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BackgroundMen with persistently elevated and/or rising PSA levels after negative prostate biopsy often undergo multiple repeat biopsies. Prostate cancer antigen 3 (PCA3) has emerged as a predictor of prostate cancer.MethodsWe sought to define the utility of PCA3 in combination with other clinical data in predicting the risk of prostate cancer on repeat biopsy. We retrospectively obtained PCA3, PSA, PSA density (PSAD), digital rectal examination (DRE) and transrectal ultrasound (TRUS) findings from 103 patients at a single institution who had at least one prior negative prostate biopsy. The sensitivity and specificity of PCA3 in detecting prostate cancer was determined. Receiver operating characteristics curves were produced for each variable individually and in multivariable analysis, controlling for PCA3, PSAD, TRUS, PSA and DRE. A nomogram was created, internally validated and compared to another recently published nomogram.ResultsOf the 103 patients, 37 (31%) had prostate cancer on repeat biopsy. The sensitivity and specificity of PCA3 (using a cut point of 25) was 0.67 and 0.64, respectively. In multivariable analyses, PCA3 was independently associated with prostate cancer (odds ratio: 1.02, 95% confidence interval: 1.01-1.04), with area under the curve (AUC) of 0.64. A multivariable model containing PCA3, PSAD, PSA, DRE and TRUS findings showed the most diagnostic accuracy (AUC: 0.82).ConclusionsIn the setting of prior negative biopsies, PCA3 was independently associated with prostate cancer in a multivariable model. In combination with other clinical data, PCA3 is a valuable tool in assessing the risk of prostate cancer on repeat biopsy.

Introduction: Health-related quality of life (HRQOL) is a legitimate construct for evaluating treatment and its side effects. Recently, predictive value of HRQOL on survival also has been of interest. In light of the longer survival in patients with prostate cancer and importance of quality of life, we seek to evaluate the association between HRQOL and survival using traditional and novel techniques.Methods: Patients from CaPSURE (Cancer of the Prostate Strategic Urologic Research Endeavor) who were treated within 6 months of diagnosis and had pre-treatment and sufficient post-treatment follow-up information constituted the study population. A sample consisting of 2,899 patients met the study criteria. SF-36 domains were used to measure HRQOL outcomes. Categorical variables were created for HRQOL based on the baseline distribution of the lower 10th percentile and the remainder of the patients. Association between HRQOL and survival (defined by all-cause mortality) in patients with prostate cancer was evaluated using Cox proportional hazards models controlling for age at diagnosis, type of treatment received, clinical risk classification, and number of comorbidities. Sequential bootstrap resampling was implemented to evaluate stability of the model. Univariate and multivariate Cox proportional hazards models were fit using various time points over the course of follow-up.Results: In the analysis looking at association of HRQOL baseline measurements, higher levels of physical function and general health were significantly associated with better survival (HR 0.49 95% CI 0.32-0.78 and HR 0.51 95% CI 0.35-0.75, respectively). Post-treatment analysis demonstrated similar results. In time-dependent analysis, higher levels of physical function, role physical, and general health were significantly associated with better survival (HR ranged from 0.57 to 0.65). In addition, analysis looking at change in HRQOL scores demonstrated an association between higher scores on physical function, role physical, vitality, social function, and general health and longer survival (HR ranged from 0.56 to 0.63).Conclusion: This study demonstrated that several domains of HRQOL were significantly associated with survival in a large group of patients with localized prostate cancer. This association was maintained over the course of disease regardless of the time of the assessment. Results from our study have both research and clinical relevance. They could provide information that enable us to not only improve communication with patients and families, but also to develop interventions and treatments best suited for the patient. [ABSTRACT FROM AUTHOR]

The article offers information on the observational safety study of patients with BRAF mutated unresectable or metastatic melanoma. It mentions in the pivotal BRAF Inhibitors in Melanoma (BRIM)-3 trial, treatment-emergent cutaneous side effects were associated with vemurafenib, including the development of epithelial tumours; and also mentions the multicentre prospective observational study evaluated the incidence of adverse events (AEs) of special interest (AESI) with vemurafenib.

