Anti-Androgen Therapy Overcomes the Time Delay in Initiation of Salvage Radiation Therapy and Rescues the Oncological Outcomes in Men with Recurrent Prostate Cancer After Radical Prostatectomy: A Post Hoc Analysis of the RTOG-9601 Trial Data.

BACKGROUND: It is unknown whether the addition of anti-androgen therapy (AAT) to late salvage radiation therapy (sRT) can lead to oncological outcomes equivalent to that of early sRT in men with recurrent prostate cancer (CaP) after surgery. METHODS: Data on 670 men who participated in the Radiation Therapy Oncology Group (RTOG)-9601 trial and who experienced biochemical recurrence were extracted using the National Clinical Trials Network (NCTN) data archive platform. Patients were stratified into four treatment groups: early sRT (pre-sRT prostate-specific antigen [PSA] < 0.7 ng/mL) and late sRT (pre-sRT PSA ≥ 0.7 ng/mL) with/without concomitant AAT, based on cut-offs reported in the original trial. Time-varying Cox proportional hazards and Fine-Gray competing-risk regression analyses assessed the adjusted hazards of overall mortality, CaP-specific mortality, and metastasis among the four treatment groups. RESULTS: At 15-years (median follow-up of 14.7 years), for patients treated with early sRT, early sRT with AAT, late sRT, and late sRT with AAT, the overall mortality, CaP-specific mortality, and metastasis rates were 22.9, 22.8, 40.1, and 22.9% (log-rank p = 0.0039), 12.1, 3.9, 22.7, and 8.0% (Gray's p = 0.0004), and 18.8, 14.6, 35.9, and 19.5% (Gray's p = 0.0004), respectively. Time-varying multivariable adjusted analysis demonstrated increased hazards of overall mortality in patients receiving delayed sRT versus early sRT (hazards ratio [HR] 1.49, 95% confidence interval [CI] 1.02-2.17); however, no difference remained after the addition of concomitant AAT to late sRT (HR 0.85, 95% CI 0.55-1.32, referent early sRT). Likewise, the hazards of cancer-specific mortality and metastatic progression were worse for late sRT when compared with early sRT, but were no different after the addition of AAT to late sRT. CONCLUSIONS: Poorer outcomes associated with late sRT in men with recurrent CaP may be rescued by delivery of concomitant AAT.

Basal Cell Carcinoma With Perineural Invasion: A Systematic Review and Pooled Survival Analysis.

BACKGROUND: Perineural invasion (PNI) is considered a high-risk histopathologic feature in many skin cancers. Perineural invasion is a well-known poor prognostic factor of squamous cell carcinoma, but is poorly understood in the context of basal cell carcinoma (BCC). OBJECTIVE: To analyze available demographic, clinical, and treatment data for BCC with PNI and the effect of these variables on recurrence patterns, disease progression, and cancer-specific mortality (CSM). METHODS: A systematic review and pooled-survival analysis was performed using case reports and series of patients with perineural BCC. RESULTS: This review included 159 patients from 49 publications. Of these cases, 57 patients reported at least one recurrence. Where reported, median follow-up time was 31 months for patients without recurrence ( n = 79) and 21 months for patients with recurrence ( n = 32). The cumulative incidence of CSM at 5 years was 8.5% (95% confidence interval [CI] 0.028-0.186) and the overall five-year survival was 90.9% (95% CI 0.796-0.961). CONCLUSION: Male gender, multifocal nerve involvement, presence of clinical symptoms, and PNI detected on imaging are associated with poor prognosis of BCC with PNI. The high rate of disease recurrence and suboptimal cumulative incidence of CSM highlights the importance of early clinical detection, before the onset of symptomatic PNI and multifocal nerve involvement.

Robotic Kidney Transplantation with Regional Hypothermia versus Open Kidney Transplantation for Patients with End Stage Renal Disease: An Ideal Stage 2B Study.

