Seminars in urologic oncology最新文献

High-grade prostatic intraepithelial neoplasia (PIN) is now accepted as the most likely preinvasive stage of adenocarcinoma, a decade after its first formal description. PIN has a high predictive value as a marker for adenocarcinoma, and its identification warrants repeat biopsy for concurrent or subsequent invasive carcinoma. The only method of detection is biopsy; PIN does not significantly elevate serum PSA concentration or its derivatives and cannot be detected by ultrasonography. Most studies suggest that most patients with PIN will develop carcinoma within 10 years. PIN is associated with progressive abnormalities of phenotype and genotype, which are similar to cancer rather than normal prostatic epithelium, indicating impairment of cell differentiation with advancing stages of prostatic carcinogenesis. Androgen deprivation therapy decreases the prevalence and extent of PIN, suggesting that this form of treatment may play a role in chemoprevention.

PSA recurrence after radical prostatectomy usually indicates recurrent prostate cancer. Identification of the recurrence site is difficult, but pathological and clinical features may suggest local versus distant recurrence. Radiographic techniques including transrectal ultrasonography, and 111indium capromab pendetide scans may help identify recurrences. The use of hormonal manipulation for rising PSA after radical prostatectomy is controversial. Androgen deprivation has been a mainstay of the management for advanced prostate cancer. The timing of such therapy is debatable, and early therapy in an asymptomatic patient may not correlate with improved survival. Maximal androgenic blockade with castration and nonsteroidal antiandrogens may offer a modest survival benefit in selected patients. Novel potency-sparing therapies with antiandrogens and finasteride afford an improved patient lifestyle, with questionable effects on survival. Intermittent androgen suppression is an experimental treatment modality that may reduce the side effects of castration. Ongoing studies are being performed to clarify these controversies, and the variety of treatment options allows patients great flexibility in considering quality of life and effective cancer control.

Prostate cancer that has relapsed biochemically after primary therapies, such as prostatectomy or radiation, remains a therapeutic challenge in that no standard treatment option exists for this patient. These patients are often young and may be offered androgen ablation as the mainstay of treatment. Many patients do not wish to undergo a regimen that may be associated with a variety of side effects that will impact on their quality of life. Delaying hormonal treatment in this group does not compromise survival and patients may try a variety of approaches in an attempt to control rising PSAs. Therefore, these patients are an interesting subgroup for whom immunological and alternative therapies may prove to be beneficial. We review new approaches for this population of men, which result in antitumor effects with minimal toxicities.

The protracted natural history of prostate cancer and the absence of a documented effective seconde line curative therapy, once primary treatment has failed, has led in the presence of biochemical failure after radical prostatectomy to a dual attitude: early treatment versus observation with delayed therapy. The objective of this review is to define the subsets of patients who might benefit from either of these attitudes. Depending on the risk of progression, three subgroups of patients may be individualized: a high-risk group (PN1, pT3 B, Gleason score equal or superior to 8), a moderate-risk group (pT3 A, NO with positive margins, and a Gleason score equal or less than 7), and a low-risk group (pT2 NO or pT3 A NO without positive margins and Gleason score equal or lower than 7). As of today, observation seems to be the appropriate option in men with a low or moderate risk of progression, whereas in the high-risk group, early therapy is a reasonable option. New treatment options with intermittent hormonal therapy or with combined adjuvant hormonoradiotherapy show a promising efficacy that may lead to reconsider this attitude.