Epstein-Barr virus-positive (EBV + ) post-transplant lymphoproliferative disease (PTLD) is an ultra-rare and aggressive condition that may occur following allogeneic hematopoietic cell transplant (HCT) due to immunosuppression. Approximately half of EBV + PTLD cases are relapsed or refractory (R/R) to initial rituximab-containing therapy. There are limited treatment options and no standard of care for patients with R/R EBV + PTLD, and little is known about their treatment history and outcomes. We performed a multinational, multicenter, retrospective chart review of patients with R/R EBV + PTLD following HCT to describe patients' demographic and disease characteristics, treatment history, and overall survival (OS) from rituximab failure. Among 81 patients who received initial treatment with rituximab as monotherapy (84.0%) or in combination with chemotherapy (16.0%), median time from HCT to PTLD diagnosis was 3.0 months and median OS was 0.7 months. Thirty-six patients received a subsequent line of treatment. The most frequent causes of death were PTLD (56.8%), graft-versus-host disease (13.5%) and treatment-related mortality (10.8%). In multivariate analysis, early PTLD onset and lack of response to initial treatment were associated with mortality. This real-world study demonstrates that the prognosis of patients with R/R EBV + PTLD following HCT remains poor, highlighting the urgent unmet medical need in this population., (© 2023. The Author(s).)

Introduction: Following hematopoietic stem cell transplantation or solid organ transplantation, patients are at risk of developing Epstein-Barr virus-positive post-transplant lymphoproliferative disease (EBV + PTLD), which is an ultra-rare and potentially lethal hematologic malignancy. Common treatments for EBV + PTLD include rituximab alone or combined with chemotherapy. Given specific considerations for this population, including severity of the underlying condition requiring transplant, the rigors of the transplant procedure, as well as risks to the transplanted organ, there is a group of patients with EBV + PTLD for whom chemotherapy may be inappropriate; however, there is limited information characterizing these patients. This study aimed to reach expert consensus on the key characteristics of patients for whom chemotherapy may be inappropriate in a real-world setting., Methods: A two-round modified Delphi study was conducted to reach consensus among clinicians with expertise treating EBV + PTLD. Articles identified in a targeted literature review guided the development of round 1 and 2 topics and related statements. The consensus threshold for round 1 statements was 75.0%. If consensus was achieved in round 1, the statement was not discussed further in round 2. The consensus thresholds for round 2 were moderate (62.5-75.0%), strong (87.5%), or complete (100.0%)., Results: The panel was composed of a total of eight clinicians (seven hematologists/hemato-oncologists) from six European countries. The panel generated a final list of 43 consensus recommendations on the following topics: terminology used to describe patients for whom chemotherapy may be inappropriate; demographic characteristics; organ transplant characteristics; comorbidities that preclude the use of chemotherapy; EBV + PTLD characteristics; and factors related to treatment-related mortality and morbidity., Conclusions: This modified Delphi panel successfully achieved consensus on key topics and statements that characterized patients with EBV + PTLD for whom chemotherapy may be inappropriate. These recommendations will inform clinicians and aid in the treatment of EBV + PTLD., (© 2022. The Author(s).)

Purpose: The utility of real-world data (RWD) for use as external controls in drug development is informed by studies that replicate trial control arms for different endpoints. The purpose of this study was to replicate control arms from four non-small cell lung cancer (NSCLC) randomized controlled trials (RCT) to analyze overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) using RWD., Patients and Methods: This study used RWD from a nationwide de-identified database and a clinico-genomic database to replicate OS, PFS, and ORR endpoints in the chemotherapy control arms of four first-line NSCLC RCTs evaluating atezolizumab [IMpower150-wild-type (WT), IMpower130-WT, IMpower131, and IMpower132]. Additional objectives were to develop a definition of real-world PFS (rwPFS) and to evaluate the real-world response rate (rwRR) endpoint., Results: Baseline demographic and clinical characteristics were balanced after application of propensity score weighting methods. For rwPFS and OS, RWD external controls were generally similar to their RCT control counterparts. Across all four trials, the hazard ratio (HR) point estimates comparing trial controls with external controls were closer to 1.0 for the PFS endpoint than for the OS endpoint. An exploratory assessment of rwRR in RWD revealed a slight but nonsignificant overestimation of RCT ORR, which was unconfounded by baseline characteristics., Conclusions: RWD can be used to reasonably replicate the OS and PFS of chemotherapy control arms of first-line NSCLC RCTs. Additional studies can provide greater insight into the utility of RWD in drug development., (©2022 The Authors; Published by the American Association for Cancer Research.)

