Describing the Spectrum of Patient Reported Outcomes after Radical Prostatectomy: Providing Information to Improve Patient Counseling and Shared Decision Making.

PURPOSE: Preoperative counseling incorporating the best case, the worst case and the most likely outcome scenarios aid patient decision making. This information is not readily available for prostate cancer counseling because most patient reported outcomes are presented as averages, which minimize individual patient experiences. Using the EPIC (Expanded Prostate Index Composite) we present data to characterize the best case and the worst case after prostatectomy. MATERIALS AND METHODS: The EPIC bowel, urinary irritation, continence and sexual function scores were measured in 1,418 men stratified by baseline function who underwent prostatectomy. Patient level functional trajectories were modeled using a Bayesian hierarchical model. The 5-year best and worst case outcomes were defined as the upper 95th and the lower 5th percentiles, respectively. RESULTS: Five years after surgery in patients with good baseline urinary continence the best case was a score of 100.0 (95% credible interval 100.0-100.0) and the worst case was 54.4 (95% credible interval 42.2-63.7). Among men with good baseline sexual function who underwent nerve sparing surgery the best case was 83.9 points (95% credible interval 74.1-93.1) and the worst case was 17.6 (95% credible interval 7.5-26.1). The differences between best and worst case for bowel and urinary irritation were relatively small (11.4 and 13.6 points, respectively). CONCLUSIONS: Prostatectomy exerted a minimal negative impact on urinary irritation and bowel function with minimal variability. There was a larger range in patient experience for urinary continence and sexual function with most patients experiencing a significant functional decline. Future studies of best and worst case outcomes of multiple treatment modalities may provide valuable information for shared decision making in prostate cancer treatment.

Relative Risks for Lethal Prostate Cancer Based on Complete Family History of Prostate Cancer Death.

BACKGROUND: There are few published familial relative risks (RR) for lethal prostate cancer. This study estimates RRs for lethal prostate cancer based on comprehensive family history data, with the goal of improving identification of those men at highest risk of dying from prostate cancer. METHODS: We used a population-based genealogical resource linked to a statewide electronic SEER cancer registry and death certificates to estimate relative risks (RR) for death from prostate cancer based upon family history. Over 600,000 male probands were analyzed, representing a variety of family history constellations of lethal prostate cancer. RR estimates were based on the ratio of the observed to the expected number of lethal prostate cancer cases using internal rates. RESULTS: RRs for lethal prostate cancer based on the number of affected first-degree relatives (FDR) ranged from 2.49 (95% CI: 2.27, 2.73) for exactly 1 FDR to 5.30 (2.13, 10.93) for ≥3 affected FDRs. In an absence of affected FDRs, increased risk was also significant for increasing numbers of affected second-degree or third degree relatives. Equivalent risks were observed for similar maternal and paternal family history. CONCLUSIONS: This study provides population-based estimates of lethal prostate cancer risk based on lethal prostate cancer family history. Many family history constellations associated with two to greater than five times increased risk for lethal prostate cancer were identified. These lethal prostate cancer risk estimates hold potential for use in identification, screening, early diagnosis, and treatment of men at high risk for death from prostate cancer. Prostate77:41-48, 2017. © 2016 Wiley Periodicals, Inc.

Genome-wide association of familial prostate cancer cases identifies evidence for a rare segregating haplotype at 8q24.21.

Previous genome-wide association studies (GWAS) of prostate cancer risk focused on cases unselected for family history and have reported over 100 significant associations. The International Consortium for Prostate Cancer Genetics (ICPCG) has now performed a GWAS of 2511 (unrelated) familial prostate cancer cases and 1382 unaffected controls from 12 member sites. All samples were genotyped on the Illumina 5M+exome single nucleotide polymorphism (SNP) platform. The GWAS identified a significant evidence for association for SNPs in six regions previously associated with prostate cancer in population-based cohorts, including 3q26.2, 6q25.3, 8q24.21, 10q11.23, 11q13.3, and 17q12. Of note, SNP rs138042437 (p = 1.7e(-8)) at 8q24.21 achieved a large estimated effect size in this cohort (odds ratio = 13.3). 116 previously sampled affected relatives of 62 risk-allele carriers from the GWAS cohort were genotyped for this SNP, identifying 78 additional affected carriers in 62 pedigrees. A test for an excess number of affected carriers among relatives exhibited strong evidence for co-segregation of the variant with disease (p = 8.5e(-11)). The majority (92 %) of risk-allele carriers at rs138042437 had a consistent estimated haplotype spanning approximately 100 kb of 8q24.21 that contained the minor alleles of three rare SNPs (dosage minor allele frequencies <1.7 %), rs183373024 (PRNCR1), previously associated SNP rs188140481, and rs138042437 (CASC19). Strong evidence for co-segregation of a SNP on the haplotype further characterizes the haplotype as a prostate cancer predisposition locus.

