Search

Surrogate endpoints (SEs), such as progression-free survival (PFS) and objective response rate (ORR), are frequently used in clinical trials. The relationship between SEs and overall survival (OS) has not been well described in metastatic urothelial cancer (MUC).We evaluated trial-level data to assess the relationship between SEs and OS. We hypothesize a moderate surrogacy relationship between both PFS and ORR with OS.We systematically reviewed phase 2/3 trials in MUC with two or more treatment arms, and report PFS and/or ORR, and OS.Linear regression was performed, and the coefficient of determination (ROf 3791 search results, 59 trials and 62 comparisons met the inclusion criteria. Of the 53 trials that reported PFS, 31 (58%) reported proportional hazard regression for PFS and OS. Linear regression across trials demonstrated an RPFS provides only a moderate level of surrogacy for OS; An HRWe examined the relationship between surrogate endpoints, common outcomes in clinical trials, with survival in urothelial cancer trials. Progression-free survival is moderately correlated, while objective response rate had a poor correlation with survival and should be de-emphasized as a primary endpoint.

Health-related quality of life (HRQoL) among patients with localized prostate cancer (PC) on active surveillance (AS) and whether it may be improved through lifestyle-focused interventions remain underdefined.To assess longitudinal changes in HRQoL in patients who received and those who did not receive a behavioral intervention that increased vegetable intake.A secondary analysis of participants in the Men's Eating and Living (MEAL) study (Cancer and Leukemia Group 70807 [Alliance]), a randomized trial of vegetable consumption in patients on AS, was conducted.Patient-reported outcomes (PROs) included the Memorial Anxiety Scale for Prostate Cancer (MAX-PC), the Expanded Prostate Cancer Index Composite 26 (EPIC-26), and the Functional Assessment of Cancer Therapy Scale-Prostate (FACT-P). Areas under the curves (AUCs) were used to summarize serial HRQoL.PROs were completed in 87% (n = 387) of the intention-to-collect population. Baseline characteristics of patients completing HRQoL measures did not differ significantly from the entire study population or between groups. Baseline scores were high for all PROs and remained stable over 24 mo, with no significant differences from baseline at any time point. In adjusted analyses, there were no significant differences in summary AUC measures comparing control with intervention for the total MAX-PC score (p = 0.173); EPIC-26 domains of urinary incontinence (p = 0.210), urinary obstruction (p = 0.062), bowel health (p = 0.607), sexual health (p = 0.398), and vitality (p = 0.363); and total FACT-P scores (p = 0.471).Among men with localized PC on AS enrolled in a randomized trial, HRQoL was high across multiple domains at baseline, remained high during follow-up, and did not change in response to a behavioral intervention that increased vegetable intake.Patients with localized prostate cancer enrolled on active surveillance experience minimal cancer-associated anxiety, suffer low levels of cancer-associated symptoms, and perceive high physical and emotional well-being.

Treatment paradigms for management of metastatic renal cell carcinoma (mRCC) are evolving. We examined impact of surgical metastasectomy on survival across in mRCC stratified by risk-group.Multicenter retrospective analysis from the Registry of Metastatic RCC database. The cohort was subdivided utilizing Motzer criteria (favorable-, intermediate-, high-risk). Primary outcome was all-cause mortality (ACM)/overall survival (OS); secondary outcome was cancer-specific mortality (CSM)/cancer-specific survival (CSS). Impact of metastasectomy was analyzed via Cox-Regression analysis adjusting for potential prognostic variables and Kaplan-Meier analysis (KMA) within each risk-group.Four hundred thirty-one patients (59 favorable-risk, 274 intermediate-risk, 98 high-risk; median follow-up 27.2 months) were analyzed. Metastasectomy was performed in 22 (37%), 66 (24%), and 32 (16%) of favorable-, intermediate- and high-risk groups (P = .012). Median number of metastases at diagnosis differed significantly (favorable-risk 2, intermediate-risk 3.4, high-risk 5.1, P.001). On Cox-regression, high-risk (HR = 1.72, P = .002) was associated with worsened ACM, while metastasectomy was associated with improved ACM (HR = 0.56, P = .005). On KMA, median OS (months) was longer with metastasectomy in favorable- (92.7 vs. 25.8, P = .003) and intermediate-risk (26.3 vs. 20.1, P = .038), but not high-risk (P = .911) groups. Metastasectomy was associated with longer CSS in favorable- (76.1 vs. 32.8, P = .004) but not intermediate- (P = .06) and high-risk (P = .595) groups.Metastasectomy was independently associated with improved ACM and CSM, as well as improved CSS and OS in favorable- and intermediate-risk mRCC patients. Metastasectomy may be considered as component of multimodal management strategy in favorable and intermediate-risk subgroups. In high-risk patients, metastasectomy should be deferred except in select circumstances.

