Development and evaluation of a proxy for baseline ECOG PS in advanced non-small cell lung cancer, bladder cancer, and melanoma: An electronic health record study.

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.

Risk of cutaneous squamous cell carcinoma after treatment of basal cell carcinoma with vismodegib.

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.

Impact of folate intake on prostate cancer recurrence following definitive therapy: data from CaPSURE™.

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.

Outcomes for patients with EBV-positive PTLD post-allogeneic HCT after failure of rituximab-containing therapy.

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.

Differing perceptions of quality of life in patients with prostate cancer and their doctors.

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.

Expert Consensus on the Characteristics of Patients with Epstein-Barr Virus-Positive Post-Transplant Lymphoproliferative Disease (EBV+ PTLD) for Whom Standard-Dose Chemotherapy May be Inappropriate: A Modified Delphi Study.

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.

Impact of calcium intake and intestinal calcium absorption on kidney stones in older women: the study of osteoporotic fractures.

PURPOSE: Intestinal calcium absorption is thought to have a critical role in nephrolithiasis. However, to our knowledge no study has directly assessed this association. Therefore, we explored the relationship among intestinal fractional calcium absorption, calcium intake and nephrolithiasis. MATERIALS AND METHODS: The Study of Osteoporotic Fractures is a prospective cohort of 9,704 postmenopausal women recruited from population based listings in 1986 and followed for more than 20 years. Secondary analyses were performed of 7,982 women who reported their history of nephrolithiasis, of which 5,452 (68%) underwent an oral radioactive calcium assay (45Ca). The impact of dietary and supplemental calcium on intestinal fractional calcium absorption was evaluated, and factors independently associated with nephrolithiasis were determined. RESULTS: Fractional calcium absorption decreased with increased calcium intake, with no difference between dietary and supplemental calcium. Fractional calcium absorption was higher in women with a nephrolithiasis history among all calcium intake groups. Increased dietary calcium intake reduced the likelihood of nephrolithiasis by 45% to 54% (p=0.03). Women with a history of nephrolithiasis were less likely to supplement calcium (p<0.001). In adjusted analyses women who supplemented calcium were 21% to 38% less likely to have a nephrolithiasis history (p=0.007) and there was a 24% increased risk of kidney stones for each 10% increase in fractional calcium absorption (p=0.008). CONCLUSIONS: Fractional calcium absorption is higher in women with a history of nephrolithiasis. Higher intestinal fractional calcium absorption is associated with a greater risk of historical nephrolithiasis. Dietary and supplemental calcium decrease fractional calcium absorption, and may protect against nephrolithiasis.

Impact of nutritional factors on incident kidney stone formation: a report from the WHI OS.

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.

Among potent men post radical prostatectomy, does the need for phosphodiesterase inhibitors have an impact on sexual bother scores?

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.

Treatment patterns and clinical outcomes for patients with melanoma and central nervous system metastases: A real-world study.

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.

Replication of Overall Survival, Progression-Free Survival, and Overall Response in Chemotherapy Arms of Non-Small Cell Lung Cancer Trials Using Real-World Data.

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.

Impact of androgen deprivation on physical well-being in patients with prostate cancer: analysis from the CaPSURE (Cancer of the Prostate Strategic Urologic Research Endeavor) registry.

BACKGROUND: As androgen deprivation therapy (ADT) becomes a standard of treatment for men with recurrent or metastatic prostate cancer, evaluation of adverse effects associated with this treatment is needed. In this study, the authors evaluated the effect of ADT administered as monotherapy and in combination with local treatment on physical well-being in a longitudinal sample of men with prostate cancer. METHODS: Exposure to ADT was defined by 3 groups: local (local treatment only), combination (local treatment with adjuvant and/or neoadjuvant ADT), and primary ADT. Associations between exposure to ADT and physical well-being measured by self-reported health-related quality of life outcomes over time were evaluated by repeated measures analysis using mixed modeling. Estimates adjusted for various clinical and demographic variables are reported. RESULTS: A total of 2922 men, who completed both pretreatment and follow-up health-related quality of life assessment, were identified from the CaPSURE (Cancer of the Prostate Strategic Urologic Research Endeavor) registry. During 24 months of follow-up, exposure to ADT was associated with worse physical well-being compared with local treatment at all time points (P < .001). Being exposed to ADT as primary therapy was associated with more severe declines compared with combination therapy. CONCLUSIONS: The potential consequence of decline in physical well-being in patients exposed to ADT has to be included in treatment decision making.

