Enhancing the efficacy of radical prostatectomy in locally advanced prostate cancer

Locally advanced prostate cancer patients comprise those with iatrogenic capsular injury, extracapsular extension resulting in positive surgical margins following radical prostatectomy, and tumors with lymph node metastases, thus representing stage T3,N0,M0 or T1-4,N1-2,M0 disease. Parameters can be combined, as shown below, in a nomogram to predict advanced prostate cancer: if, for example, stage T2c is coupled with a PSA of 16 ng/ml and a high Gleason grade, the patient will have an approximately 70% likelihood of having extracapsular extension; then again, if the Gleason score is known from biopsies and a PSA of 10-20 ng/ml is given, then a stage T2c prostate cancer patient with a Gleason of 7 will have a 39% probability of having positive lymph nodes. The following therapeutic considerations may be used to enhance the chance of eradicating advanced disease through radical prostatectomy: (1) Neoadjuvant hormonal therapy helps downsize the tumor and may eventually reduce the number of positive margins by almost 50%. However, it is a moot point if this will lead to a prolonged survival period. (2) Technical refinements on radical prostatectomy may be achieved through the principle of wide extension excision, a modification of current apical dissection procedures, which involves the use of panoramic magnifying loupes, and an examination of resection margins during surgery using repetitive frozen sections. (3) If positive (not simply 'equivocal' as defined by Epstein) margins are found, radical prostatectomy alone is not curative. Among the various options available is postoperative irradiation with or without adjuvant hormonal therapy. The latter should probably be reserved for patients with extracapsular extension, a high Gleason score or positive lymph nodes. Hormonal therapy may be used continuously or intermittently. The value of adjuvant treatment is currently being tested in phase-III trials. (4) Hormonal therapy may be commenced at the time of biochemical or clinical progression, although it is not clear whether this modality is inferior to adjuvant forms of treatment. Technical expertise in radical prostatectomy accumulated at major institutions can be used to the advantage of patients with locally advanced prostate cancer. In this regard, results of ongoing phase-III trials testing various options including this procedure are eagerly awaited.