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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Androgen deprivation therapy and cardiovascular risk.

PURPOSE: The potential association between androgen deprivation therapy (ADT) and cardiovascular mortality (CVM) remains controversial. This study assessed mortality outcomes in a large national registry to further elucidate the association between treatment selection and cause of mortality. PATIENTS AND METHODS: A total of 7,248 men in the CaPSURE registry were analyzed. Treatment was categorized as local only, primary ADT monotherapy, local treatment plus ADT, and watchful waiting/active surveillance (WW/AS). Competing hazards survival analysis was performed for prostate cancer-specific mortality (PCSM), CVM, and all-cause mortality. A propensity score-adjusted and a propensity-matched analysis were undertaken to adjust for imbalances in covariates among men receiving various treatments. RESULTS: Patients treated with ADT or WW/AS had a higher likelihood of PCSM than those treated with local therapy alone. Patients treated with primary ADT had an almost two-fold greater likelihood of CVM (HR, 1.94; 95% CI, 1.29 to 2.97) than those treated with local therapy alone; however, patients treated with WW/AS had a greater than two-fold increased risk of CVM (HR, 2.46; 95% CI, 1.53 to 3.95). A propensity-matching algorithm in a subset of 1,391 patients was unable to find a significant difference in CVM between those who did or did not receive ADT. CONCLUSION: Patients matched on propensity to receive ADT did not show an association between ADT and CVM. This suggests that potential unmeasured variables affecting treatment selection may confound the relationship between ADT use and cardiovascular risk. However, an association may yet exist, because the propensity score could not include all known risk factors for CVM.

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.

Inaccuracies in assignment of clinical stage for localized prostate cancer.

BACKGROUND: Recent data have suggested that clinical T stage is not independently associated with biochemical recurrence of localized prostate cancer after radical prostatectomy. One explanation for this lack of predictive power may be the inaccurate application of staging criteria. METHODS: Data from men in the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) database with localized prostate cancer (clinical T1-T2) were analyzed. Correct stage was determined by digital rectal examination (DRE) and transrectal ultrasound (TRUS) findings and was compared with the clinical stage reported directly by the practitioner. DRE/TRUS findings and biopsy results were evaluated to determine factors influencing staging errors. The ability of corrected stage to predict biochemical disease recurrence after prostatectomy was assessed using multivariable analysis. RESULTS: Clinical stage was assigned incorrectly in 1370 of 3875 men (35.4%). Errors more commonly resulted in patient downstaging than upstaging (55.1% vs 44.9%; P < .001). Patients with TRUS lesions were more likely to be staged incorrectly than those with abnormal DRE findings (65.8% vs 38.2%; P < .001). Biopsy laterality was found to strongly influence stage assignment. Even after correction of staging errors, there was no association noted between clinical stage and biochemical disease recurrence after radical prostatectomy. CONCLUSIONS: Errors in applying clinical staging criteria for localized prostate cancer are common. TRUS findings are frequently disregarded, and practitioners incorrectly incorporate biopsy results when assigning stage. However, staging errors do not appear to account for the inconsistent reliability of clinical stage in predicting prostate cancer outcomes. These findings further challenge the utility of a DRE-based and/or TRUS-based staging system for risk assessment of localized prostate cancer.

Fertility treatments and outcomes among couples seeking fertility care: data from a prospective fertility cohort in the United States.

OBJECTIVE: To determine the relationship between number of fertility treatment cycles and pregnancy rates. DESIGN: Prospective cohort study. SETTING: Eight community and academic infertility practices. PATIENT(S): Four hundred eight (408) couples presenting for an infertility evaluation. INTERVENTION(S): Face-to-face and telephone interviews and questionnaires. MAIN OUTCOME MEASURE(S): Incidence of pregnancy. Cox regression analysis compared the efficacy of cycle-based fertility treatments with no cycle-based fertility treatment after multivariable adjustment. RESULT(S): Couples using one to two medications-only cycles had a significantly higher pregnancy rate (hazard ratio [HR] 4.7 [95% confidence interval 1.3-16.6]), a benefit that did not persist after three or more cycles (HR 0.6 [0.1-3.2]). Couples using IUI for one (HR 2.9 [1.4-5.8]), two (HR 2.0 [0.9-4.5]), and three cycles (HR 4.5 [1.8-10.9]) were more likely to achieve a pregnancy. No additional benefit was seen for couples using four or more IUI cycles (HR 1.0 [0.4-2.6]). In vitro fertilization was associated with significant benefit for couples using one (HR 2.8 [1.5-5.2]) and two cycles (HR 2.2 [1.2-4.1]). Couples using three or more IVF cycles had a non-statistically significant higher likelihood of pregnancy (HR 1.3 [0.7-2.4]). CONCLUSION(S): Cycle-based fertility treatments may offer a point of diminishing returns for infertile couples: two cycles of medications only, three cycles of IUI, and two cycles of IVF.