Physician assessment of pretreatment functional status: a process-outcomes link.

PURPOSE: Since all interventions for localized prostate cancer have a significant impact on health related quality of life, pretherapy assessment of functional status remains an essential quality of care indicator. We determined whether accurate pretherapy assessment has a significant role in forecasting health related quality of life after definitive treatment for prostate cancer. MATERIALS AND METHODS: We examined data from CaPSURE™ to identify men who underwent treatment for localized prostate cancer between 1995 and 2006. We restricted our analysis to those who completed the UCLA-PCI survey before and after therapy. We performed multiple logistic regression for the outcome measure (decrease in each of the 6 UCLA-PCI domains) on the predictor (whether the physician performed an assessment that was in agreement with patient reported pretherapy status) while adjusting for clinical and sociodemographic characteristics. RESULTS: Of the 2,195 men included in the analysis 1,411 (64%) did not have pretherapy function documented. Of the remaining 784 men only 354 (45%) had pretherapy physician assessments that were concordant with patient reported status. On multiple logistic regression analysis men who were not assessed were more likely to experience decreased sexual function (OR 1.66, 95% CI 1.23-2.23), sexual bother (OR 1.46, 95% CI 1.09-1.97) and bowel function (OR 1.43, 95% CI 1.02-2.00) according to post-therapy UCLA-PCI scores than those who were assessed and concordant. CONCLUSIONS: Pretherapy functional assessment of patients with localized prostate cancer is associated with less decrease in health related quality of life. This simple yet mutable process of care measure serves as a potential target to improve quality of care for patients with prostate cancer.

Kidney stones and subclinical atherosclerosis in young adults: the CARDIA study.

PURPOSE: Recent reports suggest that nephrolithiasis and atherosclerosis share a number of risk factors. To our knowledge there has been no previous examination of the relationship between kidney stones and subclinical atherosclerotic disease. We studied the relationship between nephrolithiasis, and carotid wall thickness and carotid stenosis assessed by B-mode ultrasound in the general community using data from the CARDIA study. MATERIALS AND METHODS: The CARDIA study is a United States, population based, observational study of 5,115 white and African-American men and women between the ages of 18 and 30 years at recruitment in 1985 to 1986. RESULTS: By the year 20 examination 200 (3.9%) CARDIA participants had reported ever having kidney stones. Symptomatic kidney stones were associated with greater carotid wall thickness measured at the year 20 examination, particularly of the internal carotid/bulb region. Using a composite dichotomous end point of carotid stenosis and/or the upper quartile of internal carotid/bulb wall thickness, the association of kidney stones with carotid atherosclerosis was significant (OR 1.6, 95% CI 1.1-2.3, p=0.01), even after adjusting for major atherosclerotic risk factors. CONCLUSIONS: The association between a history of kidney stones and subclinical carotid atherosclerosis in young adults adds further support to the notion that nephrolithiasis and atherosclerosis share common systemic risk factors and/or pathophysiology.

Prediction of erectile function following treatment for prostate cancer.

