Comparison of Digital Rectal Examination and Serum Prostate Specific Antigen in the Early Detection of Prostate Cancer: Results of a Multicenter Clinical Trial of 6,630 Men.

To compare the efficacy of digital rectal examination and serum prostate specific antigen (PSA) in the early detection of prostate cancer, we conducted a prospective clinical trial at 6 university centers of 6,630 male volunteers 50 years old or older who underwent PSA determination (Hybritech Tandom-E or Tandem-R assays) and digital rectal examination. Quadrant biopsies were performed if the PSA level was greater than 4 µg./l. or digital rectal examination was suspicious, even if transrectal ultrasonography revealed no areas suspicious for cancer. The results showed that 15% of the men had a PSA level of greater than 4 µg./l., 15% had a suspicious digital rectal examination and 26% had suspicious findings on either or both tests. Of 1,167 biopsies performed cancer was detected in 264. PSA detected significantly more tumors (82%, 216 of 264 cancers) than digital rectal examination (55%, 146 of 264, p = 0.001). The cancer detection rate was 3.2% for digital rectal examination, 4.6% for PSA and 5.8% for the 2 methods combined. Positive predictive value was 32% for PSA and 21% for digital rectal examination. Of 160 patients who underwent radical prostatectomy and pathological staging 114 (71%) had organ confined cancer: PSA detected 85 (75%) and digital rectal examination detected 64 (56%, p = 0.003). Use of the 2 methods in combination increased detection of organ confined disease by 78% (50 of 64 cases) over digital rectal examination alone. If the performance of a biopsy would have required suspicious transrectal ultrasonography findings, nearly 40% of the tumors would have been missed. We conclude that the use of PSA in conjunction with digital rectal examination enhances early prostate cancer detection. Prostatic biopsy should be considered if either the PSA level is greater than 4 µg./l. or digital rectal examination is suspicious for cancer, even in the absence of abnormal transrectal ultrasonography findings.

Phase 3 clinical trial investigating the effect of selenium supplementation in men at high-risk for prostate cancer.

PURPOSE: This study was conducted to investigate the effect of Se supplementation on prostate cancer incidence in men at high risk for prostate cancer. METHODS: A Phase 3 randomized, double-blind, placebo-controlled clinical trial was conducted in 699 men at high risk for prostate cancer (prostate specific antigen (PSA) >4 ng/ml and/or suspicious digital rectal examination and/or PSA velocity >0.75 ng/ml/year), but with a negative prostate biopsy. Participants were randomized to receive daily oral placebo (N = 232), 200 µg selenium (N = 234), or 400 µg selenium (N = 233) as selenized yeast. They were followed every 6 months for up to 5 years. The time to diagnosis of prostate cancer was compared between treatment groups using the Cox proportional hazards model. RESULT: Compared to placebo, the hazard ratios [95% confidence intervals] for risk of developing prostate cancer in the selenium 200 µg/day or the selenium 400 µg/day group were 0.94 [0.52, 1.7] and 0.90 [0.48, 1.7], respectively. PSA velocity in the selenium arms was not significantly different from that observed in the placebo group (P = 0.18 and P = 0.17, respectively). CONCLUSION: Selenium supplementation appeared to have no effect on the incidence of prostate cancer in men at high risk. In conjunction with results of other studies, these data indicate that selenium supplementation may not have a role in prostate cancer chemoprevention.

Positive surgical margins at radical prostatectomy predict prostate cancer specific mortality.

