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Introduction: Obesity in prostate cancer survivors may increase mortality. Better characterization of this effect may allow better counseling on obesity as a targetable lifestyle factor to reduce mortality in prostate cancer survivors. The purpose of this study was to determine whether pre- and post-diagnostic obesity and weight change affect all-cause mortality, cardiovascular disease specific mortality, and prostate cancer specific mortality in patients with nonmetastatic prostate cancer., Patients and Methods: We performed a retrospective cohort analysis of 5,077 patients diagnosed with localized prostate cancer from 1997 to 2017 with median follow-up of 15.5 years. The Utah Population Database linked to the Utah Cancer Registry was used to identify patients at a variety of treatment centers., Results: Pre-diagnosis obesity was associated with a 62% increased risk of cardiovascular disease specific mortality and a 34% increased risk of all-cause mortality (HR 1.62, 95% CI 1.05-2.50; HR 1.34, 95% CI 1.07-1.67, respectively). Post-diagnosis obesity increased the risk of cardiovascular disease specific mortality (HR 1.83, 95% CI 1.31-2.56) and all-cause mortality (HR 1.37, 95% CI 1.16-1.64) relative to non-obese men. We found no association between pre-diagnostic obesity or post-diagnostic weight gain and prostate cancer specific mortality., Conclusion: Our study strengthens the conclusion that pre-, post-diagnostic obesity and weight gain increase cardiovascular disease and all-cause mortality but not prostate cancer specific mortality compared to healthy weight men. An increased emphasis on weight management may improve mortality for prostate cancer survivors who are obese., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Maximum tumor diameter (MTD) on pretreatment magnetic resonance imaging (MRI) has the potential to further risk stratify for men with prostate cancer (PCa) prior to definitive local therapy. We aim to evaluate the prognostic impact of radiographic maximum tumor diameter (MTD) in men with localized prostate cancer., Patients and Methods: From a single-center retrospective cohort of men receiving definitive treatment for PCa (radical prostatectomy [RP] or radiotherapy [RT]) with available pretreatment MRI, we conducted univariable and multivariable Cox proportional-hazards models for progression using clinical variables including age, NCCN risk group, radiographic extracapsular extension (ECE), radiographic seminal vesical invasion (SVI), and MTD. RP and RT cohorts were analyzed separately. Covariates were used in a classification and regression tree (CART) analysis and progression-free survival was estimated with the Kaplan-Meier method and groups were compared using log-rank tests., Results: The cohort included 631 patients (n = 428 RP, n = 203 RT). CART analysis identified 4 prognostic groups for patients treated with RP and 2 prognostic groups in those treated with RT. In the RP cohort, NCCN low/intermediate risk group patients with MTD>=15 mm had significantly worse PFS than those with MTD <= 14 mm, and NCCN high-risk patients with radiographic ECE had significantly worse PFS than those without ECE. In the RT cohort, PFS was significantly worse in the cohort with MTD >= 23 mm than those <= 22 mm., Conclusion: Radiographic MTD may be a useful prognostic factor for patients with locoregional prostate cancer. This is the first study to illustrate that the importance of pretreatment tumor size may vary based on treatment modality., (Copyright © 2022. Published by Elsevier Inc.)

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., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: To evaluate various Prostate-Specific Antigen (PSA) thresholds at which a 18 F-fluciclovine PET scan could be considered in the setting of biochemical recurrent prostate cancer after definitive treatment., Methods: We analyzed available records of men who underwent a 18 F-fluciclovine PET scan after definitive therapy at a single academic institution between November 2016 to May 2018. The primary outcome was the rate of positive imaging findings at specific PSA thresholds. We then employed empiric strategies including a ROC curve and decision curve analysis to identify a specific threshold for which obtaining a positive result would be optimized., Results: A total of 115 men underwent imaging with 18 F-fluciclovine PET. No concerning lesions were identified in 25 (21.7%) patients, 32 (27.8%) had a solitary lesion identified, 45 (39.1%) had 2 to 5 lesions, and 13 (11.3%) had greater than 5 suspicious lesions identified. At PSA thresholds of less than 0.5, 0.5 to 2.0, and greater than 2, lesions were detected in 55.5% (12/22), 70.6% (24/34), and 91.5% (54/59) of patients respectively [P < 0.001]. Our ROC analysis yielded a PSA threshold of 2.10 while our decision curve analysis provided a PSA cutoff of 1.38., Conclusion: This study constitutes an early single institution series evaluating the use of 18 F-fluciclovine PET scans in the assessment of biochemically recurrent prostate cancer after definitive treatment. The probability of having positive imaging findings and increasing numbers of suspicious lesions rises with increasing PSA. Utilization of a lower PSA threshold of 0.5 may allow earlier intervention with salvage therapies in biochemical recurrence. However, using a threshold below 1 carries a higher risk of negative scans. Employing a higher PSA threshold of 1 to 2 carries greater sensitivity and specificity and may maximize identifying individuals with early BCR who may benefit from early intervention, while minimizing negative scans., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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.

