"Note: Separate PDQ summaries on Prevention of Prostate Cancer and Screening for Prostate Cancer are also available. "

"Note: 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 summary on Levels of Evidence for more information.) "

"Carcinoma of the prostate is predominantly a tumor of older men, which frequently responds to treatment when widespread and may be cured when localized. The rate of tumor growth varies from very slow to moderately rapid, and some patients may have prolonged survival even after the cancer has metastasized to distant sites such as bone. Because the median age at diagnosis is 72 years, many patients?especially those with localized tumors?may die of other illnesses without ever having suffered significant disability from their cancer. The approach to treatment is influenced by age and coexisting medical problems. Side effects of various forms of treatment should be considered in selecting appropriate management. Controversy exists in regard to the value of screening, the most appropriate staging evaluation, and the optimal treatment of each stage of the disease.["

"A complicating feature of any analysis of survival after treatment of prostate cancer and comparison of the various treatment strategies is the evidence of increasing diagnosis of nonlethal tumors as diagnostic methods have changed over time. Nonrandomized comparisons of treatments may therefore be confounded not only by patient-selection factors but also by time trends. For example, a population-based study in Sweden showed that from 1960 to the late 1980s, before the use of prostate-specific antigen (PSA) for screening purposes, long-term relative survival rates after the diagnosis of prostate cancer improved substantially as more sensitive methods of diagnosis were introduced. This occurred despite the use of watchful waiting or palliative hormonal treatment as the most common treatment strategies for localized prostate cancer during the entire era (<150 radical prostatectomies per year were performed in Sweden during the late 1980s). The investigators estimated that if all cancers diagnosed between 1960 and 1964 were of the lethal variety, then at least 33% of cancers diagnosed between 1980 and 1984 were of the nonlethal variety.["

"][Level of evidence: 3iB] With the advent of PSA screening, the ability to diagnose nonlethal prostate cancers may increase further. Another issue complicating comparisons of outcomes among nonconcurrent series of patients is the possibility of changes in criteria for histologic diagnosis of prostate cancer.["

"] This phenomenon creates a statistical artifact that can produce a false sense of therapeutic accomplishment and may also lead to more aggressive therapy. For example, prostate biopsies from a population-based cohort of 1,858 men diagnosed with prostate cancer from 1990 through 1992 were re-read in 2002 to 2004.["

"] The contemporary Gleason score readings were an average of 0.85 points higher (95% confidence interval [CI], 0.79-0.91; "

" < .001) than the same slides read in 1990 to 1992. As a result, Gleason score-standardized prostate cancer mortality for these men was artifactually improved from 2.08 to 1.50 deaths per 100 person years?a 28% decrease even though overall outcomes were unchanged."

"The issue of screening asymptomatic men for prostate cancer with digital rectal examination (DRE), PSA, and/or ultrasound is controversial.["

"] Serum PSA and transrectal ultrasound are more sensitive and will increase the diagnostic yield of prostate cancer when used in combination with rectal examination (refer to the PDQ summary on Screening for Prostate Cancer for more information); however, these screening methods are also associated with high false-positive rates and may identify some tumors that will not threaten the patient?s health.["

"] The issue is further complicated by the morbidity associated with work-up and treatment of such tumors and the considerable cost beyond a routine DRE. Furthermore, because a high percentage of tumors identified by PSA screening alone have spread outside the prostate, PSA screening may not improve life expectancy. In any case, the clinician who uses PSA for the detection of prostate cancer should be aware that no uniform standard exists, so that if a laboratory changes to a different assay kit, serial assays may yield nonequivalent PSA values.["

"] In addition, the upper limit of the normal range of PSA, and therefore the threshold at which to biopsy, is not well-defined.["

"] A multicenter trial sponsored by the National Cancer Institute is under way to test the value of early detection in reducing mortality.["

"Survival of the patient with prostatic carcinoma is related to the extent of the tumor. When the cancer is confined to the prostate gland, median survival in excess of 5 years can be anticipated. Patients with locally advanced cancer are not usually curable, and a substantial fraction will eventually die of their tumor, though median survival may be as long as 5 years. If prostate cancer has spread to distant organs, current therapy will not cure it. Median survival is usually 1 to 3 years, and most such patients will die of prostate cancer. Even in this group of patients, however, indolent clinical courses lasting for many years may be observed. "

