Impact of smoking status on clinical outcomes in patients with metastatic renal cell carcinoma treated with first-line immune checkpoint inhibitor-based regimens.

BACKGROUND: Current tobacco smoking is independently associated with decreased overall survival (OS) among patients with metastatic renal cell carcinoma (mRCC) treated with targeted monotherapy (VEGF-TKI). Herein, we assess the influence of smoking status on the outcomes of patients with mRCC treated with the current first-line standard of care of immune checkpoint inhibitor (ICI)-based regimens. MATERIALS AND METHODS: Real-world data from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) were collected retrospectively. Patients with mRCC who received either dual ICI therapy or ICI with VEGF-TKI in the first-line setting were included and were categorized as current, former, or nonsmokers. The primary outcomes were OS, time to treatment failure (TTF), and objective response rate (ORR). OS and TTF were compared between groups using the log-rank test and multivariable Cox regression models. ORR was assessed between the 3 groups using a multivariable logistic regression model. RESULTS: A total of 989 eligible patients were included in the analysis, with 438 (44.3%) nonsmokers, 415 (42%) former, and 136 (13.7%) current smokers. Former smokers were older and included more males, while other baseline characteristics were comparable between groups. Median follow-up for OS was 21.2 months. In the univariate analysis, a significant difference between groups was observed for OS (P = .027) but not for TTF (P = .9), with current smokers having the worse 2-year OS rate (62.8% vs 70.8% and 73.1% in never and former smokers, respectively). After adjusting for potential confounders, no significant differences in OS or TTF were observed among the 3 groups. However, former smokers demonstrated a higher ORR compared to never smokers (OR 1.45, P = .02). CONCLUSION: Smoking status does not appear to independently influence the clinical outcomes to first-line ICI-based regimens in patients with mRCC. Nonetheless, patient counseling on tobacco cessation remains a crucial aspect of managing patients with mRCC, as it significantly reduces all-cause mortality.

Association of Cabozantinib Dose Reductions for Toxicity With Clinical Effectiveness in Metastatic Renal Cell Carcinoma (mRCC): Results From the Canadian Kidney Cancer Information System (CKCis).

BACKGROUND: Cabozantinib, an oral multi-targeted tyrosine kinase inhibitor (TKI), has demonstrated efficacy in metastatic renal cell carcinoma (mRCC). The association between toxicity and therapeutic effectiveness has been established with other TKIs. We investigated whether cabozantinib dose reductions, a surrogate for toxicity and adequate drug exposure, were associated with improved clinical outcomes in mRCC. METHODS: Employing the CKCis database, we analyzed patients treated with cabozantinib in the second line or later between 2011 to 2021. The cohort was stratified into those needing dose reductions (DR) during treatment and those not (no-DR). Outcomes, including objective response rate (ORR), time to treatment failure (TTF), and overall survival (OS), were compared based on dose reduction status. The influence of the initial dose on outcomes was also explored. RESULTS: Among 319 cabozantinib-treated patients, 48.3% underwent dose reductions. Response rates exhibited no significant difference between the DR and no-DR groups (15.1% vs. 18.2%, P = .55). Patients with DR had superior median OS (26.15 vs. 15.47 months, P = .019) and TTF (12.74 vs. 6.44 months, P = .022) compared to no-DR patients. These differences retained significance following adjustment for IMDC risk group (OS HR = 0.67, P = .032; TTF HR = 0.65, P = .008). There was no association between the initial dose and ORR, OS, or TTF. CONCLUSION: This study highlights the link between cabozantinib dose reductions due to toxicity and improved survival and time to treatment failure in mRCC patients. These findings underscore the potential of using on-treatment toxicity as an indicator of adequate drug exposure to individualize dosing and optimize treatment effectiveness. Larger studies are warranted to validate these results and develop individualized strategies for cabozantinib when given alone or in combination with immunotherapy.

An in-depth analysis on the effects of body composition in patients receiving neoadjuvant chemotherapy for urothelial cell carcinoma.