PURPOSE: Positive surgical margins in men undergoing radical prostatectomy for prostate cancer are associated with an increased risk of biochemical recurrence. Few data are available on the role of positive surgical margins in prostate cancer specific mortality. Using a large, population based national cancer registry we evaluated the risk of prostate cancer specific mortality associated with margin status. MATERIALS AND METHODS: The SEER cancer registry data for patients diagnosed between 1998 and 2006 were used to identify men undergoing radical prostatectomy for prostate cancer. Margin status, pathological stage, Gleason grade and postoperative radiation therapy were recorded along with demographic data. Multivariate Cox regression analysis was used to estimate the risk of prostate cancer specific mortality associated with positive surgical margins. RESULTS: A total of 65,633 patients comprised the cohort in which 291 (0.44%) prostate cancer specific deaths occurred during an average followup of 50 months. Positive surgical margins were reported in 21.2% of cases and were more common in pT3a than pT2 tumors (44% vs 18%, p <0.001) and higher grade tumors (28% vs 18%, p <0.001). The 7-year disease specific survival rates for those at highest risk for prostate cancer specific mortality (higher grade pT3a) were 97.6% for cases with negative surgical margins and 92.4% for those with positive surgical margins. Positive surgical margins were associated with a 2.6-fold increased unadjusted risk of prostate cancer specific mortality (HR 2.55, 95% CI 2.02-3.21). Positive surgical margins remained an independent predictor of prostate cancer specific mortality on multivariate analysis (HR 1.70, 95% CI 1.32-2.18). CONCLUSIONS: These data demonstrate the independent role of positive surgical margins in prostate cancer specific mortality. These findings support the importance of optimizing surgical techniques to achieve a sound oncological surgical outcome with negative surgical margins when possible.

Potent men undergoing radical prostatectomy: a prospective study measuring sexual health outcomes and the impact of erectile dysfunction treatments.

INTRODUCTION: Radical prostatectomy (RP) can have a significant impact on sexual health. The purpose of this study was to measure changes in sexual health after RP, assess the impact of various treatments for erectile dysfunction, and define an appropriate endpoint for maintaining sexual health after surgery. METHODS: One hundred sixteen men with good preoperative sexual health undergoing RP completed a validated anonymous survey preop and annually thereafter. Subgroup analysis was performed based on the use of erectile dysfunction (ED) treatments. Endpoints for evaluation included an erection adequate for intercourse and a return to baseline in sexual domain scores. RESULTS: Overall there was a significant reduction in scores after surgery for each of the sexual health questions and the function and bother domains. ED treatments providing an erection adequate for intercourse resulted in domain scores significantly higher than those in men unable to achieve such an endpoint, and comparable to those of men returning to good native erectile function, but still lower than preop. Even in men with good preoperative sexual health, with erections adequate for intercourse postop, the return to baseline rate was only 26% in sexual function and 40% in sexual bother. CONCLUSION: RP appears to have a significant impact on sexual health. Overall, ED treatments, when providing a functional erection, improve sexual health scores, even comparable to men returning to spontaneous erectile function. Although, men functioning well prior to surgery infrequently returned to their preoperative level of sexual health, even with return of native erectile function or the successful use of an ED treatment.

Health related quality of life outcomes after radical prostatectomy: attention to study design and the patient-based importance of single-surgeon studies.

OBJECTIVE: To define accurately health related quality of life outcomes in men undergoing radical prostatectomy (RP) by a single surgeon. MATERIALS AND METHODS: Since September 1999, men undergoing RP were asked to complete the Medical Outcomes Study Short Form-36 (SF-36) and University of California Los Angeles Prostate Cancer Index preoperatively, returning it to a third party data center. Anonymous surveys were mailed to each patient at 1 and 2 years. RESULTS: We captured 90% and 82% of men at 1 and 2 years, respectively. Mean scores in the SF-36 domains and bowel function/bother were unchanged from preoperative at 1 and 2 years. Urinary function and bother scores were lower at year 1, but stable at year 2. Men wearing > or = 1 pad/d scored significantly lower in urinary function and bother than those noted as pad-free. Pad-free rates were 82% at year 1 and 89% at year 2. Sexual function and bother scores were significantly lower at years 1 and 2. In men younger than 60 years with unilateral nerve-sparing surgery, at 2 years, 50% had erections adequate for intercourse. CONCLUSIONS: This single-surgeon outcomes study after RP showed stability in the SF-36 and bowel domains to 2 years. At 2 years, the vast majority of men were pad-free (89%), and the majority of young men after unilateral nerve-sparing surgery had erections adequate for intercourse (50%). Accurate outcomes measurement can assist in comparing treatments and physicians, and in counseling patients on expected outcomes for localized prostate cancer interventions.

Design and feasibility of integrating personalized PRO dashboards into prostate cancer care.