Inherited Variants in SULT1E1 and Response to Abiraterone Acetate by Men with Metastatic Castration Refractory Prostate Cancer.

PURPOSE: Germline variations in genes involved in androgen biosynthesis and metabolic pathways may predict the response to abiraterone acetate in men with metastatic, castration refractory prostate cancer. The variations may serve as prognostic and predictive biomarkers to allow for more individualized therapy. MATERIALS AND METHODS: We evaluated 832 single nucleotide polymorphisms from the OmniExpress genotyping platform (Illumina®) in the boundaries of 61 candidate genes reported to be involved in the androgen metabolic pathway. The purpose was to investigate them for an association with time to treatment failure in 68 white men with metastatic, castration refractory prostate cancer undergoing treatment with abiraterone acetate. Cox proportional hazard analysis was used with Gleason score, age, level of alkaline phosphatase and prostate specific antigen at treatment initiation as covariates. Each single nucleotide polymorphism was assessed using an allele carriage genetic model in which carriage of 1 or more minor alleles contributes to increased risk. Subset analyses were done to determine whether metastasis site, or prior treatment with ketoconazole or docetaxel would interact with the single nucleotide polymorphisms investigated. RESULTS: Six single nucleotide polymorphisms in the estrogen sulfotransferase gene SULT1E1 were associated with time to treatment failure on abiraterone acetate therapy after false discovery rate (q value) correction for multiple testing while controlling for Gleason score, age, level of alkaline phosphatase and prostate specific antigen at treatment initiation (q <0.05). CONCLUSIONS: Single nucleotide polymorphisms in SULT1E1 were significantly associated with time to treatment failure in men on abiraterone acetate therapy. The single nucleotide polymorphisms may serve as predictive markers for treatment with abiraterone acetate.

The Comparative Harms of Open and Robotic Prostatectomy in Population Based Samples.

PURPOSE: Robotic assisted radical prostatectomy has largely replaced open radical prostatectomy for the surgical management of prostate cancer despite conflicting evidence of superiority with respect to disease control or functional sequelae. Using population cohort data, in this study we examined sexual and urinary function in men undergoing open radical prostatectomy vs those undergoing robotic assisted radical prostatectomy. MATERIALS AND METHODS: Subjects surgically treated for prostate cancer were selected from 2 large population based prospective cohort studies, the Prostate Cancer Outcomes Study (enrolled 1994 to 1995) and the Comparative Effectiveness Analysis of Surgery and Radiation (enrolled 2011 to 2012). Subjects completed baseline, 6-month and 12-month standardized patient reported outcome measures. Main outcomes were between-group differences in functional outcome scores at 6 and 12 months using linear regression, and adjusting for baseline function, sociodemographic and clinical characteristics. Sensitivity analyses were used to evaluate outcomes between patients undergoing open radical prostatectomy and robotic assisted radical prostatectomy within and across CEASAR and PCOS. RESULTS: The combined cohort consisted of 2,438 men, 1,505 of whom underwent open radical prostatectomy and 933 of whom underwent robotic assisted radical prostatectomy. Men treated with robotic assisted radical prostatectomy reported better urinary function at 6 months (mean difference 3.77 points, 95% CI 1.09-6.44) but not at 12 months (1.19, -1.32-3.71). Subjects treated with robotic assisted radical prostatectomy also reported superior sexual function at 6 months (8.31, 6.02-10.56) and at 12 months (7.64, 5.25-10.03). Sensitivity analyses largely supported the sexual function findings with inconsistent support for urinary function results. CONCLUSIONS: This population based study reveals that men undergoing robotic assisted radical prostatectomy likely experience less decline in early urinary continence and sexual function than those undergoing open radical prostatectomy. The clinical meaning of these differences is uncertain and longer followup will be required to establish whether these benefits are durable.