INTRODUCTION: Neoadjuvant chemotherapy (NAC) is the standard of care for patients undergoing radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC); however, NAC can be associated with significant side effects and morbidity in some patients. NAC may contribute to sarcopenia, obesity, and the combination of the two. Our study examined the effects of NAC on body composition and the association between body composition and adverse events. METHODS: We created a retrospective database of patients with non-metastatic MIBC receiving NAC prior to RC. The change in skeletal muscle index (SMI) and fat mass index (FMI) was calculated using computed tomography (CT) scans done within three months prior to NAC and after the first two cycles. The association between body composition (sarcopenia, obesity, and sarcopenic obesity) and preoperative adverse events was investigated using a multivariable logistic regression. Changes in body composition were calculated using a paired Student's t-test. RESULTS: A total of 70 patients were included in our study. There was a mean decrease in SMI of 2.2±3.2 cm2/m2. Adiposity and FMI were unchanged by NAC. Sarcopenic obesity was found to be associated with adverse events among patients receiving NAC in the multivariable analysis. There were a total of 637 preoperative complications with grades 1-2 and 33 complications with grades 3-5. CONCLUSIONS: Based on our retrospective cohort study, NAC did not affect obesity and FMI, but there was a significant decrease in SMI. Sarcopenic obesity was associated with increased severity of NAC adverse events. As such, the presence of this factor may help predict tolerance of NAC.

Outcomes of Patients with Brain Metastases from Renal Cell Carcinoma Receiving First-line Therapies: Results from the International Metastatic Renal Cell Carcinoma Database Consortium.

Patients with brain metastases (BrM) from renal cell carcinoma and their outcomes are not well characterized owing to frequent exclusion of this population from clinical trials. We analyzed data for patients with or without BrM using the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC). A total of 389/4799 patients (8.1%) had BrM on initiation of systemic therapy. First-line immuno-oncology (IO)-based combination therapy was associated with longer median overall survival (OS; 32.7 mo, 95% confidence interval [CI] 22.3-not reached) versus tyrosine kinase inhibitor monotherapy (20.6 mo, 95% CI 15.7-24.5; p = 0.019), as were intensive focal therapies with stereotactic radiotherapy or neurosurgery (31.4 mo, 95% CI 22.3-37.5) versus whole-brain radiotherapy alone or no focal therapy (16.5 mo, 95% CI 10.2-21.1; p = 0.028). On multivariable analysis, IO-based regimens (HR 0.49, 95% CI 0.25-0.97; p = 0.040) and stereotactic radiotherapy or neurosurgery (HR 0.48, 95% CI 0.29-0.78; p = 0.003) were independently associated with longer OS, as was IMDC favorable or intermediate risk (HR 0.40, 95% CI 0.24-0.66; p < 0.001). Intensive systemic and focal therapies were associated with better prognosis in this population. Further studies should explore the clinical effectiveness of multimodal strategies. PATIENT SUMMARY: In a large group of patients with advanced kidney cancer, we found that 8.1% had brain metastases when starting systemic therapy. Patients with brain metastases had significantly poorer prognosis than those without brain metastases. Receipt of combination immunotherapy, stereotactic radiotherapy, or neurosurgery was associated with longer overall survival.

Real-world Assessment of Clinical Outcomes in Patients with Metastatic Renal Cell Carcinoma with or Without Sarcomatoid Features Treated with First-line Systemic Therapies.

BACKGROUND AND OBJECTIVE: Metastatic renal cell carcinoma (mRCC) patients have been reported to have better outcomes when treated with immunotherapies (IO) compared to targeted therapies (TT). This study aims to evaluate the impact of first-line systemic therapies on survival of mRCC patients with or without sarcomatoid features using real-world data. METHODS: Metastatic RCC patients of International mRCC Database Consortium (IMDC) intermediate or high risk, diagnosed from January 2011 to December 2022, treated with first-line systemic therapies, and with histological documentation of the presence or absence of sarcomatoid features in nephrectomy specimens were identified using the Canadian Kidney Cancer information system. Patients were classified by initial treatment: (1) targeted therapy (TT) used alone or (2) immunotherapy (IO)-based systemic therapies used in combination of either IO-IO or IO-TT. The inverse probability of treatment weighting using propensity scores was used to balance for covariates. Cox proportional hazard models were used to assess the impact of initial treatment received on overall survival (OS). KEY FINDINGS AND LIMITATIONS: Of the 1202 eligible patients, 791 were treated with TT and 411 with IO combinations. Of the patients, 76% were male, and the majority (91%) had a nephrectomy before systemic therapy. In nonsarcomatoid patients (639 TT and 320 IO patients), treatment with IO was associated with improved OS compared with patients treated with TT (median of 72 vs 48 mo, hazard ratio [HR] 0.63, 95% confidence interval [CI] 0.50-0.80, objective response rate [ORR] of 38.5% for IO and 23.5% for TT). In sarcomatoid patients (152 TT and 91 IO patients), treatment with IO was associated with improved OS (median of 48 vs 18 mo, HR 0.41, 95% CI 0.26-0.64, ORR of 49.5% for IO and 13.8% for TT). Similar results were observed in patients with synchronous metastatic disease only. CONCLUSIONS AND CLINICAL IMPLICATIONS: IO treatment was associated with improved survival in mRCC patients. The magnitude of benefit is increased in patients with sarcomatoid mRCC, consequently, identifying the sarcomatoid status early on could help healthcare providers make a better treatment decision. PATIENT SUMMARY: Metastatic renal cell carcinoma (mRCC) patients of International mRCC Database Consortium intermediate and high risk, diagnosed from January 2011 to December 2022, treated with first-line systemic therapies, and with histological documentation of the presence or absence of sarcomatoid features in nephrectomy specimens were identified using the Canadian Kidney Cancer information system (CKCis). In this study, treatment with immunotherapy was associated to an improved survival and response rates for mRCC patients with and without sarcomatoid features. The magnitude of benefit is increased in patients with sarcomatoid mRCC.