OBJECTIVE: Patient-reported outcomes (PROs) are a valued source of health information, but prior work focuses largely on data capture without guidance on visual displays that promote effective PRO use in patient-centered care. We engaged patients, providers, and design experts in human-centered design of "PRO dashboards" that illustrate trends in health-related quality of life (HRQOL) reported by patients following prostate cancer treatment. MATERIALS AND METHODS: We designed and assessed the feasibility of integrating dashboards into care in 3 steps: (1) capture PRO needs of patients and providers through focus groups and interviews; (2) iteratively build and refine a prototype dashboard; and (3) pilot test dashboards with patients and their provider during follow-up care. RESULTS: Focus groups (n = 60 patients) prioritized needs for dashboards that compared longitudinal trends in patients' HRQOL with "men like me." Of the candidate dashboard designs, 50 patients and 50 providers rated pictographs less helpful than bar charts, line graphs, or tables (P < .001) and preferred bar charts and line graphs most. Given these needs and the design recommendations from our Patient Advisory Board (n = 7) and design experts (n = 7), we built and refined a prototype that charts patients' HRQOL compared with age- and treatment-matched patients in personalized dashboards. Pilot testing dashboard use (n = 12 patients) improved compliance with quality indicators for prostate cancer care (P < .01). CONCLUSION: PRO dashboards are a promising approach for integrating patient-generated data into prostate cancer care. Informed by human-centered design principles, this work establishes guidance on dashboard content, tailoring, and clinical use that patients and providers find meaningful.

Preliminary Comparative Effectiveness of Robotic Versus Open Radical Cystectomy in Elderly Patients.

INTRODUCTION: Treatment for muscle-invasive bladder cancer (MIBC) remains highly morbid despite improving surgical techniques. As the median age of diagnosis is 73, many patients are elderly at the time of cystectomy. We compare perioperative surgical outcomes in elderly patients undergoing robotic vs open radical cystectomy (RC). MATERIALS AND METHODS: Patients >75 years at time of RC were identified. Demographic, clinicopathologic, and perioperative variables were examined. Estimated blood loss (EBL) and length of stay (LOS) data were collected with multivariate linear regression analysis performed to assess whether technique was independently associated with outcomes. RESULTS: Eighty-seven patients >75 years of age underwent cystectomy for MIBC (58 open, 29 robotic). Mean age was 79.6 (±3.2) and 79.2 (±3.5) for open and robotic groups, respectively (p = 0.64). There were no significant differences in baseline comorbidities, clinical or pathologic stage, or use of neoadjuvant chemotherapy. The mean number of lymph nodes removed was similar (p = 0.08). Robotic cystectomy had significantly longer mean OR times (p < 0.001). On multivariate analyses, robotic surgery was associated with -389cc less EBL (95% CI -547 to -230, p < 0.001) and a -1.5-day-shortened LOS (95%CI -2.9 to -0.2, p = 0.02) compared with open surgery. There were no significant differences in surgical complications or 90-day readmission rates between the two groups. CONCLUSIONS: Robotic cystectomy is safe and feasible in an elderly population. We observed longer OR times with robotic surgery, but with decreased EBL, shorter hospital stays, and comparable complication and readmission rates with open RC. Larger prospective studies are required to confirm these findings.

Extreme Gleason Upgrading From Biopsy to Radical Prostatectomy: A Population-based Analysis.

OBJECTIVE: To examine the risk factors associated with the odds of extreme Gleason upgrading at radical prostatectomy (RP) (defined as a Gleason prognostic group score increase of ≥2), we utilized a large, population-based cancer registry. MATERIALS AND METHODS: The Surveillance, Epidemiologic, and End Results database was queried (2010-2011) for all patients diagnosed with Gleason 3 + 3 or 3 + 4 on prostate needle biopsy. Available clinicopathologic factors and the odds of upgrading and extreme upgrading at RP were evaluated using multivariate logistic regression. RESULTS: A total of 12,459 patients were identified, with a median age of 61 (interquartile range: 56-65) and a diagnostic prostate-specific antigen (PSA) of 5.5 ng/mL (interquartile range: 4.3-7.5). Upgrading was observed in 34% of men, including 44% of 7402 patients with Gleason 3 + 3 and 19% of 5057 patients with Gleason 3 + 4 disease. Age, clinical stage, diagnostic PSA, and % prostate needle biopsy cores positive were independently associated with odds of any upgrading at RP. In baseline Gleason 3 + 3 disease, extreme upgrading was observed in 6%, with increasing age, diagnostic PSA, and >50% core positivity associated with increased odds. In baseline Gleason 3 + 4 disease, extreme upgrading was observed in 4%, with diagnostic PSA and palpable disease remaining predictive. Positive surgical margins were significantly higher in patients with extreme upgrading at RP (P < .001). CONCLUSION: Gleason upgrading at RP is common in this large population-based cohort, including extreme upgrading in a clinically significant portion.

