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Objective: Life expectancy models are useful tools to support clinical decision-making. Prior models have not been used widely in clinical practice for patients with renal masses. We sought to develop and validate a model to predict life expectancy following the detection of a localized renal mass suspicious for renal cell carcinoma., Materials and Methods: Using retrospective data from 2 large centers, we identified patients diagnosed with clinically localized renal parenchymal masses from 1998 to 2018. After 2:1 random sampling into a derivation and validation cohort stratified by site, we used age, sex, log-transformed tumor size, simplified cardiovascular index and planned treatment to fit a Cox regression model to predict all-cause mortality from the time of diagnosis. The model's discrimination was evaluated using a C-statistic, and calibration was evaluated visually at 1, 5, and 10 years., Results: We identified 2,667 patients (1,386 at Corewell Health and 1,281 at Johns Hopkins) with renal masses. Of these, 420 (16%) died with a median follow-up of 5.2 years (interquartile range 2.2-8.3). Statistically significant predictors in the multivariable Cox regression model were age (hazard ratio [HR] 1.04; 95% confidence interval [CI] 1.03-1.05); male sex (HR 1.40; 95% CI 1.08-1.81); log-transformed tumor size (HR 1.71; 95% CI 1.30-2.24); cardiovascular index (HR 1.48; 95% CI 1.32-1.67), and planned treatment (HR: 0.10, 95% CI: 0.06-0.18 for kidney-sparing intervention and HR: 0.20, 95% CI: 0.11-0.35 for radical nephrectomy vs. no intervention). The model achieved a C-statistic of 0.74 in the derivation cohort and 0.73 in the validation cohort. The model was well-calibrated at 1, 5, and 10 years of follow-up., Conclusions: For patients with localized renal masses, accurate determination of life expectancy is essential for decision-making regarding intervention vs. active surveillance as a primary treatment modality. We have made available a simple tool for this purpose., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: KS's institution receives grant funding from the National Institute of Diabetes and Digestive and Kidney Diseases, Blue Cross Blue Shield of Michigan, and Teva Pharmaceuticals for unrelated work. KS previously served on a scientific advisory board for Flatiron Health. All other authors have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: Lack of strict indications in current guidelines have led to significant variation in management patterns of small renal masses. The impact of the urologist on the management approach for patients with small renal masses has not been explored previously., Materials and Methods: Using the linked Surveillance, Epidemiology, and End Results-Medicare database, patients aged ≥66 years diagnosed with small renal masses from January 1, 2004 to December 31, 2013 were identified and assigned to primary urologists. Mixed-effects logistic models were used to evaluate factors associated with different management approaches, estimate urologist-level probabilities of each approach, assess management variation, and determine urologist impact on choice of approach., Results: A total of 12,402 patients with 2,794 corresponding primary urologists were included in the study. At the individual urologist level, the estimated case-adjusted probability of different approaches varied markedly: nonsurgical management (mean, 12.8%; range, 4.9%-36.1%); thermal ablation (mean, 10.8%; range, 2.4%-66.3%); partial nephrectomy (mean, 30.1%; range, 10.1%-66.6%); and radical nephrectomy (mean, 40.4%; range, 17.7%-71.6%). Compared to patient and tumor characteristics, the primary urologist was a more influential measured factor, accounting for 13.6% (vs. 12.9%), 33.8% (vs. 2.1%), 15.1% (vs. 8.4%), and 13.5% (vs. 4.0%) of the variation in management choice for nonsurgical management, thermal ablation, partial nephrectomy, and radical nephrectomy, respectively., Conclusions: Significant variation exists in the management of small renal masses and appears to be driven primarily by urologist preference and practice patterns. Our findings emphasize the need for unified guidance regarding management of these masses to reduce unwarranted variation in care., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: In the United States, the rate of benign histology among resected renal tumors suspected to be malignant is increasing. We evaluated the rates in the Republic of Korea and assessed the racial effect using recent multi-institutional Korean-United States data., Methods: We conducted a multi-institutional retrospective study of 11,529 patients (8,812 from The Republic of Korea and 2,717 from the United States) and compared the rates of benign histology between the two countries. To evaluate the racial effect, we divided the patients into Korean, Asian in the US, and Non-Asian in the US., Results: The rates of benign histology and small renal masses in Korean patients were significantly lower than that in United States patients (6.3% vs. 14.3%, p < 0.001) and (≤ 4 cm, 7.6% vs. 19.5%, p < 0.001), respectively. Women, incidentaloma, partial nephrectomy, minimally invasive surgery, and recent surgery were associated with a higher rate of benign histology than others., Conclusions: In Korea, the rate of benign histology among resected renal tumors was significantly lower than that in the United States. This disparity could be caused by environmental or cultural differences rather than racial differences. Our findings suggest that re-evaluating current context-specific standards of care is necessary to avoid overtreatment., (© 2024. The Author(s).)

Purpose: Active surveillance (AS) with the possibility of delayed intervention (DI) is emerging as a safe alternative to immediate intervention for many patients with small renal masses (SRMs). However, limited comparative data exist to inform the most appropriate management strategy for SRMs., Materials and Methods: Decision analytic Markov modeling was performed to estimate the health outcomes and costs of 4 management strategies for 65-year-old patients with an incidental SRM: AS (with possible DI), immediate partial nephrectomy, radical nephrectomy, and thermal ablation. Mortality, direct medical costs, quality-adjusted life-years, and incremental cost-effectiveness ratios were evaluated over 10 years., Results: The 10-year all-cause mortality was 22.6% for AS, 21.9% for immediate partial nephrectomy, 22.4% for immediate radical nephrectomy, and 23.7% for immediate thermal ablation. At a willingness-to-pay threshold of $100,000/quality-adjusted life-year, AS was the most cost-effective management strategy. The results were robust in univariate, multivariate, and probabilistic sensitivity analyses. Clinical decision analysis demonstrated that the tumor's metastatic potential, patient age, individual preferences, and health status were important factors influencing the optimal management strategy. Notably, if the annual probability of metastatic progression from AS was sufficiently low (under 0.35%-0.45% for most ages at baseline), consistent with the typical metastatic potential of SRMs <2 cm, AS would achieve higher health utilities than the other strategies., Conclusions: Compared to immediate intervention, AS with timely DI offers a safe and cost-effective approach to managing patients with SRMs. For patients harboring tumors of very low metastatic potential, AS may lead to better patient outcomes than immediate intervention.

