Extramammary Paget's disease of the penis and scrotum: excision, reconstruction and evaluation of occult malignancy.

PURPOSE: We describe treatment and reconstruction in patients after surgery for extramammary Paget's disease of the penis and scrotum. We also investigated whether this disease causes an increased risk of undiagnosed visceral malignancy. MATERIALS AND METHODS: We reviewed the databases at our institution from 1996 to 2000 and identified 6 men 67 to 87 years old (mean age 76). In addition, we reviewed the literature on the clinical and pathological features of this disease. RESULTS: In our 6 patients scrotal involvement was present in 83% and penile extramammary Paget's disease was present in 33%. Each man underwent wide local excision and large skin defects were immediately reconstructed with split-thickness skin grafts. In 1 case extramammary Paget's disease had spread to the superficial inguinal nodes. At a mean followup of 29 months there has been no local recurrence and internal malignancy has not been diagnosed. Our literature review revealed 13 patients with penoscrotal extramammary Paget's disease and visceral malignancy, including 12 (92%) with malignancy of the genitourinary system. CONCLUSIONS: Extramammary Paget's disease of the penis and scrotum is a rare disease that can be managed by excision and immediate reconstruction with skin grafting or a local skin flap. Disease may spread to the regional lymph nodes. Although genitourinary cancer may accompany penoscrotal extramammary Paget's disease, an extensive search for cancer of the thorax or abdomen may be unnecessary because only 1 reported case of colon cancer has been associated with penile or scrotal extramammary Paget's disease.

Health related quality of life differences between black and white men with prostate cancer: data from the cancer of the prostate strategic urologic research endeavor.

PURPOSE: Understanding the potential consequences of racial differences in prostate cancer outcomes, from survival rates to quality of life considerations, is important for the clinician and patient. We examined demographic, clinical and health related quality of life data comparing black with white patients just after treatment of prostate cancer and 1 year later. MATERIALS AND METHODS: We analyzed data on 1,178 patients who were newly diagnosed with prostate cancer in the Cancer of the Prostate Strategic Urologic Research Endeavor, a national observational database of men recruited from 35 community and academic urology practices throughout the United States. Patient demographics, clinical characteristics and validated health related quality of life questionnaires were reviewed. A total of 958 white and 161 black patients with prostate cancer who completed at least 2 surveys were compared. RESULTS: The black patients were younger, and had lower income and education levels than white patients. Controlling for age, education and income differences, black patients generally had worse clinical characteristics at presentation and lower baseline health related quality of life data scores in most generic and disease specific categories at treatment. The most notable exception was sexual function, which was the only score that was higher in black patients at treatment. With time, health related quality of life improved in both groups but black patients had slower rates of improvement for general health, bodily pain, physical function, role function, disease worry and bowel function. They continued to have higher sexual function. CONCLUSIONS: Significant differences exist in clinical presentation, sociodemographic characteristics, and health related quality of life between black and white men with prostate cancer. These health related quality of life differences remain after treatment. Physicians should not assume that outcomes in black men would be similar to other patients.

Malignant transformation in a nontumorigenic human prostatic epithelial cell line.

The human prostatic epithelial cell line BPH-1 is normally nontumorigenic in nude mice. The present report demonstrates that this cell line can be permanently transformed by its microenvironment to become tumorigenic. The establishment of a series of tumorigenic sublines based on this parental cell line is described. BPH-1 cells were induced to form tumors either by recombination with human prostatic carcinoma-associated fibroblasts (CAFs) or by exposure to carcinogenic doses of testosterone and estradiol (T+E2) after recombination with rat urogenital sinus mesenchyme. Epithelial cells isolated from these tumors were established as cell strains in culture. When regrafted to nude mouse hosts epithelial cells isolated from CAF- or T+E2-induced tumors were found to be consistently tumorigenic even in the absence of CAF or T+E2. The T+E2-induced cell strains have been designated BPH1(TETD)-A and -B and the CAF-induced strains are designated BPH1(CAFTD)-01 through -08. In vitro, the cells had an epithelial morphology with a less well-defined cobblestone pattern than the parental line. They express SV40 large T antigen, confirming their derivation from the parental BPH-1 line. The BPH1(CAFTD) strains formed colonies in soft agar, whereas the parental BPH-1 cells and the BPH1(TETD) sublines did not. There was no immunocytochemically detectable expression of androgen (AR), alpha-estrogen (ERalpha), or progesterone (PR) receptors by the parental BPH-1 cell line or by any of the tumor-derived cell strains. The cells uniformly coexpressed both basal and luminal cell-type cytokeratins and the basal cell marker p63. When grafted beneath the renal capsule of athymic mouse hosts, all of the tumor-derived cell strains consistently formed tumors. These were predominantly poorly or moderately differentiated squamous or adenosquamous tumors, similar in organization to the primary tumors from which the cell strains were derived. The cell strains continued to express both basal- and luminal-type cytokeratins in vivo. Some of the cell strains also coexpressed vimentin. E-cadherin expression was absent from many of the cells, although patches of cells expressing this marker were seen. The cells continued to express SV40T antigen. These cell strains, which are all derived from a common nontumorigenic progenitor, represent a useful resource for examining genetic and phenotypic changes during carcinogenesis.