Characterization of Patients with Metastatic Renal Cell Carcinoma Undergoing Deferred, Upfront, or No Cytoreductive Nephrectomy in the Era of Combination Immunotherapy: Results from the International Metastatic Renal Cell Carcinoma Database Consortium.

BACKGROUND: The role of cytoreductive nephrectomy (CN) has not yet been well characterized in the era of combination immunotherapy. OBJECTIVE: To evaluate characteristics and outcomes for patients with metastatic renal cell carcinoma (mRCC) who received immuno-oncology (IO)-based combination therapy according to CN status. DESIGN, SETTING, AND PARTICIPANTS: Using the International mRCC Database Consortium (IMDC), patients with mRCC who received frontline IO-based combinations were included. Upfront CN was defined as CN up to 3 mo before diagnosis of metastatic disease but before systemic therapy initiation. Deferred CN was defined as CN after systemic therapy initiation. OUTCOMES MEASUREMENTS AND STATISTICAL ANALYSIS: Overall survival (OS) from initiation of systemic therapy was estimated via Cox proportional-hazards regression. A 12-mo landmark time and a time-varying covariate for CN status were used to mitigate potential bias. RESULTS AND LIMITATIONS: Of the 385 patients eligible for landmark analysis, 24, 182, and 179 underwent deferred CN, upfront CN, and no CN, respectively. Patients in the no CN subgroup were older (63 yr vs 57 yr in the deferred CN subgroup and 60 yr in the upfront CN subgroup; p = 0.001) and a higher proportion had bone metastases (44% vs 26% in the deferred CN subgroup and 23% in the upfront CN subgroup; p < 0.001). A lower proportion of patients in the upfront CN subgroup had IMDC poor risk (23% vs 43% in the no CN subgroup and 47% in the deferred CN subgroup; p < 0.001). On multivariable analysis, CN receipt was an independent favorable prognostic factor (hazard ratio 0.45, 95% confidence interval 0.26-0.78; p = 0.005). The study is limited by the lack of randomization and its retrospective nature. CONCLUSIONS: Despite changes in practice patterns with the advent of novel therapeutic agents, CN may still serve as an effective surgical intervention in carefully selected patients. PATIENT SUMMARY: For patients with metastatic kidney cancer, surgery to remove the primary tumor was traditionally the treatment of choice, but immunotherapy drugs are now another option for these patients. We analyzed data for contemporary patients with metastatic kidney cancer who received combination immunotherapy as their first treatment. We found that in selected patients receiving immunotherapy, surgery to remove the primary tumor as well can result in better prognosis.

Trends of Utilization of Systemic Therapies for Metastatic Renal Cell Carcinoma in the Canadian Health Care System.