Objective: To evaluate racial, gender, and socioeconomic differences in the treatment of metastatic renal cell carcinoma (mRCC) and their impact on survival., Methods: Patients aged ≥18 years diagnosed with mRCC in the National Cancer Database (2004-2015) were analyzed. Multivariable logistic regression models were used to evaluate factors associated with systemic therapy and cytoreductive nephrectomy (CN) utilization. Cox proportional hazards regression models were used to evaluate overall survival., Results: In total, 31,989 patients with mRCC were identified with 30.2% receiving CN, 51.6% receiving systemic therapy, and 25.8% receiving no treatment. Females were at lower odds of receiving systemic therapy (OR 0.91, P <.01) and increased odds of no treatment (OR 1.14, P <.01). Non-Hispanic Black and Hispanic patients were at decreased odds of receiving CN (OR 0.75, P <.01 and OR 0.86, P = .01, respectively). Black patients were at decreased odds of receiving systemic therapy (OR 0.85, P <.01) and increased odds of no treatment (OR 1.41, P <.01). Adjusting for demographic and disease variables, Black patients were at increased risk of death (HR 1.06, P = .03), largely due to less use of systemic therapy and CN; survival differences disappeared after accounting for receipt of therapy (HR 0.99, P = .66)., Conclusion: There are racial, gender, and socioeconomic differences in the treatment of mRCC which are associated with a disparity in overall survival. Dismantling systemic barriers and improving access to care may lead to reduced disparities and improved outcomes for mRCC., (Copyright © 2021. Published by Elsevier Inc.)

Purpose: The role of endogenous testosterone in de novo prostate cancer pathogenesis in humans remains unclear. The effect of testosterone on the tumor genome is not explored. We sought to explore the correlation between perioperative testosterone level and genomic risk score in a cohort of men who underwent radical prostatectomy., Materials and Methods: We included patients who underwent radical prostatectomy (2013-2018) and had adverse pathological features in their final surgical specimens (positive margin, and/or pT3a or higher). The outcome of interest was the genomic risk score: low (<0.45), intermediate (0.45-0.6) and high (>0.6). The associations between serum testosterone level and 188 gene expression-based signatures were examined. Secondary outcomes of interest included biochemical recurrence and receipt of secondary treatment., Results: The median genomic risk score was lower in the low testosterone group compared to the intermediate and normal testosterone groups (0.38 vs 0.52 vs 0.53, respectively; p=0.049). There was no difference in biochemical recurrence-free survival between the 3 testosterone groups (p=0.9). Patients with low testosterone levels had higher odds of receiving secondary treatment (OR: 2.27; 95% CI: 1.14-4.50; p=0.02) than those with normal levels. A total of 43 (of 188) gene expression signatures were associated with testosterone level (p <0.05). In total, 33 signatures were positively associated with serum testosterone levels, including 12 signatures involved in DNA repair pathways., Conclusions: This is the first study to assess the correlation of preoperative testosterone level on the tumor transcriptome and showed no clinical correlation between pre-defined genomic risk score groups and testosterone groups. This study adds to the notion of the limited role of endogenous testosterone on the development of de novo high-risk localized prostate cancer.

Background: This study evaluated the utility of self-reported quality of life (QOL) metrics in predicting mortality among all-comers with renal cell carcinoma (RCC) and externally tested the findings in a registry of patients with small renal masses., Methods: The Surveillance, Epidemiology, and End Results-Medicare Health Outcomes Survey (SEER-MHOS) captured QOL metrics composed of mental component summary (MCS) and physical component summary (PCS) scores. Regression models assessed associations of MCS and PCS with all-cause, RCC-specific, and non-RCC-specific mortality. Harrell's concordance statistic (the C-index) and the Akaike information criterion (AIC) determined predictive accuracy and parsimony, respectively. Findings were tested in the prospective Delayed Intervention and Surveillance for Small Renal Masses (DISSRM) registry., Results: In SEER-MHOS, 1494 patients had a median age of 73.4 years and a median follow-up time of 5.6 years. Each additional MCS and PCS point reduced the hazard of all-cause mortality by 1.3% (95% CI, 0.981-0.993; P < .001) and 2.3% (95% CI, 0.971-0.984; P < .001), respectively. Models with QOL metrics demonstrated higher predictive accuracy (C-index, 72.3% vs 70.1%) and parsimony (AIC, 9376.5 vs 9454.5) than models without QOL metrics. QOL metrics exerted a greater effect on non-RCC-specific mortality than RCC-specific mortality. External testing in the DISSRM registry confirmed these findings with similar results for all-cause mortality., Conclusions: Models with self-reported QOL metrics predicted all-cause mortality in patients with RCC with higher accuracy and parsimony than those without QOL metrics. Physical health was a stronger predictor of mortality than mental health. The findings support the incorporation of QOL metrics into prognostic models and patient counseling for RCC., (© 2021 American Cancer Society.)