Prostate cancer risk prediction based on complete prostate cancer family history.

BACKGROUND: Prostate cancer (PC) relative risks (RRs) are typically estimated based on status of close relatives or presence of any affected relatives. This study provides RR estimates using extensive and specific PC family history. METHODS: A retrospective population-based study was undertaken to estimate RRs for PC based on complete family history of PC. A total of 635,443 males, all with ancestral genealogy data, were analyzed. RRs for PC were determined based upon PC rates estimated from males with no PC family history (without PC in first, second, or third degree relatives). RRs were determined for a variety of constellations, for example, number of first through third degree relatives; named (grandfather, father, uncle, cousins, brothers); maternal, paternal relationships, and age of onset. RESULTS: In the 635,443 males analyzed, 18,105 had PC. First-degree RRs ranged from 2.46 (=1 first-degree relative affected, CI = 2.39-2.53) to 7.65 (=4 first-degree relatives affected, CI = 6.28-9.23). Second-degree RRs for probands with 0 affected first-degree relatives ranged from 1.51 (≥1 second-degree relative affected, CI = 1.47-1.56) to 3.09 (≥5 second-degree relatives affected, CI = 2.32-4.03). Third-degree RRs with 0 affected first- and 0 affected second-degree relatives ranged from 1.15 (≥1 affected third-degree relative, CI = 1.12-1.19) to 1.50 (≥5 affected third-degree relatives, CI = 1.35-1.66). RRs based on age at diagnosis were higher for earlier age at diagnoses; for example, RR = 5.54 for ≥1 first-degree relative diagnosed before age 50 years (CI = 1.12-1.19) and RR = 1.78 for >1 second-degree relative diagnosed before age 50 years, CI = 1.33, 2.33. RRs for equivalent maternal versus paternal family history were not significantly different. CONCLUSIONS: A more complete PC family history using close and distant relatives and age at diagnosis results in a wider range of estimates of individual RR that are potentially more accurate than RRs estimated from summary family history. The presence of PC in second- and even third-degree relatives contributes significantly to risk. Maternal family history is just as significant as paternal family history. PC RRs based on a proband's complete constellation of affected relatives will allow patients and care providers to make more informed screening, monitoring, and treatment decisions.

Identification of specific Y chromosomes associated with increased prostate cancer risk.

BACKGROUND: Evidence supports the possibility of a role of the Y chromosome in prostate cancer, but controversy exists. METHODS: A novel analysis of a computerized population-based resource linking genealogy and cancer data was used to test the hypothesis of a role of the Y chromosome in prostate cancer predisposition. Using a statewide cancer registry from 1966 linked to a computerized genealogy representing over 1.2 million descendants of the Utah pioneers, 1,000 independent sets of males, each set hypothesized to share the same Y chromosome as represented in genealogy data, were tested for a significant excess of prostate cancer. RESULTS: Multiple Y chromosomes representing thousands of potentially at-risk males were identified to have a significant excess risk for prostate cancer. CONCLUSIONS: This powerful and efficient in silico test of an uncommon mode of inheritance has confirmed evidence for Y chromosome involvement in prostate cancer.

Climacturia after definitive treatment of prostate cancer.