Chronic lung disease is often accompanied by disabling extrapulmonary symptoms, notably skeletal muscle dysfunction and atrophy. Moreover, the severity of respiratory symptoms correlates with decreased muscle mass and in turn lowered physical activity and survival rates. Previous models of muscle atrophy in chronic lung disease often modeled COPD and relied on cigarette smoke exposure and LPS-stimulation, but these conditions independently affect skeletal muscle even without accompanying lung disease. Moreover, there is an emerging and pressing need to understand the extrapulmonary manifestations of long-term post-viral lung disease (PVLD) as found in Covid-19. Here, we examine the development of skeletal muscle dysfunction in the setting of chronic pulmonary disease using a mouse model of PVLD caused by infection due to the natural pathogen Sendai virus. We identify a significant decrease in myofiber size when PVLD is maximal at 49 d after infection. We find no change in the relative types of myofibers, but the greatest decrease in fiber size is localized to fast-twitch type IIB myofibers based on myosin heavy chain immunostaining. Remarkably, all biomarkers of myocyte protein synthesis and degradation (total RNA, ribosomal abundance, and ubiquitin-proteasome expression) were stable throughout the acute infectious illness and chronic post-viral disease process. Together, the results demonstrate a distinct pattern of skeletal muscle dysfunction in a mouse model of long-term PVLD. The findings thereby provide new insight into prolonged limitations in exercise capacity in patients with chronic lung disease after viral infections and perhaps other types of lung injury.

Introduction: Evidence is unclear for invention in patients with a mild stroke (low NIHSS) and LVO (large vessel occlusion) as only 15-17 patients with NIHSS < 6 were included in the randomized trials. Cohort studies report good and poor outcomes in low NIHSS LVO cases, with some reporting poor complications secondary to complications and associated with burden of chronic illness. The THRIVE (Total Health Risk in Vascular Events) score was previously associated with poor outcomes in stroke patients. We hypothesized that the THRIVE score may be associated with poor outcomes in low NIHSS LVO patients. Methods: An IRB approved retrospective stroke study from January 2015 to December 2019 was used. Out of 2401 eligible acute ischemic stroke patients, 107 patients with an NIHSS < 6 with an LVO were included in the analysis. Non-parametric t-test, Chi-squared, and logistic regression were used for statistical analysis. Results: Of the 107 patients, the median age was 65 (55-74, interquartile range (IQR), 36% were female, 79% Caucasian, 44% had a discharge modified Rankin Score (mRS) of 0-1, 65% had a THRIVE score < 3, and time from LSN to presentation was 210 minutes (89 – 723 IQR). There was no difference in age, gender, race, time from LSN, or percent of patients with a THRIVE score < 3 (55% with IR vs 65% No IR). However, patients treated with a thrombectomy were significantly less likely to have a good neurologic outcome with discharge mRS of 0-1 if taken for thrombectomy (0% IR group versus 49% No IR, p= Conclusion: Decision-making on IR for patients with low NHISS should be tailored to the patient, as it is likely that the inherent clinical factors prompting thrombectomy to be considered despite the low NIHSS are the important driving factors increasing the likelihood of worse outcomes. Further research is needed to evaluate the type of neurologic deficits and the eloquence of the tissue involved.

Chronic lung disease is often accompanied by disabling extrapulmonary symptoms, notably skeletal muscle dysfunction and atrophy. Moreover, the severity of respiratory symptoms correlates with decreased muscle mass and in turn lowered physical activity and survival rates. Previous models of muscle atrophy in chronic lung disease often modeled COPD and relied on cigarette smoke exposure and LPS-stimulation, but these conditions independently affect skeletal muscle even without accompanying lung disease. Moreover, there is an emerging and pressing need to understand the extrapulmonary manifestations of long-term post-viral lung disease (PVLD) as found in Covid-19. Here, we examine the development of skeletal muscle dysfunction in the setting of chronic pulmonary disease using a mouse model of PVLD caused by infection due to the natural pathogen Sendai virus. We identify a significant decrease in myofiber size when PVLD is maximal at 49 d after infection. We find no change in the relative types of myofibers, but the greatest decrease in fiber size is localized to fast-twitch type IIB myofibers based on myosin heavy chain immunostaining. Remarkably, all biomarkers of myocyte protein synthesis and degradation (total RNA, ribosomal abundance, and ubiquitin-proteasome expression) were stable throughout the acute infectious illness and chronic post-viral disease process. Together, the results demonstrate a distinct pattern of skeletal muscle dysfunction in a mouse model of long-term PVLD. The findings thereby provide new insight into prolonged limitations in exercise capacity in patients with chronic lung disease after viral infections and perhaps other types of lung injury.