Background: The aim of the study was to test the effect of active surveillance (AS) versus primary intervention (PI) on overall mortality (OM) in elderly patients diagnosed with SRM., Methods: Elderly patients (75 years or older) diagnosed with SRMs (<4 cm) and treated with either PI (i.e. partial nephrectomy or kidney ablation) or AS between 2009 and 2018 were abstracted from the renal surgery in the elderly (RESURGE) and Delayed Intervention and Surveillance for small Renal Masses (DISSRM) datasets, respectively. OM rates were estimated among groups with Kaplan Meier method and Cox proportional hazards regression models after applying inverse probability of treatment weighting (IPTW). Multivariable logistic regression model was used to estimate IPTW. Covariates of interest were those unbalanced and/or significantly correlated with the treatment choice or with OM., Results: A total of 483 patients were included; 121 (25.1%) underwent AS. Sixty patients (12.4%) died. Overall, 6.7% of all deaths were related to cancer. IPTW-Kaplan Meier curves showed a 5-year overall survival rates of 70.0±3.5% and 73.2±4.8% in AS and PI groups, respectively (IPTW-Log-rank P value=0.308). IPTW-Cox regression model did not show meaningfully increased OM rates in AS group (HR: 1.31, 95% CI: 0.69-2.49)., Conclusions: AS represents an appealing treatment option for very elderly patients presenting with SRM, as it avoids the risks of a PI while not compromising the survival outcomes of these patients.

Background: Cancer-specific survival for men with clinical stage I (CSI) seminoma approaches 100%, regardless of the management approach chosen after orchiectomy. Given the young age and high survival rate of these patients, there has been a shift toward minimizing treatment-related morbidity and cost. In this context, non-risk-adapted active surveillance (NRAS) has emerged as a desirable management strategy., Objective: To evaluate the clinical, quality of life, and economic values of postorchiectomy NRAS for CSI seminoma., Design, Setting, and Participants: We developed a decision analytic Markov model to estimate the costs and health outcomes of competing postorchiectomy management strategies for otherwise healthy 30-yr-old men with CSI seminoma., Intervention: Real-world current practice, comprising active surveillance and adjuvant therapies (reference arm), was compared with empiric adjuvant radiotherapy (option 1), empiric adjuvant chemotherapy (option 2), risk-adapted active surveillance (RAAS; option 3), and NRAS (option 4)., Outcome Measurements and Statistical Analysis: Quality-adjusted life-years (QALYs), medical costs, incremental cost-effectiveness ratio, mortality, and unnecessary treatment avoidance were estimated over a 10-yr period. Uncertainties in model input values were accounted for using univariate, scenario, and probabilistic sensitivity analyses., Results and Limitations: NRAS dominated all other management options, offering the lowest per-patient health care cost ($3839) and the highest QALYs gained (7.74) over 10 yr. On probabilistic sensitivity analysis, NRAS had the highest chance of being most cost effective. Although NRAS resulted in the highest rate of salvage chemotherapy (20% vs 6% radiotherapy, 6% chemotherapy, 15% current practice, and 16% RAAS), it had the same mortality rate compared to current practice (2.5%). NRAS also allowed 80% of patients to avoid unnecessary treatment compared with 46% for current practice and 52% for RAAS. Study limitations included model simplifications, model parameter assumptions, as well as the absence of patient preference as a decision factor., Conclusions: NRAS maintains high cure rates for CSI seminoma, minimizes unnecessary treatment, and is cost effective compared with other management strategies., Patient Summary: Clinical stage I (CSI) seminoma is one of the most common forms of testicular cancer. Surgery is the first step in the treatment of men with this disease, and some men may receive additional treatment with radiation or chemotherapy afterward. As most men are cured with surgery alone, non-risk-adapted active surveillance (NRAS), which involves routine monitoring with imaging and blood tests for disease recurrence after surgery, has become a desirable treatment option. Our study shows that in addition to maintaining high survival rates and avoiding unnecessary radiation and chemotherapy, NRAS is cost effective for the health care system., (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To evaluate outcomes for patients with local recurrence (LR) of clinically localized renal cell carcinoma (RCC) without concurrent systemic metastasis from our institution, an event that occurs rarely (1%-3%) after surgery. LR may be a harbinger of poor outcomes, and the best management of these patients is unclear., Materials/methods: We retrospectively reviewed patients surgically treated for clinically localized RCC (cT1-2N0M0) with subsequent LR (in the partial or radical nephrectomy bed) and/or regional recurrence (RR; in the abdomen distant from the direct site of surgery) without concurrent metastasis from our institutional database (2004-2018). Comparative and survival analyses were performed., Results: Out of 3038 total patients, 1895 had clinically localized RCC, with 30 patients (1.6%) having isolated LR/RR. Median time to recurrence was 26.5 months (IQR:16-35). Of 26 patients treated with local therapy, 14 (53.8%) recurred over a median follow-up time of 29.5 months (IQR:12-45). The 1-year and 2-year secondary recurrence-free survival rates are 60.7% and 49.7%, respectively. Two or more sites of locoregional recurrence significantly predicted secondary recurrence/metastasis after local therapy for local recurrence (hazard ratio: 2.22, P= .04)., Conclusion: Our results suggest local therapy is appropriate for select patients with LR/RR, with almost 50% of patients undergoing a second local therapy remaining alive with "local cure" and no secondary recurrence. The number of sites of recurrence can be used to better select patients that will benefit from local therapy or systemic/combination therapy. This work provides a framework onto which further studies regarding local therapy and locoregional recurrence of RCC can be performed., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Provider and hospital factors influence healthcare quality, but data are lacking to assess their impact on renal cancer surgery. We aimed to assess factors related to surgeon and hospital volume and study their impact on 30-day outcomes after radical nephrectomy., Materials and Methods: Renal surgery data were abstracted from Maryland's Health Service Cost Review Commission from 2000 to 2018. Patients ≤18 years old, without a diagnosis of renal cancer, and concurrently receiving another major surgery were excluded. Volume categories were derived from the mean annual cases distribution. Multivariable logistic and linear regression models assessed the association of volume on length of stay, intensive care days, cost, 30-day mortality, readmission, and complications., Results: 7,950 surgeries, completed by 573 surgeons at 48 hospitals, were included. Demographic, surgical, and admission characteristics differed between groups. Radical nephrectomies performed by low volume surgeons demonstrated increased post-operative complication frequency, mortality frequency, length of stay, and days spent in intensive care relative to other groups. However, after logistic regression adjusting for clinical risk and socioeconomic factors, only increased length of stay and ICU days remained associated with lower surgeon volume. Similarly, after adjusted logistic regression, hospital volume was not associated with the studied outcomes., Conclusions: Surgeons and hospitals differ in regards to patient demographic and clinical factors. Barriers exist regarding access to high-volume care, and thus some volume-outcome trends may be driven predominantly by disparities and case mix., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To review the current literature on quality of care in the diagnosis and management of early-stage testicular cancer., Methods: PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched for studies on quality of care in testicular cancer diagnosis and management from January 1980 to August 2018. Major overlapping themes related to quality of care in the diagnosis and management of TGCT were identified and evidence related to these themes were abstracted., Evidence: 62 studies were included in the review. A number of themes were identified including (1) trends in survival and outcomes, (2) management patterns, (3) adherence to evidence-based clinical guidelines, (4) delays in care, (5) treatment complications and toxicities, (6) sociodemographic factors, (7) volume of patients treated, (8) gaps in provider knowledge and medical errors, and (9) multidisciplinary approaches to care., Evidence Summary: As survival for patients with testicular cancer improves, there has been a greater emphasis on other components of quality of care, such as reducing treatment toxicity and minimizing delays in diagnosis. Efforts to meet these goals include encouragement of adherence to evidence-based guidelines, greater utilization of surveillance, and promotion of multidisciplinary team-based care. Although outcomes have improved, social determinants of health, such as insurance status, race, and geographical residence all may influence survival and cancer-related outcomes. Additionally, qualitative review indicates patients who receive care at high-volume institutions appear to experience better outcomes than those treated at smaller centers., Conclusions: As outcomes and survival improve for patients with testicular cancer, quality of care has become an important consideration. Future avenues of research on this topic include identifying an appropriate balance between centralization of care and expanding access to underserved areas, minimizing delays in care, ensuring greater adherence to clinical guidelines, and addressing sociodemographic and racial disparities in outcomes., (Copyright © 2021. Published by Elsevier Inc.)