"Other factors affecting the prognosis of patients with prostate cancer that may be useful in making therapeutic decisions include histologic grade of the tumor, patient?s age, other medical illnesses, and level of PSA.["

"] Poorly differentiated tumors are more likely to have already metastasized by the time of diagnosis and are associated with a poorer prognosis. For patients treated with radiation therapy, the combination of clinical tumor stage, Gleason score, and pretreatment PSA level can be used to more accurately estimate the risk of relapse.["

"][Level of evidence: 3iDi] In most studies, flow cytometry has shown that nuclear DNA ploidy is an independent prognostic indicator for progression and for cause-specific survival in patients with pathologic stages III and IV prostate cancer without metastases (Jewett stages C and D1). Diploid tumors have a more favorable outcome than either tetraploid or aneuploid tumors. The use of flow cytometry techniques and histogram analysis to determine prognosis will require standardization.["

"] radical prostatectomy with intent to cure. Preoperative nomograms are based on clinical stage, PSA, and Gleason score. Postoperative nomograms add pathologic findings, such as capsular invasion, surgical margins, seminal vesicle invasion, and lymph node involvement. The nomograms, however, were developed at academic centers and may not be as accurate when generalized to nonacademic hospitals, where the majority of patients are treated.["

"] In addition, the nomograms use nonhealth (intermediate) outcomes such as PSA rise or pathologic surgical findings, and subjective endpoints such as the physician's perceived need for additional therapy. In addition, the nomograms may be affected by changing methods of diagnosis or neoadjuvant therapy over time.["

"Definitive treatment is usually considered for younger men with prostate cancer and no major comorbid medical illnesses because younger men are more likely to die of prostate cancer than older men or men with major comorbid medical illness. Elevations of serum acid phosphatase are associated with poor prognosis in both localized and disseminated disease. PSA, an organ-specific marker with greater sensitivity and high specificity for prostate tissue, is often used as a tumor marker.["

"] After radical prostatectomy, detectable PSA levels identify patients at elevated risk of local treatment failure or metastatic disease;["

"] however, a substantial proportion of patients with elevated or rising PSA levels after surgery may remain clinically free of symptoms for extended periods of time.["

"] Biochemical evidence of failure on the basis of elevated or slowly rising PSA alone therefore may not be sufficient to alter treatment. For example, in a retrospective analysis of nearly 2,000 men who had undergone radical prostatectomy with curative intent and who were followed for a mean of 5.3 years, 315 men (15%) demonstrated an abnormal PSA =0.2 ng/mL, felt to be evidence of biochemical recurrence. Of these 315 men, 103 men (34%) developed clinical evidence of recurrence. The median time to development of clinical metastasis after biochemical recurrence was 8 years. After the men developed metastatic disease, the median time to death was an additional 5 years.["

"After radiation therapy with curative intent, persistently elevated or rising PSA may be a prognostic factor for clinical disease recurrence; however, reported case series have used a variety of definitions of PSA failure. Criteria have been developed by the American Society for Therapeutic Radiology and Oncology Consensus Panel.["

"] It is difficult to base decisions about instituting additional therapy on biochemical failure. The implication of the various definitions of PSA failure for overall survival is not known, and as in the surgical series, many biochemical relapses (rising PSA alone) may not be clinically manifested in patients treated with radiation therapy.["

"Preliminary data from a retrospective cohort of 8,669 patients with clinically localized prostate cancer treated with either radical prostatectomy or radiation therapy suggested that short posttreatment PSA doubling time (<3 months in this study) is a useful surrogate endpoint for all-cause mortality and prostate cancer mortality after surgery or radiation therapy.["

"] Another retrospective cohort study of 379 men with biochemical recurrence after radical prostatectomy found that PSA doubling time, pathologic Gleason score, and time to biochemical recurrence were all significant risk factors for prostate cancer-specific mortality.["

"] These observations should be independently confirmed in prospective study designs and may not apply to patients treated with hormonal therapy."