Patient with "very small" (2 cm) renal mass can be offered active surveillance, thermal ablation, or partial nephrectomy. The management strategy will consider patient preferences and prioritize potential harms associated with each of these options. To date, outcomes of robot-assisted partial nephrectomy (RAPN) in patients with "very small" renal masses have not been reported.To assess the outcomes of RAPN among patients with "very small" renal masses.This was a retrospective analysis of a multi-institutional database including RAPN cases performed at eight high-volume US and European centers between 2009 and 2019. Patients were stratified into two groups according to clinical tumor size:2 cm ("very small" renal mass, study group) and 2-4 cm (control group).RAPN for renal masses.Baseline characteristics and intraoperative, pathological, and postoperative data were compared between the study and the control group. A "trifecta" was used as surrogate of "surgical quality."Overall, a total of 1019 patients were included in the analysis. Of these, 352 had a renal mass of2 cm (34.5%) and 667 (65.5%) had a renal mass of 2-4 cm. At baseline, the study group presented a lower rate of chronic kidney disease ≥stage III (p0.001), a lower RENAL score (p = 0.001), and lower rates of hilar (p = 0.04) and endophytic (p = 0.02) masses. Warm ischemia time was shorter for the study group (median 14 vs 18 min, p0.001), which also showed a lower rate of overall postoperative complications (9.6% vs 14.7%, p0.001) and no major complications. In terms of oncological outcomes, three and ten patients developed a local recurrence in the study and the control group, respectively (p = 0.1). In the study group, higher estimated glomerular filtration rates were found at discharge (p = 0.001) and at the last follow-up (p = 0.007), which showed a "trifecta" achievement of 90.6%. The retrospective design may limit the generalizability of the findings.Whenever an active treatment is indicated or warranted, RAPN represents a minimally invasive management option for "very small" renal masses, as it carries minimal risk of complications and has minimal impact on renal function. While both active surveillance and kidney ablation remain valid management options in these cases, RAPN can be offered and discussed with patients as it provides excellent outcomes with low morbidity.In this report, we observed that robot-assisted partial nephrectomy represents a true minimally invasive active treatment for "very small" renal masses (2 cm), as it carries minimal risk of complications and has minimal impact on renal function.

Multicenter retrospective analysis of robotic partial nephrectomy for completely endophytic renal tumors (i.e. 3 points for the 'E' domain of the R.E.N.A.L. nephrometry score) was performed.Patients' demographics, tumor characteristics, perioperative, functional, pathological and oncological data were analyzed and compared with those of patients with exophytic and mesophytic masses (i.e. 1 and 2 points for the 'E' domain, respectively). Multivariable logistic regression analysis was used to assess variables for trifecta achievement (negative margin, no postoperative complications, and 90% estimated glomerular filtration rate [eGFR] recovery).Overall, 147 patients were included in the study group. Patients with a completely endophytic mass had bigger tumors (mean 4.2 vs. 4.1 vs. 3.2 cm; p 0.001) on preoperative imaging and higher overall R.E.N.A.L. score. There was no difference in mean operative time. Estimated blood loss was higher in the endophytic group (mean 177.75 vs. 185.5 vs. 130 ml; p = 0.001). Warm ischemia time was shorter for the exophytic group (median 16 vs. 21 vs. 22 min; p 0.001). Postoperative complications were more frequent in patients with endophytic tumor (24.8% vs. 19.5% vs. 14.8%; p 0.001). Six (4.5%) patients had positive surgical margins, there was no difference between groups. Trifecta was achieved in 44 patients in endophytic group (45.4 vs. 68.8 and 50.9%, p 0.001). Multivariable analysis for trifecta revealed that clinical tumor size (odds ratio: 0.667, 95% confidence interval: 0.56-0.79, p 0.001) was only significant predictor for trifecta achievement.Our findings confirm that RAPN in case of completely endophytic renal masses can be performed with acceptable outcomes in centers with significant robotic expertise.

Multiparametric MRI is highly sensitive for detection of clinically significant prostate cancer, but has a 10–20% false negative rate. It is unknown if there are clinical factors that predict MRI invisibility. We sought to identify predictors of MRI-invisible (MRI(−)) disease. Men undergoing MRI/US-fusion targeted + systematic biopsy by two surgeons at our institution from 2015 to 2018 were reviewed. Patient demographics, clinical data, MRI metrics, and biopsy pathology results were obtained by chart review. An MRI(−) tumor was defined as a positive systematic biopsy in a zone without an MRI lesion. Factors associated with presence of MRI(−) tumors were identified using stepwise multivariable logistic regression. Of 194 men included in the analysis, 79 (41%) and 25 (13%) men had GG1+ and GG2+ MRI(−) tumors, respectively. On multivariable analysis, only Black race was associated with presence of GG1+ MRI(−) tumors (OR 2.2, 95% CI 1.02–4.96). Black race (OR 3.5, 95% CI 1.24–9.87) and higher PSA density (OR 2.0, 95% CI 1.34–3.20) were associated with presence of GG2+ MRI(−) tumors. In non-Black and Black men, detection of MRI(−) tumors on systematic biopsy upgraded patients from no disease to GG2+ disease 1% and 11% of the time, respectively, and from GG1 to GG2+ disease 42% and 60% of the time, respectively. Black race and PSA density were associated with presence of MRI(−) prostate cancer. Further study on racial differences is warranted based on these results. Surgeons should consider pre-biopsy risk factors before deciding to omit systematic prostate biopsy regardless of mpMRI results.

