Effects of omega-3 supplementation on psychological symptoms in men with prostate cancer: Secondary analysis of a double-blind placebo-controlled randomized trial.

BACKGROUND: In the general population, a higher omega-3 polyunsaturated fatty acids intake is associated with lower levels of several psychological symptoms, especially depression. However, the existing evidence in cancer is equivocal. METHODS: This phase IIB double-blind, placebo-controlled trial was aimed at comparing the effects of eicosapentaenoic acid monoacylglyceride (MAG-EPA) supplementation and high oleic acid sunflower oil (HOSO; placebo) on depression levels (primary outcome) and other symptoms (anxiety, fear of cancer recurrence, fatigue, insomnia, perceived cognitive impairments; secondary outcomes). Participants, recruited in a prostate cancer clinic, were randomized to MAG-EPA (3.75 g daily; n = 65) or HOSO (3.75 g daily; n = 65) for 1 year post-radical prostatectomy (RP), starting 4-10 weeks before surgery. Patients completed self-report scales at baseline (before RP) and 3, 6, 9, and 12 months after: Hospital Anxiety and Depression Scale (HADS), Fear of Cancer Recurrence Inventory (FCRI), Insomnia Severity Index (ISI), Fatigue Symptom Inventory (FSI), and Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog). RESULTS: Analyses showed significant reductions in HADS-depression, HADS-anxiety, FCRI, ISI, FSI-number of days, and FACT-Cog-impact scores over time. A significant group-by-time interaction was obtained on FACT-Cog-Impact scores only; yet, the temporal change was significant in HOSO patients only. CONCLUSIONS: Several symptoms significantly decreased over time, mainly within the first months of the study. However, MAG-EPA did not produce greater reductions than HOSO. Omega-3 supplementation does not seem to improve psychological symptoms of men treated with RP.

Effects of Concentrated Long-Chain Omega-3 Polyunsaturated Fatty Acid Supplementation on Quality of Life after Radical Prostatectomy: A Phase II Randomized Placebo-Controlled Trial (RCT-EPA).

Prostate cancer (PCa) and associated treatments incur symptoms that may impact patients' quality of life. Studies have shown beneficial relationships between diet, especially omega-3 fatty acids, and these symptoms. Unfortunately, only few data describing the relationship between long-chain omega-3 fatty acids (LCn3) and PCa-related symptoms in patients are available. The purpose of this study was to evaluate the effects of LCn3 supplementation on PCa-specific quality of life in 130 men treated by radical prostatectomy. Men were randomized to receive a daily dose of either 3.75 g of fish oil or a placebo starting 7 weeks before surgery and for up to one-year post-surgery. Quality of life was assessed using the validated EPIC-26 and IPSS questionnaires at randomization, at surgery, and every 3 months following surgery. Between-group differences were assessed using linear mixed models. Intention-to-treat analyses showed no significant difference between the two groups. However, at 12-month follow-up, per-protocol analyses showed a significantly greater increase in the urinary irritation function score (better urinary function) (MD = 5.5, p = 0.03) for the LCn3 group compared to placebo. These results suggest that LCn3 supplementation may improve the urinary irritation function in men with PCa treated by radical prostatectomy and support to conduct of larger-scale studies.

Effects of omega-3 fatty acids supplementation on perioperative blood loss and complications after radical prostatectomy.