Lessons Learned: Pazopanib was not effective in altering the premetastatic niche in the neoadjuvant setting.Pazopanib was safe and well tolerated without any new safety signals., Background: Vascular endothelial growth factor receptor 1 (VEGFR1) expressing myeloid-derived suppressor cells (VEGFR1+ MDSCs) potentially foster metastases by establishing a premetastatic niche. In a preclinical study, VEGFR1+ clustering in lymph nodes (LNs) independently predicted time to biochemical recurrence (TTBR) in localized prostate cancer [1]. The hypothesis was that neoadjuvant pazopanib therapy will decrease VEGFR1+ clusters in pelvic lymph nodes and improve outcomes., Methods: This is a phase II trial (NCT01832259) of neoadjuvant pazopanib 800 mg versus placebo daily for 4 weeks in high-risk localized prostate cancer. The primary endpoint was a decrease in VEGFR1+ MDSC clustering assessed by immunohistochemistry (IHC) analysis. Secondary endpoints were safety, feasibility, and TTBR., Results: Thirty patients were randomized to pazopanib versus placebo, with 15 patients randomized to each arm. Demographic and disease characteristics were similar in both arms. There was no difference in the VEGFR1+ clustering between the treatment arms (p = .345). Neoadjuvant therapy with pazopanib was well tolerated, and surgical complications were similar in both arms., Conclusion: Neoadjuvant pazopanib therapy did not alter the premetastatic niche; however, treatment targeting vascular endothelial growth factor (VEGF) in the preoperative period was safe and feasible, which may open up the avenue to investigate novel combinatorial regimens, including a VEGF inhibitor in combination with immune checkpoint inhibitor in this setting., (© AlphaMed Press; the data published online to support this summary is the property of the authors.)

Background: The strong association between family history and prostate cancer (PCa) suggests a significant genetic contribution, yet specific highly penetrant PCa susceptibility genes have not been identified. Certain single-nucleotide-polymorphisms have been found to correlate with PCa risk; however uncertainty remains regarding their clinical utility and how to best incorporate this information into clinical decision-making. Genetic testing is available directly to consumers and both patients and healthcare providers are becoming more aware of this technology. Purchasing online allows patients to bypass their healthcare provider yet patients may have difficulty interpreting test results and providers may be called upon to interpret results. Determining optimal ways to educate both patients and providers, and strategies for appropriately incorporating this information into clinical decision-making are needed., Methods: A mixed-method study was conducted in Utah between October 2011 and December 2011. Eleven focus group discussions were held and surveys were administered to 23 first-degree relatives of PCa patients living in Utah and 24 primary-care physicians and urologists practicing in Utah to present specific information about these assessments and determine knowledge and attitudes regarding health implications of using these assessments., Results: Data was independently coded by two researchers (relative Kappa = .88; provider Kappa = .77) and analyzed using a grounded theory approach. Results indicated differences in attitudes and behavioral intentions between patient and provider. Despite the test's limitations relatives indicated interest in genetic testing (52%) while most providers indicated they would not recommend the test for their patients (79%). Relatives expected providers to interpret genetic test results and use results to provide personalized healthcare recommendations while the majority of providers did not think the information would be useful in patient care (92%) and indicated low-levels of genetic self-efficacy., Conclusions: Although similarities exist, discordance between provider and patient attitudes may influence the effective translation of novel genomic tests into clinical practice suggesting both patient and provider perceptions and expectations be considered in development of clinical decision-support tools.

Purpose: We assessed variation among surgeons in patient quality of life outcomes., Materials and Methods: A survey of standard questions used to examine current urinary and sexual function was mailed to 1,500 randomly selected patients from the Utah Cancer Registry who met certain criteria, including prostatectomy for cancer cure more than 1 year previously, current age 70 years or less and no metastatic disease or other cancer therapy. Questionnaire information was linked to cancer registry and hospital discharge abstract information. Hierarchical mixed models were used to examine whether surgeons varied with respect to risk adjusted outcomes., Results: The cooperation rate was 64%. Of the 678 qualifying responders 22% reported leaking urine more than once per day, 7% used more than 1 pad per day and 40% reported no erection without medication. Surgeon variation was significant for 3 patient outcomes, including erectile strength, urine leakage and length of hospital stay (each p <0.001). Surgeon risk adjusted erectile outcomes significantly correlated with leakage outcomes (r = 0.84, p <0.0001) and length of stay (r = -0.55, p = 0.0004). Annual surgeon volume significantly correlated with less leakage and shorter length of stay (r = 0.34 and -0.36, respectively, each p = 0.05). Compared to open retropubic surgery, robotic surgery was associated with a shorter stay. The perineal approach was associated with shorter stay, less urine leakage and weaker erection., Conclusions: Patient quality of life outcomes after prostatectomy varies substantially among surgeons. Administering patient surveys through cancer registries may provide valuable data for improving prostatectomy outcomes statewide., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)