PURPOSE: Prostate cancer treatment results in several sexually related side effects beyond the well studied erectile dysfunction. Climacturia (leakage of urine during orgasm) has been reported after prostatectomy but studies have been limited by multiple factors. In this study we examine the prevalence, causes and impact on orgasm function of climacturia after definitive treatment of prostate cancer with surgery or radiation. MATERIALS AND METHODS: A total of 906 anonymous surveys were sent to patients with prostate cancer treated with surgery and/or radiation. Respondents were asked about the presence of urinary leakage, climacturia and various elements related to sexual and orgasmic function. We estimated the prevalence of climacturia, evaluated the differences between those with and without climacturia, and assessed the impact of climacturia on orgasmic function. RESULTS: Overall 412 surveys were returned and available for analysis, and of these respondents 75.2% were sexually active or experiencing orgasms. Climacturia was reported by 22.6% of these respondents, and by 28.3%, 5.2% and 28.6% of those treated with surgery, radiation, or both, respectively (p <0.001). The use of aides to obtain an erection (OR 2.24, 95% CI 1.08-4.93, p = 0.035) and the presence of urinary incontinence (OR 3.09, 95% CI 1.66-5.88, p <0.001) were also associated with climacturia in a multivariate logistic regression model. Climacturia had no significant impact on orgasmic function and satisfaction. CONCLUSIONS: Climacturia is experienced by a substantial proportion of men after undergoing definitive treatment of prostate cancer. We found a complex relationship between stress urinary incontinence and climacturia, and noted that the presence of climacturia does not necessarily negatively impact sexual satisfaction.

Contemporary open and robotic radical prostatectomy practice patterns among urologists in the United States.

PURPOSE: We describe current trends in robotic and open radical prostatectomy in the United States after examining case logs for American Board of Urology certification. MATERIALS AND METHODS: American urologists submit case logs for initial board certification and recertification. We analyzed logs from 2004 to 2010 for trends and used logistic regression to assess the impact of urologist age on robotic radical prostatectomy use. RESULTS: A total of 4,709 urologists submitted case logs for certification between 2004 and 2010. Of these logs 3,374 included 1 or more radical prostatectomy cases. Of the urologists 2,413 (72%) reported performing open radical prostatectomy only while 961 (28%) reported 1 or more robotic radical prostatectomies and 308 (9%) reported robotic radical prostatectomy only. During this 7-year period we observed a large increase in the number of urologists who performed robotic radical prostatectomy and a smaller corresponding decrease in those who performed open radical prostatectomy. Only 8% of patients were treated with robotic radical prostatectomy by urologists who were certified in 2004 while 67% underwent that procedure in 2010. Median age of urologists who exclusively performed open radical prostatectomy was 43 years (IQR 38-51) vs 41 (IQR 35-46) for those who performed only robotic radical prostatectomy. CONCLUSIONS: While the rate was not as high as the greater than 85% industry estimate, 67% of radical prostatectomies were done robotically among urologists who underwent board certification or recertification in 2010. Total radical prostatectomy volume almost doubled during the study period. These data provide nonindustry based estimates of current radical prostatectomy practice patterns and further our understanding of the evolving surgical treatment of prostate cancer.

Metastasis, Mortality, and Quality of Life for Men With NCCN High and Very High Risk Localized Prostate Cancer After Surgical and/or Combined Modality Radiotherapy.

PURPOSE: To compare metastasis-free survival, overall survival, and patient-reported quality of life (QOL) of men with National Comprehensive Cancer Network high or very high risk prostate cancer after definitive surgery and/or multimodal radiotherapy (RT). PATIENTS AND METHODS: We studied a retrospective cohort study of 586 patients treated between the years 2000 and 2017 receiving radical prostatectomy with or without postoperative RT, external-beam RT (EBRT) with androgen deprivation therapy (ADT), or EBRT plus brachytherapy (Brachy) boost + ADT. Patient-reported QOL for urinary, bowel, sexual, and overall physical and mental functioning was assessed using the American Urological Association symptom scale, the Sexual Health Inventory in Men, the Rectal-Function Assessment Scale, the Expanded Prostate Cancer Index Composite, and the Veterans RAND 12-Item Health Survey. RESULTS: Median follow-up for survival was 5 years. No significant differences between the treatments were observed for overall survival or metastasis-free survival at the P < .05 threshold. The propensity-adjusted 5-year metastasis-free survival estimates for EBRT + ADT, EBRT + Brachy + ADT, and surgery were 74.6%, 94.8%, and 83.1%, respectively. The EBRT + Brachy + ADT and surgery cohorts had significantly worse mean American Urological Association symptom scores at 6 months than the EBRT + ADT cohort, which resolved by 1 year. Surgical patients had better rectal function scores than EBRT + ADT patients at years 1 to 3, but similar function thereafter. Adjuvant or salvage RT resulted in significant declines in various Expanded Prostate Cancer Index Composite urinary, sexual, and bowel domains, and Veterans RAND 12-Item Health Survey physical but not mental domains. CONCLUSION: Men with very and/or high-risk localized prostate cancer are likely to require multimodal therapy. The overall differences in survival and long-term QOL are similar for men choosing surgical versus RT pathways.

