Rate of benign histology after resection of suspected renal cell carcinoma: multicenter comparison between Korea and the United States.

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.

Self-reported quality of life as a predictor of mortality in renal cell carcinoma.

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.

Active Surveillance versus Immediate Intervention for Small Renal Masses: A Cost-Effectiveness and Clinical Decision Analysis.

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.

Does Perioperative Testosterone Predict Post-Prostatectomy Genomic Risk Score?

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.

Minimally invasive retroperitoneal lymph node dissection for men with testis cancer: a retrospective cohort study of safety and feasibility.

PURPOSE: To describe the perioperative safety, functional and immediate post-operative oncological outcomes of minimally invasive RPLND (miRPLND) for testis cancer. METHODS: We performed a retrospective multi-centre cohort study on testis cancer patients treated with miRPLND from 16 institutions in eight countries. We measured clinician-reported outcomes stratified by indication. We performed logistic regression to identify predictors for maintained postoperative ejaculatory function. RESULTS: Data for 457 men undergoing miRPLND were studied. miRPLND comprised laparoscopic (n = 56) or robotic (n = 401) miRPLND. Indications included pre-chemotherapy in 305 and post-chemotherapy in 152 men. The median retroperitoneal mass size was 32 mm and operative time 270 min. Intraoperative complications occurred in 20 (4%) and postoperative complications in 26 (6%). In multivariable regression, nerve sparing, and template resection improved ejaculatory function significantly (template vs bilateral resection [odds ratio (OR) 19.4, 95% confidence interval (CI) 6.5-75.6], nerve sparing vs non-nerve sparing [OR 5.9, 95% CI 2.3-16.1]). In 91 men treated with primary RPLND, nerve sparing and template resection, normal postoperative ejaculation was reported in 96%. During a median follow-up of 33 months, relapse was detected in 39 (9%) of which one with port site (< 1%), one with peritoneal recurrence and 10 (2%) with retroperitoneum recurrences. CONCLUSION: The low proportion of complications or peritoneal recurrences and high proportion of men with normal postoperative ejaculatory function supports further miRPLND studies.

Comparative Effectiveness of Surveillance, Primary Chemotherapy, Radiotherapy and Retroperitoneal Lymph Node Dissection for the Management of Early Stage Testicular Germ Cell Tumors: A Systematic Review.

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.

Outcomes of Active Surveillance for Young Patients with Small Renal Masses: Prospective Data from the DISSRM Registry.

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, χ2 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.

Cancer in Syrian refugees in Jordan and Lebanon between 2015 and 2017.

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.

Performance Characteristics of Clinical Staging Modalities for Early Stage Testicular Germ Cell Tumors: A Systematic Review.

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.

Diagnosis and Management of Intratubular Germ Cell Neoplasia In Situ: A Systematic Review.

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.

Site of extranodal metastasis impacts survival in patients with testicular germ cell tumors.

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.

Higher prevalence of benign tumors in men with testicular tumors and history of treated cryptorchidism.

OBJECTIVES: To identify if surgically treated cryptorchidism correlated with testicular tumor pathology at presentation. MATERIALS AND METHODS: An institutional database of patients treated for testicular cancer between 2003 and 2020 was reviewed. Inclusion criteria included orchiectomy patients. Exclusion criteria included unknown cryptorchidism history or pathology or laterality of orchiectomy. Data collection included demographics, surgical history, and tumor marker status. RESULTS: A total of 435 patients were included. Thirty-three of these patients had a history of UDT. There was no statistical difference in age at orchiectomy, laterality of orchiectomy, or lymphovascular invasion with regard to UDT history. There was a statistical difference in tumor pathology after orchiectomy, P = 0.03. On secondary analysis, benign pathology was significantly more common in patients with a history of UDT (15.2%) than without (4.7%), P = 0.01. Mixed GCT was also found at a significantly lower rate in patients with a history of UDT (18.2%) compared to those with no history of UDT (37.3%), P = 0.03. There were no statistically significant differences in other pathology. CONCLUSION: Previous studies have shown that there is a greater rate of seminoma in patients with testicular cancer in an undescended testis. This study shows that in patients with a history of UDT compared to those without a history of UDT, there is a greater percentage of patients with benign testicular masses after orchiectomy. Guideline based practices including monthly self-examination and testis-sparing surgery for appropriate patients may reduce rates of radical orchiectomy for benign tumors.

Development and validation of a multicenter Cox regression model to predict all-cause mortality in patients with renal masses suspicious for renal cancer.

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.

Urologist-level variation in the management of T1a renal cell carcinoma: A population-based cohort study.

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.

Disparities in the Treatment and Survival of Metastatic Renal Cell Carcinoma.

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.

Characterizing Tumor Thrombus Arising from Non-Clear Cell Renal Cell Carcinoma.

Background: Renal cell carcinoma (RCC) can exhibit a unique vascular tropism that enables tumor thrombus extension into the inferior vena cava (IVC). While most RCC subtypes that form tumor thrombi are of clear cell (cc) histology, non-clear cell (ncc) subtypes can also exhibit this unique growth pattern. Objective: To characterize clinicopathologic differences and survival outcomes among patients with IVC tumor thrombus arising from ccRCC versus nccRCC. Design setting and participants: Patients diagnosed with IVC tumor thrombus secondary to RCC in our institutional experience from 2003 to 2021 were identified. Outcome measurements and statistical analysis: Clinicopathologic characteristics were compared by histology. Perioperative and oncologic outcomes including recurrence-free (RFS), overall (OS), and cancer-specific (CSS) survival were assessed using multivariable Cox regression analyses. Results and limitations: The analyzed cohort included 103 patients (82 ccRCC and 21 nccRCC). There were no significant differences in baseline demographic parameters. Patients with nccRCC were more likely to have regional lymph node involvement (42.9% vs 20.7%, p = 0.037). No differences in perioperative outcomes, IVC resection, or IVC reconstruction were observed between groups. The median follow-up time was 30 mo. The median RFS was 30 (nccRCC) versus 53 (ccRCC) mo (p = 0.1). There was no significant difference in OS or CSS. This study was limited by its small sample size. Conclusions: Patients with IVC tumor thrombus arising from ccRCC and nccRCC exhibit similar perioperative and oncologic outcomes. While surgical appropriateness was not impacted by histologic subtype, multimodal strategies are needed to improve outcomes for patients with tumor thrombus. Patient summary: Renal cell carcinoma (RCC) can uniquely invade vasculature and form a tumor thrombus. This study examined the difference in outcomes of patients with tumor thrombus based on RCC subtype (clear cell vs non-clear cell). We found that patients exhibited similar surgical and survival outcomes regardless of RCC type.

Clinical utility of the AJCC 8th edition pT1 subclassification and impact on practice patterns in stage I seminoma.

BACKGROUND: The American Joint Committee on Cancer 8th 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.