William A. See

Bicalutamide 150 mg plus standard care vs standard care alone for early prostate cancer

To evaluate, in the ongoing Early Prostate Cancer (EPC) trial programme, the efficacy and tolerability of bicalutamide 150 mg once daily in addition to standard care for localized or locally advanced, nonmetastatic prostate cancer.

Bicalutamide as Immediate Therapy Either Alone or as Adjuvant to Standard Care of Patients with Localized or Locally Advanced Prostate Cancer: First Analysis of the Early Prostate Cancer Program

PURPOSE We determine the efficacy and tolerability of bicalutamide as immediate therapy, either alone or as adjuvant to treatment of curative intent, in patients with clinically localized or locally advanced prostate cancer. MATERIALS AND METHODS This international program consists of 3 ongoing, randomized, double-blind, placebo controlled clinical trials (trials 23, 24, and 25). Men with localized or locally advanced (T1-T4, Nx/N0, M0) prostate cancer were randomized to receive 150 mg. bicalutamide daily or placebo, in addition to standard care with radical prostatectomy, radiotherapy or watchful waiting. Primary end points are time to objective progression and overall survival. In this first analysis data from the trials were combined in a single overview analysis according to protocol. RESULTS Data are available for 8,113 patients (4,052 randomized to bicalutamide, 4,061 to standard care alone) at a median followup of 3.0 years. Treatment with bicalutamide provided a highly significant reduction of 42% in the risk of objective progression compared with standard care alone (9.0% versus 13.8%, hazards ratio 0.58; 95% confidence interval 0.51, 0.66; p <<0.0001). The overall result was reflected in 2 of the 3 trials (trials 24 and 25) with trial 3 (trial 23) showing a nonsignificant difference at this time. Reductions in the risk of disease progression were seen across the entire patient population, irrespective of primary treatment or disease stage. Overall survival data are currently immature and longer followup will determine if there is also a survival benefit with bicalutamide. The most frequently reported side effects of bicalutamide were gynecomastia and breast pain. CONCLUSIONS Immediate treatment with 150 mg. bicalutamide daily, either alone or as adjuvant to treatment of curative intent, significantly reduces the risk of disease progression in patients with localized or locally advanced prostate cancer. This benefit must be balanced with the morbidity associated with long-term hormonal therapy. Followup is ongoing to determine potential survival benefits of this treatment approach.

Exosomal miR-1290 and miR-375 as Prognostic Markers in Castration-resistant Prostate Cancer

BACKGROUND Extracellular microRNAs (miRNAs) embedded in circulating exosomes may serves as prognostic biomarkers in cancer. OBJECTIVE To identify and evaluate plasma exosomal miRNAs for prognosis in castration-resistant prostate cancer (CRPC). DESIGN, SETTING, AND PARTICIPANTS RNA sequencing was performed to identify candidate exosomal miRNAs associated with overall survival in a screening cohort of 23 CRPC patients. Candidate miRNAs were further evaluated for prognosis using quantitative real-time polymerase chain reaction in a follow-up cohort of 100 CRPC patients. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Cox regression and Kaplan-Meier survival analyses were used to evaluate survival association using candidate miRNAs along with clinical prognostic factors. RESULTS AND LIMITATIONS RNA sequencing in screening cohort generated approximately 6.80 million mappable reads per patient. Of those with normalized read counts ≥ 5, 43% were mapped to miRNAs for a total of 375 known and 57 novel miRNAs. Cox regression analysis identified an association of miR-1290, -1246, and -375 with overall survival (false discover rate < 0.05). Of those, higher levels of miR-1290 and -375 were significantly associated with poor overall survival (p < 0.004) in the follow-up cohort. Incorporation of miR-1290/-375 into putative clinical prognostic factors-based models in CRPC stage significantly improved predictive performance with a time-dependent area under the curve increase from 0.66 to 0.73 (p = 6.57 × 10(-6)). CONCLUSIONS Plasma exosomal miR-1290 and miR-375 are promising prognostic biomarkers for CRPC patients. Prospective validation is needed for further evaluation of these candidate miRNAs. PATIENT SUMMARY In this study, we evaluated whether small RNAs circulating in blood could be used to predict clinical outcomes in late-stage prostate cancer patients. We identified two blood-based small RNAs whose levels showed significant association with survival. Our results warrant further investigation because the noninvasive blood-based test has great potential in the management of late-stage prostate cancer.