Objective: To evaluate gender differences in the management of clinical T1a (cT1a) renal cell carcinoma (RCC) before and after release of the AUA guidelines for management in 2009, which prioritized nephron-sparing approaches., Methods: Patients aged ≥66 years diagnosed with cT1a RCC from 2004 to 2013 in Surveillance, Epidemiology, and End Results-Medicare were analyzed. Multivariable mixed-effects logistic regression models were used to evaluate factors associated with radical nephrectomy (RN) for cT1a RCC before (2004 to 2009) and after (2010 to 2013) guidelines release. Predictors of pathologic T3 upstaging and high grade pathology in the postguidelines period were examined using multivariable logistic regression among patients who underwent RN or partial nephrectomy., Results: Twelve thousand four hundred and two patients with cT1a RCC were identified, 42% of whom were women. Overall, the likelihood of RN decreased postguidelines (odds ratio [OR] = 0.44, P <.001), but women were at increased odds of undergoing RN both before and after guideline release (OR = 1.27, P <.001 and OR = 1.37, P <.001, respectively) upon multivariable mixed-effects logistic regression. Tumor size >2 cm was also associated with increased likelihood of RN before and after guidelines (OR = 2.61, P <.001 and OR = 2.51, P <.001, respectively). In the postguidelines period, women had significantly lower odds of pathologic upstaging (OR = 0.75, P = .024) and harboring high grade pathology (OR = 0.71, P <.001) compared to men., Conclusion: Gender differences persist in the management of cT1a RCC, with women having higher odds of undergoing RN, even after release of AUA guidelines and despite having lower odds of pathologic upstaging and high-grade disease., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: A paradigm shift in the management of small renal masses has increased utilization of active surveillance. However, questions remain regarding safety and durability in younger patients., Materials and Methods: Patients aged 60 or younger at diagnosis were identified from the Delayed Intervention and Surveillance for Small Renal Masses registry. The active surveillance, primary intervention, and delayed intervention groups were evaluated using ANOVA with Bonferroni correction, χ 2 and Fisher's exact tests, and Kruskal-Wallis and Wilcoxon signed-rank tests. Survival outcomes were calculated using the Kaplan-Meier method and compared with the log-rank test., Results: Of 224 patients with median followup of 4.9 years 30.4% chose surveillance. There were 20 (29.4%) surveillance progression events, including 4 elective crossovers, and 13 (19.1%) patients underwent delayed intervention. Among patients with initial tumor size ≤2 cm, 15.1% crossed over, compared to 33.3% with initial tumor size 2-4 cm. Overall survival was similar in primary intervention and surveillance at 7 years (94.0% vs 90.8%, log-rank p=0.2). Cancer-specific survival remained at 100% for both groups. There were no significant differences between primary and delayed intervention with respect to minimally invasive or nephron-sparing interventions. Recurrence-free survival at 5 years was 96.0% and 100% for primary and delayed intervention, respectively (log-rank p=0.6)., Conclusions: Active surveillance is a safe initial strategy in younger patients and can avoid unnecessary intervention in a subset for whom it is durable. Crucially, no patient developed metastatic disease on surveillance or recurrence after delayed intervention. This study confirms active surveillance principles can effectively be applied to younger patients.

The objectives were to evaluate the safety and oncologic efficacy of primary robotic retroperitoneal lymph node (R-RPLND) dissection for testicular germ cell tumors. A retrospective analysis was performed on all primary R-RPLND cases performed by a single surgeon, who performs both open and R-RPLND at a high-volume academic institution, between August 2013 and August 2019. Data on patient demographics, operative techniques, perioperative outcomes, and tumor characteristics were obtained. 28 men were identified who underwent primary R-RPLND. The majority of patients (N = 21, 75%) had clinical stage I disease, and a bilateral template was more commonly performed than either single side alone (N = 13, 46%). Of note, two cases involving clinical stage II disease were converted electively from robotic to open procedures at the discretion of the surgeon. R-RPLND patients experienced no intraoperative complications. The median follow-up time was 8 months (interquartile range 4-29 months). One (4%) patient developed a disease recurrence at 10 months after R-RPLND. Conclusion: primary R-RPLND is a safe and efficacious procedure for carefully selected men with stage I and II non-seminomatous germ cell tumors of the testis. Long-term data are needed to evaluate the comparative oncologic efficacy with open surgery and the notably high rate of chylous ascites.