"After hormonal therapy, reduction of PSA to undetectable levels provides information regarding the duration of progression-free status;["

"] Yet, because PSA expression itself is under hormonal control, androgen deprivation therapy can decrease the serum level of PSA independent of tumor response. Clinicians, therefore, cannot rely solely on the serum PSA level to monitor a patient?s response to hormone therapy; they must also follow clinical criteria.["

"More than 95% of primary prostate cancers are adenocarcinomas, and this discussion is confined to patients with this diagnosis. In general, the degree of tumor differentiation and abnormality of histologic growth pattern directly correlate with likelihood of metastases and with death. Because of marked variability in tumor differentiation from one microscopic field to another, many pathologists will report the range of differentiation among the malignant cells that are present in a biopsy (Gleason grade).["

"When the cytopathologist is experienced in the technique, and the specimen is adequate for analysis, fine-needle aspiration of the prostate (usually performed transrectally) has been shown to have an accuracy of diagnosis equal to that of traditional core needle biopsy.["

"] Fine-needle aspiration is less painful than core biopsy and, therefore, can be performed as an outpatient procedure and at periodic intervals for serial follow-up. Controversy exists as to whether it is as reliable for grading purposes, particularly with grade range apparent in different fields.["

"] Many urologists now use a bioptic gun with ultrasound guidance, which is relatively painless. The risk of complications with this technique is low. A transperineal, ultrasound-guided approach can be used in those patients who may be at increased risk of complications through a transrectal approach.["

"] In a series of 670 men undergoing biopsy with an 18-gauge needle, the complication rate was 2%, with only 4 patients requiring hospitalization.["

"Detection of asymptomatic metastatic disease in prostate cancer is greatly affected by the staging tests performed. Radionuclide bone scans are currently the most widely used tests for metastases to the bone, which is the most common site of distant tumor spread. Magnetic resonance imaging (MRI) is more sensitive than radionuclide bone scans but is impractical for evaluating the entire skeletal system. Some evidence suggests that serum prostate-specific antigen (PSA) levels can predict the results of radionuclide bone scan in newly diagnosed patients. In one series, only 2 of 852 patients (0.23%) with a PSA <20 µg/L had a positive bone scan in the absence of bone pain.["

"] In another series of 265 prostate cancer patients, 0 of 23 with a PSA <4 had a positive bone scan, and 2 of 114 with a PSA <10 had a positive bone scan.["

"Whether to subject all patients to a pelvic lymph node dissection (PLND) is debatable, but in patients undergoing a radical retropubic prostatectomy, the nodal status is ascertained as a matter of course. In patients who are undergoing a radical perineal prostatectomy in whom the PSA value is <20 and the Gleason sum is low, however, evidence is mounting that a PLND is probably unnecessary, especially in patients whose malignancy was not palpable but detected on ultrasound.["

"] A PLND remains the most accurate method to assess metastases to pelvic nodes, and laparoscopic PLND has been shown to accurately assess pelvic nodes as effectively as an open procedure.["

"] The exact role of PLND in diagnosis and subsequent treatment is being evaluated, though it has already been determined that the length of hospital stay following laparoscopic PLND is shorter than that following an open procedure. The determining factor when deciding if any type of PLND is indicated is whether definitive therapy may be altered. Likewise, preoperative seminal vesicle biopsy may be useful in patients with palpable nodules who are being considered for radical prostatectomy (unless they have a low Gleason score) because seminal vesicle involvement could affect choice of primary therapy and predicts for pelvic lymph node metastasis.["

"In patients with clinically localized (stage I or stage II) prostate cancer, Gleason pathologic grade and enzymatic serum prostatic acid phosphatase values (even within normal range) predict the likelihood of capsular penetration, seminal vesicle invasion, or regional lymph node involvement.["

"] Analysis of a series of 166 patients with clinical stage I and stage II prostate cancer undergoing radical prostatectomy revealed an association between Gleason biopsy score and the risk of lymph node metastasis found at surgery. The risks of node metastasis for patients grouped according to their Gleason biopsy score was 2%, 13%, and 23% for Gleason scores 5, 6, and 8, respectively.["

"Transrectal ultrasound (TRUS) may facilitate diagnosis by directing needle biopsy; however, ultrasound is operator dependent and does not assess lymph node size. Moreover, a prospective multi-institutional study of preoperative TRUS in men with clinically localized prostate cancer felt to be eligible for radical prostatectomy showed that TRUS was no better than digital rectal examination in predicting extracapsular tumor extension or seminal vesicle involvement.["

