Michael Perrotti

National trends in the epidemiology of prostate cancer, 1973 to 1994: evidence for the effectiveness of prostate-specific antigen screening

OBJECTIVES The use of prostate-specific antigen (PSA) to screen for prostate cancer remains controversial. Although it is still too early to measure directly the effects of PSA screening on mortality, we examined changes in the epidemiology of prostate cancer to determine if there is other evidence of the effectiveness of PSA as a screening tool. METHODS We examined trends in age at diagnosis, and age-adjusted trends in stage and grade at diagnosis, for 140,936 white and 15,662 African American men diagnosed with prostate cancer from 1973 to 1994 in the National Cancer Institutes Surveillance Epidemiology and End Results data base. RESULTS We found a significant downward trend in age at diagnosis, concomitant with a downward shift in stage of disease at diagnosis, starting with the advent of the PSA era in the late 1980s. We noted most cancers detected since the PSA era to be moderately well differentiated (International Classification of Diseases of the World Health Organization grade 2; Gleason score 5, 6, 7) and organ confined. Although findings were similar for both whites and African Americans, African Americans experienced a greater increase in poorly differentiated disease than did whites. CONCLUSIONS Changes in the epidemiology of prostate cancer since the advent of the PSA era are consistent with the introduction of an effective screening test. This is evidenced by an increase in detection of significant prostate cancer in individuals who will likely benefit from treatment.

URETEROENTERIC ANASTOMOSIS IN CONTINENT URINARY DIVERSION: LONG-TERM RESULTS AND COMPLICATIONS OF DIRECT VERSUS NONREFLUXING TECHNIQUES

PURPOSE Controversy exists over the importance of antireflux mechanisms in large volume, low pressure intestinal bladder substitutions. Despite the theoretical benefits of reflux prevention, antirefluxing ureteral reimplantations may have a greater risk of anastomotic stricture. We hypothesize that this inherent stricture rate may outweigh the potential benefits associated with reflux prevention. To assess this question critically we compare our results to those of direct and nonrefluxing techniques of ureterointestinal anastomosis during continent diversion. MATERIALS AND METHODS Between 1990 and 1998, 58 patients underwent continent urinary diversion using an Indiana pouch or ileal orthotopic neobladder following cystectomy for muscle invasive bladder cancer. A total of 56 renal units were implanted using an end-to-side Nesbit direct anastomosis and 60 were implanted in a nonrefluxing manner. Clinical end points included anastomotic stricture formation, hydronephrosis, pyelonephritis, upper tract stone formation and renal deterioration, and were assessed with a mean followup of 41 months. RESULTS Of 60 nonrefluxing ureteroenteric anastomoses 8 (13%) resulted in nonneoplastic stricture formation compared to 1 of 56 (1.7%) direct anastomoses, which was statistically significant (Fishers exact test p <0.05). Strictures occurred up to 6 years following the original surgery. There was no significant difference between the 2 groups in regard to hydronephrosis, pyelonephritis, upper tract stone formation or azotemia. CONCLUSIONS Nonrefluxing methods of ureterointestinal reimplantation resulted in a statistically significant higher rate of anastomotic stricture than the end-to-side direct anastomosis. This finding appears to outweigh any theoretical benefits of preventing pyelonephritis, stones or azotemia. For patients undergoing large volume, low pressure continent diversion the refluxing ureterointestinal anastomosis may be the technique of choice since it preserves renal function as well as the nonrefluxing method, is technically easier to perform and poses less risk of stricture. Delayed stricture formation years after surgery underscores the necessity for long-term radiological followup in patients following continent diversion.