Introduction: Current preoperative evaluation methods fail to detect the difference in frailty among patients with the same chronological age. Hence, we sought to assess the ability of a simple 5-item frailty index (5-iFI) score to predict surgical outcomes post radical prostatectomy (RP). Methods: The American College of Surgeons National Surgical Quality Improvement Program was queried for patients who underwent RP between 2008 and 2017. The 5-iFI score was calculated by assigning a point for each of the following conditions: (1) chronic obstructive pulmonary disease or pneumonia, (2) congestive heart failure, (3) dependent functional status, (4) hypertension, and (5) diabetes. Multivariable regression was performed to assess the association between the 5-iFI score and perioperative outcomes. Results: The cohort included 15,546 (46.2%), 14,541 (46.2%), and 3556 (10.6%) patients with 5-iFI scores of 0, 1, and ≥2, respectively. Patients >65 years, nonwhite, and with an American Society of Anesthesiology ≥3 were more likely to have a 5-iFI score ≥2 ( p  < 0.0001). Similarly, a 5-iFI ≥2 score was associated with higher Clavien-Dindo grades complications ( p -trend <0.0001). In addition, a 5-iFI score ≥2 had 1.66 (1.31-2.11) and 1.85 (1.39-2.46) times the odds of Clavien-Dindo grades ≥3 and ≥4 adverse events, respectively. Moreover, a 5-iFI score ≥2 had 28% increased risk of length of stay >1 day ( p  < 0.0001) and increased incidence of early mortality ( p  = 0.01). Conclusions: Frailty, as measured by a simple 5-point frailty index, is an independent predictor of adverse outcomes and early mortality in patients undergoing RP. Preoperative frailty assessment may improve risk stratification and patient counseling before surgery.

Background: The American Joint Committee on Cancer 8 th edition staging guidelines for testicular cancer established a 3 cm cutoff to subclassify stage T1 seminomas (<3 cm = pT1a and ≥3 cm = pT1b). The efficacy of this cutoff in predicting metastatic disease and impact on treatment patterns have not been studied., Methods: We retrospectively reviewed patients with pT1 testicular seminoma in the National Cancer Database from 2004 to 2016. Receiver operating curves were used to determine the efficacy of the 3 cm tumor cutoff in identifying metastatic disease, and multivariable regression was used to compute the effect of tumor size on the rate of adjuvant therapy among Stage I patients., Results: A total of 10,134 patients with pT1 seminoma were evaluated. The current size cutoff of 3 cm for subclassification did not exhibit high discrimination in identifying metastatic disease (area under receiver operating curve: 0.546). Surveillance has grown as the preferred treatment after orchiectomy -32.1% in 2004 to 81.2% in 2015. However, the rate of adjuvant therapy for pT1, Stage I seminomas associated positively with tumor size even with adjustment for year of diagnosis. For tumors above 3 cm, the odds ratio stabilized around 1.9. By using the 3 cm cutoff to guide adjuvant therapy, up to 85% of T1b patients may be overtreated., Conclusion: The 3 cm cutoff for subclassification of Stage I seminoma does not predict metastatic recurrence but is associated with increased receipt of adjuvant therapy. A 3 cm cutoff and the pT1a/b classification may therefore contribute to overtreatment in many young patients with a long life expectancy for whom minimizing adverse effects should be prioritized., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Cancer specific survival for men with early stage (I to IIB) testicular germ cell tumors is greater than 90% with any management strategy. The data regarding the comparative effectiveness of surveillance, primary chemotherapy, radiotherapy and retroperitoneal lymph node dissection were synthesized with a focus on oncologic outcomes, patient reported outcomes, and short and long-term toxicities., Materials and Methods: PubMed®, Embase® and the Cochrane Central Register of Controlled Trials were searched from 1980 to 2018 for studies addressing the effectiveness of surveillance, chemotherapy, radiotherapy and retroperitoneal lymph node dissection, according to pathology and clinical stage, for men with an early stage testicular germ cell tumor., Results: Cancer specific survival ranged from 94% to 100% for patients with early stage testicular germ cell tumors regardless of tumor histology and initial management strategy. For men with seminoma the median cancer specific survival was 99.7% (range 97% to 100%), 99.5% (96.8% to 100%) and 100% (100% to 100%) among those managed by surveillance, radiotherapy and chemotherapy, respectively. Median cancer specific survival for men with nonseminomatous testicular germ cell tumors was 100% (range 98.6% to 100%), 100% (96.9% to 100%) and 100% (94% to 100%) when managed by surveillance, retroperitoneal lymph node dissection and chemotherapy, respectively. Recurrence rates and toxicities varied by management strategy. For men with seminoma surveillance, chemotherapy and radiotherapy were associated with median recurrence rates of 15%, 2% and 3.7%, respectively. For men with nonseminomatous testicular germ cell tumors the median recurrence rates were 20.5%, 3.3% and 11.1% for surveillance, chemotherapy and retroperitoneal lymph node dissection, respectively. Surveillance was associated with minimal toxicities compared to other approaches. Primary chemotherapy had the highest rate of short-term toxicities and was associated with long-term risks of metabolic syndrome, hypogonadism, renal impairment, neuropathy, infertility and secondary malignancies. Toxicities with radiotherapy included acute dermatitis and long-term gastrointestinal complications, infertility and high rates of secondary malignancies (2% to 3%). Patients undergoing retroperitoneal lymph node dissection had significant risk of toxicity perioperatively and long-term infertility in men with anejaculation. Transient detriments in patient reported outcomes and quality of life were noted with all management options., Conclusions: Men with early stage testicular germ cell tumors experience excellent cancer specific survival regardless of management strategy. Management options, however, differ in terms of associated recurrence rates, short and long-term toxicities, and patient reported outcomes. The profile for each approach should be clearly communicated to patients and matched with patient preferences to offer the best individual outcome.