"] Although MRI has been used to detect extracapsular extension of prostate cancer, a positive-predictive value of about 70% and considerable interobserver variation are problems that make its routine use in staging uncertain.["

"] Ultrasound and MRI, however, can reduce clinical understaging and thereby improve patient selection for local therapy. Preliminary data with the endorectal MRI coil for prostate imaging report the highest sensitivity and specificity for identification of organ-confined and extracapsular disease.["

"Two systems are in common use for the staging of prostate cancer. The Jewett system (stages A through D) was described in 1975 and has since been modified.["

"] In 1997, the American Joint Committee on Cancer (AJCC) and the International Union Against Cancer adopted a revised tumor, nodes, metastasis (TNM) system that employs the same broad T stage categories as the Jewett system but includes subcategories of T stage, such as a stage to describe patients diagnosed through PSA screening. This revised TNM system is clinically useful and more precisely stratifies newly diagnosed patients. In 2002, the AJCC further revised the TNM classification system.["

"] Both staging systems are shown below, and both are used in the text of this summary discussing treatment options. A thorough review of the controversies of staging in prostate cancer has been published.["

"*Tumor that is found in one or both lobes by needle biopsy but is not palpable or reliably visible by imaging, is classified as T1c."

"**Invasion into the prostatic apex or into (but not beyond) the prostatic capsule is not classified as T3, but as T2."

"Stage A is clinically undetectable tumor confined to the prostate gland and is an incidental finding at prostatic surgery. "

"Stage C is tumor clinically localized to the periprostatic area but extending through the prostatic capsule; seminal vesicles may be involved. "

"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 radiation therapy. This development is the result of the high incidence of clinical understaging, even with current diagnostic techniques. Metastatic tumor is currently not curable. "

"] These patients should have tumors confined to the prostate gland (stage I and stage 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.["

"] For small, well-differentiated nodules, the incidence of positive pelvic nodes is <20%, and pelvic node dissection may be omitted.["

"] 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; 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.["

"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.["

"] Results of the outcome of patients with positive surgical margins have not been reported. 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.["

"][Level of evidence: 3iiiDiii] Cryosurgery is less well established than standard prostatectomy, and long-term outcomes are not as well established as with prostatectomy or radiation therapy. Serious toxic effects include bladder outlet injury, urinary incontinence, sexual impotence, and rectal injury. The technique of cryosurgery is under development. Impotence is a common side effect of cryosurgery. The frequency of other side effects and the probability of cancer control at 5 years' follow-up have varied among reporting centers, and series are small compared with surgery and radiation therapy.["

"Candidates for definitive radiation therapy must have a confirmed pathological diagnosis of cancer that is clinically confined to the prostate and/or surrounding tissues (stage I, stage II, and stage III). Patients should have a computed tomographic scan negative for metastases, but staging laparotomy and lymph node dissection are not required. Prophylactic radiation therapy to clinically or pathologically uninvolved pelvic lymph nodes does not appear to improve overall survival (OS) or prostate cancer-specific survival.["

"][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 the delivery technique.["

"] Long-term results with radiation therapy are dependent on stage. A retrospective review of 999 patients treated with megavoltage radiation therapy showed cause-specific survival rates to be significantly different at 10 years by T-stage: T1 (79%), T2 (66%), T3 (55%), and T4 (22%).["

"] An initial serum prostate-specific antigen (PSA) level >15 ng/mL is a predictor of probable failure with conventional radiation therapy.["

"] Several randomized studies have demonstrated an improvement in freedom from biochemical (PSA-based) recurrence with higher doses of radiation therapy (78 Gy-79 Gy) as compared to conventional doses (68 Gy-70 Gy).["

"][Level of evidence: 1iiDii The higher doses were delivered using conformal techniques. None of the studies demonstrated a cause-specific survival benefit to higher doses; however, an ongoing study through the Radiation Therapy Oncology Group is going to be powered for OS. "

"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.["

"Asymptomatic patients of advanced age or with concomitant illness may warrant consideration of careful observation without immediate active 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-differentiated or moderately well-differentiated tumors clinically confined to the prostate, irrespective of age.["

"] None of these men were detected by PSA screening, since PSA was not available at the time. The patient cohort was followed for a mean of 21 years after initial diagnosis.["