Upper-Tract Tumors After an Initial Diagnosis of Bladder Cancer: Argument for Long-Term Surveillance

PURPOSE To determine the relative risk (RR) of upper-tract tumors (UTT) after bladder cancer, stratified by bladder tumor characteristics, demographic factors, and follow-up duration, in order to develop an improved risk-based surveillance strategy. PATIENTS AND METHODS The 1973 to 1996 Surveillance, Epidemiology, and End Results (SEER) database was used to determine the observed and expected number of UTT after bladder cancer. The RR with 95% confidence intervals (CI) were calculated, stratifying by race, sex, stage, grade, histology, and follow-up duration. The tumor characteristics and clinical outcome were compared in patients with UTT after bladder cancer and those with de novo UTT. RESULTS A total of 94,591 patients had a first diagnosis of bladder cancer, of whom 91,245 had follow-up (median, 4.1 years), with no antecedent or synchronous UTT. UTT developed subsequently in 657 of 91,245 (0.7%), with 12.80 expected cases (RR = 51.3; 95% CI, 47.5 to 55.4). The respective RRs for UTT for white men and women were 64.2 (95% CI, 55.1 to 74.3) and 75.4 (95% CI, 57.7 to 96.9) at less than 2 years, 44.3 (95% CI, 36.7 to 53.0) and 40.5 (95% CI, 27.9 to 56.8) at 2 to 5 years, 50.8 (95% CI, 42.2 to 60.7) and 42.1 (95% CI, 28.8 to 59.4) at 5 to 10 years, and 43.2 (95% CI, 32.6 to 56.1) and 22.2 (95% CI, 10.1 to 42.2) at >or= 10 years. Similar RRs were seen among different strata of race, stage, grade, and histology. Patients with UTT after bladder cancer had lower stage and improved disease-specific survival compared with those with de novo UTT. CONCLUSION The incidence of UTT is stable on long-term follow-up, with no significant risk factors identified. These findings suggest that upper-tract surveillance remain rigorous on extended follow-up of bladder cancer patients.

Phase I Trial of Weekly Docetaxel With Concurrent Three-Dimensional Conformal Radiation Therapy in the Treatment of Unfavorable Localized Adenocarcinoma of the Prostate

PURPOSE A phase I trial was conducted to determine the maximally tolerated dose (MTD) of concurrent weekly docetaxel and three-dimensional conformal radiation therapy (3-D CRT) in unfavorable localized adenocarcinoma of the prostate. PATIENTS AND METHODS Patients with unfavorable localized adenocarcinoma of the prostate underwent daily 3-D CRT to a total dose of 70.2 Gy at 1.8 Gy/fraction and concurrent docetaxel given once a week for 8 to 9 weeks. The initial weekly docetaxel dose level was 5 mg/m(2) and the docetaxel doses were escalated as follows: 8, 12, 16, 20, and 25 mg/m(2). RESULTS Between January 2000 and August 2002, 22 men completed the chemoradiation therapy protocol. The dose-limiting toxicity was grade 3 diarrhea, which occurred in the first two patients treated at the 25 mg/m(2) docetaxel dose level. The MTD of weekly docetaxel was determined to be 20 mg/m(2). The overall incidence of grade 2 diarrhea and grade 2 dysuria was 36% and 23%, respectively. Seven (32%) and 15 (68%) patients did not experience any diarrhea or dysuria, respectively. No neutropenia or thrombocytopenia was observed. One patient required intermittent urinary catheterization 10 months postcompletion of therapy, which resolved without any surgical intervention. Seventeen patients remain in prostate-specific antigen remission. At a median follow-up interval of 8 months (range, 2 to 27 months), all patients are alive. CONCLUSION Concurrent weekly docetaxel in conjunction with 3-D CRT is well tolerated with acceptable toxicity. The MTD of weekly docetaxel was determined to be 20 mg/m(2) with concurrent 3-D CRT.

Lymphatic mapping and intraoperative lymphoscintigraphy for identifying the sentinel node in penile tumors.

Lymph node mapping has become an integral part of the management of melanoma and breast cancer with regard to both staging and treatment. We report our technique for lymphatic mapping and intraoperative lymphoscintigraphy applied to a patient with penile melanoma. This technique may improve the sensitivity of identifying the sentinel lymph node in patients with malignant penile lesions.