The consequences of chromosomal aneuploidy on gene expression profiles in a cell line model for prostate carcinogenesis.

Here we report the genetic characterization of immortalized prostate epithelial cells before and after conversion to tumorigenicity using molecular cytogenetics and microarray technology. We were particularly interested to analyze the consequences of acquired chromosomal aneuploidies with respect to modifications of gene expression profiles. Compared with nontumorigenic but immortalized prostate epithelium, prostate tumor cell lines showed high levels of chromosomal rearrangements that led to gains of 1p, 5, 11q, 12p, 16q, and 20q and losses of 1pter, 11p, 17, 20p, 21, 22, and Y. Of 5700 unique targets on a 6.5K cDNA microarray, approximately 3% were subject to modification in expression levels; these included GRO-1, -2, IAP-1,- 2, MMP-9, and cyclin D1, which showed increased expression, and TRAIL, BRCA1, and CTNNA, which showed decreased expression. Thirty % of expression changes occurred in regions the genomic copy number of which remained balanced. Of the remainder, 42% of down-regulated and 51% of up-regulated genes mapped to regions present in decreased or increased genomic copy numbers, respectively. A relative gain or loss of a chromosome or chromosomal arm usually resulted in a statistically significant increase or decrease, respectively, in the average expression level of all of the genes on the chromosome. However, of these genes, very few (e.g., 5 of 101 genes on chromosome 11q), and in some instances only two genes (MMP-9 and PROCR on chromosome 20q), were overexpressed by > or =1.7-fold when scored individually. Cluster analysis by gene function suggests that prostate tumorigenesis in these cell line models involves alterations in gene expression that may favor invasion, prevent apoptosis, and promote growth.

Predicting risk of prostate specific antigen recurrence after radical prostatectomy with the Center for Prostate Disease Research and Cancer of the Prostate Strategic Urologic Research Endeavor databases.

PURPOSE: Biostatistical models to predict stage or outcome in patients with clinically localized prostate cancer with pretreatment prostate specific antigen (PSA), Gleason sum on biopsy or prostatectomy specimen, clinical or pathological stage and other variables, including ethnicity, have been developed. However, to date models have relied on small subsets from academic centers or military populations that may not be representative. Our study validates and updates a model published previously with the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE, UCSF, Urology Outcomes Research Group and TAP Pharmaceutical Products, Inc.), a large multicenter, community based prostate cancer database and Center for Prostate Disease Research (CPDR), a large military database. MATERIALS AND METHODS: We validated a biostatistical model that includes pretreatment PSA, highest Gleason sum on prostatectomy specimen, prostatectomy organ confinement status and ethnicity, including white and black patients. We then revised it with the Cox regression analysis of the combined 503 PSA era surgical cases from the CPDR prospective cancer database and 1,012 from the CaPSURE prostate cancer outcomes database. RESULTS: The original equation with 3 risk groups stratified CaPSURE cases into distinct categories with 7-year disease-free survival rates of 72%, 42.1% and 27.6% for low, intermediate and high risk men, respectively. Parameter estimates obtained from a Cox regression analysis provided a revised model equation that calculated the relative risk of recurrence as: exponent (exp)[(0.54 x Race) + (0.05 x sigmoidal transformation of PSA [PSA(ST)]) + (0.23 x Postop Gleason) + (0.69 x Pathologic stage). The relative risk of recurrence, as calculated by the aforementioned equation, was used to stratify the cases into 4 risk groups. Very low-4.7 or less, low-4.7 to 7.1, high-7.1 to 16.7 and very high-greater than 16.7, and patients at risk had 7-year disease-free survival rates of 85.4%, 66.0%, 50.6% and 21.3%, respectively. CONCLUSIONS: With a broad cohort of community based, academic and military cases, we developed an equation that stratifies men into 4 discrete risk groups of recurrence after radical prostatectomy and confirmed use of a prior 3 risk group model. Although the variables of ethnicity, pretreatment PSA, highest Gleason sum on prostatectomy specimen and organ confinement status on surgical pathology upon which the model is based are easily obtained, more refined modeling with additional variables are needed to improve prediction of intermediate risk in individuals.