Germline Variant in SLCO2B1 and Response to Abiraterone Acetate Plus Prednisone (AA) in New-onset Metastatic Castration-resistant Prostate Cancer (mCRPC).

There are many treatment options available for men with metastatic castration-resistant prostate cancer (mCRPC). Yet, biomarkers predictive of differential response to treatment are currently unavailable. A recent translational study suggested that SLCO2B1 genotype could predict response to abiraterone acetate for men with advanced prostate cancer. Here, we investigate whether germline variants in SLCO2B1 are predictive of response to first-line abiraterone acetate in men with new mCRPC. Clinical data and samples were analyzed from a prospective prostate cancer registry at the University of Utah (Salt Lake City, UT). Genotyping was performed using the Illumina OmniExpress genotyping platform. Primary endpoint was progression-free survival (PFS) on first-line abiraterone acetate in men with mCRPC. We performed a prespecified multivariate Cox regression analysis to assess the independent predictive value of rs12422149 and rs1789693 on PFS on abiraterone acetate. Of 401 men with advanced prostate cancer genotyped, 323 were homozygous wild-type for rs12422149 (80.5%), 74 were heterozygous (18.5%), and 4 were homozygous variant (1.0%). In a multivariate analysis of 79 men treated with first-line abiraterone acetate for mCRPC, men heterozygous for rs12422149 had significantly improved median PFS compared with the homozygous wild-type group (8.9 months vs. 6.3 months; HR, 0.46; 95% confidence interval, 0.23-0.94; P = 0.03). No significant difference in median PFS was seen by rs1789693 genotype. In this first clinical validation of translational data reported by Mostaghel and colleagues, germline variant alleles in rs12422149 of SLCO2B1 are common and predict improved response to first-line abiraterone acetate in men with mCRPC.

5-year urinary and sexual outcomes after radical prostatectomy: results from the Prostate Cancer Outcomes Study.

PURPOSE: Prior studies of postoperative outcomes following radical prostatectomy have been limited by selection bias and short-term followup. In this study we assessed temporal changes in urinary and sexual function up to 5 years following radical prostatectomy in a population based cohort. MATERIALS AND METHODS: A sample of 1,288 men with localized prostate cancer who underwent radical prostatectomy and completed a baseline survey within 6 to 12 months of diagnosis were included in the analysis. Two and 5-year functional and quality of life data were collected, as was information on the use of erectile aids. Temporal functional changes and potentially confounding or modifying factors were assessed using longitudinal regression models. RESULTS: Of these men 14% reported frequent urinary leakage or no urinary control 60 months after diagnosis, which was slightly higher than the 10% reporting incontinence at 24 months (p = 0.007). At 60 months 28% of the men had erections firm enough for intercourse compared with 22% at 24 months (p = 0.003). Sildenafil was the most commonly used erectile aid (43% ever used) and 45% of users reported that it helped "somewhat" or "a lot." CONCLUSIONS: Urinary and sexual dysfunction were common 5 years following radical prostatectomy in this large, community based cohort of prostate cancer survivors. While a small minority of subjects experienced changes in urinary or sexual function between years 2 and 5 after prostatectomy, functional outcomes remained relatively stable in the majority of participants.

Risk stratification for positive lymph nodes in prostate cancer.