Paclitaxel in Advanced Urothelial Carcinoma: Its Role in Patients with Renal Insufficiency and as Salvage Therapy

PURPOSE We evaluated the role of paclitaxel in patients with advanced urothelial carcinoma and renal insufficiency or as second line therapy for metastatic disease. MATERIALS AND METHODS Nine patients with advanced urothelial carcinoma received 175 to 250 mg./m2. paclitaxel intravenously as a 24-hour infusion. Six patients had renal insufficiency with a median serum creatinine of 2.25 mg./dl. (range 1.9 to 3.2) and 3 with normal renal function were treated after disease progression following 1 to 2 prior chemotherapy regimens. RESULTS Of 9 patients 5 (56%) achieved a partial response, including 4 of 6 with renal insufficiency. Toxicity was primarily hematological with 4 patients experiencing febrile neutropenia. There was no adverse impact on renal function. CONCLUSIONS Paclitaxel as a single agent represents an effective therapeutic alternative for patients with advanced transitional cell carcinoma of the urothelium and renal insufficiency precluding cisplatin or gallium nitrate based chemotherapy. Additionally, paclitaxel appears to be effective in patients in whom prior cisplatin based therapy failed.

Laparoscopic practice patterns among north american urologists 5 years after formal training

PURPOSE We assessed urologist laparoscopy practice patterns 5 years after a postgraduate training course in urological laparoscopic surgery. Results were compared to findings from similar studies performed on the same cohort at 3 and 12 months after training. MATERIALS AND METHODS Between January 1991 and November 1992, 11, 2-day university sponsored, postgraduate laparoscopic surgery training programs were held. A survey was mailed to the 322 North American participants in the summer of 1997 to determine current laparoscopic use and experience. RESULTS Of the 166 respondents (51% response rate) 53.6% (89) had performed 1 or more laparoscopic procedures in the previous year, compared to 84% 1 year following course completion. Of the respondents 37% believed their laparoscopic experience was sufficient to maintain skills compared to 66% at 1 year. Of the respondents 6% had performed more laparoscopic procedures while 82% had performed fewer than anticipated. Reasons cited for decreased use included decreasing and/or lack of indications, increased cost, decreased patient interest, higher complication rates, decreased institutional support and increased operative time. Respondents practicing in academic or residency affiliated centers, or those who had completed residency after 1980 were more likely to have performed more procedures than anticipated (p = 0.044) compared to community based colleagues. CONCLUSIONS Laparoscopic use by urologists trained in the postgraduate setting is decreasing. Few respondents are maintaining the skills acquired during the original training course. Decreased use appears to be multifactorial.

Multidetector Computerized Tomography Urography as the Primary Imaging Modality for Detecting Urinary Tract Neoplasms in Patients With Asymptomatic Hematuria

PURPOSE We determined whether multidetector computerized tomography urography is sensitive and specific for detecting urinary tract neoplasms when used as the primary imaging modality for evaluating patients with hematuria. MATERIALS AND METHODS A retrospective review was performed of the radiological, urological and pathological records of 468 patients without a history of urinary neoplasms who presented with hematuria. All patients underwent multidetector computerized tomography urography and complete urological evaluation, including cystoscopy. Laboratory urinalysis and cytology were done in 350 and 318 of the 468 patients, respectively. Multivariate logistic regression analysis was performed using the variables multidetector computerized tomography urography diagnosis, worst urine cytology, number of red blood cells per high power field, gross hematuria, age and gender to predict urinary tract neoplasm. RESULTS A total of 50 urinary neoplasms were diagnosed in 468 patients. Multidetector computerized tomography urography detected 32 of 50 neoplasms for a sensitivity of 64%, specificity of 98%, positive predictive value of 76% and negative predictive value of 96%. There were 10 false-positive and 18 false-negative multidetector computerized tomography urography studies. Multivariate logistic regression showed that abnormal multidetector computerized tomography urography findings, ie neoplasm (p <0.0001), and suspicious or positive urine cytology (p = 0.0009) were significant. Patients with an abnormal multidetector computerized tomography urography diagnosis and suspicious or positive urine cytology had 44 and 47 times greater odds, respectively, of having urinary neoplasms compared to the odds in those with normal examinations. CONCLUSIONS Multidetector computerized tomography urography is relatively sensitive and highly specific for detecting urinary neoplasms. It may serve as the primary imaging modality to evaluate patients with hematuria. Multidetector computerized tomography urography does not eliminate the role of cystoscopy in the evaluation of hematuria.

The bicalutamide Early Prostate Cancer Program. Demography.