Orthotopic urinary diversion with the ileal neobladder.

Orthotopic lower urinary tract reconstruction is the procedure of choice in appropriately selected men and women requiring cystectomy. Despite extensive experience with this technique, no consensus exists regarding which intestinal segment or reservoir configuration provides the best results. Consequently, various bowel segments and neobladder designs have been described. In 1988, Hautmann and colleagues initially described the ileal neobladder as a safe, reliable method of orthotopic urinary diversion. In this article, we describe our technique and experience with the modified ileal neobladder.

Minichromosome maintenance protein 2 expression in prostate: characterization and association with outcome after therapy for cancer.

The minichromosome maintenance (MCM) proteins are highly conserved proteins essential for initiating and regulating eukaryotic DNA replication. Recent studies have demonstrated the potential use of MCM proteins as markers of proliferation. We characterized the pattern of Mcm 2 staining in benign and malignant prostate tissues and examined the role of Mcm 2 expression in disease-free survival after surgery in men with localized prostate cancer. Tumors from 92 patients who underwent radical prostatectomy for prostate cancer (median follow-up of 54 months) were examined for Mcm 2 expression by immunohistochemistry using a monoclonal antibody. Prostate tissue from five men without histopathological evidence of prostate cancer was also stained for Mcm 2. Mcm 2 expression was quantified by calculating a labeling index, and patients were grouped according to degree of staining. An analysis of the association between Mcm 2 expression with traditional clinicopathological characteristics of prostate cancer was carried out. A Cox proportional hazards analysis was performed to determine whether Mcm 2 staining was a significant independent predictor of disease-free survival. Mcm 2 expression is low (<2%) and limited to the basal cell layer in nonmalignant prostate glands. Mcm 2 expression is consistently increased in malignant glands and is significantly associated with disease-free survival in univariate (P = 0.002) and multivariate (P = 0.01) analyses. Patients with high Mcm 2 expression exhibited shorter disease-free survival. Mcm 2 expression was not associated with any traditional clinical or pathological factors and therefore is an independent predictor of survival in these patients with prostate cancer. These data support evidence that Mcm 2 may serve as a novel proliferation marker in the prostate. Mcm 2 expression is an independent predictor of disease-free survival after definitive local therapy and has potential as a molecular marker for clinical outcome in prostate cancer.

The effect of androgen deprivation therapy on health-related quality of life in men with prostate cancer.

Treatment for prostate cancer has a significant impact on health-related quality of life (HRQOL). We examined HRQOL in a cohort of men receiving androgen deprivation therapy (ADT) and a cohort who opted for surveillance. The cohort consisted of 1178 newly diagnosed patients from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) database (a national longitudinal registry of patients with prostate cancer). General and disease-specific HRQOL outcomes were measured with validated instruments (the SF-36 and University of California at Los Angeles [UCLA] Prostate Cancer Index) at study entry and quarterly thereafter. Individuals were grouped by initial treatment: ADT, surveillance, radical prostatectomy, or radiation therapy. There were 106 men who selected surveillance, 167 men receiving ADT, 351 men treated by radical prostatectomy, and 75 men receiving radiation therapy in the first year after diagnosis. Mean age at diagnosis was 73 years of age, with surveillance patients the oldest and radical prostatectomy patients the youngest. Men receiving ADT reported poorer urinary and sexual function and a higher rate of urinary and sexual bother than patients selecting surveillance. ADT and surveillance HRQOL scores remained low (ie, poorer function) in the year after treatment, whereas men undergoing radical prostatectomy showed improvement in these scales. Patients who received ADT had reduced energy, poorer sexual and urinary function, and were more bothered by their urine and sexual function than patients undergoing other treatments, except surveillance. Longer follow-up time after start of ADT and surveillance is needed to discern the impact of comorbidities on HRQOL.

