Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. Refer to the PDQ levels of evidence summary for more information.

State-of-the-art treatment in prostate cancer provides prolonged disease-free survival for many patients with localized disease, but is rarely curative in patients with locally extensive tumor. Even when the cancer appears clinically localized to the prostate gland, a substantial fraction of patients will develop disseminated tumor after local therapy with surgery or irradiation. This is due to the high incidence of clinical understaging even with current diagnostic techniques. Metastatic tumor is currently not curable.

Surgery is usually reserved for patients in good health who are under the age of 70 and who elect surgical intervention.[1-3] These patients should have a negative bone scan and tumors confined to the prostate gland (stages I and II). Prostatectomy can be performed by the perineal or retropubic approach. The perineal approach requires a separate incision for lymph node dissection. Laparoscopic lymphadenectomy is technically possible and accomplished with much less patient morbidity.[4] For small, well-differentiated nodules, the incidence of positive pelvic nodes is less than 20%, and pelvic node dissection may be omitted.[5] With larger, less differentiated tumors, a pelvic lymph node dissection is more important. The value of pelvic node dissection (open surgical or laparoscopic) is not therapeutic, but spares patients with positive nodes the morbidity of prostatectomy. Radical prostatectomy is not usually performed if frozen section evaluation of pelvic nodes reveals metastases, and such patients should be considered for entry into existing clinical trials or receive radiation therapy to control local symptoms. The role of preoperative ("neoadjuvant") hormonal therapy is not established at the present time.[6,7]

Following radical prostatectomy, pathological evaluation stratifies tumor extent into organ-confined, specimen-confined, and margin-positive disease. The incidence of disease recurrence increases when the tumor is not specimen-confined (extracapsular) and/or the margins are positive.[8,9] Patients with extraprostatic disease are suitable candidates for clinical trials. These trials include evaluation of postoperative radiation delivery, cytotoxic agents, and hormonal treatment using luteinizing hormone-releasing hormone (LHRH) agonists and/or antiandrogens.

Cryosurgery is a surgical technique that involves destruction of prostate cancer cells by intermittent freezing of the prostate tissue with cryoprobes followed by thawing.[10][Level of evidence: 3iiiDiii] It is less well established than standard prostatectomy and long-term outcomes are not known. Serious toxic effects include bladder outlet injury, urinary incontinence, sexual impotence, and rectal injury. The technique of cryosurgery is under development.

Candidates for definitive radiation therapy must have a confirmed pathological diagnosis of cancer that is clinically confined to the prostate and/or surrounding tissues (stages I, II, and III). Patients should have a bone scan and computed tomographic scan negative for metastases, but staging laparotomy and lymph node dissection are not required. Prophylactic irradiation of clinically or pathologically uninvolved pelvic lymph nodes does not appear to improve overall survival or prostate cancer-specific survival.[11][Level of evidence: 1iiA] In addition, patients considered poor medical candidates for radical prostatectomy can be treated with acceptably low complications if care is given to delivery technique.[12] Long-term results with radiation therapy are dependent on stage. A retrospective review of 999 patients treated with megavoltage irradiation showed cause-specific survival rates to be significantly different at 10 years by T-stage: T1 (79%), T2 (66%), T3 (55%), and T4 (22%).[13] An initial serum prostate-specific antigen (PSA) level of greater than 15 nanograms per milliliter is a predictor of probable failure with conventional radiation therapy.[14]

Interstitial brachytherapy has been employed in several centers, generally for patients with T1 and T2 tumors. Patients are selected for favorable characteristics, including low Gleason score, low PSA level, and stage T1 to T2 tumors. Information and further study are required to better define the effects of modern interstitial brachytherapy on disease control and quality of life, and to determine the contribution of favorable patient selection to outcomes.[15][Level of evidence: 3iiiDiii]

Asymptomatic patients of advanced age or with concomitant illness may warrant consideration of careful observation without immediate active treatment, especially those patients with low-grade and early-stage tumors.[16,17] The variable history of carcinoma of the prostate emphasizes the need for randomized studies to identify the statistical benefit of any definitive treatment. One population-based study with 15 years of follow-up (mean observation time=12.5 years) has shown excellent survival without any treatment in patients with well- or moderately well-differentiated tumors clinically confined to the prostate, irrespective of age.[8] A second, smaller population-based study of 94 patients with clinically localized prostate cancer managed by a "watch and wait" strategy gave very similar results at 4 to 9 years of follow-up.[18] In fact, in a selected series of 50 stage C patients, 48 of whom had well- and moderately well-differentiated tumors, the prostate cancer-specific survival rates at 5 and 9 years were 88% and 70%.[9] Since the early 1980s, there has been a dramatic increase in rates of radical prostatectomy in the United States for men ages 65 to 79 (5.75-fold rise from 1984-1990). There is wide geographic variation in these rates, probably a reflection of uncertainty about the indications for and efficacy of radical prostatectomy.[19] In fact, a structured literature review of 144 papers has been done in an attempt to compare the 3 primary treatment strategies for clinically localized prostate cancer: 1) radical prostatectomy, 2) definitive radiation therapy, and 3) watchful waiting.[20] The authors concluded that poor reporting and selection factors within all series precluded a valid comparison of efficacy for the 3 management strategies, and proponents of any of the 3 strategies cannot look to the current literature for convincing support. In another literature review of a case series of patients with palpable, clinically localized disease, the authors found that 10-year prostate cancer-specific survival rates were best in radical prostatectomy series (about 93%), worst in radiation therapy series (about 75%), and intermediate with deferred treatment (about 85%).[21] Since it is highly unlikely that radiation would worsen disease-specific survival, the most likely explanation is that selection factors affect choice of treatment. Such selection factors make comparisons of therapeutic strategies imprecise.[22] Unfortunately, these series constitute the same data on which opinions regarding management of clinically localized cancer are based.

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