BACKGROUND AND AIMS: Many dietary supplements, including omega-3 fatty acids (ω3), are suspected to affect blood coagulation and platelet function. Despite no clinical evidence, discontinuation is recommended before radical prostatectomy. However, long-chain ω3 (LCω3) appear beneficial against prostate cancer progression. Here, we aim to determine the effect of LCω3 supplements on perioperative bleeding, hemoglobin, platelets, and postoperative complications after radical prostatectomy. METHODS: This is a planned exploratory analysis of 130 patients diagnosed with prostate cancer grade group 2 or greater enrolled in a randomized controlled trial (NCT02333435) testing the effects of LCω3, on prostate cancer biological and pathological outcomes at radical prostatectomy as main outcomes. The LCω3 intervention (MAG-EPA 3 g daily) or equivalent placebo was given 4-10 weeks prior to radical prostatectomy. An intention-to-treat analysis approach was used with bi-variate statistical testing of bleeding and complications outcomes. We also estimated the difference between groups using linear regression and non-parametric quantile regression models. All models were adjusted for confounding variables selected on clinical relevance. RESULTS: We found no clinically significant effect of LCω3 versus placebo on perioperative bleeding, laboratory tests or postoperative complications. In contrast, as expected, we found a significant increase in perioperative bleeding in open retropubic radical prostatectomy compared to robot-assisted radical prostatectomy (adjusted difference 115.8 mL, p = 0.04). CONCLUSIONS: Our results suggest that ω3 supplements can be safely taken before radical prostatectomy without increasing surgical bleeding risk. These findings are relevant since ω3 may beneficially affect prostate cancer evolution.

Contemporary outcomes of palliative transurethral resection of the prostate in patients with locally advanced prostate cancer.

BACKGROUND: Advanced prostate cancer may cause significant local complications which affect quality of life, including bladder outlet obstruction and hematuria. We performed a detailed review of our outcomes of palliative transurethral resection of the prostate (pTURP) in the era of taxane chemotherapy and potent androgen receptor antagonists at our tertiary-care institution. METHODS: Using hospital coding data, we identified patients with a diagnosis of prostate cancer who underwent a TURP at Hotel-Dieu Hospital in Quebec City between 2006 and 2016 for detailed chart review. Co-morbidities were classified using the Charlson comorbidity index (CCI). Cox regression analyses assessed predictors of perioperative mortality and morbidity. RESULTS: Of 137 patients identified, 58 were included in our study. Median age was 68 years; 27 (47%) men had castration-resistant prostate cancer and 28 (48%) were metastatic at time of pTURP. Mean follow-up from the first pTURP was 2.2 years, with an estimated 5-year overall survival of 16.3% (95% CI: 6.5%-29.8%). Castration-resistant prostate cancer, CCI ≥5, and age predicted poorer survival. Primary indication for pTURP was bladder outlet obstruction (69%) or hematuria (22%). Postoperative Clavien 0, 1, 2, 3, 4, 5 complications occurred in 20 (34%), 16 (28%), 18 (31%), 3 (5%), 0, and 1 (2%) patients, respectively. Overall, 17 (27%) men underwent ≥1 redo pTURPs and 16 (28%) eventually had an indwelling catheter. Nephrostomy tubes or ureteral stents in place before pTURP remained indefinitely in all cases. CONCLUSIONS: We conclude palliative TURP remains an important surgical option to relieve bladder outlet obstruction in patients with locally advanced prostate cancer, but is ineffective to relieve ureteral obstruction.

Progression from high-grade prostatic intraepithelial neoplasia to cancer: a randomized trial of combination vitamin-E, soy, and selenium.

PURPOSE: High-grade prostatic intraepithelial neoplasia (HGPIN) is a putative precursor of invasive prostate cancer (PCa). Preclinical evidence suggests vitamin E, selenium, and soy protein may prevent progression of HGPIN to PCa. This hypothesis was tested in a randomized phase III double-blind study of daily soy (40 g), vitamin E (800 U), and selenium (200 µg) versus placebo. PATIENTS AND METHODS: Three hundred three men in 12 Canadian centers were analyzed. The main eligibility criterion was confirmed HGPIN in at least one of two biopsies within 18 months of random assignment. Treatment was administered daily for 3 years. Follow-up prostate biopsies occurred at 6, 12, 24, and 36 months postrandomization. The primary end point was time to development of invasive PCa. Kaplan-Meier plots and log-rank tests were used to compare two treatment groups for this end point. RESULTS: For all patients, the median age was 62.8 years. The median baseline prostate-specific antigen (PSA; n = 302) was 5.41 ug/L; total testosterone (n = 291) was 13.4 nmol/L. Invasive PCa developed among 26.4% of patients. The hazard ratio for the nutritional supplement to prevent PCa was 1.03 (95% CI, 0.67 to 1.60; P = .88). Gleason score distribution was similar in both groups with 83.5% of cancers graded Gleason sum of 6. Baseline age, weight, PSA, and testosterone did not predict for development of PCa. The supplement was well tolerated with flatulence reported more frequently (27% v 17%) among men receiving micronutrients. CONCLUSION: This trial does not support the hypothesis that combination vitamin E, selenium, and soy prevents progression from HGPIN to PCa.