Intermittent androgen deprivation: update of cycling characteristics in patients without clinically apparent metastatic prostate cancer.

OBJECTIVES: To update the cycling characteristics and patterns of treatment in patients receiving intermittent androgen deprivation (IAD) for clinically localized and recurrent prostate cancer. METHODS: We report our experience with 61 patients treated with IAD. Thirty-four patients had received no prior treatment, and 27 had developed recurrent disease after previous local therapy. No patient had clinically apparent metastatic disease before the initiation of therapy. The mean and median serum prostate-specific antigen (PSA) level before treatment was 25.3 ng/mL and 16.0 ng/mL, respectively (range 0.5 to 190 ng/mL). For each cycle, androgen deprivation was continued until PSA became undetectable or a nadir level was reached. Patients were then observed without treatment, and therapy was reinstituted after the serum PSA value reached a predetermined level. Patients were no longer eligible to cycle off treatment when their serum PSA increased despite ongoing androgen deprivation or if any objective evidence of disease progression was present on imaging studies. RESULTS: Follow-up ranged from 7 to 60 months (mean 30) from the start of treatment. Patients received from one to five treatment cycles (median two), with a median cycle length of 14 months. The median nadir serum PSA level during androgen deprivation was 0.01 ng/mL and was reached within an average of 6 months (range 4 to 9) after beginning treatment. Patients spent an average of 45% of the time not receiving therapy, but the time off therapy decreased as the number of treatment cycles increased. Five patients (8.1%) demonstrated progressive disease, with a median time to progression of 48 months. When examining the cycling characteristics of these patients, no consistent pattern of failure emerged. CONCLUSIONS: IAD appears to be a viable treatment option in select patients with localized prostate cancer. With each consecutive cycle, the amount of time the patient was not receiving therapy decreased, despite achieving a low nadir PSA. Longer follow-up with more patients failing IAD will be required before clear patterns of failure emerge in these patients.

Androgen deprivation therapy for patients with clinically localized (stages T1 to T3) prostate cancer and for patients with biochemical recurrence after radical prostatectomy.

Recently published studies suggest a benefit for androgen deprivation therapy (ADT) delivered early in the course of prostate cancer. However, the use of ADT specifically in patients with clinically localized disease or biochemical-disease recurrence after local therapy is not well defined. Potential candidates for primary ADT include patients who are poor candidates for definitive local therapy because of advanced age or comorbid conditions, as well as patients with significant local disease who refuse standard therapy. Treatment strategies designed to minimize the side effects of prolonged therapy, such as intermittent ADT or antiandrogen monotherapy, show promise as alternatives to continuous ADT in some patients. The role of ADT in patients with clinically localized and recurrent prostate cancer, whether it is delivered in a continuous or intermittent fashion, must be determined in randomized, prospective trials.

Is anastomotic biopsy necessary before radiotherapy after radical prostatectomy?

PURPOSE: External beam radiotherapy may be given after radical prostatectomy as adjuvant (immediate) or therapeutic (delayed) treatment, the latter in response to evidence of disease recurrence. In patients receiving delayed radiotherapy the necessity of a positive anastomotic biopsy before treatment remains unclear. We determined whether a positive anastomotic biopsy predicted the response to radiation in this setting. MATERIALS AND METHODS: We reviewed the records of 67 patients who received radiotherapy for biochemical or biopsy proved recurrent prostate cancer after radical prostatectomy. Patients underwent surgery at our institution or its affiliated hospitals, or were referred to our institution for radiotherapy. All patients had a negative metastatic evaluation before receiving radiotherapy. Biochemical failure after radiotherapy was defined as serum prostate specific antigen (PSA) 0.2 ng./dl. or greater on 2 or more consecutive occasions. Biochemical recurrence-free survival was calculated using the Kaplan-Meier method. Independent predictors of PSA failure after radiotherapy were identified using the multivariate Cox proportional hazards model. RESULTS: Of the 67 patients evaluated 33 and 34 received radiotherapy for biochemical failure and biopsy proved local recurrence, respectively. The 3-year recurrence-free survival rate was 49% in patients treated for biochemical failure and 39% in those with biopsy proved local recurrence. There was no significant difference in PSA-free survival in these 2 groups. Only pre-radiotherapy PSA 1 ng./dl. or greater (p = 0.02) and seminal vesicle invasion (p = 0.02) were significant independent predictors of biochemical failure. CONCLUSIONS: A positive anastomotic biopsy did not predict an improved outcome after radiotherapy following radical prostatectomy. Anastomotic biopsy was associated with a longer time to salvage radiotherapy. However, this delay did not translate into worse disease-free outcomes in patients who underwent anastomotic biopsy. High pre-radiotherapy PSA greater than 1 ng./ml. was the most significant predictor of biochemical failure after therapeutic radiotherapy. Decisions regarding local radiation therapy after radical prostatectomy may be made without documenting recurrent local disease.