TRENDS IN POORLY DIFFERENTIATED PROSTATE CANCER 1973 to 1994: OBSERVATIONS FROM THE SURVEILLANCE, EPIDEMIOLOGY AND END RESULTS DATABASE

PURPOSE Using the Surveillance, Epidemiology and End Results Program, we evaluated the changing demographics of poorly differentiated prostate cancer since early detection measures, such as serum prostate specific antigen screening, were introduced into clinical practice in the United States. MATERIALS AND METHODS Trends between 1973 and 1994 in the proportion, stage and treatment of poorly differentiated tumors (International Classification of Diseases [ICD]-O code 3, Gleason score 8, 9, 10) were assessed, and multivariate Cox proportional hazards models were used to identify independent correlates of disease specific survival. RESULTS The number of ICD-O grade 3 tumors increased during the study period, although these comprised a decreased proportion of all diagnosed cases (24.4% of 29,588 in 1980 to 1984 versus 21.4% of 81,932 in 1990 to 1994, chi-square p < 0.001). ICD-O grade 3 tumors were less often metastatic in 1990 to 1994 compared to 1980 to 1984 (17.4% versus 33.1%, chi-square p < 0.0001) and more often treated with radical prostatectomy or radiotherapy in 1990 to 1994 compared to 1983 to 1984 (37.5 versus 15.6%, chi-square p < 0.001). Although treatment group (radiotherapy versus radical prostatectomy) among patients with clinically confined tumors was an independent correlate of disease specific survival (hazard ratio 2.3, 1983 to 1984 and 3.3, 1990 to 1994), one must recognize potential selection biases inherent to this nonrandomized tumor registry study. The observed 12-year actuarial disease specific survival rates were 67.6% for radical prostatectomy and 46.3% for radiotherapy. CONCLUSIONS In the present era ICD-O grade 3 tumors are being detected in increasing number, are less likely to be metastatic at presentation and are more likely to be treated definitively with radical prostatectomy or radiotherapy. Disease specific survival rates observed with radical prostatectomy and radiotherapy in patients with clinically confined tumors support current efforts to detect and treat these highly aggressive tumors while clinically localized.

Dutasteride monotherapy in men with serologic relapse following radical therapy for adenocarcinoma of the prostate: a pilot study.

OBJECTIVE The objective of this study was to assess the effect of dutasteride on serum prostate specific antigen (PSA) levels in men with serologic relapse following radical prostatectomy and/or radiation therapy for clinically localized adenocarcinoma of the prostate. METHODS A prospective, single institution, IRB approved trial was conducted. Entry criteria required that all participants have serologic disease relapse only with serum PSA levels between 0.4 and 10.0 ng/ml. Enrolled participants were treated with 0.5 mg dutasteride daily. The primary endpoints were serum PSA level and clinical recurrence. The rate of durable decline in PSA was assessed according to the recommendations of the Prostate-Specific Antigen Working Group. RESULTS Thirty-five patients provided informed consent and participated in the present study. At a median follow-up duration of 27 months (range, 4-42 months), 46% of enrolled men had a serum PSA decrease of greater than 10%, and 25% had a serum PSA decrease of greater than 50% (P < 0.001). Pre-study PSA doubling time (PSADT) (≥12 months vs. <12 months), and Gleason score (≤6 vs. ≥7) were associated with a better response to dutasteride, but only PSADT was statistically significant (P < 0.001). Thirty percent of patients experienced PSA progression (increase in serum PSA of greater than 50%). Two (6%) patients developed bone metastasis. No patient was removed from the study for drug-related toxicity. CONCLUSIONS In the present pilot study, treatment with dutasteride resulted in a significant decrease in serum PSA in men with serologic relapse following radical treatment for adenocarcinoma of the prostate. These data appear to suggest that dutasteride may delay or prevent progression of prostate cancer in some men with biochemical relapse after radical therapy. These findings require confirmation in the setting of a larger, longer trial.