OBJECTIVE To evaluate patient-specific and perioperative factors that may be predictive of bladder perforation during midurethral sling placement. METHODS A retrospective chart review of women who underwent a midurethral sling procedure at our institution between 2013 and 2017 was completed. All cases with bladder perforation were included. Patient demographics and perioperative factors were explored for associations with perforation. Bivariate analysis was used to compare baseline characteristics between those with and without perforation. Logistic regression modeling was used to identify predictors of perforation and associations between bladder perforation and postoperative sequelae. RESULTS Four hundred and ten women had a urethral sling procedure at our institution between 2013 and 2017. Of these, 35 (9%) had evidence of bladder perforation on cystoscopy. This rate was higher for retropubic slings (15%) compared to transobturator slings (2%). Those with a perforation were younger (54 vs 61 years, P= .004) and had a lower average BMI (24.1 kg/m2 vs 26.3 kg/m2, P = .022). Other risk factors included lack of pre-existing apical prolapse (11% vs 4%, P = .012) and concomitant urethrolysis (27% vs 8%, P = .024). In multivariable analysis, age, BMI, and sling type were significantly associated with perforation. In univariate analysis, perforation was associated with postoperative lower urinary tract symptoms (OR 2.3, P = .21) and urinary tract infection within 30 days of surgery (OR 2.2, P = .047). CONCLUSIONS Intraoperative bladder perforation was associated with younger patient age and lower BMI. Additionally, bladder perforation is a risk factor for postoperative urinary tract infection and lower urinary tract symptoms.

Introduction:Patients who are older and sicker are ideal candidates for bladder sparing therapy for muscle invasive bladder cancer given risks of treatment related morbidity with radical cy...

AIM To analyze the cost impact of cesarean versus vaginal delivery in the United States on the development of stress urinary incontinence (SUI) and pelvic organ prolapse (POP). METHODS We compared average cost of delivery method to the lifetime risk and cost of pelvic floor disorders (PFDs) in women

Cancer vaccines, cytokines, and checkpoint inhibitors are immunotherapeutic agents that act within the cancer immunity cycle. Prostate cancer has provided unique opportunities for, and challenges to, immunotherapy drug development, including low tumor mutational burdens, limited expression of PD-L1, and minimal T-cell intratumoral infiltrates. Nevertheless, efforts are ongoing to help prime prostate tumors by turning a "cold" prostate cancer "hot" and thus rendering them more susceptible to immunotherapy. Combination treatments, use of molecular biomarkers, and use of new immunotherapeutic agents provide opportunities to enhance the immune response to prostate tumors.

To compare functional outcomes of partial nephrectomy (PN) and active surveillance (AS) in oncocytoma. Multicenter retrospective analysis of patients with oncocytoma managed with PN or AS (biopsy-confirmed). Primary outcome development of de novo chronic kidney disease (CKD) (eGFR

BACKGROUND The impact of race on prostate cancer skeletal-related events (SREs) remains understudied. In the current study, the authors tested the impact of race on time to SREs and overall survival in men with newly diagnosed, bone metastatic castration-resistant prostate cancer (mCRPC). METHODS The authors performed a retrospective study of patients from 8 Veterans Affairs hospitals who were newly diagnosed with bone mCRPC in the year 2000 or later. SREs comprised pathologic fracture, spinal cord compression, radiotherapy to the bone, or surgery to the bone. Time from diagnosis of bone mCRPC to SREs and overall mortality was estimated using the Kaplan-Meier method. Cox models tested the association between race and SREs and overall mortality. RESULTS Of 837 patients with bone mCRPC, 232 patients (28%) were black and 605 (72%) were nonblack. At the time of diagnosis of bone mCRPC, black men were found to be more likely to have more bone metastases compared with nonblack men (29% vs 19% with ≥10 bone metastases; P = .021) and to have higher prostate-specific antigen (41.7 ng/mL vs 29.2 ng/mL; P = .005) and a longer time from the diagnosis of CRPC to metastasis (17.9 months vs 14.3 months; P