Prostate cancer detection in men with prior high grade prostatic intraepithelial neoplasia or atypical prostate biopsy.

PURPOSE: We used clinical variables to predict prostate cancer detection on re-biopsy among patients diagnosed with high grade prostatic intraepithelial neoplasia (PIN) or atypia on initial prostate biopsy. MATERIALS AND METHODS: A total of 45 men with atypia and 43 with high grade PIN were eligible for our study. Clinical variables were tested with univariate and multivariate logistic regression to predict who would have cancer on re-biopsy. We also calculated the odds of detecting cancer with various repeat sampling strategies and determined whether the location of initial atypia or high grade PIN is correlated to that of cancer on re-biopsy. RESULTS: Of the patients in the atypia and high grade PIN groups 51% had cancer on re-biopsy. Cancer was diagnosed significantly earlier in the high grade PIN than in the atypia cohort (average 7.5 versus 22.9 months, respectively, p = 0.005). Multivariate logistic modeling showed that digital rectal examination and patient age were independent predictors of cancer in atypia, whereas no variables were significantly predictive for high grade PIN. Of cancers in the atypia and high grade PIN 65% and 74%, respectively, would have been detected if re-biopsy was focused only at the initial site of disease. CONCLUSIONS: Men with atypia or high grade PIN merit close followup because 50% will have cancer on re-biopsy as will those who are older with an abnormal digital rectal examination. Although re-biopsy should focus primarily on the original site of atypia or high grade PIN, cancer detection significantly increases with the sampling of adjacent sites.

Asymptomatic microscopic hematuria in adults: summary of the AUA best practice policy recommendations.

The American Urological Association (AUA) convened the Best Practice Policy Panel on Asymptomatic Microscopic Hematuria to formulate policy statements and recommendations for the evaluation of asymptomatic microhematuria in adults. The recommended definition of microscopic hematuria is three or more red blood cells per high-power microscopic field in urinary sediment from two of three properly collected urinalysis specimens. This definition accounts for some degree of hematuria in normal patients, as well as the intermittent nature of hematuria in patients with urologic malignancies. Asymptomatic microscopic hematuria has causes ranging from minor findings that do not require treatment to highly significant, life-threatening lesions. Therefore, the AUA recommends that an appropriate renal or urologic evaluation be performed in all patients with asymptomatic microscopic hematuria who are at risk for urologic disease or primary renal disease. At this time, there is no consensus on when to test for microscopic hematuria in the primary care setting, and screening is not addressed in this report. However, the AUA report suggests that the patient's history and physical examination should help the physician decide whether testing is appropriate.

Under staging and under grading in a contemporary series of patients undergoing radical prostatectomy: results from the Cancer of the Prostate Strategic Urologic Research Endeavor database.

PURPOSE: We determined the prevalence of under staging and under grading in contemporary patients undergoing radical prostatectomy in academic and community based urology practices, and defined important predictors of under staging in this population. MATERIALS AND METHODS: We compared clinical T stage and biopsy Gleason score with pathological T stage and prostatectomy Gleason score in 1,313 patients enrolled in the Cancer of the Prostate Strategic Urologic Research Endeavor database, a longitudinal registry of patients with prostate cancer, who underwent radical prostatectomy, including 53% since 1995. Under grading was determined for the primary and secondary Gleason patterns and defined as a biopsy Gleason pattern of 1 to 3 that became pathological Gleason pattern 4 or 5. Under staging was defined as a clinically organ confined tumor that was extraprostatic stages pT3 to 4 or N+ at radical prostatectomy. Univariate and multivariate analysis was performed to determine important risk factors for under staging and significant risk factors were used to identify the likelihood of under staging in clinically relevant patient subgroups. The importance of the percent of positive biopsies in regard to the likelihood of under staging was determined by assigning patients to previously described risk groups based on serum prostate specific antigen (PSA) at diagnosis and biopsy Gleason score. RESULTS: Under grading of primary and secondary Gleason patterns occurred in 13% and 29% of patients, respectively, while under staging occurred in 24%. Univariate and multivariate analysis revealed that PSA at diagnosis, biopsy Gleason score and the percent of positive biopsies were significant predictors of under staging. The percent of positive biopsies appeared to be most important for predicting the likelihood of extraprostatic disease extension in intermediate or high risk disease based on serum PSA at diagnosis and biopsy Gleason grade. CONCLUSIONS: The prevalence of under grading and under staging in contemporary patients undergoing radical prostatectomy may be lower than previously reported. PSA at diagnosis, biopsy Gleason score and the percent of positive biopsies are important predictors of under staging. The percent of positive biopsies should be incorporated into risk assessment models of newly diagnosed prostate cancer.