Background: Patients with melanoma and central nervous system (CNS) metastases have poor survival outcomes. We investigated real-world treatment patterns and overall survival (OS) of patients with melanoma and CNS metastases., Methods: A retrospective analysis utilizing a nationwide de-identified electronic health record-derived database was undertaken in patients diagnosed with advanced melanoma between January 2011 and September 2018. Patients with any visit ≤90 days of metastatic diagnosis and with confirmed CNS metastases were included., Results: Of 3473 patients diagnosed with advanced melanoma, 791 patients with confirmed CNS metastases were identified and included in this analysis. Synchronous CNS metastasis (≤30 days of metastatic diagnosis) was associated with longer median OS than metachronous CNS metastasis (>30 days after metastatic diagnosis, 0.58 vs 0.42 years). Stereotactic radiosurgery (SRS) was the most common treatment (40.5%) alone or in combination with other local or systemic therapies, being more frequent in patients diagnosed in 2015+ versus 2011-2014 (44.1% vs 35.5%, respectively). The most common systemic treatment was immune checkpoint inhibitors (ICIs; 30.5%), predominantly anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) alone (2011-2014) and anti-programmed death-1 alone or in combination with anti-CTLA-4 (2015+). Median OS was longest in SRS-treated patients (1.17 years) regardless of number of CNS metastases. Median OS for SRS-treated patients increased from 0.83 years (2011-2014) to 1.75 years (2015+). In multivariable analysis, the effect of SRS remained significant after adjustment for sex, race, intracranial and extracranial disease burden, and timing of CNS metastases. Interaction testing to examine potential synergy between SRS/whole-brain radiation therapy and ICIs found no significant interaction., Conclusions: Despite advances in treatment, patients with melanoma and CNS metastases have poor survival outcomes. Prevalence of SRS increased over time and was associated with improved outcomes., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: Eastern Cooperative Oncology Group performance status (ECOG PS) is an important predictor for receipt of treatment and overall survival (OS) but is often unreported in routine care. We developed a proxy for baseline ECOG PS using electronic health records (EHRs)., Methods: We analyzed patients who were diagnosed with advanced non-small cell lung cancer (aNSCLC), advanced bladder cancer (aBCa), and advanced melanoma (aMEL) between 2011 and 2018 and had a baseline (reported between diagnosis and treatment) ECOG PS in a real-world database. We used stepwise multivariable logistic regression to model associations between baseline ECOG PS good (<2) versus poor (≥2) and sociodemographic, clinical, and laboratory measures in each cancer type. Predictive accuracy of classifying ECOG PS was assessed. We tested the association between OS and observed and predicted ECOG PS., Results: In total, 20 697 aNSCLC patients, 2627 aBCa patients, and 2558 aMEL patients constituted the study population. Percentage of patients with poor ECOG PS ranged from 15.3% (aMEL) to 28.5% (aNSCLC). Poor ECOG PS was associated with more comorbid conditions, older age, lower body mass index, metastases, and abnormal laboratory indicators. Overall prediction accuracy using a 0.50 cutpoint was 73.3% for NSCLC, 73.8% for aBCa, and 85.4% for aMEL. The association of OS with ECOG PS was consistent between the observed and proxy measures., Conclusions: In the EHR-derived data, clinical, sociodemographic, and laboratory information were used to assign ECOG PS and enhance the use of real-world data in outcome studies., (© 2021 John Wiley & Sons Ltd.)