External beam radiation therapy and abiraterone in men with localized prostate cancer: safety and effect on tissue androgens.

PURPOSE: Optimizing androgen suppression may provide better control of localized prostate cancer (PCa). Numerous trials have supported the benefit of combining androgen deprivation therapy with definitive radiation therapy in men with locally advanced or high-grade disease. Addition of abiraterone to luteinizing hormone-releasing hormone agonist (LHRHa) with radiation has not been reported. We examined the safety of this combination as well as its impact on androgen suppression. METHODS AND MATERIALS: A prospective, phase 2 study was conducted in men with localized PCa treated with 6 months of neoadjuvant and concurrent abiraterone with LHRHa and radiation. Duration of adjuvant LHRHa was at the discretion of the treating clinician. Prostate biopsy assays were obtained prior to the start of therapy and prior to radiation. Sera and tissue androgen levels were measured by liquid chromatography-tandem mass spectrometry. RESULTS: A total of 22 men with intermediate- (n=3) and high-risk PCa (n=19) received study therapy. Sixteen men completed the intended course of abiraterone, and 19 men completed planned radiation to 77.4 to 81 Gy. Radiation to pelvic nodes was administered in 20 men. The following grade 3 toxicities were reported: lymphopenia (14 patients), fatigue (1 patient), transaminitis (2 patients), hypertension (2 patients), and hypokalemia (1 patient). There were no grade 4 toxicities. All 21 men who complied with at least 3 months of abiraterone therapy had a preradiation prostate-specific antigen (PSA) concentration nadir of <0.3 ng/mL. Median levels of tissue androgen downstream of CYP17A were significantly suppressed after treatment with abiraterone, and upstream steroids were increased. At median follow-up of 21 months (range: 3-37 months), only 1 patient (who had discontinued abiraterone at 3 months) had biochemical relapse. CONCLUSIONS: Addition of abiraterone to LHRHa with radiation is safe and achieves effective prostatic androgen suppression. Preliminary analysis of the clinical data is also promising, with excellent PSA nadir and no relapse to date in this high-risk population.

Different phenotypes in human prostate cancer: alpha6 or alpha3 integrin in cell-extracellular adhesion sites.

The distribution of alpha6/alpha3 integrin in adhesion complexes at the basal membrane in human normal and cancer prostate glands was analyzed in 135 biopsies from 61 patients. The levels of the polarized alpha6/alpha3 integrin expression at the basal membrane of prostate tumor glands were determined by quantitative immunohistochemistry. The alpha6/alpha3 integrin expression was compared with Gleason sum score, pathological stage, and preoperative serum prostate-specific antigen (PSA). The associations were assessed by statistical methods. Eighty percent of the tumors expressed the alpha6 or alpha3 integrin and 20% was integrin-negative. Gleason sum score, but not serum PSA, was associated with the integrin expression. Low Gleason sum score correlated with increased integrin expression, high Gleason sum score with low and negative integrin expression. Three prostate tumor phenotypes were distinguished based on differential integrin expression. Type I coexpressed both alpha6 and alpha3 subunits, type II exclusively expressed alpha6 integrin, and type III expressed alpha3 integrin only. Fifteen cases were further examined for the codistribution of vinculin, paxillin, and CD 151 on frozen serial sections using confocal laser scanning microscopy. The alpha6/alpha3 integrins, CD151, paxillin, and vinculin were present within normal glands. In prostate carcinoma, alpha6 integrin was colocalized with CD 151, but not with vinculin or paxillin. In tumor phenotype I, the alpha6 subunit did not colocalize with the alpha subunit indicating the existence of two different adhesion complexes. Human prostate tumors display on their cell surface the alpha6beta1 and/or alpha3beta1 integrins. Three tumor phenotypes associated with two different adhesion complexes were identified, suggesting a reorganization of cell adhesion structures in prostate cancer.