PURPOSE: We report on comparative effectiveness of minimally invasive versus traditional open kidney transplantation. MATERIALS AND METHODS: We undertook a prospective cohort study of 654 patients who underwent open or robotic kidney transplantation at a single tertiary care hospital between January 2013 and December 2015. Primary outcome was delayed graft function, defined as the need for dialysis within 1 week of surgery. Secondary outcomes included postoperative complications, pain, graft rejection, and graft and patient survival. Nonparsimonious propensity score and Ding-VanderWeele analytical methods were used to account for confounding bias. RESULTS: Within the 1:3 matched cohort (robotic 126, open 378; well matched with standardized mean difference ∼10%), the robotic approach was associated with lower rates of wound infections (0% vs 4%, p=0.023) and symptomatic lymphoceles (0% vs 7% at 36 months, p=0.003), as well as reduced postoperative pain, requirement for narcotic analgesia and blood loss. There were no differences between the 2 groups, robotic versus open, with respect to graft function (delayed graft function 0% vs 2.4%, p=0.081), hospital stay (median 8 days for both, p=0.647), graft rejection (16.2% vs 18.6% at 36 months, p=0.643), and graft (95.2% vs 96.3% at 36 months, p=0.266) and overall survival (94.5% vs 98.1% at 36 months, p=0.307). Ding-VanderWeele analysis suggested minimal influence of unknown confounders on study findings. CONCLUSIONS: Robotic kidney transplantation with regional hypothermia was associated with a lower rate of postoperative complications and improved patient comfort in comparison to open kidney transplantation. Graft function, and graft and overall survival were comparable between the 2 techniques.

COVID-19 Infection in Men on Testosterone Replacement Therapy.

BACKGROUND: Men who contract coronavirus disease 2019 (COVID-19) appear to have worse clinical outcomes compared with women which raises the possibility of androgen-dependent effects. AIM: We sought to determine if testosterone replacement therapy (TRT) is associated with worse clinical outcomes. METHODS: Through a retrospective chart review, we identified 32 men diagnosed with COVID-19 and on TRT. They were propensity score matched to 63 men diagnosed with COVID-19 and not on TRT. Data regarding comorbidities and endpoints such as hospital admission, intensive care unit admission, ventilator utilization, thromboembolic events, and death were extracted. Chi-square and Kruskal-Wallis tests examined differences in categorical and continuous variables, respectively. Logistic regression analysis tested the relationship between TRT status and the study endpoints. RESULTS: There were no statistically significant differences between the 2 groups, and TRT was not a predictor of any of the endpoints on multivariate analysis. CONCLUSION: These results suggest that TRT is not associated with a worse clinical outcome in men diagnosed with COVID-19. Rambhatla A, Bronkema CJ, Corsi N, et al. COVID-19 Infection in Men on Testosterone Replacement Therapy. J Sex Med 2021;18:215-218.

External validation of genomic classifier-based risk-stratification tool to identify candidates for adjuvant radiation therapy in patients with prostate cancer.

OBJECTIVE: To externally validate a Genomic Classifier (GC) based risk-stratification nomogram identifying candidates who would benefit from adjuvant radiation (aRT) therapy after radical prostatectomy (RP). METHODS: We identified 350 patients who underwent RP, between 2013 and 2018, and had adverse pathological features (positive margin, and/or pT3a or higher) on final pathology. Genomic profile was available for all these men. The clinical recurrence-free survival was estimated using the Kaplan-Meier method. The external validity of the nomogram was tested using the concordance index (c-index), calibration plot, and decision curve analysis. RESULTS: The median follow-up of the cohort was 26.5 months. Overall, 14% of the patients received aRT. During the follow-up period, 3.4% of the patients developed metastasis. Overall 3-year metastasis-free survival was 95% (95% CI 0.92-0.98). The c-index of the nomogram was 0.84. The calibration of the model was favorable. Decision-curve analysis showed a positive net benefit for probabilities ranging between 0.01 and 0.09, with the highest difference at threshold probability around 0.05. At that threshold, the net benefit is 0.06 for the model and 0 for treating all the patients. CONCLUSION: Our report is the first to confirm the validity of this genomic-based risk-stratification tool in identifying men who might benefit from aRT after RP. As such, it can be a useful instrument to be incorporated in shared decision making on whether administration of aRT will lead to a clinically meaningful benefit. Such a model can also be useful for patients' classification in future clinical trials.