"] The risk of prostate cancer progression and prostate cancer death persisted throughout the follow-up period. By the end of follow-up, 91% of the cohort had died, 16% had died of prostate cancer. 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.["

"] In a selected series of 50 stage C patients, 48 of whom had well-differentiated and moderately well-differentiated tumors, the prostate cancer-specific survival rates at 5 and 9 years were 88% and 70%, respectively.["

"Long-term follow-up of a population-based cohort of 767 men with clinically localized prostate cancer diagnosed in the pre-PSA era and managed with either watchful waiting or androgen withdrawal has also been reported in the United States.["

"][Level of evidence: 3iiiA] After a follow-up of 20 years, prostate cancer-specific mortality was 6 per 1,000 person-years in men with Gleason scores of 2 to 4. Men with Gleason scores of 8 to 10, however, had a prostate-specific mortality of 121 per 1,000 person years, and men with Gleason scores of 5 to 7 had intermediate prostate cancer mortality (i.e., 12, 30, and 65 deaths per 1,000 person years for Gleason scores 5, 6, and 7, respectively)."

"Since the early 1980s, a dramatic increase has occurred in the rates of radical prostatectomy in the United States for men aged 65 to 79 years (5.75-fold rise from 1984 to 1990). Wide geographic variation is seen with these rates.["

"] 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:["

"The authors concluded that poor reporting and selection factors within all series precluded a valid comparison of efficacy for the 3 management strategies. 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%).["

"] Because it is highly unlikely that radiation therapy 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.["

"] A retrospective analysis of outcomes of men demonstrated a 10-year disease-specific survival rate of 94% for expectant management for Gleason score 2 to 4 tumors and 75% for Gleason score 5 to 7 tumors;["

"] this is similar to a previous study using the Surveillance, Epidemiology, and End Results database with survival rates of 93% and 77%, respectively.["

"A randomized trial comparing radical prostatectomy to watchful waiting in men with early-stage disease in the pre-PSA screening era (clinical stages T1b, T1c, or T2) showed a statistically significant difference in OS at 10 years.["

"][Level of evidence: 1iiA] (See stage II and treatment section below for additional details.) After 10 years, the difference in OS was approximately 73% versus 68%; absolute difference 5.0%; relative risk of death 0.74 (95% confidence interval, 0 .56-0.99). This benefit was restricted to men <65 years at the time of surgery ("

"] Results from an ongoing randomized trial Prostate Intervention Versus Observation Trial (PIVOT) in the United States comparing radical prostatectomy to watchful waiting have not been reported.["

"Complications of radical prostatectomy can include urinary incontinence, urethral stricture, impotence, and the morbidity associated with general anesthesia and a major surgical procedure. An analysis of Medicare records on 101,604 radical prostatectomies performed from 1991 to 1994 showed a 30-day operative mortality rate of 0.5%, a rehospitalization rate of 4.5%, and a major complication rate of 28.6%; over the study period, these rates decreased by 30%, 8%, and 12%, respectively.["

"] Prostatectomies done at hospitals where fewer prostatectomies were performed were associated with higher rates of 30-day postoperative mortality, major acute surgical complications, longer hospital stays, and higher rates of rehospitalization than those done at hospitals where more prostatectomies were performed. Morbidity and mortality rates increase with age.["

"] Comorbidity, especially underlying cardiovascular disease and a history of stroke, accounts for a portion of the age-related increase in 30-day mortality. In a cohort of all men with prostate cancer who underwent radical prostatectomy from 1990 to 1999 in Ontario, 75-year-old men with no comorbidities had a predicted 30-day mortality of 0.74%.["

"] Thirty-day surgical complication rates also depended more on comorbidity than age (i.e., about 5% vs. 40% for 0 vs. 4 or more underlying comorbid conditions). "

"In one large case series of men undergoing the anatomic (nerve-sparing) technique of radical prostatectomy, only about 6% of men required the use of pads for urinary incontinence, but an unknown additional proportion of men had occasional urinary dribbling. About 40% to 65% of men who were sexually potent before surgery retained potency adequate for vaginal penetration and sexual intercourse.["

"] Preservation of potency with this technique is dependent on tumor stage and patient age, but the operation probably induces at least a partial deficit in nearly all patients.["