OBJECTIVES: Chronic idiopathic constipation (CIC) is characterized by unsatisfactory defecation and difficult or infrequent stools. CIC affects 9%–20% of adults in the United States, and although prevalent, gaps in knowledge remain regarding CIC healthcare seeking and medication use in the community. We recruited a population-based sample to determine the prevalence and predictors of (i) individuals having discussed their constipation symptoms with a healthcare provider and (ii) the use of constipation therapies. METHODS: We recruited a representative sample of Americans aged 18 years or older who had experienced constipation. Those who met the Rome IV criteria for irritable bowel syndrome and opioid-induced constipation were excluded. The survey included questions on constipation severity, healthcare seeking, and the use of constipation medications. We used multivariable regression methods to adjust for confounders. RESULTS: Overall, 4,702 participants had experienced constipation (24.0% met the Rome IV CIC criteria). Among all respondents with previous constipation, 37.6% discussed their symptoms with a clinician (primary care provider 87.6%, gastroenterologist 26.0%, and urgent care/emergency room physician 7.7%). Age, sex, race/ethnicity, marital status, employment status, having a source of usual care, insurance status, comorbidities, locus of control, and constipation severity were associated with seeking care (P < 0.05). Overall, 47.8% of respondents were taking medication to manage their constipation: over-the-counter medication(s) only, 93.5%; prescription medication(s) only, 1.3%; and both over-the-counter medication(s) and prescription medication(s), 5.2%. DISCUSSION: We found that 3 of 5 Americans with constipation have never discussed their symptoms with a healthcare provider. Furthermore, the use of prescription medications for managing constipation symptoms is low because individuals mainly rely on over-the-counter therapies.

Background: Most hospitalized patients with inflammatory bowel disease (IBD) experience pain. Despite the known risks associated with opioids in IBD including risk for misuse, overdose, infection, readmission, and even death, opioid use is more prevalent in IBD than any other chronic gastrointestinal condition. Most hospitalized IBD patients receive opioids; however, opioids have not been shown to improve pain during hospitalization. Methods: We conducted a randomized controlled trial in hospitalized patients with IBD to evaluate the impact of a proactive opioid-sparing analgesic protocol. Wearable devices measured activity and sleep throughout their hospitalization. Chronic opioid users, post-operative, and pregnant patients were excluded. The primary endpoint was a change in pain scores from admission to discharge. Secondary endpoints included opioid use, functional activity, sleep duration and quality, and length of stay.Results: Of 329 adults with IBD evaluated for eligibility, 33 were enrolled and randomized to the intervention or usual care. Both the intervention and control group demonstrated significant decreases in pain scores from admission to discharge (-2.6±2.6 vs. -3.0±3.2). Those randomized to the intervention had lower pain scores than the control group regardless of hospital day (3.02±0.90 vs 4.29±0.81, p=0.059), used significantly fewer opioids (daily MME 11.8±15.3 vs 30.9±42.2, p=0.027), and had a significantly higher step count by Day 4 (2330±1709 vs 1050±1214; p=0.014). There were no differences in sleep duration, sleep quality, readmission, or length-of-stay between the two groups.Conclusions: A proactive analgesic protocol does not result in worsening pain but does significantly reduce opioid-use in hospitalized IBD patients.

Background Radical nephroureterectomy (RNU) represents the standard of care for high grade upper tract urothelial carcinoma (UTUC). Open and laparoscopic approaches are well-established treatments, but evidence regarding robotic RANU is growing. The introduction of the Xi® system facilitates the implementation of this multi-quadrant procedure. The aim of this video-article is to describe the surgical steps and the outcomes of Xi® robotic RNU. Methods Single stage Xi® robotic RNU without patients repositioning and robot re-docking were done between 2015 and 2019 and collected in a large worldwide multi-institutional study, the ROBotic surgery for Upper tract Urothelial cancer STudy (ROBUUST). Institutional review board approval and data share agreement were obtained at each center. Surgical technique is described in detail in the accompanying video. Descriptive statistics of baseline characteristics and surgical, pathological, and oncological outcomes were analyzed. RESULTSː Overall, 148 patients were included in the analysis; 14% had an ECOG >1 and 68.2% ASA ≥3. Median tumor dimension was 3.0 (IQR:2.0-4.2) cm and 34.5% showed hydronephrosis at diagnosis. Forty-eight% were cT1 tumors. Bladder cuff excision and lymph node dissection were performed in 96% and 38.1% of the procedures, respectively. Median operative time and estimated blood loss were 215.5 (IQR:160.5-290.0) minutes and 100.0 (IQR: 50.0-150.0) mL, respectively. Approximately 56% of patients took opioids during hospital stay for a total morphine equivalent dose of 22.9 (IQR:16.0-60.0) milligrams equivalent. Postoperative complications were 26 (17.7%), with 4 major (15.4%). Seven patients underwent adjuvant chemotherapy, with median number of cycles of 4.0 (IQR:3.0-6.0). Conclusions Single stage Xi® RNU is a reproducible and safe minimally invasive procedure for treatment of UTUC. Additional potential advantages of the robot might be a wider implementation of LND with a minimally invasive approach.