Background: Central nervous system (CNS) metastasis is common in advanced melanoma patients. New treatment options have improved overall prognosis, but information is lacking for patients with CNS metastases. We investigated treatment patterns and survival outcomes in older melanoma patients with and without CNS metastases., Methods: A retrospective analysis of SEER-Medicare, a population-based linked database, was undertaken in patients aged > 65 years with advanced melanoma diagnosed from 2004 to 2011 and followed until 2013., Results: A total of 2522 patients were included. CNS metastases were present in 24.8% of patients at initial metastatic diagnosis; 16.5% developed CNS metastases during follow-up. Chemotherapy was the most common treatment regardless of CNS metastases. Overall survival (OS) was better for patients without CNS metastases (median, 9.5 months; 95% confidence interval [CI], 8.8-10.2) vs patients with CNS metastases (3.63 months; 95% CI, 3.4-3.9). Among patients with CNS metastases, median OS for targeted therapy, immunotherapy, and chemotherapy was 6 (95% CI, 2.5-9.6), 5.5 (95% CI, 3.8-7.5), and 4.5 (95% CI, 3.8-5.4) months, respectively, vs 2.4 (95% CI, 2.1-2.7) and 2.1 (95% CI, 1.8-2.7) months for local radiotherapy and no treatment, respectively. Stereotactic radiosurgery demonstrated higher OS vs whole-brain radiation therapy (median, 4.98 [95% CI, 3.5-7.5] vs 2.4 [95% CI, 2.1-2.7] months)., Conclusion: Patients with CNS metastases from melanoma remain a population with high unmet medical need despite recent advances in treatment. Systemic treatments (eg, BRAF-targeted therapy and immunotherapy) and stereotactic radiosurgery demonstrated meaningful but modest improvements in OS. Further explorations of combinations of radiotherapy, BRAF-targeted therapies, and immunotherapies are needed., (© 2020 Roche/Genentech. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Vismodegib is a first-in-class agent targeting the hedgehog signaling pathway for treatment of patients with locally advanced basal cell carcinoma (BCC) and metastatic BCC. There have been concerns about the development of squamous cell carcinoma (SCC) in patients treated with this drug., Objective: We sought to determine whether treatment with vismodegib is associated with an increase in the risk of cutaneous SCC., Methods: In this retrospective cohort study, patients treated with vismodegib as part of phase I and II clinical studies were compared with participants from the University of California, San Francisco, Nonmelanoma Skin Cancer Cohort who received standard therapy for primary BCC. In total, 1675 patients were included in the analysis, and the development of SCC after vismodegib exposure was assessed., Results: The use of vismodegib was not associated with an increased risk of subsequent development of SCC (adjusted hazard ratio, 0.57; 95% confidence interval, 0.28-1.16). Covariates including age, sex, history of previous nonmelanoma skin cancer, and number of visits per year were significantly associated with the development of SCC., Limitations: A limitation of the study was that a historic control cohort was used as a comparator., Conclusions: Vismodegib was not associated with an increased risk of subsequent SCC when compared with standard surgical treatment of BCC., (Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: A randomized, placebo controlled clinical trial of folic acid supplementation for the chemoprevention of colorectal adenoma revealed an increased incidence of prostate cancer in the treatment group. Limited data exist on postdiagnostic folate/folic acid intake and the risk of prostate cancer progression. We prospectively examined the association between postdiagnostic folate consumption and the risk of prostate cancer recurrence after radical prostatectomy, external beam radiation therapy and brachytherapy., Materials and Methods: This study was done in 1,153 men treated with radical prostatectomy, external beam radiation therapy and brachytherapy who had clinical stage T1-T2c prostate adenocarcinoma and participated in the CaPSURE Diet and Lifestyle substudy by completing the semiquantitative Food Frequency Questionnaire in 2004 to 2005. We used Cox proportional hazards regression to analyze the association between folate intake and prostate cancer progression., Results: Prostate cancer progressed in 101 men (8.76%) during a mean 34-month followup. After multivariate adjustment we observed no evidence of an association of the intake of total folate, dietary folate or dietary folate equivalents with prostate cancer recurrence. On secondary analysis by treatment after radical prostatectomy patients in the lowest decile of dietary folate intake had a 2.6-fold increase in the risk of recurrence (HR 2.56, 95% CI 1.23-5.29, p = 0.01). In patients treated with external beam radiation and brachytherapy we observed no evidence of an association between prostate cancer progression and increased folate intake., Conclusions: Results suggest that the consumption of foods and multivitamins that contain folate is not associated with prostate cancer progression after definitive treatment., (Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: As the number of prostate cancer survivors increases, urologists must recognize their quality of life impairment. In the past physician ratings of patient symptoms did not correlate with patient self-assessments. We determined if urologists have improved their reporting of patient health related quality of life. We also