Rare Histological Variants of Prostate Adenocarcinoma: A National Cancer Database Analysis.

PURPOSE: The American Joint Committee on Cancer recognizes 6 rare histological variants of prostate adenocarcinoma. We describe the contemporary presentation and overall survival of these rare variants. MATERIALS AND METHODS: We examined 1,345,618 patients who were diagnosed with prostate adenocarcinoma between 2004 and 2015 within the National Cancer Database. We focused on the variants mucinous, ductal, signet ring cell, adenosquamous, sarcomatoid and neuroendocrine. Characteristics at presentation for each variant were compared with nonvariant prostate adenocarcinoma. Cox regression was used to study the impact of histological variant on overall mortality. RESULTS: Few (0.38%) patients presented with rare variant prostate adenocarcinoma. All variants had higher clinical tumor stage at presentation than nonvariant (all p <0.001). Metastatic disease was most common with neuroendocrine (62.9%), followed by sarcomatoid (33.3%), adenosquamous (31.1%), signet ring cell (10.3%) and ductal (9.8%), compared to 4.2% in nonvariant (all p <0.001). Metastatic disease in mucinous (3.3%) was similar to nonvariant (p=0.2). Estimated 10-year overall survival was highest in mucinous (78.0%), followed by nonvariant (71.1%), signet ring cell (56.8%), ductal (56.3%), adenosquamous (20.5%), sarcomatoid (14.6%) and neuroendocrine (9.1%). At multivariable analysis, mortality was higher in ductal (HR 1.38, p <0.001), signet ring cell (HR 1.53, p <0.01), neuroendocrine (HR 5.72, p <0.001), sarcomatoid (HR 5.81, p <0.001) and adenosquamous (HR 9.34, p <0.001) as compared to nonvariant. CONCLUSIONS: Neuroendocrine, adenosquamous, sarcomatoid, signet ring cell and ductal variants more commonly present with metastases. All variants present with higher local stage than nonvariant. Neuroendocrine is associated with the worst and mucinous with the best overall survival.

Effect of Lesion Location on Prostate Cancer Detection Rate with Magnetic Resonance Imaging Targeted Biopsy in African Americans.

PURPOSE: The updated PI-RADS™ (Prostate Imaging Reporting and Data System) version 2 defines different grading parameters for lesions located in the peripheral zone vs the transition zone. It has contributed to the implementation of magnetic resonance imaging targeted biopsy. In this study we evaluated the efficacy of magnetic resonance imaging targeted biopsy among African American patients with additional consideration for lesion location on magnetic resonance imaging. MATERIALS AND METHODS: We performed a retrospective review of magnetic resonance imaging targeted biopsy at a single institution where a racially diverse population is treated. A single radiology group read the prostate multiparametric magnetic resonance imaging scans and followed PI-RADS version 2 algorithms to categorize lesions. RESULTS: A total of 214 lesions from 125 men were included in the analysis, of which 162 (75.7%) were in the peripheral zone and 52 (24.3%) were in the transition zone. There were 64 lesions from African American patients and 150 from Caucasian patients with tumor location distributed proportionately. The 48 anterior lesions (22.4%) had a higher PI-RADS version 2 score and trended toward a larger size. The overall cancer detection rate was 50%, which did not differ significantly between prostate zones (p = 0.5468) or racial groups (p = 0.2294). The cancer upgrade rate was 41% and it also did not differ significantly between prostate zones (p = 0.5134) or racial groups (p = 0.2365). Anterior lesions had a higher cancer detection rate (p = 0.0117) and trended toward a higher cancer upgrade rate (p = 0.0781). CONCLUSIONS: This study provides evidence that magnetic resonance imaging targeted biopsy is equally effective in African American and Caucasian men, and does not preferentially identify prostate cancer in the peripheral zone or the transition zone.

White Blood Cell and C-Reactive Protein Levels Are Similar in Obese Hispanic White Women Reporting Adherence to a Healthy Plant, Unhealthy Plant, or Animal-Based Diet, unlike in Obese Non-Hispanic White Women.