PURPOSE: To evaluate the risk of positive lymph nodes using preoperative clinical parameters. METHODS AND MATERIALS: We reviewed our prospectively collected database for all patients who received RRP and PLND between January 1993 and November 2005 as primary therapy for prostate cancer. We excluded patients who had hormonal ablation or radiation therapy prior to surgery and patients with missing PSA, clinical stage, or biopsy Gleason score. We evaluated risk for nodal disease using the following definitions: low risk: PSA or=T(2b), or Gleason score of 7; and high risk: PSA >or=20 ng/mL, or clinical stage >or=T(2c), or Gleason score >or=8. Logistic regression was used to determine the association between the risk groups and pathologic lymph node involvement, and a receiver operating characteristics (ROC) curve was constructed to evaluate the performance of the stratification scheme in detecting nodal disease. RESULTS: A total of 760 patients with 43 (5.7%) patients with node-positive disease were available for analysis. Risk classification was significantly associated with positive nodes (P<0.001), even after controlling for year of surgery and age. The area under the ROC curve was 0.77 (95% CI: 0.69, 0.83). Omitting PLND in the low-risk group would have spared 368 (49.2%) of the entire cohort with a false-negative rate of 5/369 (1.3%) for the low-risk group, and 5/760 (0.7%) for the entire cohort. Sensitivity was 88.4%, and negative predictive value was 98.7%. CONCLUSION: Patients can be risk stratified for node-positive disease and potentially excluded from lymphadenectomy with minimal risk.

Quality of Life Following Prostatectomy as a Function of Surgery Type and Degree of Nerve Sparing.

OBJECTIVES: To compare robotic-assisted laparoscopic prostatectomy with conventional retropubic radical prostatectomy in maintaining pre-surgery levels of urinary and sexual functioning and to evaluate the efficacy of nerve sparing in prostatectomies in protecting urinary functioning. MATERIAL AND METHODS: Patients (n = 385) receiving both surgical procedures were surveyed prior to surgery. Multiple measures, including the Expanded Prostate Cancer Index Composite, the Sexual Health Inventory for Men, and the International Prostate Symptom Score, assessed sexual and urinary function at an average of 12 months post-surgery. RESULTS: Across multiple measures, while controlling for pre-surgical sexual functioning, robotic-assisted surgery did not offer an advantage in maintaining sexual or urinary function an average of a year following the prostatectomy. Bilateral nerve sparing offered a strong and reliable advantage in the maintenance of sexual function, but not so regarding urinary function. CONCLUSION: While robotic-assisted prostatectomies may offer a number of medical advantages over open procedures, we found no significant effect on important quality of life outcomes associated with the technique.

Quality of life following localized prostate cancer treated initially with androgen deprivation therapy or no therapy.

BACKGROUND: Many men diagnosed with clinically localized prostate cancer are initially treated conservatively, receiving neither surgery nor radiotherapy for the first year. Treatment patterns and quality-of-life outcomes have not been previously reported for a population-based sample of such men. METHODS: A population-based random sample of men (n = 661) from six geographic regions who had been newly diagnosed with clinically localized prostate cancer from 1994 through 1995 were followed for up to 1 year. Eligible subjects received neither surgery nor radiotherapy within 1 year of initial diagnosis. We assessed disease-specific and generic quality-of-life outcomes in men receiving androgen deprivation therapy (ADT) compared with men receiving no therapy. All statistical tests were two-sided. RESULTS: Two hundred and forty-five study patients received ADT and the remaining 416 patients received no therapy. Approximately two thirds of the patients (n = 159) receiving ADT had either baseline Gleason scores greater than six or serum prostate-specific antigen values above 20 ng/mL. Among men who were sexually potent before diagnosis (ADT = 88 patients; no therapy = 223 patients), 80% of those on ADT reported being impotent after 1 year compared with 30% of those receiving no treatment (P < .001). Patients receiving ADT reported more physical discomfort 1 year after diagnosis than did men who had received no therapy. However, patients receiving ADT, compared with those receiving no therapy, were more likely to be satisfied with their treatment decision (56% pleased versus 45.3%; P =.001). Patients on ADT also experienced a statistically significant decline in vitality, but not in physical function, after adjustment for the confounding factors (P =.05). CONCLUSION: ADT is a commonly used primary therapy for clinically localized prostate cancer. Therefore, men considering ADT as an initial treatment should be aware that sexual function and some aspects of physical well-being are likely to be affected in the first year following this treatment.

General quality of life 2 years following treatment for prostate cancer: what influences outcomes? Results from the prostate cancer outcomes study.