Effect of patient age on early detection of prostate cancer with serum prostate-specific antigen and digital rectal examination.

This study was designed to determine the effects of age by decade on the efficacy of digital rectal examination (DRE) and serum prostate-specific antigen (PSA) for early detection of prostate cancer in men aged fifty and over. A prospective multicenter clinical trial was conducted at six university centers. All 6,630 male volunteers underwent a serum PSA (Hybritech, Tandem) determination and DRE. Quadrant biopsies of the prostate were performed if PSA was > 4 ng/mL or DRE suspicious. A total of 1,167 biopsies were performed, and 264 cancers were detected. The cancer detection rate increased from 3 percent in men aged fifty to fifty-nine to 14 percent in men eighty years or older (p < 0.0001). PSA detected significantly more of the total cancers than DRE at all age ranges (p < 0.05). The positive predictive values (PPV) for PSA were 32 percent (50-59 years), 30 percent (60-69 years), 34 percent (70-79 years), and 38 percent (80+ years). The corresponding PPVs for DRE were 17 percent, 21 percent, 25 percent, and 38 percent. Eighteen percent of the cancers were detected solely by DRE, whereas 45 percent of cancers were detected solely by PSA. Thus, the use of both tests in combination provided the highest rate of detection in all age groups. One hundred-sixty patients underwent radical prostatectomy and pathologic staging. Cancer was organ-confined in 74 percent (25/34) of men aged fifty to fifty-nine, 76 percent (65/86) of men aged sixty to sixty-nine, and 60 percent (24/40) of men aged seventy or over (chi 2, < 70 vs. > or = 70, p < 0.05). Early detection programs yield a lower, yet still substantial, cancer detection rate in younger men, and there is a greater likelihood for detection of organ-confined disease in this age range. Younger men have the longest projected life expectancy and, therefore, the most to gain from early prostate cancer detection.

User-centered design of quality of life reports for clinical care of patients with prostate cancer.

BACKGROUND: Primary treatment of localized prostate cancer can result in bothersome urinary, sexual, and bowel symptoms. Yet clinical application of health-related quality-of-life (HRQOL) questionnaires is rare. We employed user-centered design to develop graphic dashboards of questionnaire responses from patients with prostate cancer to facilitate clinical integration of HRQOL measurement. METHODS: We interviewed 50 prostate cancer patients and 50 providers, assessed literacy with validated instruments (Rapid Estimate of Adult Literacy in Medicine short form, Subjective Numeracy Scale, Graphical Literacy Scale), and presented participants with prototype dashboards that display prostate cancer-specific HRQOL with graphic elements derived from patient focus groups. We assessed dashboard comprehension and preferences in table, bar, line, and pictograph formats with patient scores contextualized with HRQOL scores of similar patients serving as a comparison group. RESULTS: Health literacy (mean score, 6.8/7) and numeracy (mean score, 4.5/6) of patient participants was high. Patients favored the bar chart (mean rank, 1.8 [P = .12] vs line graph [P < .01] vs table and pictograph); providers demonstrated similar preference for table, bar, and line formats (ranked first by 30%, 34%, and 34% of providers, respectively). Providers expressed unsolicited concerns over presentation of comparison group scores (n = 19; 38%) and impact on clinic efficiency (n = 16; 32%). CONCLUSION: Based on preferences of prostate cancer patients and providers, we developed the design concept of a dynamic HRQOL dashboard that permits a base patient-centered report in bar chart format that can be toggled to other formats and include error bars that frame comparison group scores. Inclusion of lower literacy patients may yield different preferences.

Intense androgen-deprivation therapy with abiraterone acetate plus leuprolide acetate in patients with localized high-risk prostate cancer: results of a randomized phase II neoadjuvant study.