While modifying dietary patterns can reduce the effects of inflammation in obesity, less is known about the impact of dietary patterns on inflammation levels in women of different ethnicities. This study investigated the link between dietary patterns and mediators associated with inflammation, such as C-reactive protein (CRP) and white blood cells (WBCs), among obese Hispanic and Non-Hispanic White women. CRP and WBC counts were extracted from the National Health and Nutrition Examination Survey conducted between 2003 and 2010. Based on their recorded responses to two 24 h recall interviews, individuals were grouped into one of three dietary patterns: healthy plant-based, less healthy plant-based, or animal-based. Comparisons were run between obese Hispanic and Non-Hispanic women assigned to the same dietary pattern groups and between dietary pattern groups within ethnic groups. CRP and WBCs increased in obese Non-Hispanics as dietary patterns moved from healthy plant-based to animal-based (pCRP = 0.002 and pWBC = 0.017). Regardless of the dietary pattern, CRP and WBC expression were similar in Hispanic women. In addition, WBCs were higher in Hispanics compared to Non-Hispanics when both populations adhered to healthy plant and less healthy plant dietary patterns. The results indicate that dietary patterns may influence Hispanics' inflammation differently than Non-Hispanics.

Equivalence in osteoporosis workup and management after femoral neck fracture fixation and vertebral compression fracture cement augmentation: A single-center retrospective study highlighting persistent Underdiagnosis and Undertreatment.

Background: The purpose of this study was to evaluate pre- and post-fracture medical management of osteoporosis among patients who underwent surgical fixation of femoral neck fractures (FNF) and vertebral compression fractures (VCF), and to investigate if there is a difference in treatment, management, and subsequent fractures between FNF and VCF patients. Methods: Patients who underwent surgical fixation of FNF or VCF were retrospectively reviewed at a minimum 1 year follow up. Patients were excluded if their fracture was caused by high energy trauma or malignancy, <50 years-old, deceased, or lost to follow up. Patient demographics such as age, sex, BMI, American Society of Anesthesiology Physical Status Classification System and Charleston Comorbidity index were recorded. Management of osteoporosis, including medication regimen and dual-energy X-ray absorptiometry (DEXA) scans were assessed preoperatively and at minimum one year follow up. Subsequent fractures were also recorded. Results: In the analysis of 370 patients (74.7% FNF, 25.2% VCF), demographics showed a predominantly female population (mean age 78.1). Preoperatively, 21.6% were diagnosed with osteoporosis, consistent between FNF and VCF. Postoperatively, there were no significant differences in new osteoporosis diagnoses, bisphosphonate use, or subsequent fractures. VCF patients, however, were more likely to receive denosumab and post-operative DEXA scans (p < 0.05). Within a year, 6.2% experienced subsequent fractures, with no significant FNF-VCF difference. Only 12.7% received appropriate post-operative osteoporosis treatment, 27.1% had DEXA scans, and 25% had a recorded osteoporosis diagnosis. Multivariable analysis highlighted pre-fracture osteoporosis diagnosis as the sole predictor for post-operative DEXA scans and anti-osteoporotic medication (p < 0.001). Conclusions: This study suggests that factors beyond the type of fragility fracture may influence subsequent fracture risk and anti-osteoporotic medication administration in elderly patients. These findings underscore the importance of a comprehensive approach to fracture risk assessment and treatment decisions in this population. Level of evidence: III.

Electroencephalographic Patterns on Follow-Up Visits in Extremely Premature Infants With Periventricular Leukomalacia: An Observational Study.