PURPOSE: The goal of this study was to determine the relationship between primary treatment, urinary dysfunction, sexual dysfunction, and general health-related quality of life (HRQOL) in prostate cancer. METHODS: A sample of men with newly diagnosed prostate cancer between 1994 and 1995 was randomly selected from six population-based Surveillance, Epidemiology, and End Results registries. A baseline survey was completed by 2,306 men within 6 to 12 months of diagnosis, and these men also completed a follow-up HRQOL survey 2 years after diagnosis. Logistic regression models were used to determine whether primary treatment, urinary dysfunction, and sexual dysfunction were independently associated with general HRQOL outcomes approximately 2 years after diagnosis as measured by the Medical Outcomes Study 36-item Short Form Health Survey. The magnitude of this effect was estimated using least square means models. RESULTS: After adjustment for potential confounders, primary treatment was not associated with 2-year general HRQOL outcomes in men with prostate cancer. Urinary function and bother were independently associated with worse general HRQOL in all domains. Sexual function and bother were also independently associated with worse general HRQOL, although the relationship was not as strong as in the urinary domains. CONCLUSION: Primary treatment is not associated with 2-year general HRQOL outcomes in prostate cancer. Although both sexual and urinary function and bother are associated with quality of life, men who are more bothered by their urination or impotence are more likely to report worse quality of life. This implies that future research should be directed toward finding ways to improve treatment-related outcomes or help patients better cope with their posttreatment urinary or sexual dysfunction.

Multiple abnormalities detected by dye reversal genomic microarrays in prostate cancer: a much greater sensitivity than conventional cytogenetics.

Prostate cancer remains the most common male malignancy in Western countries, yet limited information exists regarding genetic changes and clinical correlations. The advent of comparative genomic hybridization microarray (GM) technology has recently allowed for precise screening of DNAs for genetic copy number changes; this offers an advantage over previous techniques, including conventional cytogenetics. A problem with cytogenetic prostate cancer analysis has been the study of the appropriate cell types because this is a highly heterogeneous tumor. We have performed GM using the Spectral Genomics Inc. dye reversal platform on 20 primary prostate tumors. These tumor samples were from frozen tissue collected over the last 10 years and multiple clinical parameters, including follow-up were collected on these patients; cytogenetic analysis was previously attempted on all patients. Eighty percent (16/20) of specimens showed copy number changes, 65% of which were losses and 35% were gains of genetic material. The most common changes observed were loss of an interstitial region of 2q (8 cases, 40%), followed by loss of interstitial 6q (6 cases, 30%), loss at 8p and 13q (5 cases each, 25%), gain at 3p and loss at 5q, 16q, and Xq (4 cases each, 20%), and gain at 8p (3 cases, 15%). There was evidence of correlation of loss at 5q with a positive node status. Cytogenetic studies on these same patients only detected clonal changes in 40% (8/20) specimens and did not detect the majority of abnormalities seen by the GM technique. We propose this technology for the evaluation of prostate and other heterogeneous cancers as a rapid and efficient way to detect genetic copy number changes.

Prostate cancer trends in the era of prostate-specific antigen. An update of incidence, mortality, and clinical factors from the SEER database.

Concurrent with the successful life-saving efforts in terms of prostate cancer diagnosis and treatment, some men who do not need treatment are receiving it. These are men destined to die of causes other than prostate cancer. Unfortunately, at diagnosis, men needing treatment for prostate cancer cannot be differentiated from men who do not. To make such decisions correctly for individual patients would require extremely precise measures of the time to death from prostate cancer versus when the patient would die from a competing cause. Predictive tools with this level of accuracy will never be available given the inherent uncertainty of life. At the time of prostate cancer diagnosis, the date and the cause of death for the patient are matters of weak statistical speculation. Unless the date of death from prostate cancer and the date of death from non-prostate cancer causes can be precisely determined for each patient, some men will always be overtreated or undertreated. Conservative strategies result in the undertreatment of some patients who would benefit from treatment while sparing other patients unneeded treatment. Aggressive strategies result in the overtreatment of patients who do not need therapy while curing other men of prostate cancer. Both strategies are correct, but only some of the time. Better methods of determining the length of life and cause of death may improve this situation, but not by much. [figure: see text] Dramatic shifts in the incidence, grade, stage, and age of men with prostate cancer have been observed with the advent of widespread PSA-based cancer detection in the United States. Grade and stage trends suggest that more biologically relevant (the shift from well-differentiated to moderately differentiated tumors) and yet therapeutically amenable (earlier stage) tumors have been identified in large numbers of patients during the PSA era. Clearly many men have been diagnosed and treated who will not benefit from such treatment. The relative mix of these two groups of men is not known. Given the long delay between treatment and mortality that is inherent in prostate cancer (Fig. 14), the full effects of treatment on prostate cancer mortality are probably not yet seen in prostate cancer mortality data.