PURPOSE: Standard-of-care therapies for metastatic renal cell carcinoma (mRCC) have greatly evolved. However, the availability of emerging options in global health care systems can vary. We sought to describe the integration and usage of systemic therapies for mRCC in Canada since 2011. METHODS: We included patients with mRCC enrolled in the Canadian Kidney Cancer Information System, a prospective cohort of patients from 14 Canadian academic centers, who received systemic therapy from January 1, 2011, to December 31, 2021. Patients were stratified by treatment era (cohort 1: 2011-2015, cohort 2: 2016-2021). Stacked bar charts were used to present treatment proportions; Sankey diagrams were used to show the evolution of treatment sequencing between the two cohorts. RESULTS: Four thousand one hundred seven patients were diagnosed with mRCC, of whom 2,752 (67%) received systemic therapy. Among these patients, mean age was 64 years, 74% were male, 75% had clear cell histology, and International Metastatic RCC Database Consortium risk classification was favorable, intermediate, and poor in 16%, 56%, and 28%, respectively. Utilization of immune checkpoint inhibition (ICI)-based treatments has increased in Canada and reflects global and local patterns of approval and adoption. The use of therapies after doublet ICI has mostly shifted toward vascular endothelial growth factor-tyrosine kinase inhibitors (VEGF-TKIs) that were previously used in first line with subsequent treatments reflecting approved and available agents after previous VEGF-TKI. Clinical trial participation among patients who received systemic therapy was 18% in first, 21% in second, and 24% in third line. CONCLUSION: In Canada's publicly funded health care system, availability of standard mRCC therapies broadly reflects access from government-funded clinical trials and compassionate access program sources. In an evolving therapeutic landscape, ongoing advocacy is required to continue to facilitate patient access to efficacious therapies.

Perioperative systemic therapy in renal cell carcinoma.

PURPOSE OF REVIEW: Renal cell carcinoma (RCC) is the most common kidney neoplasm. Localized RCC can be cured with nephrectomy. However, a proportion of patients will recur with incurable distant metastatic disease. There is a clear need for treatments to reduce the risk of RCC recurrence and thus improve survival. This review describes the landscape of perioperative therapy for RCC, focusing on more recent trials involving immune checkpoint inhibitors (ICIs). RECENT FINDINGS: ICIs have significantly changed outcomes in advanced RCC. Four trials investigating the role of perioperative ICI for RCC are now reported. Only one trial utilizing adjuvant pembrolizumab (Keynote-564) has shown a disease-free survival benefit in resected RCC. SUMMARY: Patients with resected RCC should be counselled on their risk of recurrence and the potential option of adjuvant pembrolizumab, recognizing that overall survival data are not yet available.

The Use of Salvage Chemotherapy for Patients with Relapsed Testicular Germ Cell Tumor (GCT) in Canada: A National Survey.

BACKGROUND: Although metastatic germ cell tumor (GCT) is highly curable with initial cisplatin-based chemotherapy (CT), 20-30% of patients relapse. Salvage CT options include conventional (CDCT) and high dose chemotherapy (HDCT), however definitive comparative data remain lacking. We aimed to characterize the contemporary practice patterns of salvage CT across Canada. METHODS: We conducted a 30-question online survey for Canadian medical and hematological oncologists with experience in treating GCT, assessing treatment availability, patient selection, and management strategies used for relapsed GCT patients. RESULTS: There were 30 respondents from 18 cancer centers across eight provinces. The most common CDCT regimens used were TIP (64%) and VIP (25%). HDCT was available in 13 centers (70%). The HDCT regimen used included carboplatin and etoposide for two cycles (76% in 7 centers), three cycles (6% in 2 centers), and the TICE protocol (11%, in 2 centers). "Bridging" CDCT was used by 65% of respondents. Post-HDCT treatments considered include surgical resection for residual disease (87.5%), maintenance etoposide (6.3%), and surveillance only (6.3%). CONCLUSIONS: HDCT is the most commonly used GCT salvage strategy in Canada. Significant differences exist in the treatment availability, selection, and delivery of HDCT, highlighting the need for standardization of care for patients with relapsed testicular GCT.

Adjuvant therapy for renal cell carcinoma: 2023 Canadian Kidney Cancer Forum consensus statement.

INTRODUCTION: Several recent randomized trials evaluated the impact of adjuvant immune checkpoint inhibitor (ICI)-based therapy on post-surgical outcomes in renal cell carcinoma (RCC), with disparate results. The objective of this consensus statement is to provide data-driven guidance regarding the use of ICIs after complete resection of clear-cell RCC in a Canadian context. METHODS: An expert panel of genitourinary medical oncologists, urologic oncologists, and radiation oncologists with expertise in RCC management was convened in a dedicated session during the 2022 Canadian Kidney Cancer Forum in Toronto, Canada. Topic statements on the management of patients after surgery for RCC, including counselling, risk stratification, indications for medical oncology referral, appropriate followup, eligibility and management for adjuvant ICIs, as well as treatment options for patients with recurrence who received adjuvant immunotherapy, were discussed. Participants were asked to vote if they agreed or disagreed with each statement. Consensus was achieved if greater than 75% of participants agreed with the topic statement. RESULTS: A total of 22 RCC experts voted on 14 statements. Consensus was achieved on all topic statements. The panel felt patients with clear-cell RCC at increased risk of recurrence after surgery, as per the Keynote-564 group definitions, should be counselled about recurrence risk by a urologist, should be informed about the potential role of adjuvant ICI systemic therapy, and be offered referral to discuss risks and benefits with a medical oncologist. The panel felt that one year of pembrolizumab is currently the only regimen that should be considered if adjuvant therapy is selected. Panelists emphasized current opinions are based on disease-free survival given the available results. Significant uncertainty regarding the benefit and harms of adjuvant therapy remains, primarily due to a lack of consistent benefit observed across similar trials of adjuvant ICI-based therapies and immature overall survival (OS) data. CONCLUSIONS: This consensus document provides guidance from Canadian RCC experts regarding the potential role of ICI-based adjuvant systemic therapy after surgery. This rapidly evolving field requires frequent evidence-based re-evaluation.