BACKGROUND: Periventricular leukomalacia (PVL) is a common brain injury in premature infants, and epilepsy remains a significant complication. One concerning electroencephalographic (EEG) pattern found is developmental and/or epileptic encephalopathy with spike-and-wave activation in sleep (DEE-SWAS). This pattern is associated with persistent neuropsychological and motor deficits, even without a diagnosis of epilepsy. The purpose of this study is to identify the relationships between various PVL grades and EEG patterns in this population on follow-up visits, especially the occurrence of DEE-SWAS pattern on EEG. METHODS: This is a retrospective study of <36 weeks gestational age newborns who were followed in the neurodevelopmental clinic at Corewell Health East/Corewell Health Children's Hospital in Royal Oak, Michigan, between 2020 and 2022. Patients' demographics along with prematurity complications, diagnostic head ultrasound (HUS), and EEG studies were reviewed and graded. EEG studies are usually ordered when seizures were suspected. RESULTS: A total of 155 newborns met the inclusion criteria. Twenty-six patients had PVL. Nine patients had grade 2 to 3 PVL based on HUS review. EEG was performed on 15 patients with PVL at a mean age of 22 months. More severe PVL grades were significantly associated with worse EEG patterns (P = 0.005). Five patients had DEE-SWAS pattern on EEG, all of whom had grade 2 or 3 PVL. Epilepsy was eventually diagnosed in three infants with PVL. CONCLUSIONS: EEG can help identify important abnormal electrographic patterns in premature infants with PVL early in life; this might give a window of opportunity to intervene early and improve long-term developmental outcomes in this population.

Frailty Among Revision Total Knee Arthroplasty Recipients: Epidemiology and Propensity Score-weighted Analysis of Effect on In-hospital Postoperative Outcomes.

BACKGROUND: Frailty has been shown to correlate with worse outcomes after total knee arthroplasty (TKA), although less is known regarding its effect on revision TKA (rTKA). This study examines the epidemiologic characteristics and inpatient outcomes of patients with frailty undergoing rTKA. METHODS: Discharge data from National Inpatient Sample registry were used to identify all patients aged 50 years or older who underwent rTKA between 2006 and 2015. Patients were stratified into frail and nonfrail groupings, based on the presence of specific International Classification of Diseases-9 diagnostic coding. An analysis comparing the epidemiology, medical comorbidities, and propensity score-weighted postoperative clinical and economic outcomes of the two groups was done. RESULTS: From 2006 to the third quarter of 2015, a total of 576,920 patients (17,727 frail) who underwent rTKA were included. The average age in the study's population was 67.2 years, with a female distribution of 57.4%. Frail patients were more likely to exhibit markedly higher rates of almost all modified Elixhauser Comorbities than their nonfrail counterparts. Frail patients were also more likely to undergo different types of revisions, including an increased rate of removal of the prosthesis without replacement. In addition, frail patients displayed increased likelihood of experiencing any postoperative complication, deep vein thrombosis, postoperative anemia, respiratory complications, and wound dehiscence. Frail patients experienced lower rates of discharge home and increased length of stay than the nonfrail cohort. DISCUSSION: Patients with frailty undergoing rTKA are at markedly higher risk for inpatient postoperative complications and increased length of stay. Understanding the implications of frailty within rTKA is essential for risk assessment and preoperative optimization for this expanding population.

Pediatric Patients with Osteomyelitis and/or Septic Joint Undergoing Surgical Debridement Have Equivalent Short-Term Outcomes with or without Preoperative MRI.

The purpose of this study was to determine if short-term outcomes differed for pediatric patients with suspected musculoskeletal infection with or without a preoperative MRI. This was a multicenter, retrospective review of patients aged 0-16 years who presented with atraumatic extremity pain, underwent irrigation and debridement (I&D), and received at least one preoperative or postoperative MRI over a 10-year period. Primary outcomes were time to OR, total I&Ds, readmission rate, time from OR to discharge, and total number of MRIs. Secondary outcomes entailed the rate at which concurrent osteomyelitis was identified in patients with septic arthritis and the extent of the resulting surgical debridement. Of the 104 patients, 72.1% had a preoperative MRI. Patients with a preoperative MRI were significantly less likely to have surgery on the day of admission. No difference was found between groups regarding total I&Ds, readmission rate, time from OR to discharge, and total number of MRIs. Of the 57 patients diagnosed with septic arthritis, those with a preoperative MRI were significantly more likely to have concurrent osteomyelitis identified and to undergo bony debridement in addition to arthrotomy of the joint. In conclusion, patient outcomes are not adversely affected by obtaining a preoperative MRI despite the delay in time to OR. Although preoperative MRI can be beneficial in ruling out other pathologies and identifying the extent of concurrent osteomyelitis, the decision to obtain a preoperative MRI and timing of surgery should be left to the discretion of the treating surgeon.