"A national survey of Medicare patients who underwent radical prostatectomy in 1988 to 1990 reported more morbidity than in the case series.["

"] In that survey, more than 30% of men reported the need for pads or clamps for urinary wetness, and 63% of all patients reported a current problem with wetness. About 60% reported having no erections since surgery; about 90% had no erections sufficient for intercourse during the month before the survey. About 28% reported follow-up treatment of cancer with radiation therapy and/or hormonal therapy within 4 years after their prostatectomy. "

"In a population-based longitudinal cohort (Prostate Cancer Outcomes Study) of 901 men aged 55 to 74 years who had recently undergone radical prostatectomy for prostate cancer, 15.4% had either frequent urinary incontinence or no urinary control at 5 years after surgery, and 20.4% wore pads to stay dry.["

"] Inability to have an erection sufficient for intercourse was reported by 79.3% of men. Reasons for the difference in outcomes between the population-based surveys and previous case series could include:"

"Case series of 93,459, and 89 men who had undergone radical prostatectomy by experienced surgeons showed rates of impotence as high as those in the national Medicare survey when men were carefully questioned about sexual potency, though the men in the case series were on average younger than those in the Medicare survey.["

"A cross-sectional survey of prostate cancer patients who had been treated in a managed care setting by radical prostatectomy, radiation therapy, or watchful waiting showed substantial sexual and urinary dysfunction in the prostatectomy group.["

"] Results reported by the patients were consistent with those from the national Medicare survey. In addition, though statistical power was limited, differences in sexual and urinary dysfunction between men who had undergone either nerve-sparing or standard radical prostatectomy were not statistically significant. This issue, therefore, requires more study. "

"] In a national survey sample of 907 men who had undergone radical prostatectomy at least 1 year before the survey, 32% of the men who had undergone perineal (nerve-sparing) radical prostatectomy and 17% of the men who had undergone retropubic radical prostatectomy reported accidents of fecal leakage. Ten percent and 4% reported moderate and large amounts of fecal leakage, respectively. Fewer than 15% of men with fecal incontinence had reported it to a physician or health care provider. "

"] These conditions are generally reversible but may be chronic and rarely require surgical intervention. Potency, in the short term, is preserved with radiation therapy in most cases but may diminish over time.["

"] A cross-sectional survey of prostate cancer patients who had been treated in a managed care setting by radical prostatectomy, radiation therapy, or watchful waiting showed substantial sexual and urinary dysfunction in the radiation therapy group.["

"Morbidity may be reduced with the employment of sophisticated radiation therapy techniques?such as the use of linear accelerators?and careful simulation and treatment planning.["

"] Radiation side effects of 3-dimensional conformal versus conventional radiation therapy using similar doses (total dose of 60-64 Gy) have been compared in a randomized nonblinded study.["

"][Level of evidence: 1iiC] No differences were observed in acute morbidity, and late side effects serious enough to require hospitalization were infrequent with both techniques; however, the cumulative incidence of mild or greater proctitis was lower in the conformal arm than in the standard therapy arm (37% vs. 56%, "

" = .004). Urinary symptoms were similar in the 2 groups, as were local tumor control and OS rates at 5 years? follow-up. "

"Radiation therapy can be delivered after an extraperitoneal lymph node dissection without an increase in complications, if careful attention is paid to radiation technique. The treatment field should not include the dissected pelvic nodes. Previous transurethral resection of the prostate (TURP) increases the risk of stricture above that seen with radiation therapy alone, but if radiation therapy is delayed 4 to 6 weeks after the TURP, the risk of stricture can be minimized.["

"] Pretreatment TURP to relieve obstructive symptoms has been associated with tumor dissemination; however, multivariate analysis in pathologically staged cases indicates that this is the result of a worse underlying prognosis of the cases that require TURP rather than the result of the procedure itself.["

"A population-based survey of Medicare recipients who had received radiation therapy as primary treatment of prostate cancer (similar in design to the survey of Medicare patients who underwent radical prostatectomy,["

"] described above) has been reported, showing substantial differences in posttreatment morbidity profiles between surgery and radiation therapy.["