CONTEXT: Sexual function is the health-related quality of life (HRQOL) domain most commonly impaired after prostate cancer treatment; however, validated tools to enable personalized prediction of erectile dysfunction after prostate cancer treatment are lacking. OBJECTIVE: To predict long-term erectile function following prostate cancer treatment based on individual patient and treatment characteristics. DESIGN: Pretreatment patient characteristics, sexual HRQOL, and treatment details measured in a longitudinal academic multicenter cohort (Prostate Cancer Outcomes and Satisfaction With Treatment Quality Assessment; enrolled from 2003 through 2006), were used to develop models predicting erectile function 2 years after treatment. A community-based cohort (community-based Cancer of the Prostate Strategic Urologic Research Endeavor [CaPSURE]; enrolled 1995 through 2007) externally validated model performance. Patients in US academic and community-based practices whose HRQOL was measured pretreatment (N = 1201) underwent follow-up after prostatectomy, external radiotherapy, or brachytherapy for prostate cancer. Sexual outcomes among men completing 2 years' follow-up (n = 1027) were used to develop models predicting erectile function that were externally validated among 1913 patients in a community-based cohort. MAIN OUTCOME MEASURES: Patient-reported functional erections suitable for intercourse 2 years following prostate cancer treatment. RESULTS: Two years after prostate cancer treatment, 368 (37% [95% CI, 34%-40%]) of all patients and 335 (48% [95% CI, 45%-52%]) of those with functional erections prior to treatment reported functional erections; 531 (53% [95% CI, 50%-56%]) of patients without penile prostheses reported use of medications or other devices for erectile dysfunction. Pretreatment sexual HRQOL score, age, serum prostate-specific antigen level, race/ethnicity, body mass index, and intended treatment details were associated with functional erections 2 years after treatment. Multivariable logistic regression models predicting erectile function estimated 2-year function probabilities from as low as 10% or less to as high as 70% or greater depending on the individual's pretreatment patient characteristics and treatment details. The models performed well in predicting erections in external validation among CaPSURE cohort patients (areas under the receiver operating characteristic curve, 0.77 [95% CI, 0.74-0.80] for prostatectomy; 0.87 [95% CI, 0.80-0.94] for external radiotherapy; and 0.90 [95% CI, 0.85-0.95] for brachytherapy). CONCLUSION: Stratification by pretreatment patient characteristics and treatment details enables prediction of erectile function 2 years after prostatectomy, external radiotherapy, or brachytherapy for prostate cancer.

Health related quality of life for men treated for localized prostate cancer with long-term followup.

PURPOSE: Men who undergo primary treatment for prostate cancer can expect changes in health related quality of life. Long-term changes after treatment are not yet fully understood. We characterized health related quality of life evolution from baseline to 4 years after treatment. MATERIALS AND METHODS: We identified 1,269 men in CaPSURE who underwent primary treatment for clinically localized prostate cancer and completed followup health related quality of life questionnaires for at least 4 years. The men underwent radical prostatectomy, external beam radiotherapy, brachytherapy, combined external beam radiotherapy/brachytherapy or androgen deprivation therapy. Health related quality of life was measured using patient reported questionnaires. Effects of select covariates on quality of life were measured with a multivariate mixed model. RESULTS: Age at diagnosis, time from treatment and primary treatment were significant predictors of health related quality of life in all domains (p <0.05) except primary treatment on sexual bother. Men who underwent radical prostatectomy experienced the most pronounced worsening urinary function but also had the greatest recovery. All treatments worsened urinary bother, and sexual function and bother. All forms of radiotherapy moderately worsened bowel function and bother after treatment but eventual recovery to baseline was noted. CONCLUSIONS: Age at diagnosis, time from treatment and primary treatment type affect health related quality of life. Treatment has a greater impact on disease specific than general health related quality of life. All treatments adversely affect urinary and sexual function. Most adverse changes develop immediately after treatment. Recovery occurs mostly within 2 years after treatment with little change beyond 3 years.

Adequacy of a single 24-hour urine collection for metabolic evaluation of recurrent nephrolithiasis.

PURPOSE: There is much debate about whether 1 or 2, 24-hour urinalyses are adequate for metabolic evaluation of stone formers. We determined whether repeat 24-hour urine collection provides information similar to that of the initial 24-hour urine collection and whether repeat collection is necessary. MATERIALS AND METHODS: We analyzed 2, 24-hour urine collections in 777 patients obtained from 2001 to 2005. Samples were collected 3 days or less apart before pharmacological intervention and analyzed elsewhere for routine stone risk profiles of urine calcium, oxalate, citrate, uric acid, sodium, potassium, magnesium, phosphorus, ammonium, chloride, urea nitrogen and creatinine. RESULTS: No parameters showed a statistically significant difference between 24-hour urine samples 1 and 2 when mean values were compared (pairwise t test each p >0.05, range 0.06 to 0.87). Using Pearson's correlation all parameters showed positive correlation coefficients (r = 0.68 to 0.89, each p <0.0001). The mean of individual patient differences in samples 1 and 2 were compared to 0 and 6 of 12 showed no difference (p >0.05) while for the remaining 6 p value was <0.05. The percent difference was 0.5% to 4.19% for all urinary parameters. CONCLUSIONS: One 24-hour urine sample is sufficient for metabolic evaluation of recurrent stone disease. There is no significant difference in 12 urinary parameters between 24-hour urine samples collected within 3 days of each other. This information is useful to providers and may decrease patient inconvenience and the overall cost of metabolic stone evaluation.