The evolution of leadership: analyzing the presidents of American Dermatology Societies overtime.

Within organized dermatology, it is imperative that leaders embody a diverse group of individuals, reflective of the dermatologists they represent and the greater U.S. population. Despite women constituting more than half of the dermatologic workforce, they represent a leadership minority in dermatology society higher level positions. This gap is evident by fewer women holding presidency positions within prominent dermatological societies; however, a comprehensive comparison across multiple societies has yet to be made. Our study analyzes and compares demographic as well as academic metrics of presidents from 16 prominent dermatology societies spanning 22 years, 2000-2021. Data were collected using organization websites, which demonstrated 247 unique presidents over 22 years. Of these presidents, 175 (70.9%) were male and 72 (29.1%) were female. Surgically focused societies had 63 (87.5%) male presidents and nine (12.5%) female presidents, while clinically focused societies had 112 (64.0%) male presidents and 63 (36.0%) female presidents (P < 0.0002). The publication h-index, academic rank, chairmanship, and number of advanced degrees, and total number of years in practice prior to election did not significantly differ between male and female leaders. There was no statistically significant difference in the proportion of female presidents across all societies between 2000 and 2021 by Cochran Armitage Trend Test. However, between 2016 and 2021, 35% of presidents were female and a general trend toward more gender balance may be noticed. This equality goal should continue to be emphasized in organized medicine.

Frailty Among Total Hip and Knee Arthroplasty Recipients: Epidemiology and Propensity Score-weighted Analysis of Effect on In-hospital Postoperative Outcomes.

INTRODUCTION: Total joint arthroplasty (TJA) is one of the most successful and frequently performed procedures in the United States. The number of these procedures is projected to continue growing rapidly in the coming years, and with it comes the demand for more sophisticated perioperative risk and complication assessment. This study examines the effect of frailty on postoperative inpatient complications and hospital resource utilization after TJA. METHODS: Discharge data from the National Inpatient Sample were used to identify all patients aged 50 years or older who underwent TJA between 2006 and 2015. Nonelective admissions and hip fractures were excluded. Patients were stratified into two groups with and without concomitant ICD-9 diagnostic criteria that qualified them has having frailty. An analysis comparing the 2 groups' epidemiology, medical comorbidities, and propensity score-weighted postoperative clinical and economic outcomes was done. RESULTS: A total of 7,854,890 TJAs were included in this analysis, with 136,516 meeting the criteria for frailty and 7,718,374 being nonfrail. Among these patients, the average age was 67.3 years and the female distribution was 61.1%. Frail patients were found to have markedly higher rates of all but two individual comorbidities constituting the Modified Elixhauser Profile compared with nonfrail patients. Compared with the control group, frail patients were found to have increased risk of any postoperative complication, central nervous system complications, hematoma/seroma, wound dehiscence, infection, and postoperative anemia. Frail patients also had longer length of stay, higher discharge to rehabilitation facilities, and higher hospital charges. DISCUSSION: Patients with frailty undergoing TJA procedures are at a markedly higher risk for developing postoperative complications and worse hospital economic outcomes. As this patient population continues to increase, it is imperative for clinicians to use their risk factors in optimizing their perioperative care and support.

Mortality Outcomes in Patients With Cardiac Implantable Electronic Devices Before and After Transcatheter Aortic Valve Replacement.