Additional treatments and reimbursement rates associated with prostate cancer treatment for patients undergoing radical prostatectomy, interstitial brachytherapy, and external beam radiotherapy.

OBJECTIVES: To define patterns of treatment among contemporary patients undergoing radical prostatectomy, interstitial radiation, and external beam radiation for prostate cancer. METHODS: We analyzed 291 consecutive patients (Stage T1-T3NXM0) who underwent definitive local treatment for prostate cancer with radical prostatectomy, interstitial seed implantation, or external beam radiation. Patients were stratified into three risk groups based on clinical T stage, serum prostate-specific antigen level at diagnosis, and biopsy Gleason score. The frequency of additional treatments, including androgen deprivation and external beam radiation, given within 3 months of initial local therapy was assessed. Patterns of care were compared and adjusted for risk. RESULTS: Of the 291 patients, 107 (36. 8%) underwent radical prostatectomy, 94 (32.3%) underwent interstitial seed implantation, and 90 (30.9%) underwent external beam radiation. Use of combination therapy differed significantly according to the type of initial local treatment and risk category. No patient in the low-risk group received combination therapy. For patients in the intermediate and high-risk groups, the frequency of combination therapy was significantly lower in the radical prostatectomy group when compared with either the interstitial seed implantation (P <0.001 and P <0.02, respectively) or external beam radiation group (P <0.001 and P <0.001, respectively). CONCLUSIONS: There are significant differences in resource utilization for contemporary patients undergoing definitive local therapy for prostate cancer. These differences may have a significant effect on treatment cost and morbidity, and they will likely make short-term comparisons between different treatment modalities difficult because of the high use of androgen deprivation in men treated with radiation therapy.

Prospective trial of the herbal supplement PC-SPES in patients with progressive prostate cancer.

PURPOSE: PC-SPES is an herbal supplement for which there are anecdotal reports of anti-prostate cancer activity. This phase II study was undertaken to assess the efficacy and toxicity of PC-SPES in prostate cancer patients. PATIENTS AND METHODS: Thirty-three patients with androgen-dependent prostate cancer (ADPCa) and 37 patients with androgen-independent prostate cancer (AIPCa) were treated with PC-SPES at a dose of nine capsules daily. Clinical outcome was assessed with serial serum prostate-specific androgen (PSA) level measurement and imaging studies. RESULTS: One hundred percent of ADPCa patients experienced a PSA decline of >/= 80%, with a median duration of 57+ weeks. No patient has developed PSA progression. Thirty-one patients (97%) had declines of testosterone to the anorchid range. Two ADPCa patients had positive bone scans; both improved. One patient with a bladder mass measurable on computed tomography scan experienced disappearance of this mass. Nineteen (54%) of 35 AIPCa patients had a PSA decline of >/= 50%, including eight (50%) of 16 patients who had received prior ketoconazole therapy. Median time to PSA progression was 16 weeks (range, 2 to 69+ weeks). Of 25 patients with positive bone scans, two had improvement, seven had stable disease, 11 had progressive disease, and five did not have a repeat bone scan because of PSA progression. Severe toxicities included thromboembolic events (n = 3) and allergic reactions (n = 3). Other frequent toxicities included gynecomastia/gynecodynia, leg cramps, and grade 1 or 2 diarrhea. CONCLUSION: PC-SPES seems to have activity in the treatment of both ADPCa and AIPCa and has acceptable toxicity. Further study is required to determine whether its effects exceed those expected with estrogen therapy.