Purpose: Metastatic recurrence occurs in over 25% of upper tract urothelial carcinoma patients treated with radical nephroureterectomy. While metastatic recurrence suggests poor prognosis, the impact of the specific site of recurrence on prognosis is not well documented., Materials and Methods: We retrospectively analyzed 188 patients who underwent radical nephroureterectomy for high-grade, node-negative upper tract urothelial carcinoma at our institution from 2003 to 2018 without receiving neoadjuvant or adjuvant chemotherapy. Competing-risks survival analysis was performed to evaluate the cumulative incidence and predictors of metastatic recurrence. The Kaplan-Meier method and log-rank test were used to estimate and compare recurrence site-specific survival probabilities following metastatic recurrence. Cox regression analyses were performed to assess site-specific prognoses., Results: Of the 188 patients, 47 (25%) developed metastatic recurrence over a median follow-up of 30 months (interquartile range: 10.5-58.5 months). The 1- and 2-year cumulative incidences of metastatic recurrence were 13.6% and 23.6%, respectively. On multivariable analysis, lymphovascular invasion was significantly predictive of metastatic recurrence (subhazard ratio: 2.6, P = 0.01). Of the 47 patients who developed recurrence, 38 (80.9%) died over a median follow-up of 10 months (interquartile range: 5-20 months). Metastatic recurrence was most common in the lungs (n= 13, 28%) and at multiple sites (n= 14, 30%). Median time to recurrence was shorter for recurrences at multiple sites (6.5 months) and those in the liver (13 months) and bone (18 months) compared to other sites. Patients who recurred in the liver (hazard ratio: 6.3, P = 0.007), bone (hazard ratio: 4.9, P = 0.02), and multiple sites (hazard ratio: 4.6, P = 0.01) had significantly worse prognosis compared to those who recurred in lymph nodes. Statistical significance persisted after adjusting for treatment with salvage therapy., Conclusions: A significant proportion of high-grade upper tract urothelial carcinoma patients recur systemically after radical nephroureterectomy. Lymphovascular invasion is a predictor of metastatic recurrence and may inform decisions regarding perioperative chemotherapy. Hepatic and osseous recurrences have relatively quicker onset and less favorable prognosis compared to other sites. These findings may benefit future efforts to develop recurrence site-specific treatment plans and highlight the necessity of subsequent endeavors to explore the genetic associations of recurrence in upper tract urothelial carcinoma., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To demonstrate the safety and efficacy of testis-sparing surgery (TSS) in 2 specific circumstances: small, nonpalpable masses suspected to be benign and masses suspicious for germ cell tumor in a solitary or functionally solitary testicle or bilateral disease., Methods: Our institutional review board-approved testicular cancer registry was reviewed for men who underwent inguinal exploration with intent for TSS (2013-2020). The attempted TSS and completed TSS groups were evaluated for differences using Student's t test for normally-distributed variables, chi-squared and Fisher's exact tests for proportions, and Wilcoxon rank-sum test for nonparametric variables., Results: TSS was attempted in 28 patients and completed in 14. TSS was completed only if intraoperative frozen section demonstrated benign disease, except for 1 patient with stage I seminoma and solitary testicle. Sensitivity and specificity of frozen section analysis was 100% and 93%, respectively. There were no significant differences in demographics between attempted vs completed TSS cohorts. Median tumor size was significantly smaller in the completed TSS cohort (1.0 cm vs 1.7 cm, P = .03). In patients with unilateral masses without history of testis cancer, the testis was successfully spared in 9 of 22 cases (41%). In patients with bilateral disease or germ cell tumor in solitary testis, the testis was spared in 5 of 6 cases (83%). At a median follow up of 12.2 months, all patients were alive, and 27 of 28 had no evidence of disease (96%)., Conclusion: TSS is safe and effective for small, benign masses and in the setting of bilateral disease or tumor in a solitary testis., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: We performed a systematic review of studies assessing the diagnosis and effectiveness of management strategies for germ cell neoplasia in situ., Materials and Methods: Paired investigators independently searched for studies on the diagnosis and management of testicular germ cell neoplasia in situ using PubMed®, Embase® and the Cochrane Central Register of Controlled Trials from January 1, 1980 through August 2018. The reviewers then extracted data and assessed quality., Results: Eighteen studies met inclusion criteria. Among patients with a testicular germ cell tumor the prevalence of contralateral germ cell neoplasia in situ was 4.0% to 8.1%. No significant difference in the risk of metachronous malignancy was identified between unscreened groups vs those with routine contralateral testicular screening (cumulative incidence 1.9% vs 3.1%, p=0.097, respectively). Patients who presented with a history of testicular atrophy, age less than 40 years or cryptorchidism had an elevated risk of germ cell neoplasia in situ. In patients with germ cell neoplasia in situ the use of 18 to 20 Gy radiation therapy demonstrated the lowest rate of disease on followup biopsies (0% to 2.5%), compared to a median of 30% on biopsies in patients treated with cisplatin based chemotherapy. Carboplatin based treatment regimens demonstrated positive disease in 66% to 75% on repeat biopsies. Rates of treatment related hypogonadism were 30.8% to 38.5% and 13% to 20% for patients treated with 18 to 20 Gy and cisplatin based chemotherapy, respectively., Conclusions: In patients with a testicular germ cell tumor the risk of having contralateral germ cell neoplasia in situ is 4% to 8%, with a greater risk in patients with testicular atrophy, cryptorchidism or age less than 40 years. The risk is high enough to support use of contralateral testicular biopsy in patients with these risk factors for germ cell neoplasia in situ. However, routine screening is not advised. Radiation therapy with 18 to 20 Gy was associated with much better eradication of germ cell neoplasia in situ than chemotherapy. Chemotherapy may eradicate germ cell neoplasia in situ in up to two-thirds of patients undergoing chemotherapy as adjuvant treatment for a primary germ cell tumor. Further research and data are needed to strengthen many aspects of the evidence base.