Use of a polytetrafluoroethylene (GORE-TEX) bolster to close the renal parenchymal defect during open partial nephrectomy.

INTRODUCTION: Numerous surgical techniques have been described to facilitate closure of the renal parenchymal defect. We sought to describe the operative technique and define the safety and efficacy of using an expanded polytetrafluoroethylene (GORE-TEX; WL Gore and Associates, Flagstaff, AZ) bolster to aid in closure of the renal parenchymal defect at the time of open partial nephrectomy (OPN). TECHNICAL CONSIDERATIONS: A retrospective review of 175 patients who underwent an OPN using an expanded polytetrafluoroethylene (ePTFE) bolster at the Huntsman Cancer Hospital, University of Utah and Salt Lake City Veterans Affairs Medical Center from March 2005 to February 2013 was conducted. Postoperative complications occurring within 90 days were graded using the Clavien grading system. CONCLUSION: Overall, 57 patients (32.6%) experienced a postoperative complication. Fifteen patients (8.5%) had a Clavien ≥ grade-III complication. Ten patients (5.7%) received blood transfusions. Urine leak requiring intervention occurred in 2 patients (1.1%). Delayed hemorrhage requiring nephrectomy and pseudoaneurysm formation were rare, occurring in 1 patient each (0.6%). Infection of the ePTFE material occurred in 2 patients (1.1%). In both cases, it was explanted without requiring nephrectomy. The use of an ePTFE bolster is an effective and safe method of closing the renal parenchymal defect after OPN with an acceptable 90-day postoperative complication rate and a low risk of infection.

Activated lymphocyte recruitment into the tumor microenvironment following preoperative sipuleucel-T for localized prostate cancer.

BACKGROUND: Sipuleucel-T is a US Food and Drug Administration-approved immunotherapy for asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). Its mechanism of action is not fully understood. This prospective trial evaluated the direct immune effects of systemically administered sipuleucel-T on prostatic cancer tissue in the preoperative setting. METHODS: Patients with untreated localized prostate cancer were treated on an open-label Phase II study of sipuleucel-T prior to planned radical prostatectomy (RP). Immune infiltrates in RP specimens (posttreatment) and in paired pretreatment biopsies were evaluated by immunohistochemistry (IHC). Correlations between circulating immune response and IHC were assessed using Spearman rank order. RESULTS: Of the 42 enrolled patients, 37 were evaluable. Adverse events were primarily transient, mild-to-moderate and infusion related. Patients developed T cell proliferation and interferon-γ responses detectable in the blood following treatment. Furthermore, a greater-than-three-fold increase in infiltrating CD3(+), CD4(+) FOXP3(-), and CD8(+) T cells was observed in the RP tissues compared with the pretreatment biopsy (binomial proportions: all P < .001). This level of T cell infiltration was observed at the tumor interface, and was not seen in a control group consisting of 12 concurrent patients who did not receive any neoadjuvant treatment prior to RP. The majority of infiltrating T cells were PD-1(+) and Ki-67(+), consistent with activated T cells. Importantly, the magnitude of the circulating immune response did not directly correlate with T cell infiltration within the prostate based upon Spearman's rank order correlation. CONCLUSIONS: This study is the first to demonstrate a local immune effect from the administration of sipuleucel-T. Neoadjuvant sipuleucel-T elicits both a systemic antigen-specific T cell response and the recruitment of activated effector T cells into the prostate tumor microenvironment.