Changes in specific domains of sexual function and sexual bother after radical prostatectomy.

OBJECTIVE: To quantitatively assess the effect of radical prostatectomy (RP) on the specific domains that comprise overall sexual function (SF), focusing on the relationships among these domains and overall SF, and to identify predictors for recovery of SF over time, as a decline in SF and sexual bother (SB) are known potential complications of treatment for prostate cancer. PATIENTS AND METHODS: Within the Cancer of the Prostate Strategic Urologic Research Endeavor database, we identified men diagnosed between 1995 and 2001 with localized prostate cancer treated with RP. SF and SB outcomes, measured using the University of California Los Angeles Prostate Cancer Index, were assessed at 6-month intervals for 4 years after RP. RESULTS: In all, 620 men met the study criteria; at 6 months after RP, overall and all the specific domains of SF declined, with improvement in most specific domains by 2 years after RP. The greatest declines were in the ability to achieve erections, high-quality erections, and frequent erections; these domains were also most strongly correlated with overall SF. Sexual desire was relatively preserved, and there was a weak correlation between overall SF and sexual desire after RP, when there was the greatest discrepancy between sexual desire and other domains of function. SB showed continued improvement over time to 4 years but was not well correlated with any measurements of SF assessed. Younger age, college education, sexual aid and medication use, the absence of comorbid conditions, and nerve-sparing surgery were predictive of significant recovery of function in several specific domains of SF. CONCLUSIONS: RP affects specific domains of SF to differing degrees. Compromised erectile function is most commonly reported among these specific domains and seems to play a more dominant role in determining overall SF, but notably none of the domains of function were closely linked to SB. Because education is protective in the perception of bother, appropriate counselling and the setting of expectations for outcomes in overall and specific domains of SF might lead to improved quality of life after treatment for prostate cancer.

Survival outcomes in an older US population with advanced melanoma and central nervous system metastases: SEER-Medicare analysis.

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.

The impact of obesity on overall and cancer specific survival in men with prostate cancer.

PURPOSE: We examined the impact of obesity on disease specific and overall survival in patients with prostate cancer. MATERIALS AND METHODS: We identified 7,274 men from the Cancer of the Prostate Strategic Urological Research Endeavor database with clinically localized prostate cancer, known body mass index and clinicopathological disease characteristics. Patients were classified by body mass index as normal (less than 25 kg/m(2)), overweight (25 to 29.9 kg/m(2)), obese (30 to 34.9 kg/m(2)) and severely obese (35 kg/m(2) or greater). Associations between body mass index and need for secondary treatment, disease specific survival and overall survival were analyzed using univariate and multivariate models. RESULTS: Patients were classified by body mass index category as normal (28.8%), overweight (50%), obese (16.4%) and very obese (4.8%). Mean followup was 51.3 +/- 38.5 months. During followup there were 1,044 deaths with 220 (21.1%) from prostate cancer. Stratified by body mass index category the groups differed with regard to the need for secondary treatment (p = 0.05) and overall mortality (p <0.01) but there were no significant differences with regard to disease specific survival (p = 0.09). On multivariate analysis age 65 to 74 years (HR 2.4, p = 0.002), age older than 75 years (HR 3.2, p = 0.0001), high risk disease (HR 1.6, p <0.0001), conservative treatment (HR 1.2, p <0.0001) and presence of diabetes (HR 1.6, p <0.0001) were associated with decreased overall survival. Only conservative treatment (HR 1.4, p <0.0001), high risk disease (HR 8.4, p <0.0001) and intermediate risk disease (HR 2.5, p = 0.004) were associated with decreased disease specific survival. CONCLUSIONS: In a prospective, community based cohort we were unable to establish a relationship between body mass index and prostate cancer disease specific survival or overall survival.