The purpose of this article is to review the available means to investigate whether an elevated serum prostate-specific antigen (PSA) after radical prostatectomy may be explained by the presence of residual benign tissue. To answer this question, one may consider the following features: the kinetics of recurrent/ persistent PSA, the incidence of rising PSA in the presence of capsular incisions exposing benign glands only, the level of urinary PSA and the ratio of free/total PSA in the urine, the results of anastomotic biopsy samples, and the detection of circulating prostate cells by PSA reverse transcriptase-polymerase chain reaction (RT-PCR) after surgery. Capsular incisions exposing benign tissue are not associated with a significant risk of biochemical failure. In case of an organ-confined cancer with negative surgical margins but a rising postoperative PSA, the systematic reevaluation of the initial pathological slides constantly shows capsular effraction or focal positive margins that have been overlooked at the first evaluation. Even when anastomotic biopsies document only benign tissue, the study of PSA doubling time is usually characteristic of the coexistence of residual tumoral cells. However, in a few cases, the persistent negative results of the detection of circulating prostate cells by PSA, RT-PCR in patients with organ-confined cancer and negative margins but elevated postoperative PSA might be explained by the presence of residual benign prostatic hyperplasia tissue. Most of the data in the literature are in favor of the responsibility of persistent/recurrent cancer in the recurring PSA rather than that of benign prostatic hyperplasia/normal residual tissue. Therefore, a persistent/recurrent detectable level of PSA is the serum after radical prostatectomy characterizes biochemical failure.

With the advent of routine prostate-specific antigen (PSA) testing in asymptomatic young men, the number of patients undergoing radical prostatectomy is increasing. Effective therapy for the 30% to 40% of men who recur following radical prostatectomy is essential. Salvage radiation therapy for a rising serum PSA level is an effective therapy for controlling local recurrence. The impact of salvage radiotherapy on disease-free survival is promising, but the guidelines of therapy are not well established. The best candidates for salvage radiotherapy are those with a serum PSA level < 2 ng/mL with no palpable recurrence and complete urinary continence.

We report on the various methods used to determine local or distant recurrences in patients with detectable serum prostate-specific antigen (PSA) after radical prostatectomy (RP). Studies show that variables that help predict distant metastases are PSA recurrence less than 2 years following surgery, tumors with Gleason score (GS) greater than 7, and positive seminal vesicles or positive lymph nodes at the time of surgery. In addition, studies in PSA kinetics show that short PSA doubling times, especially less than 6 months, are associated with distant recurrence and better correlated with the pattern and incidence of clinical recurrence than preoperative PSA, specimen GS, or stage alone. Studies show that although positive surgical margins are a significant risk factor for recurrence, only 40% to 50% of patients with positive margins developed an elevated PSA level within 5 years. When suspecting a local recurrence, transrectal ultrasound (TRUS) and TRUS-guided biopsies enhance the relatively inaccurate detection of local recurrence by digital rectal examination and initial prostate fossa biopsies. For distant recurrence, bone scintigrams of patients with a PSA recurrence following RP are only rarely positive and are found to have limited usefulness until the PSA increases to above 30 ng/mL. The role of immunoscintography to differentiate between local and distant recurrence is still evolving and requires further investigation. Further studies are clearly needed to enhance our ability to distinguish local from distant recurrence and to ultimately help guide therapy.

In 1999, we continue to be faced with difficulties in treating prostate cancer, which remains the leading cause of cancer and the second leading cause of cancer-related deaths in men. In the prostate-specific antigen (PSA) era, we must also determine which therapies, if any, are appropriate for the treatment of a biochemical or PSA relapse. In view of the limited number of efficacious and durable treatments for prostate cancer recurrence, the medical community has had to investigate nontraditional therapies. In the recent past, an expanding body of evidence has implicated certain nutrients in carcinogenesis and cancer progression. This article discusses the role of diet in prostate carcinogenesis and the rationale for dietary manipulation as a treatment strategy for the prevention of primary and secondary (recurrent) prostate cancer.

Vitamin E is one of the most researched compounds in medicine. Vitamin E is actually a general name for potentially eight different compounds, so supplements can contain several forms and vitamin E in the diet also differs from the form found over the counter. There has been a strong interest in this supplement in the prostate cancer arena primarily because of a Finnish study that demonstrated a lower morbidity and mortality from this disease in men taking 50 mg of synthetic (alpha-tocopherol) vitamin E daily. In addition, observations from laboratory and clinical studies dealing with heart disease have found that gamma-tocopherol may also play a significant role in prevention; therefore, we decided to test the ability of this compound (versus synthetic vitamin E) to control the growth of a human prostate cancer cell line. Gamma-tocopherol was found to be superior to alpha-tocopherol in terms of cell inhibition in vitro. Both forms of vitamin E (and others) should be thoroughly evaluated in the future to provide the most effective chemoprevention information to the patient.