BACKGROUND: The optimal treatment for early prostate cancer has yet to be established. A well-tolerated hormonal therapy such as bicalutamide could be a useful treatment option in this setting, either as adjuvant or immediate therapy. A major collaborative clinical trials program was set up to investigate bicalutamide as a treatment option for local prostate cancer (localized or locally advanced disease). METHODS: The bicalutamide Early Prostate Cancer program comprises three randomized, double-blind, placebo-controlled trials of similar design that are being conducted in distinct geographical areas (North America; Australia, Europe, Israel, South Africa and Mexico; and Scandinavia). Men with T1b-4N0-1M0 (TNM 1997) prostate cancer have been randomized on a 1:1 basis to receive bicalutamide 150 mg daily or placebo. Recruitment to the program closed in July 1998, and follow-up is ongoing. Study endpoints include time to clinical progression, overall survival and tolerability. RESULTS: 8113 men aged 38 to 93 years (mean 66.9) were randomized over a 3-year period. 67.4% of the enrolled patients had localized disease (T1-2) and 66.4% had a Gleason score </=6 at study entry, while the majority of patients had node-negative (N0) disease; only 3.1% in two of the studies and none in the third study had confirmed N+ disease. Overall, 71.8% of the patients received therapy of primary curative intent within 16 weeks of randomization; the remainder received watchful waiting as their primary approach. Across the program, the two randomized groups are well balanced. CONCLUSION: This is the largest randomized clinical trial program to date in local prostate cancer and is expected to provide critical information on the role of bicalutamide as an addition to standard care for patients with local prostate cancer who have received a therapy of curative intent or are candidates for watchful waiting.

Intermediate Results of Laparoscopic Cryoablation in 59 Patients at the Medical College of Wisconsin

PURPOSE We report our experience with LC for small renal tumors. MATERIALS AND METHODS Patients who underwent LC at our institution between February 2000 and September 2004 were included in the study. A retrospective chart review was done for perioperative and postoperative parameters as well as clinical outcomes. RESULTS A total of 65 LCs were performed in 59 patients during the period reviewed. Overall 81 renal tumors were cryoablated. Median patient age was 62 years. Median tumor size was 2.5 cm. Median operative time was 190 minutes. Median estimated blood loss was 50 ml. Median hospital stay was 2 days. Conversion to open surgery occurred in 2 patients. Nephrectomy for bleeding occurred in 1 patient. Median followup was 26.8 months. Two recurrences were identified after LC. CONCLUSIONS LC is an alterative modality to laparoscopic partial nephrectomy or open partial nephrectomy for small renal tumors. Tumor recurrence rates in the studies published to date are comparable to those of partial nephrectomy, although longer followup is needed.

Antiandrogen monotherapy in patients with localized or locally advanced prostate cancer: final results from the bicalutamide Early Prostate Cancer programme at a median follow-up of 9.7 years

Study Type – Therapy (RCT)
Level of Evidence 1b

The Bicalutamide 150 Mg Early Prostate Cancer Program: Findings of the North American Trial at 7.7-Year Median Followup

PURPOSE We describe the results of North American Trial 23 of the bicalutamide (Casodex) early prostate cancer program in the context of the overall early prostate cancer program findings. MATERIALS AND METHODS In Trial 23, 3,292 men with T1b-4, N0-Nx (N+ not allowed) M0 prostate cancer who had undergone radical prostatectomy or radiotherapy at 96 specialist referral centers in the United States (2,974) and Canada (318) were randomized 1:1 to 150 mg bicalutamide daily or placebo in addition to standard care for 2 years. RESULTS In Trial 23 at a 7.7-year median followup there were few clinical events in the bicalutamide or standard care groups and the rates of objective progression were 15.4% and 15.3%, respectively. Mortality rates were 12.9% in the treatment group and 12.3% in the standard care group, including 11.2% and 11.0% for nonprostate cancer deaths in the absence of objective progression and 1.6% and 0.9%, respectively, for mortality due to prostate cancer. No differences in the primary end points (objective progression-free and overall survival) were seen between patients treated with bicalutamide and those treated with standard care alone. Bicalutamide (150 mg) significantly improved time to PSA progression (HR 0.80, 95% CI 0.72 to 0.90, p <0.001). The tolerability profile of bicalutamide was similar to that previously described. CONCLUSIONS In Trial 23 the current data suggest that early or adjuvant therapy may not benefit patients at low risk for recurrence, such as those with localized disease. The findings of Trial 23 contrast with the results in the overall early prostate cancer program and in other published literature, in which bicalutamide has been shown to provide significant clinical benefit for locally advanced disease.