Background CDK12 inactivation leading to increased neoantigen burden has been hypothesized to sensitize tumors to immune checkpoint inhibition. Pan‐cancer data regarding the frequency of CDK12 alterations are limited. We aimed to characterize CDK12 alterations across all cancer types through real‐world clinical‐grade sequencing. Methods This was a single‐center retrospective analysis of 4994 cancer patients who underwent tissue or blood genomic profiling, including CDK12 assessment, conducted as part of routine care from December 2012 to January 2020. Prevalence, clinical characteristics, and treatment outcomes of patients with tumors with pathogenic CDK12 alterations were described. Results In all, 39 (0.78%, n = 39/4994) patients had pathogenic CDK12 alterations. Among CDK12‐altered tumors, the most common organ site was prostate (n = 9, 23.1%) followed by colorectal (n = 5, 12.8%). Adenocarcinoma was the most common histology (n = 26, 66.7%). Median follow‐up from time of diagnosis was 4.02 years. Median overall survival from time of metastasis was 4.43 years (95% CI: 3.11–5.74). Ten patients with CDK12‐altered tumors received at least one immune checkpoint inhibitor‐containing regimen. The majority of patients (n = 6/10, 60%) experienced an objective response. Progression‐free survival for patients who had metastatic disease and received a checkpoint inhibitor‐containing regimen was 1.16 years (95% CI: 0.32–2.00). Conclusion CDK12 alterations are rare events across hematologic and solid tumor malignancies. They represent a clinically distinct molecular cancer subtype which may have increased responsiveness to checkpoint inhibition. Prospective studies are warranted to investigate checkpoint inhibition in CDK12‐altered tumors.

Mapping protein interactions driving cancer Cancer is a genetic disease, and much cancer research is focused on identifying carcinogenic mutations and determining how they relate to disease progression. Three papers demonstrate how mutations are processed through networks of protein interactions to promote cancer (see the Perspective by Cheng and Jackson). Swaney et al . focus on head and neck cancer and identify cancer-enriched interactions, demonstrating how point mutant–dependent interactions of PIK3CA, a kinase frequently mutated in human cancers, are predictive of drug response. Kim et al . focus on breast cancer and identify two proteins functionally connected to the tumor-suppressor gene BRCA1 and two proteins that regulate PIK3CA. Zheng et al . developed a statistical model that identifies protein networks that are under mutation pressure across different cancer types, including a complex bringing together PIK3CA with actomyosin proteins. These papers provide a resource that will be helpful in interpreting cancer genomic data. —VV

Patients with high-risk localized prostate cancer benefit from multimodality therapy of curative intent. Androgen-deprivation therapy (ADT) combined with radiation improves survival in this population. However, prior clinical trials of neoadjuvant ADT and surgery failed to consistently demonstrate a survival advantage. The development of novel, more potent hormonal agents presents an opportunity to revisit the potential for neoadjuvant therapy to improve long-term outcomes for patients with localized prostate cancer. We review recent advances in neoadjuvant approaches for prostate cancer and emerging clinical trials data supporting the use of neoadjuvant therapy prior to radical prostatectomy.

INTRODUCTION AND OBJECTIVE:Impact of lymph node dissection (LND) at the time of radical nephrectomy (RN) for renal cell carcinoma (RCC) remains contentious, though the prognostic benefit in advance...

INTRODUCTION AND OBJECTIVE:Management of small renal masses (SRM) represents a therapeutic quandary given the low oncologic risk of most tumors and increasing incidental detection. We investigated ...

Key Points Question Was the Patient Protection and Affordable Care Act (ACA) associated with changes in insurance coverage and stage of diagnosis for patients with renal cell carcinoma (RCC), and were differences based on income? Findings In this cohort study of 78 099 patients with RCC, the ACA was associated with increased insurance coverage through Medicaid for low-income patients and detection at an earlier stage of disease. Insurance coverage increased to a greater degree in states that expanded their Medicaid eligibility. Meaning These findings suggest that the ACA was associated with significant increases in insurance coverage for lower-income patients and early diagnosis of RCC., Importance The association of the Patient Protection and Affordable Care Act (ACA) with insurance status and cancer stage at diagnosis among patients with renal cell carcinoma (RCC) is unknown. Objective To test the hypothesis that the ACA may be associated with increased access to care through expansion of insurance, which may vary based on income. Design, Setting, and Participants This retrospective cohort analysis included patients diagnosed with RCC from January 1, 2010, to December 31, 2016, in the National Cancer Database. Data were analyzed from July 1 to December 31, 2020. The periods from 2010 to 2013 and from 2014 to 2016 were defined as pre- and post-ACA implementation, respectively. Patients were categorized as living in a Medicaid expansion state or not. Exposures Implementation of the ACA. Main Outcomes and Measures The absolute percentage change (APC) of insurance coverage was calculated before and after ACA implementation in expansion and nonexpansion states. Secondary outcomes included change in stage at diagnosis, difference in the rate of insurance change, and change in localized disease between expansion and nonexpansion states. Adjusted difference-in-difference modeling was performed. Results The cohort included 78 099 patients (64.7% male and 35.3% female; mean [SD] age, 54.66 [6.46] years), of whom 21.2% had low, 46.2% had middle, and 32.6% had high incomes. After ACA implementation, expansion states had a lower proportion of uninsured patients (adjusted difference-in-difference, −1.14% [95% CI, −1.98% to −1.41%]; P = .005). This occurred to the greatest degree among low-income patients through the acquisition of Medicaid (APC, 11.0% [95% CI, 8.6%-13.3%]; P, This cohort study tests the hypothesis that implementation of the Patient Protection and Affordable Care Act may be associated with increased access to care through expansion of insurance, which may vary based on income, among patients with renal cell carcinoma.

