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Effects of nonlinear aerobic training on erectile dysfunction and cardiovascular function following radical prostatectomy for clinically localized prostate cancer.

ABSTRACT: Erectile dysfunction (ED) is a major adverse effect of radical prostatectomy (RP). We conducted a randomized controlled trial to examine the efficacy of aerobic training (AT) compared with usual care (UC) on ED prevalence in 50 men (n=25 per group) after RP. AT consisted of five walking sessions per week at 55-100% of peak oxygen uptake (VO2peak) for 30-60 min per session following a nonlinear prescription. The primary outcome was change in the prevalence of ED, as measured by the International Index of Erectile Function (IIEF), from baseline to 6 mo. Secondary outcomes were brachial artery flow-mediated dilation (FMD), VO2peak, cardiovascular (CV) risk profile (eg, lipid profile, body composition), and patient-reported outcomes (PROs). The prevalence of ED (IIEF score ? 21) decreased by 20% in the AT group and by 24% in the UC group (difference: p=0.406). There were no significant between-group differences in any erectile function subscale (p>0.05). Significant between-group differences were observed for changes in FMD and VO2peak, favoring AT. There were no group differences in other markers of CV risk profile or PROs. In summary, nonlinear AT does not improve ED in men with localized prostate cancer in the acute period following RP.Clinicaltrials.gov identifier NCT00620932.

SUBMITTER: Jones LW

PROVIDER: S-EPMC4089506 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Effects of nonlinear aerobic training on erectile dysfunction and cardiovascular function following radical prostatectomy for clinically localized prostate cancer.

Jones Lee W LW Hornsby Whitney E WE Freedland Stephen J SJ Lane Amy A West Miranda J MJ Moul Judd W JW Ferrandino Michael N MN Allen Jason D JD Kenjale Aarti A AA Thomas Samantha M SM Herndon James E JE Koontz Bridget F BF Chan June M JM Khouri Michel G MG Douglas Pamela S PS Eves Neil D ND

European urology 20131122 5

<h4>Unlabelled</h4>Erectile dysfunction (ED) is a major adverse effect of radical prostatectomy (RP). We conducted a randomized controlled trial to examine the efficacy of aerobic training (AT) compared with usual care (UC) on ED prevalence in 50 men (n=25 per group) after RP. AT consisted of five walking sessions per week at 55-100% of peak oxygen uptake (VO2peak) for 30-60 min per session following a nonlinear prescription. The primary outcome was change in the prevalence of ED, as measured by ...[more]

PMID: 24315706

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Project description:We have previously demonstrated a significant correlative relationship between PTEN deletion and ERG rearrangement, both in the development of clinically localized prostate cancers and metastases. Herein, we evaluate the cooperative role of ERG and PTEN in oncological outcomes after radical prostatectomy for clinically localized prostate cancer. We evaluated ERG and PTEN status using three previously described cohorts. The first cohort included 235 clinically localized prostate cancer cases represented on tissue microarrays (TMA), evaluated using previously validated FISH assays for ERG and PTEN. The second cohort included 167 cases of clinically localized prostate cancer on TMAs evaluated for PTEN by FISH, and for PTEN and ERG by dual IHC. The third cohort comprised 59 clinically localized prostate cancer cases assessed by array comparative genomic hybridization (aCGH). Kaplan-Meir plots and long rank tests were used to assess the association of ERG and PTEN status with biochemical recurrence after radical prostatectomy for clinically localized prostate cancer. Of the 317 cases eligible for analyses with evaluable ERG and PTEN status, 88 (27.8%) patients developed biochemical recurrence over a median follow-up of 5.7 years. Overall, 45% (142/317) of cases demonstrated ERG rearrangement and 20% (62/317) of cases demonstrated PTEN loss. Hemizygous and homozygous deletion of PTEN was seen in 10% (18/175) and 3% (5/175) of ERG-negative cases, respectively. In contrast, hemizygous and homozygous deletion of PTEN was seen in 11% (15/142) and 17% (24/123) of ERG-positive cases, respectively. PTEN loss (heterozygous or homozygous) was significantly associated with shorter time to biochemical recurrence compared to no PTEN loss (p < 0.001). However, ERG rearrangement versus no rearrangement was not associated with time to PSA recurrence (p = 0.15). Patients who exhibited ERG rearrangement and loss of PTEN had no significant difference in time to recurrence compared to patients with wild-type ERG and loss of PTEN (p = 0.30). Our findings confirm a mutual cooperative role of ERG and PTEN in the pathogenesis of prostate cancer, particularly for homozygous PTEN deletion. ERG did not stratify outcome either alone or in combination with PTEN in this cohort.