Radical inguinal orchiectomy is the standard of care for men diagnosed with a testicular mass suspicious for germ cell tumor (TGCT). Nontraditional approaches to management, including testis-sparing surgery (TSS) and scrotal orchiectomy, occur in clinical practice. We systematically reviewed studies evaluating outcomes after TSS and scrotal violation for the management of a suspected TGCT. We used PubMed, Embase, and the Cochrane Central Register of Controlled Trials (January 1980-December 2018) to search for studies addressing morbidity and oncologic outcomes after TSS or scrotal violation for testicular masses concerning for TGCT. Paired reviewers independently screened abstracts for inclusion, sequentially extracted data, and assessed study quality. Twenty-one studies were included (10 TSS, 11 scrotal violation). Risk of local recurrence after TSS on meta-analysis was 7.5% after 3 to 5 years (absolute proportion reported in studies: 10.9%). Aggregated rates of positive margins (1.4%) and testicular atrophy (2.8%) across studies were low with 7.1% of patients requiring subsequent androgen therapy. Scrotal violation led to a higher aggregate risk of local recurrence compared to no scrotal violation (2.5% vs. 0.0%, P < 0.001) but did not appear to impact subsequent metastasis and survival in the short term (3-5 years). Most patients received adjuvant therapy after scrotal violation with 9.3% found to harbor residual primary tumor after scrotal scar excision. TSS carries a quantifiable risk of local recurrence after 3 to 5 years despite the majority receiving adjuvant radiation or chemotherapy. Scrotal violation carries a risk of local recurrence but does not appear to impact subsequent metastasis and survival in the short term., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: We synthesized evidence on the comparative performance characteristics, benefits and harms of diagnostic imaging modalities used in combination with serum tumor markers for clinical staging of testicular germ cell tumors. The diagnostic imaging modalities included computerized tomography, magnetic resonance imaging, positron emission tomography and chest radiographs., Materials and Methods: Paired reviewers independently searched PubMed, Embase® and the Cochrane Central Register of Controlled Trials from 1980 to 2018 using title-abstract and full-text screening to identify original studies of the use of computerized tomography, magnetic resonance imaging, positron emission tomography, chest radiographs and serum tumor markers for the clinical staging of early stage testicular germ cell tumors., Results: We found 21 studies of a total of 1,702 patients. With significant bias and limitations to the data, the performance characteristics of computerized tomography, magnetic resonance imaging and positron emission tomography for staging of the retroperitoneum were similar, with median sensitivity ranging from 67% to 80% and median specificity ranging from 95% to 100%. Computerized tomography of the chest (median sensitivity 100%) was more sensitive than a chest radiograph (median sensitivity 76%), especially in men with nonseminomatous germ cell tumors. The addition of serum tumor markers to diagnostic imaging improved staging sensitivity from 38% to 41% to 59% to 60%. No study specifically reported on harms of the imaging modalities., Conclusions: The combination of axial imaging with computerized tomography or magnetic resonance imaging and serum tumor markers demonstrates optimal performance characteristics for staging early stage testicular germ cell tumors. There is little use for chest computerized tomography in men with seminoma, negative abdominal imaging and negative serum tumor markers.

Protracted conflicts in the Middle East have led to successive waves of refugees crossing borders. Chronic, non-communicable diseases are now recognised as diseases that need to be addressed in such crises. Cancer, in particular, with its costly, multidisciplinary care, poses considerable financial and ethical challenges for policy makers. In 2014 and with funding from the United Nations High Commissioner for Refugees, we reported on cancer cases among Iraqi refugees in Jordan (2010-12) and Syria (2009-11). In this Policy Review, we provide data on 733 refugees referred to the United Nations High Commissioner for Refugees in Lebanon (2015-17) and Jordan (2016-17), analysed by cancer type, demographic risk factors, treatment coverage status, and cost. Results show the need for increased funding and evidence-based standard operating procedures across countries to ensure that patients have equitable access to care. We recommend a holistic response to humanitarian crises that includes education, screening, treatment, and palliative care for refugees and nationals and prioritises breast cancer and childhood cancers., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Ultrasound is the imaging modality of choice to evaluate scrotal pathology. However, differentiating malignant and benign testicular tumors is not always possible, and there is interest in evaluating magnetic resonance imaging (MRI) as a potential adjunct for diagnosis. We conducted a systematic review and found 9 studies related to MRI diagnosis of testicular masses. A total of 220 testicular masses (217 patients) undergoing MRI were identified. Notable findings include malignant masses having a lower apparent diffusion coefficient compared to benign masses (3 of 4 studies) and that quantitative enhancement patterns could differentiate Leydig cell tumors from germ cell tumors in 2 studies. While there were some distinct qualitative characterizations of testicular masses on MRI, further research is needed to identify appropriate clinical contexts for use., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Active surveillance (AS) is a safe and reasonable management strategy for many patients with small renal masses (SRM) suspicious for a clinical T1a renal cell carcinoma based on excellent metastasis-free and cancer-specific survival. However, the expansion of robotic extirpation of SRM has outpaced the adoption of AS, resulting in the possibility of overtreatment for select patients with SRM, especially the elderly and comorbid. In this review of AS for SRM, with a focus on the Delayed Intervention and Surveillance for Small Renal Masses (DISSRM) Registry, we detail the rationale behind AS, review lessons learned from the past decades of literature, and offer suggestions for appropriate patient selection and follow-up. An improved understanding of the data supporting AS will empower physicians and patients to more comfortably pursue AS to avoid over-treatment and provide individualized care to patients with SRM., (© 2020 MedReviews®, LLC.)

