The CT-derived ratio between donated kidney cortical volume and recipient pretransplant weight is a noninvasively and readily obtained reproducible biomarker that is predictive of 12- and 24-month renal transplant outcomes.
Background: How 5-alpha reductase inhibitor (5-ARI) use influences prostate cancer mortality is unclear. The objective of this study was to determine whether men taking 5-ARIs with regular healthcare access have increased prostate cancer mortality. Methods: We undertook two analyses in the Health Professionals Follow-up Study examining 5-ARI use, determined by biennial questionnaires, and prostate cancer. A cohort analysis followed 38,037 cancer-free men for prostate cancer incidence from 1996 through January 2017 and mortality through January 2019. A case-only analysis followed 4,383 men with localized/locally advanced prostate cancer for mortality over a similar period. Hazard ratios (HR) and 95% confidence intervals were calculated for prostate cancer incidence and mortality. Results: Men using 5-ARIs underwent more PSA testing, prostate exams and biopsies. Over 20 years of follow-up, 509 men developed lethal disease (metastases or prostate cancer death). Among men initially free from prostate cancer, 5-ARI use was not associated with developing lethal disease (HR 1.02, 0.71-1.46), but was associated with reduced rates of overall and localized disease (HR 0.71, 0.60-0.83). Among men diagnosed with prostate cancer, there was no association between 5-ARI use and cancer-specific (HR 0.78, 0.48-1.27) or overall survival (HR 0.88, 0.72-1.07). Conclusions: Men using 5-ARIs were less likely to be diagnosed with low-risk prostate cancer, without increasing long-term risk of lethal prostate cancer or cancer-specific death after diagnosis. Impact: Our results provide evidence that 5-ARI use is safe with respect to prostate cancer mortality in the context of regular healthcare access.
288 Background: MRI/Ultrasound fusion biopsy of the prostate has enhanced the detection of clinically significant prostate cancer (csPCa). Detection of csPCa is greatest when fusion and systematic biopsies are combined. However, the finding of a negative fusion and negative systematic biopsy in patients with suspicious lesion on imaging raises the question of either falsely positive imaging or a false negative biopsy. Methods: We retrospectively reviewed our database of patients undergoing MRI/transrectal US-guided fusion biopsy. All images were graded according to the Prostate Imaging Reporting and Data System version (PIRADS) 2.0. Patients underwent targeted biopsy followed by systematic 12-core double sextant biopsy within the same session. csPCa was defined as Grade Group (GG) ≥2 PCa. Patients with no prostate cancer (PCa) found on biopsies were followed. MRI studies with PIRADS v2 score ≤ 2 were considered to have no MRI evidence of PCa. Results: A total of 400 patients had at least one PIRADS ≥3 lesion and underwent fusion/systematic biopsy. Of these, 113 (28.3%) patients had no evidence of PCa on either fusion or systematic biopsy. Median follow-up was 32.5 months. 44 (39%) patients underwent repeat MRI and of these, 24 (54%) had no evidence of PCa on repeat MRI. PIRADS lesion disappearance was associated with lower PSA Density (PSAd) (0.12 vs 0.20; P = 0.0319) and decreased progression to repeat biopsy (8.33% vs 95%; P < 0.0001). Patients who had a repeat biopsy had a greater PSAd ( 0.21 vs 0.12; P = 0.0054). Of 113 patients with negative initial biopsy, 23 (20.4 %) underwent repeat biopsy: 16 (14.2 %) had PCa and 11 (9.7%) had csPCa. Thus, 48% of patients who underwent repeat biopsy had csPCa. Among patients with a PCa on repeat biopsy, cancer was sampled by MRI targeted cores in 80% of patients. Conclusions: Despite a negative initial fusion/systematic biopsy, at least 10% of patients were subsequently diagnosed with clinically significant PCa. The combination of elevated PSAd and the persistence of a suspicious lesion on repeat MRI appears selective for previously missed PCa. However, after negative fusion biopsy, repeat MRI yields a high rate of PIRADS lesion disappearance in patients with low PSAd.