"] Although the men who had undergone radiation therapy were older at the time of initial therapy, they were less likely to report the need for pads or clamps to control urinary wetness (7% vs. more than 30%). A larger proportion of patients treated with radiation therapy before surgery reported the ability to have an erection sufficient for intercourse in the month before the survey (men <70 years, 33% who received radiation therapy vs. 11% who underwent surgery alone; men =70 years, 27% who received radiation therapy vs. 12% who underwent surgery alone). Men receiving radiation therapy were more likely to report problems with bowel function, however, especially frequent bowel movements (10% vs. 3%). As in the results of the surgical patient survey, about 24% of radiation patients reported additional subsequent treatment of known or suspected cancer persistence or recurrence within 3 years of primary therapy. "

"Sildenafil citrate may be effective in the management of sexual dysfunction after radiation therapy in some men. In a randomized placebo-controlled crossover design study of 60 men who had undergone radiation therapy for clinically localized prostate cancer, and who reported erectile dysfunction that began after their radiation therapy, 55% reported successful intercourse after sildenafil versus 18% after placebo ("

"A prospective community-based cohort of men 55 to 74 years treated with radical prostatectomy (n = 1156) or external-beam radiation therapy (n = 435) attempted to compare acute and chronic complications of the 2 treatment strategies after adjusting for baseline differences in patient characteristics and underlying health.["

"] Regarding acute treatment-related morbidity, radical prostatectomy was associated with higher rates of cardiopulmonary complications (5.5% vs. 1.9%), as well as the need for treatment of urinary strictures (17.4% vs. 7.2%). Radiation therapy was associated with more acute rectal proctitis (18.7% vs. 1.6%). With regard to chronic treatment-related morbidity, radical prostatectomy was associated with more urinary incontinence (9.6% vs. 3.5%) and impotence (80% vs. 62%). Radiation therapy was associated with slightly greater declines in bowel function. "

"Several different hormonal approaches can benefit men in various stages of prostate cancer. These approaches include bilateral orchiectomy, estrogen therapy, LHRH agonists, antiandrogens, ketoconazole, and aminoglutethimide. "

"Benefits of bilateral orchiectomy include ease of the procedure, compliance, its immediacy in lowering testosterone levels, and low cost. Disadvantages include psychologic effects, loss of libido, impotence, hot flashes, and osteoporosis.["

"Estrogens at a dose of 3 mg per day of diethylstilbestrol will achieve castrate levels of testosterone. Like orchiectomy, estrogens may cause loss of libido and impotence. Gynecomastia may be prevented by low-dose radiation therapy to the breasts; however, estrogen is seldom used today because of the risk of serious side effects, including myocardial infarction, cerebrovascular accident, and pulmonary embolism. "

"LHRH agonists such as leuprolide, goserelin, and buserelin will lower testosterone to castrate levels. Like orchiectomy and estrogens, LHRH agonists cause impotence, hot flashes, and loss of libido. Tumor flare reactions may occur transiently but can be prevented by antiandrogens or by short-term estrogens at low dose for several weeks. "

"The pure antiandrogen flutamide may cause diarrhea, breast tenderness, and nausea. Case reports show fatal and nonfatal liver toxic effects.["

"Long-term use of ketoconazole can result in impotence, pruritus, nail changes, and adrenal insufficiency. Aminoglutethimide commonly causes sedation and skin rashes. A national Medicare survey of men who had undergone radical prostatectomy for prostate cancer showed a decrease in all 7 health-related quality-of-life measures (impact of cancer and treatment, concern regarding body image, mental health, general health, activity, worries about cancer and dying, and energy) in men who had received androgen depletion therapy (either medically or surgically induced) versus those who had not.["

"][Level of evidence: 3iC] Additional studies that evaluate the effects of various hormone therapies on quality of life are required.["

"Androgen deprivation therapy also can cause osteoporosis and bone fractures. In a population-based sample of 50,613 Medicare patients aged 66 or older followed for a median of 5.1 years, men who had been treated with either a gonadotropin-releasing hormone (GnRH) or orchiectomy had a 19.4% bone fracture rate compared to 12.6% in men who had not received hormone deprivation therapy. The effect was similar in men whether or not they had metastatic bone disease.["

"] A small nonblinded study with short follow-up suggests that the bisphosphonate pamidronate can prevent bone loss in men receiving a GnRH agonist for prostate cancer.["

"] Forty-seven prostate cancer patients (41 evaluable) with
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