both have cancer lengths above 3 mm, a cancer of between 1 cc and 6 cc is indicated. If two biopsies from each side of the prostate are positive, in roughly 50% of the cases the contralateral biopsy emanates from a second incidental cancer, in which case the larger tumor is probably between 0.5 cc and 3 cc. Otherwise it means that the tumor is probably above 5 cc. Tumors located in the anterior part of the gland usually give small cancer lengths. A practical volume threshold for radical prostatectomy is probably 0.5 cc provided the Gleason grade is less than 4. The future tumor biological characterization of prostate cancer will undoubtedly include the relevance of eg. proliferation markers, expression of PSA, p53, neuroendocrine differentiation and changes in surface adhesion molecules, extracellular matrix and proteases as well as molecular genetic markers indicating their relationship to prognosis. Finally, the potential prognostic significance of heterogeneity and multicentricity of prostate cancer is underlined. Without accurate methods to assess tumor volume, grade and distribution during our diagnostic evaluation of the patient, inadequate sampling is a major risk. Thus, the combined efforts of urologists, radiologists, pathologists and others in longitudinal studies of disease progression will be required to perfect meaningful prognostic systems.