Transcatheter aortic valve replacement (TAVR) carries a risk of high-grade AV block requiring cardiac implantable electronic device (CIED) implantation, which has been associated with a higher mortality rate. However, the outcomes of TAVR in patients with preexisting CIEDs are not well understood. We conducted a retrospective analysis of consecutive patients who underwent TAVR from December 2014 to December 2019 at our institution. Patients were categorized into 3 groups: preexisting CIED pre-TAVR (group 1), CIED implanted within 30 days after TAVR (group 2), and no CIED implanted (group 3). Cox proportional hazard was conducted to determine the primary end point of all-cause mortality. A total of 366 patients were included, of whom 93 (25.4%), 51 (13.9%), and 222 (60.7%) comprised group 1, 2, and 3, respectively. The median follow-up time was 2.3 years. The all-cause mortality rate was higher in group 1 than group 2 (hazard ratio [HR] 2.60, 95% confidence interval [CI] 1.09 to 6.18, p = 0.03) and group 3 (HR 1.96, 95% CI 1.24 to 3.08, p = 0.004). On the multivariate analysis, there was no statistically significant difference in mortality among the groups (group 1 vs group 2: HR 1.95, 95% CI 0.70 to 5.44, p = 0.20 and group 1 vs group 3: HR 1.27, 95% CI 0.66 to 2.43, p = 0.47). Preoperative hemoglobin ≤12 g/100 ml was an independent predictor of all-cause mortality (HR 1.75, 95% CI 1.10 to 2.80, p = 0.02). Group 1 had a higher 1 year congestive heart failure readmission rate (29%) than group 2 (17.6%) and group 3 (8.1%; p <0.0001). In conclusion, there was no difference in the adjusted long-term survival based on the CIED grouping. However, patients with preexisting CIEDs had higher all-cause mortality and 1-year congestive heart failure readmission rates owing to their higher co-morbidity burden, irrespective of their Society of Thoracic Surgeons score. This can be taken into account for preoperative risk stratification.

Optimizing anti-androgen treatment use among men with pathologic lymph-node positive prostate cancer treated with radical prostatectomy: the importance of postoperative PSA kinetics.

BACKGROUND: Optimal postsurgical management of prostate cancer (PCa) patients with nodal metastasis at the time of radical prostatectomy remains unclear. We sought to examine the role of postoperative PSA kinetics and pathologic tumor characteristics in guiding additional hormonal therapy use in pN1 men. METHODS: In total, 297 pN1 PCa patients treated with radical prostatectomy and ePLND between 2002 and 2018 were identified within our prospectively maintained institutional cancer data-registry. Following surgery, these patients were managed with either immediate androgen deprivation therapy (iADT) or observation with deferred ADT (dADT). The former was defined as ADT given within ≤6 months of surgery and the latter as >6 months. The primary outcome was metastasis. Regression-tree analysis was used to stratify patients into novel risk-groups based on post-prostatectomy tumor characteristics and PSA kinetics and the corresponding metastasis risk. Multivariable Cox regression analyses tested the impact of iADT versus observation ± dADT on metastasis, cancer-specific mortality, and overall mortality within each risk-group separately. RESULTS: The median follow-up was 6.1 years (IQR 3.2-9.0). Regression-tree analysis stratified patients into 3 novel risk-groups (Harrell's C-index 0.79) based on PSA-nadir and time to biochemical failure: group 1 (low-risk) included patients with time to biochemical recurrence >6 months (n = 115), while groups 2 and 3 included patients with biochemical failure within ≤6 months with a postoperative PSA-nadir <1.05 ng/mL (group 2 [intermediate-risk], n = 125) or ≥1.05 ng/mL (group 3 [high-risk], n = 57), respectively. No other patient or tumor characteristics were significant for risk stratification. Within each risk-group, the 10-year metastasis-free survival rates with iADT versus observation ± dADT use were: group 1, 100% versus 95.4% (Log-rank p = 0.738), group 2, 80.6% versus 53.5% (Log-rank p = 0.016), and group 3, 41.5% versus 0% (Log-rank p = 0.015), respectively. Adjusted Cox regression analyses confirmed the benefit of iADT utilization in reducing metastasis in group 2 (p = 0.029) and group 3 (p = 0.008) patients, with no benefit for group 1 patients (p = 0.918). Similar results were noted for cancer-specific and overall mortality. CONCLUSIONS: Following radical prostatectomy, early postoperative PSA kinetics may provide valuable information for guiding the timing of ADT initiation-this may reduce over- and undertreatment of pN1 PCa men.

High-intensity local treatment of clinical node-positive urothelial carcinoma of the bladder alongside systemic chemotherapy improves overall survival.

