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Back To Vidyya Treatment Options For Prostate Cancer


Information For Health Professionals


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. 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. For small, well-differentiated nodules, the incidence of positive pelvic nodes is less than 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, 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.

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. 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. 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. In addition, patients considered poor medical candidates for radical prostatectomy can be treated with acceptably low complications if care is given to delivery technique. 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%). 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.

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, especially those patients with low-grade and early-stage tumors. 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. 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 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%. 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. 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. 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%). 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. Unfortunately, these series constitute the same data on which opinions regarding management of clinically localized cancer are based.

Surgical complications

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 0.54%, 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 and were appreciably greater in those patients older than 75 years. In 1 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, over 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 prior to the survey. About 28% reported follow-up treatment of cancer with radiation and/or hormonal therapy within 4 years after their prostatectomy. Reasons for the difference in outcomes between the national survey and previous case series could include: 1) the older Medicare population in the former, 2) surgical expertise at the major reporting centers, 3) selection factors, 4) publication bias of favorable series, or 5) different methods of collecting information from patients. Case series of 93, 459, and 89 men who had undergone radical prostatectomy by experienced surgeons showed similarly high rates of impotence as in the national Medicare survey when men were carefully questioned about sexual potency, although the men in the case series were on average younger than those in the Medicare survey. In 1 of the case series the same questionnaire was used as in the Medicare survey. The urinary incontinence rate in that series was also similar to that in the Medicare survey.

A cross-sectional survey of prostate cancer patients who had been treated in a managed care setting by either radical prostatectomy, radiation, 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 anatomic (nerve-sparing) or standard radical prostatectomy were not statistically significant. This issue, therefore, requires more study.

Radical prostatectomy may also cause fecal incontinence, and the incidence may vary with surgical method. In a national survey sample of 907 men who had undergone radical prostatectomy at least 1 year prior to the survey, 32% of the men who had undergone perineal (anatomic "nerve-sparing") radical prostatectomy and 17% of the men who had undergone retropubic radical prostatectomy reported accidents of fecal leakage. Ten percent and 4%, respectively, reported moderate to large amounts of fecal leakage. Less than 15% of men with fecal incontinence had reported it to a physician or health care provider.

Radiation complications

Definitive external-beam radiation therapy can result in acute cystitis, proctitis, and sometimes enteritis. These are generally reversible but may be chronic and rarely require surgical intervention. Potency, in the short term, is preserved with irradiation in the majority of cases, but may diminish over time. A cross-sectional survey of prostate cancer patients who had been treated in a managed care setting by either radical prostatectomy, radiation, or watchful waiting showed substantial sexual and urinary dysfunction in the radiation therapy group. Morbidity may be reduced with the employment of sophisticated radiation techniques, such as the use of linear accelerators, and careful simulation and treatment planning. Radiation side effects of three-dimensional conformal versus conventional radiation therapy using similar doses (total dose of 60-64 Gy) have been compared in a randomized non-blinded study. There were no differences 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% versus 56%, p=0.004). Urinary symptoms were similar in the 2 groups, as were local tumor control and overall survival rates at 5 years' follow-up. Radiation therapy can be delivered after an extra-peritoneal 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. Prior transurethral resection of the prostate (TURP) increases the risk of stricture above that seen with radiation alone, but if radiation is delayed 4 to 6 weeks after the TURP, the risk of stricture can be minimized. Although pretreatment TURP to relieve obstructive symptoms has been associated with tumor dissemination, multivariate analysis in pathologically staged cases indicates that this is due to a worse underlying prognosis of the cases that require transurethral resection rather than to 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 described above of Medicare patients who underwent radical prostatectomy, has been reported, showing substantial differences in post-treatment morbidity profiles between surgery and radiation. Although the men who had undergone radiation 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% versus more than 30%). A larger proportion of patients treated with radiation before surgery reported the ability to have an erection sufficient for intercourse in the month prior to the survey (men <70 years of age, 33% who received radiation versus 11% who underwent surgery alone; men >/=70 years of age, 27% who received radiation versus 12% who underwent surgery alone). However, men receiving radiation were more likely to report problems with bowel function, especially frequent bowel movements (10% versus 3%). Similar to 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.

Hormone therapy complications

Several different hormonal approaches can benefit men with various stages of prostate cancer. These 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 milligrams per day of diethylstilbestrol will achieve castrate levels of testosterone. Similar to orchiectomy, estrogens may cause loss of libido and impotence. Gynecomastia may be prevented by low-dose radiation 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. Similar to 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. There have been case reports of fatal and nonfatal liver toxic effects. Bicalutamide may cause nausea, breast tenderness, hot flashes, loss of libido, and impotence. The steroidal antiandrogen megestrol acetate suppresses androgen production incompletely and is generally not used as initial therapy. Long-term use of ketoconazole can result in impotence, pruritus, nail changes, and adrenal insufficiency. Aminoglutethimide commonly causes sedation and skin rashes. Additional studies that evaluate the effects of various hormone therapies on quality of life are required.

This information was developed by The National Cancer Institute. The complete data can be found at cancernet.nci.nih.gov.


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Editor: Susan K. Boyer, RN
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