To assess the outcomes of retroperitoneal robot-assisted partial nephrectomy (r-RAPN) in a large cohort of patients with postero-lateral renal masses comparing to those of transperitoneal RAPN (t-RAPN). Patients with posterior (R.E.N.A.L. score grading P) or lateral (grading X) renal mass who underwent RAPN in six high-volume US and European centers were identified and stratified into two groups according to surgical approach: r-RAPN (“study group”) and t-RAPN (“control group”). Baseline characteristics, intraoperative, and postoperative data were collected and compared. Overall, 447 patients were identified for the analysis. 231 (51.7%) and 216 (48.3%) patients underwent r-RAPN and t-RAPN, respectively. Baseline characteristics were not statistically significantly different between the groups. r-RAPN group reported lower median operative time (140 vs. 170 min, p

Cancer vaccines, cytokines, and checkpoint inhibitors are immunotherapeutic agents that act within the cancer immunity cycle. Prostate cancer has provided unique opportunities for, and challenges to, immunotherapy drug development, including low tumor mutational burdens, limited expression of PD-L1, and minimal T-cell intratumoral infiltrates. Nevertheless, efforts are ongoing to help prime prostate tumors by turning a "cold" prostate cancer "hot" and thus rendering them more susceptible to immunotherapy. Combination treatments, use of molecular biomarkers, and use of new immunotherapeutic agents provide opportunities to enhance the immune response to prostate tumors.

Objective To test for an association between surgical delay and overall survival (OS) for patients with T2 renal masses. Many health care systems are balancing resources to manage the current COVID-19 pandemic, which may result in surgical delay for patients with large renal masses. Methods Using Cox proportional hazard models, we analyzed data from the National Cancer Database for patients undergoing extirpative surgery for clinical T2N0M0 renal masses between 2004 and 2015. Study outcomes were to assess for an association between surgical delay with OS and pathologic stage. Results We identified 11,848 patients who underwent extirpative surgery for clinical T2 renal masses. Compared with patients undergoing surgery within 2 months of diagnosis, we found worse OS for patients with a surgical delay of 3-4 months (hazard ratio [HR] 1.12, 95% confidence interval [CI] 1.00-1.25) or 5-6 months (HR 1.51, 95% CI 1.19-1.91). Considering only healthy patients with Charlson Comorbidity Index = 0, worse OS was associated with surgical delay of 5-6 months (HR 1.68, 95% CI 1.21-2.34, P= .002) but not 3-4 months (HR 1.08, 95% CI 0.93-1.26, P = 309). Pathologic stage (pT or pN) was not associated with surgical delay. Conclusion Prolonged surgical delay (5-6 months) for patients with T2 renal tumors appears to have a negative impact on OS while shorter surgical delay (3-4 months) was not associated with worse OS in healthy patients. The data presented in this study may help patients and providers to weigh the risk of surgical delay versus the risk of iatrogenic SARS-CoV-2 exposure during resurgent waves of the COVID-19 pandemic.

OBJECTIVE To investigate association of preoperative C-reactive protein (CRP) and non-cancer mortality (NCM) in a cohort of patients undergoing surgery for localised renal cell carcinoma (RCC). PATIENTS AND METHODS Retrospective multicentre analysis of patients surgically treated for clinical Stage 1-2 RCC from 2006 to 2017, excluding all cases of cancer-specific mortality. Descriptive analyses were obtained between the pre-treatment normal-CRP (≤5 mg/L) and elevated-CRP (>5 mg/L) groups. The primary outcome was NCM. The secondary outcomes included progression to de novo chronic kidney disease Stages 3-4 (estimated glomerular filtration rate [eGFR] of