PD-L1 (B7-H1) expression by urothelial carcinoma of the bladder and BCG-induced granulomata: associations with localized stage progression.

BACKGROUND: PD-L1 (programmed death ligand 1, B7-H1) is a cell surface glycoprotein that can impair T-cell function. PD-L1 is aberrantly expressed by multiple human malignancies and has been shown to carry a highly unfavorable prognosis in patients with kidney cancer. The role of PD-L1 was evaluated as a mechanism for local stage progression in urothelial carcinoma (UC) of the bladder. METHODS: Using immunohistochemistry, PD-L1 expression was evaluated in a cohort of 280 high-risk UCs of the bladder. PD-L1 was modeled as a predictor of bladder cancer stage using ordinal logistic regression. Other covariates evaluated as potential confounders included age, gender, tumor grade, and lymphocytic infiltration. Further, PD-L1 was evaluated as a potential mechanism of bacillus Calmette-Guerin (BCG) failure in the subset of high-risk nonmuscle-invasive tumors that received this treatment. RESULTS: PD-L1 expression was observed in 7% of pTa, 16% of pT1, 23% of pT2, 30% of pT3/4, and 45% of carcinoma in situ (CIS) tumors. PD-L1 expression was associated with high-grade tumors (odds ratio [OR] = 2.4, P = .009) and tumor infiltration by mononuclear cells (OR = 5.5, P = .004). We observed that the key determinants of stage progression in this cohort were World Health Organization/International Society of Urologic Pathology (WHO/ISUP) high-grade tumor pathology (OR = 4.77, 95% confidence interval [CI]: 2.73-8.34; P < .001) and PD-L1 expression (OR = 2.20, P = .012). PD-L1 expression was found to be extremely abundant in the BCG-induced bladder granulomata in 11 of 12 patients failing BCG treatment. CONCLUSIONS: Collectively, these data indicate that tumor PD-L1 may facilitate localized stage-advancement of UC and attenuate responses to BCG immunotherapy by neutralizing T cells that normally guard against cancer invasion from the epithelium into the bladder musculature.

Prostatic intraepithelial neoplasia in TURP specimens and subsequent prostate cancer.

PURPOSE: Prostatic intraepithelial neoplasia (PIN) is considered as a precursor lesion for adenocarcinoma of the prostate. Most data supporting this relationship comes from the short-term follow-up of patients with repeated biopsies. We report a study in which patients were followed-up for 11 years to assess the relationships between the presence of high grade PIN, low grade PIN, and atypical adenomatous hyperplasia (AAH) and the subsequent occurrence of prostate cancer. MATERIALS AND METHODS: For 601 men treated by TURP in 1990-1993, prostate specimens were reviewed to assess the presence of high grade PIN, low grade PIN, and AAH. Incidental carcinoma was observed in 67 men. Follow-up of the 534 men without incidental prostate cancer was conducted until December 2003 and 24 new prostate cancers were diagnosed. Multivariate regression models were used to assess the relationships between PIN and AAH and prostate cancer on both cross-sectional and prospective data. RESULTS: High grade PIN (odds ratio (OR) = 6.16, 95% confidence interval (CI): 3.28-11.58), low grade PIN (OR = 3.06, 95% CI: 1.45-6.46), and AAH (OR = 2.06, 95% CI: 1.00-4.29) were significantly associated with incidental prostate cancer. In the prospective study, only high grade PIN was associated with a statistically significant increased risk of prostate cancer: hazard ratio = 3.12, 95% CI: 1.15-8.49. CONCLUSION: Although high grade PIN, low grade PIN, and AAH were all associated with incidental prostate cancer, the long-term prospective study showed that only high grade PIN was a significant determinant of the subsequent occurrence of prostate cancer.