investigated if urologists assessed health related quality of life more accurately in the short or long term., Materials and Methods: We identified 1,366 men from CaPSURE™, a national, prospective cohort, who had undergone prostatectomy, brachytherapy or external beam radiation therapy. At each visit urologists assessed fatigue, pain, and sexual, urinary and bowel dysfunction. Participants independently completed the SF-36™ and the UCLA-PCI. We contrasted the frequency of impairment reported by physicians and participants in select health related quality of life domains in the short (less than 1 year) and long (greater than 2 years) term. We also compared physician-patient concordance between the periods 1995 to 2000 and 2001 to 2007., Results: In short-term and long-term followup, and for the 1995 to 2000 and 2001 to 2007 cohorts, physician and participant assessments differed in all analyzed domains. Urologists noted impairment in urinary and sexual function more often than fatigue or pain. Disagreement between physician and participant ratings did not vary dramatically from short-term to long-term followup, or from the earlier to the later cohort., Conclusions: In men treated for localized prostate cancer physician ratings of symptoms do not correlate well with patient self-assessments of health related quality of life. Physician reporting did not improve over time. It is increasingly important to recognize and address impairments in quality of life from prostate cancer and its treatment., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Unlabelled: Study Type - Therapy (case series) Level of Evidence 4. What's known on the subject? and What does the study add? Although phosphodiesterase inhibitor use post radical prostatectomy improves potency, little is known about its affects on sexual bother. We found no difference in sexual bother scores between patients who use and do not use phosphodiesterase inhibitors. This suggests that the current definition of potency, inclusive of medication use, is valid with respect to sexual bother., Objective: To determine whether the current definition of potency, inclusive of phosphodiesterase inhibitor (PDEi) use, is valid with respect to sexual bother (SB). This will be assessed by characterizing the effect of PDEi use on SB scores in men who are potent post radical prostatectomy., Patients and Methods: The study population consisted of patients who were potent both before and after radical prostatectomy, with at least 2 years of follow-up. Disease-specific quality of life data were evaluated by the University of California, Los Angeles, Prostate Cancer Index (PCI) survey. The relationships between changes in sexual function (SF) and SB and use of PDEi over time were evaluated by mixed model analysis controlling for age, clinical risk group, marital status, and time of PCI assessment., Results: Of the 246 patients who met the study criteria, 39% reported PDEi use at some point after treatment. PDEi use was not associated with improved SF (P= 0.81). Furthermore, PDEi use was not associated with a change in SB (P= 0.36). Both SF and SB were significantly associated with time of assessment and age, and SF and SB each improved over time. In addition, SB was significantly associated with marital status., Conclusions: In this analysis, there was no difference in SF scores between men who were potent with or without the use of PDEi. Furthermore, there was no difference in SB scores between men who were potent with or without the use of PDEi. This suggests that the current, inclusive, definition of potency is valid with respect to SB., (© 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.)

Purpose: Increased fluid intake, and decreased dietary sodium and animal protein intake are thought to reduce the risk of kidney stones but the role of calcium intake is controversial. We evaluated the relationship between dietary factors and incident kidney stone formation., Materials and Methods: Secondary analysis was done of 78,293 women from the prospective WHI OS (Women's Health Initiative Observational Study) with no history of nephrolithiasis who completed the validated food frequency questionnaire. Multivariate logistic regression was used to determine demographic and dietary factors, and supplement use independently associated with incident kidney stones., Results: Overall 1,952 women (2.5%) reported an incident kidney stone in 573,575 person-years of followup. The risk of incident kidney stones was decreased by 5% to 28% (p = 0.01) with higher dietary calcium intake and by 13% to 31% (p = 0.002) with higher water intake after adjusting for nephrolithiasis risk factors. Conversely higher dietary sodium intake increased the risk of nephrolithiasis by 11% to 61% (p <0.001) after adjustment with the most pronounced effect in women with the highest intake. Higher body mass index independently increased the risk of incident nephrolithiasis (adjusted OR 1.19-2.01, p <0.001). Animal protein intake was not associated with nephrolithiasis on multivariate analysis., Conclusions: This study adds to the growing evidence underscoring the importance of maintaining adequate fluid and dietary calcium intake. Greater dietary calcium intake significantly decreased the risk of incident kidney stones. In contrast, excess sodium intake increased the risk of incident nephrolithiasis, especially in women with the highest intake. Animal protein intake was not independently associated with nephrolithiasis., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)