Background and Aims Inflammation of the pouch after ileal pouch-anal anastomosis (IPAA) can significantly impact quality of life and be difficult to treat. We assessed the effectiveness and safety of vedolizumab in Crohn’s disease (CD) of the pouch and chronic antibiotic-dependent or antibiotic-refractory pouchitis. Methods This was a retrospective, multicenter cohort study at 5 academic referral centers in the United States. Adult patients with endoscopic inflammation of the pouch who received vedolizumab were included. The primary outcome was clinical response at any time point. Secondary outcomes included clinical remission, endoscopic response, and remission. Univariate analysis and multivariate analysis were performed for the effect of the following variables on clinical response: fistula, onset of pouchitis less than 1 year after IPAA, younger than 35 years old, gender, previous tumor necrosis factor inhibitor-alpha use, and BMI >30. Results Eighty-three patients were treated with vedolizumab for inflammation of the pouch between January 2014 and October 2017. Median follow-up was 1.3 years (interquartile range 0.7–2.1). The proportion of patients that achieved at least a clinical response was 71.1%, with 19.3% achieving clinical remission. Of the 74 patients with a follow-up pouchoscopy, the proportion of patients with endoscopic response and mucosal healing was 54.1% and 17.6%, respectively. Patients who developed pouchitis symptoms less than 1 year after undergoing IPAA were less likely to respond to vedolizumab, even after controlling for other risk factors. Conclusions Vedolizumab is safe and effective in the management of CD of the pouch and chronic pouchitis. Further studies are needed to compare vedolizumab with other biologic therapies for pouchitis and CD of the pouch.

To evaluate trends and factors predicting use of renal mass biopsy (RMB) for localized Renal Cell Carcinoma in the United States (US) in the context of current guidelines recommendations.We queried the National Cancer Database for cT1-cT3N0M0 Renal Cell Carcinoma diagnosed between 2004 and 2015. Temporal trends of RMB were characterized based on tumor size, treatment (partial nephrectomy [PN], radical nephrectomy [RN], ablation, and no treatment), age and Charlson Comorbidity Index with slopes compared using analysis of variance. Multivariable analysis was used to determine factors associated with use of RMB.Of 338,252 patients analyzed, 11.9% (40,276) underwent RMB. Use of RMB increased throughout the study period from 1,586 (7.6%) in 2004 to 5,629 (16.2%) in 2015 (P0.001). Use of RMB increased greatest for ablation (27 to 63%, P0.001) and tumors 2-4 cm (9 to 20%, P0.001). Multivariable analysis showed year of diagnosis (OR = 1.06; P0.001), higher education (OR = 1.09; P0.001) and insured status (OR = 1.23; P0.001) were associated with increased RMB. Compared to tumors ≤2 cm, tumors 2.1-4 cm (OR = 1.36; P=0.001), 4.1-7 cm (OR = 1.18; P0.001) and7 cm (OR = 1.05; P = 0.03) were associated with higher rates of RMB. Compared to RN, PN was not associated with increased RMB (OR = 1.00; P = 0.92), while ablation (OR = 10.90; P0.001) and no surgical treatment (OR = 4.83; P0.001) were.RMB utilization increased overall, with largest increase associated with ablation. Nonetheless, only two-thirds of patients underwent RMB with ablation, suggesting persistent underutilization. Rates of RMB for tumors ≤2 cm and in those undergoing no treatment increased less, suggesting less utilization for surveillance. However, rates for tumors2-4 cm increased more, suggesting selective utilization of RMB to guide decision-making and risk stratification in small renal masses.

We sought to analyze the usefulness of pretreatment C-reactive protein (CRP) as a predictor of survival and oncological outcomes in patients with renal cell carcinoma (RCC).Retrospective international analysis of patients with RCC with pretreatment CRP values from 2006 to 2017. A CRP of more than5 mg/L was deemed elevated. The cohort was subdivided into 2 groups for analysis (normal CRP ≤5 mg/L; elevated CRP5). Primary outcome was overall survival (OS) and secondary outcome was recurrence-free survival (RFS). Kaplan-Meier analyses (KMA) and multivariable analyses (MVA) were used to delineate survival outcomes and their predictors.We analyzed 2445 patients (1641 male/804 female; normal CRP 1056/elevated CRP 1389; mean follow-up 36 months). Patients with elevated CRP had a higher incidence of hypertension (P = .001), higher body mass index (P.001), and larger tumor size (6.0 cm vs 3.9 cm; P.001). MVA for RFS demonstrated elevated CRP (hazard ratio [HR], 1.85; P = .005), tumor size (HR, 1.1; P.001), and high tumor grade (HR, 3.1; P.001) to be independent risk factors. For normal vs elevated CRP, KMA for RFS of stages 1-4 RCC revealed a 5-year RFS of 93% vs 88% (P = .001), 95% vs 83% (P = .163), 84% vs 62% (P = .001), and 58% vs 60% (P = .513), respectively. KMA MA KMA for OS of stages 1-4 RCC revealed a 5-year OS of 98% vs 81% (P = .001), 94% vs 80% (P = .103), 94% vs 65% (P = .001), and 99% vs 38% (P.001), respectively.Pretreatment CRP was an independent predictor of RFS and OS in an international multicenter cohort of patients with RCC.

INTRODUCTION AND OBJECTIVE:Upper tract urothelial cell carcinoma (UTUC) is an uncommon malignancy with disparate outcomes. We developed a novel pre-operative morphometric scoring system for predict...

INTRODUCTION AND OBJECTIVE:Impact of delay in treatment for localized renal cell carcinoma (RCC) is controversial. We sought to determine the survival impact of time to definitive surgical treatmen...