Project description:BackgroundThe effectiveness of surgery versus observation for men with localized prostate cancer detected by means of prostate-specific antigen (PSA) testing is not known.MethodsFrom November 1994 through January 2002, we randomly assigned 731 men with localized prostate cancer (mean age, 67 years; median PSA value, 7.8 ng per milliliter) to radical prostatectomy or observation and followed them through January 2010. The primary outcome was all-cause mortality; the secondary outcome was prostate-cancer mortality.ResultsDuring the median follow-up of 10.0 years, 171 of 364 men (47.0%) assigned to radical prostatectomy died, as compared with 183 of 367 (49.9%) assigned to observation (hazard ratio, 0.88; 95% confidence interval [CI], 0.71 to 1.08; P=0.22; absolute risk reduction, 2.9 percentage points). Among men assigned to radical prostatectomy, 21 (5.8%) died from prostate cancer or treatment, as compared with 31 men (8.4%) assigned to observation (hazard ratio, 0.63; 95% CI, 0.36 to 1.09; P=0.09; absolute risk reduction, 2.6 percentage points). The effect of treatment on all-cause and prostate-cancer mortality did not differ according to age, race, coexisting conditions, self-reported performance status, or histologic features of the tumor. Radical prostatectomy was associated with reduced all-cause mortality among men with a PSA value greater than 10 ng per milliliter (P=0.04 for interaction) and possibly among those with intermediate-risk or high-risk tumors (P=0.07 for interaction). Adverse events within 30 days after surgery occurred in 21.4% of men, including one death.ConclusionsAmong men with localized prostate cancer detected during the early era of PSA testing, radical prostatectomy did not significantly reduce all-cause or prostate-cancer mortality, as compared with observation, through at least 12 years of follow-up. Absolute differences were less than 3 percentage points. (Funded by the Department of Veterans Affairs Cooperative Studies Program and others; PIVOT ClinicalTrials.gov number, NCT00007644.).

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Project description:Prostate cancer (PC) is the most commonly diagnosed noncutaneous malignancy in American men. PC, which exhibits a slow growth rate and multiple potential target epitopes, is an ideal candidate for immunotherapy. GVAX for prostate cancer is a cellular immunotherapy, composed of PC-3 cells (CG1940) and LNCaP cells (CG8711). Each of the components is a prostate adenocarcinoma cell line that has been genetically modified to secrete granulocyte-macrophage colony-stimulating factor. Hypothesizing that GVAX for prostate cancer could be effective in a neoadjuvant setting in patients with locally advanced disease, we initiated a phase II trial of neoadjuvant docetaxel and GVAX. For the trial, the clinical effects of GVAX were assessed in patients undergoing radical prostatectomy (RP).Patients received docetaxel administered at a dose of 75 mg/m(2) every 3 weeks for 4 cycles. GVAX was administered 2-3 days after chemotherapy preoperatively for four courses of immunotherapy. The first dose of GVAX was a prime immunotherapy of 5×10(8) cells. The subsequent boost immunotherapies consisted of 3×10(8) cells. After RP, patients received an additional six courses of immunotherapy. Pathologic complete response, toxicity, and clinical response were assessed. The primary endpoint of the trial was a pathologic state of pT0, which is defined as no evidence of cancer in the prostate.Six patients completed neoadjuvant docetaxel and GVAX therapy. No serious drug-related adverse events were observed. Median change in prostate-specific antigen (PSA) following neoadjuvant therapy was 1.47 ng/ml. One patient did not undergo RP due to the discovery of positive lymph nodes during exploration. Of the five patients completing RP, four had a downstaging of their Gleason score. Undetectable PSA was achieved in three patients at 2 months after RP and in two patients at 3 years after RP.Neoadjuvant docetaxel/GVAX is safe and well tolerated in patients with high-risk locally advanced PC. No evidence of increased intraoperative hemorrhage or increased length of hospital stay postoperatively was noted. These results justify further study of neoadjuvant immunotherapy.

Dataset Information

Effects of nonlinear aerobic training on erectile dysfunction and cardiovascular function following radical prostatectomy for clinically localized prostate cancer.

Publications

Effects of nonlinear aerobic training on erectile dysfunction and cardiovascular function following radical prostatectomy for clinically localized prostate cancer.

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