PURPOSE: Cure rates for localized high-risk prostate cancers (PCa) and some intermediate-risk PCa are frequently suboptimal with local therapy. Outcomes are improved by concomitant androgen-deprivation therapy (ADT) with radiation therapy, but not by concomitant ADT with surgery. Luteinizing hormone-releasing hormone agonist (LHRHa; leuprolide acetate) does not reduce serum androgens as effectively as abiraterone acetate (AA), a prodrug of abiraterone, a CYP17 inhibitor that lowers serum testosterone (< 1 ng/dL) and improves survival in metastatic PCa. The possibility that greater androgen suppression in patients with localized high-risk PCa will result in improved clinical outcomes makes paramount the reassessment of neoadjuvant ADT with more robust androgen suppression. PATIENTS AND METHODS: A neoadjuvant randomized phase II trial of LHRHa with AA was conducted in patients with localized high-risk PCa (N = 58). For the first 12 weeks, patients were randomly assigned to LHRHa versus LHRHa plus AA. After a research prostate biopsy, all patients received 12 additional weeks of LHRHa plus AA followed by prostatectomy. RESULTS: The levels of intraprostatic androgens from 12-week prostate biopsies, including the primary end point (dihydrotestosterone/testosterone), were significantly lower (dehydroepiandrosterone, Δ(4)-androstene-3,17-dione, dihydrotestosterone, all P < .001; testosterone, P < .05) with LHRHa plus AA compared with LHRHa alone. Prostatectomy pathologic staging demonstrated a low incidence of complete responses and minimal residual disease, with residual T3- or lymph node-positive disease in the majority. CONCLUSION: LHRHa plus AA treatment suppresses tissue androgens more effectively than LHRHa alone. Intensive intratumoral androgen suppression with LHRHa plus AA before prostatectomy for localized high-risk PCa may reduce tumor burden.

Primary cilia are lost in preinvasive and invasive prostate cancer.

Prostate cancer is the second most commonly diagnosed cancer in men worldwide. Little is known about the role of primary cilia in preinvasive and invasive prostate cancer. However, reduced cilia expression has been observed in human cancers including pancreatic cancer, renal cell carcinoma, breast cancer, cholangiocarcinoma, and melanoma. The aim of this study was to characterize primary cilia expression in preinvasive and invasive human prostate cancer, and to investigate the correlation between primary cilia and the Wnt signaling pathway. Human prostate tissues representative of stages of prostate cancer formation (normal prostate, prostatic intraepithelial neoplasia (PIN), and invasive prostate cancer (including perineural invasion)) were stained for ciliary proteins. The frequency of primary cilia was determined. A decrease in the percentage of ciliated cells in PIN, invasive cancer and perineural invasion lesions was observed when compared to normal. Cilia lengths were also measured to indirectly test functionality. Cilia were shorter in PIN, cancer, and perineural invasion lesions, suggesting dysfunction. Primary cilia have been shown to suppress the Wnt pathway. Increased Wnt signaling has been implicated in prostate cancer. Therefore, we investigated a correlation between loss of primary cilia and increased Wnt signaling in normal prostate and in preinvasive and invasive prostate cancer. To investigate Wnt signaling in our cohort, serial tissue sections were stained for ß-catenin as a measure of Wnt signaling. Nuclear ß-catenin was analyzed and Wnt signaling was found to be higher in un-ciliated cells in the normal prostate, PIN, a subset of invasive cancers, and perineural invasion. Our results suggest that cilia normally function to suppress the Wnt signaling pathway in epithelial cells and that cilia loss may play a role in increased Wnt signaling in some prostate cancers. These results suggest that cilia are dysfunctional in human prostate cancer, and increase Wnt signaling occurs in a subset of cancers.

Response of the insulin-like growth factor (IGF) system to IGF-IR inhibition and androgen deprivation in a neoadjuvant prostate cancer trial: effects of obesity and androgen deprivation.