65 Background: DNA repair genes including BRCA1 are commonly altered in metastatic prostate tumors. However, mutations and copy number aberrations in these genes are rare in primary tumors. Instead, preliminary studies suggest that higher tumor expression of the BRCA1 protein may be associated with worse prognosis. Methods: We undertook a prospective study of tumor BRCA1 protein expression and lethal prostate cancer among men with clinically localized prostate cancer in the Health Professionals Follow-up Study. We performed immunohistochemical staining for BRCA1 on tumor tissue microarrays using a validated antibody and scored expression as positive or negative. We also assessed tumor proliferation by immunostaining for Ki67, angiogenesis by immunostaining for CD34, and apoptosis using a TUNEL assay. Proportional hazards regression was used to evaluate the association between BRCA1 protein expression and development of lethal prostate cancer (metastasis or cancer-specific death). Results: Ten percent of tumors (60 of 589) stained positive for the BRCA1 protein. BRCA1-positive tumors were characterized by higher Gleason scores, a higher proliferative index, and a higher apoptotic index. During a median follow-up of 14.3 years, 18 men (34%) in the BRCA1-positive group and 74 men (14%) in the BRCA1-negative group developed lethal prostate cancer. There was a strong positive association between BRCA1 protein expression and lethal prostate cancer in both unadjusted analyses (HR 2.71, 95% CI 1.73–4.26) and after adjusting for clinical factors (HR 2.00, 95% CI 1.26–3.18). The positive association with BRCA1 protein expression was also independent of proliferation index. Conclusions: Primary prostate tumors expressing the BRCA1 protein have a highly proliferative phenotype and are more likely to progress to lethal disease, independent of its higher proliferative index. Assessing tumor protein expression of BRCA1 may help elucidate the Janus-faced role of DNA repair pathways in prostate cancer progression.[Table: see text]
Rural patients travel a fourfold longer distance for complex urological surgery than their metropolitan counterparts. These findings guide future work on how geographical distance can lead to delays in diagnosis/treatment, enrollment in clinical trials and provision of follow up care after surgery for rural patients.
on outcome after 1 RPLND for men with NSGCT. However, this has yet to be corroborated in a nationally representative dataset.METHODS: Using the National Cancer Database, patients who received a 1 RPLND from 2004-2014 for CS I & IIA/B NSGCT were identified. The analytic cohort was stratified according to LN count ( 20,(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40) and >40 LNs). Sociodemographic characteristics were compared among groups. The Kaplan-Meier method was calculated and pairwise comparisons performed. Based on sensitivity analyses to determine LN cutoff that impacts survival, subsequent analysis compared patients with 20 and >20 LNs resected. Multivariate analysis using stepwise regression was used to determine factors associated with receipt of an RPLND with >20 LNs resected.RESULTS: Of 1,376 men who received 1 RPLND for Stage I or IIA/B NSGCT, 35.6%, 27.4%, and 14% had 20, 21-40, and >40 LNs resected, respectively. LN count was associated with overall survival (OS), with 95%, 97%, and 98% 8-year OS for men with LN count 20, 21-40, and >40 LNs, respectively. OS in men with 20 vs 21-40 (p[0.018) and >40 LNs (p[0.042) resected differed significantly. However, no significant difference was observed when 21-40 vs >40 LNs were resected (p[0.677). Therefore, subsequent analysis compared those who had 20 and >20 LN resected, and OS between these two groups differed significantly (Figure). Multivariate analysis demonstrated that patients with private insurance, surgery having been performed at an academic center or in the Northeast, and those with pT2 disease were more likely to have >20 LNs resected at the time of RPLND.CONCLUSIONS: Lymph node count after 1 RPLND for NSGCT is significantly associated with overall survival, with more favorable survival seen in those who receive an RPLND with >20 LNs resected when compared to 20 LNs.
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