PURPOSE: Clinical node-positive urothelial carcinoma of the bladder (cN+UCaB) is a rapidly fatal disease with limited information on comparative-effectiveness of available treatment options. We sought to examine the impact of high-intensity vs. conservative local treatment (LT) regimens in management of these patients alongside systemic chemotherapy. MATERIALS AND METHODS: We identified 3,227 patients within the National Cancer Data Base who underwent multiagent systemic chemotherapy along with either high-intensity or conservative LT for primary cN+UCaB between 2004-2016. Patients who received no LT, TURBT alone, or <50 Gy radiation therapy to the bladder were included in the conservative group, while patients that received radical cystectomy with pelvic lymphadenectomy or ≥50 Gy radiation therapy with TURBT were included in the high-intensity group. Inverse probability of treatment weighting (IPTW) adjusted Kaplan-Meier and Cox regression analyses were used to assess overall survival (OS). Additionally, to assess whether the benefit of high-intensity LT differs by baseline mortality risk, we tested an interaction between 5-year predicted life-expectancy and the LT type. RESULTS: Overall, 784 (24.3%) and 2,443 (75.7%) cN+UCaB patients underwent high-intensity and conservative LT, respectively. IPTW-adjusted Kaplan-Meier analysis demonstrated OS to be significantly higher in the high-intensity group compared to the conservative group: 5-year OS 28.4% vs. 18.3%, respectively (Log-rank P<0.001). IPTW-adjusted multivariable Cox regression analysis confirmed the benefit of high-intensity LT in prolonging OS (HR 0.63, P<0.001). Interaction analysis showed that high-intensity LT approach was associated with longer OS in all patients regardless of their baseline 5-year life-expectancy (Pinteraction=0.79). CONCLUSION: Eligible patients with cN+UCaB should be considered for aggressive local treatment alongside multiagent systemic chemotherapy. Prospective trials are needed to validate these preliminary findings.

Risk-Based Assessment Of the Impact Of Intravesical Therapy on Recurrence-Free Survival Rate Following Resection of Suspected Low-grade, Non-muscle-invasive Bladder Cancer (NMIBC): A Southwest Oncology Groups (SWOG) S0337 Posthoc Analysis.

BACKGROUND: Nonmuscle invasive bladder cancer (NMIBC) has an elevated risk of recurrence, and immediate postresection intravesical instillation of chemotherapy (IVC) significantly reduces the risk of recurrence. Questions remain about which subpopulation may maximally benefit from IVC. Our aim was to develop risk groups based on recurrence risk in NMIBC, and then evaluate the impact of a single, postoperative instillation of IVC on the subsequent risk of recurrence for each risk group. MATERIAL AND METHODS: Using the SWOG S0337 trial cohort, we performed a posthoc analysis of 345 patients who were diagnosed with suspected low-grade NMIBC, underwent transurethral resection of the bladder tumor (TURBT), and received post-operative IVC (gemcitabine vs. saline). Using regression tree analysis, the regression tree stratified patients based on their risk of recurrence into low-risk - single tumor and aged < 57 years, intermediate-risk - single tumor and aged ≥ 57 years, and high-risk - multiple tumors. We used Cox proportional hazard models to test the impact of recurrence-free rate, and after adjustment to available covariates. RESULTS: Median age of the cohort was 66.5 (IQR: 59.7-75.8 years) with 85% of patients being males. Median overall follow-up time was 3.07 years (IQR: 0.75-4.01 years). When testing the impact of treatment in each risk group separately, we found that patients in the intermediate-risk treated with gemcitabine had a 24-month recurrence free rate of 77% (95% CI: 68%-86%) vs. 59% (95% CI: 49%-70%) in the saline group. This survival difference was confirmed on multivariable analysis (hazard ratio: 0.39, 95% CI: 23%-66%, P < 0.001). This group represented 53% of our cohort. Conversely, we did not observe a significant difference in recurrence-free survival among patients in the low- (P = 0.7) and high-risk (P = 0.4) groups. CONCLUSION: Our findings indicate that older patients with a single tumor of suspected low-grade NMIBC at TURBT maximally benefit from immediate postresection IVC (gemcitabine).