CONTEXT: Prostate cancer patients at increased risk for relapse after prostatectomy were treated in a neoadjuvant study with androgen deprivation therapy (ADT) in combination with cixutumumab, an inhibitory fully human monoclonal antibody against IGF receptor 1 (IGF-IR). OBJECTIVE: A clinical trial with prospective collection of serum and tissue was designed to test the potential clinical efficacy of neoadjuvant IGF-IR blockade combined with ADT in these patients. The effect of body mass index (BMI) on response of IGF-IR/insulin components to IGF-IR blockade was also examined. DESIGN: Eligibility for the trial required the presence of high-risk prostate adenocarcinoma. Treatment consisted of bicalutamide, goserelin, and cixutumumab for 13 weeks before prostatectomy. Here we report on an analysis of serum samples from 29 enrolled patients. Changes in IGF and glucose homeostasis pathways were compared to control samples from patients in a concurrent clinical trial of neoadjuvant ADT alone. RESULTS: Significant increases were seen in GH (P = .001), IGF-I (P < .0001), IGF-II (P = .003), IGF binding protein (IGFBP)-3 (P < .0001), C-peptide (P = .0038), and insulin (P = .05) compared to patients treated with ADT alone. IGFBP-1 levels were significantly lower in the cixutumumab plus ADT cohort (P = .001). No significant changes in blood glucose were evident. Patients with BMIs in the normal range had significantly higher GH (P < .05) and IGFBP-1 (P < 0.5) levels compared to overweight and obese patients. CONCLUSIONS: Patients with IGF-IR blockade in combination with ADT demonstrated significant changes in IGF and glucose homeostasis pathway factors compared to patients receiving ADT alone. In the patients receiving combination therapy, patients with normal BMI had serum levels of glucose homeostasis components similar to individuals in the ADT-alone cohort, whereas patients with overweight and obese BMIs had serum levels that differed from the ADT cohort.

The failure of a nerve sparing template to improve urinary continence after radical prostatectomy: attention to study design.

PURPOSE: To accurately assess the relationship between nerve sparing radical prostatectomy and urinary continence using an anonymous validated survey in men undergoing surgical treatment for prostate cancer. MATERIALS AND METHODS: From September 1999 to February 2006, men undergoing radical prostatectomy (RP) by one surgeon were given the UCLA Prostate Cancer Index to complete preop, and then annually thereafter to 2 years. We have 285 men who have completed the pre-op and year 1 and /or year 2 surveys. Continence was defined as requiring "no pads" on the survey. Analysis was based on attempted nerve sparing status of the surgery; none, unilateral, or bilateral. Subgroup analysis was then performed on successful nerve sparing surgery, defined as men responding they have an erection "firm enough for intercourse." RESULTS: Overall continence rates were 81% at year 1 and 87% at year 2. Attempted nerve sparing surgery, or successful nerve sparing surgery, did not result in better rates of continence than non-nerve sparing surgery. CONCLUSIONS: Using a validated survey with anonymous data collection, we found no improvement in continence, defined as pad-free, with attempted or successful nerve sparing RP. Based on our study, the goal of improving urinary outcomes should not be used as a justification for a nerve sparing template at radical prostatectomy.

Coccidioidomycosis of the prostate: a determination of incidence, report of 4 cases, and treatment recommendations.

OBJECTIVE: To describe the incidence of Coccidioides immitis infection of the prostate gland in an endemic area, to describe four new cases discovered, and to propose treatment recommendations for this diagnosis. METHODS: The pathology reports of all prostate tissue specimens collected at the Arizona Health Sciences Center from February 1, 1994 through January 1, 2000 and the Southern Arizona Veterans' Affairs Health Care System from January 1, 1990 through January 1, 2000 were reviewed. RESULTS: A total of 3676 pathology reports were reviewed. Forty-four cases of granulomatous prostatitis were identified (incidence=1.2%). Among these, four cases of C. immitis prostatitis were identified (incidence of granulomatous prostatitis=10%; overall incidence=0.1%). Two cases were found at radical retropubic prostatectomy and two were found on prostate needle biopsy. Five months post-radical prostatectomy one man developed symptomatic coccidioidomycosis and died of complications despite treatment with amphotericin B. Another patient who underwent a radical retropubic prostatectomy was treated with oral fluconazole for 14 months immediately after surgery and had a good response. The remaining two patients received no anti-fungal therapy and are being observed. CONCLUSIONS: Coccidioidomycosis of the prostate is rare. However, when identified, the finding should not be ignored. Patients with symptomatic coccidioidomycosis require immediate anti-fungal therapy. When the diagnosis is an incidental finding and the patient does not manifest symptoms, the degree of tissue violation involved in making the diagnosis influences the need for treatment. Patients with minimal tissue violation (i.e. needle biopsy) can be observed whereas patients with more extensive tissue violation (i.e. prostatectomy) should receive anti-fungal therapy.