Objectives: Conditional survival (CS) represents the probability that a cancer patient will survive some additional number of years, given that the patient has already survived for a certain period of time. CS estimates, therefore, serve as better measures of survival probability compared to standard estimates as they incorporate patient survivorship. Stage-specific CS has not been widely investigated in the context of renal cell carcinoma (RCC) after nephrectomy. We aimed to examine this phenomenon., Materials and Methods: We analyzed retrospective data on a population-based cohort of 87,225 surgically-treated RCC patients extracted from the Surveillance, Epidemiology, and End Results database (2004-2015) and on a similar validation cohort of 1,642 patients from our institution (1995-2015). 5-year cancer-specific CS estimates stratified by stage were obtained using the Kaplan-Meier method. Multivariable Cox regression analyses were performed to evaluate the possible variation in risk of cancer-specific mortality by stage at nephrectomy and with increasing postoperative survivorship., Results: 5-year cancer-specific survival rates at time of nephrectomy for stage I, II, III, and IV patients in the population-based cohort were 97.4%, 89.9%, 77.9%, and 26.7%, respectively. Improvement in 5-year CS was mainly observed in surviving patients with advanced-stage disease; given 1, 2, 3, 4, and 5 years of survivorship after nephrectomy, the subsequent 5-year cancer-specific survival rates were, respectively, 79.3% (+1.8% increase over previous survival probability), 81.3% (+2.5%), 83.3% (+2.5%), 84.3% (+1.2%), and 85.1% (+1.0%) for stage III, and 34.6% (+29.6%), 42.5% (+22.8%), 49.0% (+15.3%), 55.7% (+13.7%), and 58.6% (+5.2%) for stage IV. A similar trend was established in the validation cohort. Findings were confirmed upon multivariable analyses., Conclusions: CS after nephrectomy for RCC varies dramatically by stage of disease. Gains in CS over time occur primarily among patients with advanced-stage disease. Stage-specific CS estimates can help urologists better plan postoperative surveillance for RCC patients., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To determine whether use of renal mass biopsy may be associated with a reduction in surgery for patients with small, localized renal cell carcinoma (cT1aN0M0), especially among older patients and patients with greater comorbidity burden., Methods: A total of 106,258 patients with cT1aN0M0 renal cell carcinoma from 2004 to 2015 were analyzed in the National Cancer Data Base. Multivariable logistic regression identified independent associations with nonsurgical management, receipt of biopsy, and pathologic upstaging. Marginal effects were derived by age and comorbidity. A sensitivity analysis was conducted in years identifying patients undergoing active surveillance (2010-2015)., Results: There was increased use of biopsy (8.0%-15.3%) and nonsurgical management (11.7%-15.6%) over time. Biopsy was significantly associated with use of nonsurgical management (OR 4.80 [95%CI 4.58-5.02], P <.001) as well as active surveillance (OR 1.87 [1.69-2.07], P <.001) in the sensitivity analysis. Individual predicted probability of undergoing nonsurgical management ranged from 3% to 92% (median 31.4% with use of biopsy) and increased with age and comorbidity. Pathologic tumor upstaging (≥pT3a) occurred more frequently for patients receiving biopsy compared to no biopsy (5.8% vs 3.3%, P <.001). After adjustment, biopsy remained a statistically significant predictor of upstaging (OR 1.31 [95%CI 1.24-1.38], P <.001)., Conclusion: Overall, biopsy demonstrated a strong, independent association with reduced use of surgery for cT1aN0M0 kidney cancer, especially with increasing age and comorbidity. The potential association of renal mass biopsy with upstaging warrants caution, but it is uncertain whether it impacts prognosis relative to true perinephric fat invasion., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Using a large, nationally representative, population-based cancer registry, this study systematically evaluated the impact of the location and burden of extranodal testicular germ cell tumor (TGCT) metastases on survival., Methods: Men with stage III TGCTs captured by the Surveillance, Epidemiology, and End Results registry from 2010 to 2015 with distant extranodal metastases were identified. Clinicopathologic information was collected, and patients were subdivided according to the specific organ site or sites of metastatic involvement (lung, liver, bone, and/or brain). Kaplan-Meier analysis and multivariable Cox regression were used to evaluate cancer-specific survival (CSS), and model performance was assessed with Harrell's C statistic., Results: Nine hundred sixty-nine patients with stage III TGCTs were included with predominantly nonseminomatous histology (84%). Most patients (91%) had pulmonary metastases, whereas 20%, 10%, and 10% had liver, bone, and brain metastases, respectively. Over a median follow-up of 21 months, 19% of these men died of TGCTs. When they were grouped by the primary site of metastasis, patients with more than 1 extrapulmonary metastasis exhibited the worst CSS (hazard ratio [HR] vs isolated pulmonary involvement, 4.27; 95% confidence interval [CI], 2.60-7.00; P < .01). Among patients with isolated extrapulmonary involvement, those with brain metastases had the poorest survival (HR, 3.24; 95% CI, 1.98-5.28; P < .01), and they were followed by patients with liver (HR, 2.29; 95% CI, 1.56-3.35; P < .01) and bone metastases (HR, 1.97; 95% CI, 1.11-3.50; P = .02). Harrell's C statistic (multivariable) was 0.71., Conclusions: The site of metastatic involvement affects survival outcomes for patients with TGCTs, and this may reflect both the aggressive biology and the challenging treatment of these tumors. Further incorporation of organotropism into current prognostic models for metastatic TGCTs warrants attention., (© 2019 American Cancer Society.)

There are various management options for localized kidney cancer, including active surveillance, thermal ablation, partial nephrectomy, and radical nephrectomy. Choosing the optimal management requires consideration of oncologic outcomes, overall survival, and potential harms associated with each option. Oncologic outcomes and overall survival are determined by tumor and patient characteristics, respectively, and represent relatively objective metrics. The comparative harms of different management approaches are less predictable and result in treatment-related uncertainty. Active surveillance offers less uncertainty for many patients with localized kidney cancer: operative risks are completely forgone, oncologic outcomes are excellent, anxiety and illness uncertainty are well managed, and delayed intervention can be safely pursued. PATIENT SUMMARY: We reviewed the causes of treatment-related uncertainty associated with management options for localized kidney cancer. We discuss how active surveillance offers a certain degree of certainty according to the available literature. This could influence the decision to place patients on active surveillance., (Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.)