Comparison of patients with renal cell carcinoma in adjuvant therapy trials to a real-world population.

PURPOSE: To compare characteristics and outcomes of patients included versus those not in adjuvant therapy trials post complete resection of renal cell carcinoma (RCC). METHODS: Adult patients following complete resection for clear cell RCC between January 1, 2011, and March 31, 2021, were included. Patients had intermediate high, high risk nonmetastatic disease (modified UCLA Integrated Staging System) or fully resected metastatic (M1) disease as per the inclusion criteria of adjuvant studies. Demographic, clinical, and outcomes between trial and nontrial patients were compared. RESULTS: Of 1,459 eligible patients, 63 (4.3%) participated in an adjuvant trial. Disease characteristics were similar between groups. Trial patients were younger (mean age 58.1 vs. 63.6 years; P < 0.0001) and had lower Charlson Comorbidity Index scores (mean 4.2 vs. 4.9; P = 0.009). Unadjusted disease-free survival (DFS) at 5 years for trial patients was 48.6% and 39.2% for nontrial patients (HR 0.71, 0.48-1.05, P = 0.08). Median DFS was higher for trial patients in comparison to nontrial patients (4.4 years, IQR 1.7- not reached; vs. 3.0 years, IQR 0.8-8.6; P = 0.08). Cancer specific survival (CSS) at 5 years for trial patients was 85.2% in comparison to 78.6% for nontrial patients (HR 0.45, 0.22-0.92, P = 0.03). Unadjusted estimated overall survival (OS) at 5 years was 80.8% for trial patients and 74.8% (HR 0.42, 0.18-0.94; P = 0.04) for nontrial patients. CONCLUSIONS: Patients in adjuvant trials were younger and healthier with longer CSS and OS in comparison to those not included in adjuvant trials. These findings may have implications when we generalize trial results to real world patients.

Impact of the COVID-19 Pandemic on Medical Oncology Workload: A Provincial Review.

(1) Background: Cancer is the leading cause of death in Canada, with significant resource limitation impacting the delivery of cancer care nationwide. The onset of the COVID-19 pandemic forced additional resource restriction and diversion, further impacting care delivery. Our intention is to analyze the impact COVID-19 on a provincial medical oncology workload and bring attention to the limitations of the current workload metric for oncologists. (2) Methods: All medical oncology patient encounters were extracted and compared, collected by year and encounter type, from April 2014 through March 2022. (3) Results: There was an increase in all patient encounters by an average of 9.5% per year, including during the strictest COVID-19 restrictions. There was an increase in virtual care encounters from 37.9% to 52.1%. (4) Conclusions: Medical Oncology workloads have increased over time and estimates suggest growing demand. Little data exist to inform workforce requirements and actual workload is not captured by the current metric. Though volume of new consults continues to increase, COVID-19 has highlighted additional changes in the delivery of care, likely with lasting impact, little of which are included in the current workload metric.

Evaluation of Trends in Treatment of Metastatic Hormone Sensitive Prostate Cancer (mHSPC) Across Canada During the COVID-19 Pandemic.

BACKGROUND: In metastatic hormone sensitive prostate cancer (mHSPC), treatment intensification with either docetaxel or an androgen-receptor-axis targeted therapy (ARAT), added to androgen deprivation therapy (ADT) is the new standard of care. To better understand patterns of treatment intensification in Canada and specifically how it has been influenced by the COVID-19 pandemic, we conducted a national survey of genitourinary medical oncologists from across Canada. METHODS: Using SurveyMonkey, we conducted an online survey of 119 medical oncologists in Canada from January 15 to January 27, 2021. The survey consisted of 16 questions, including demographics, and asked specifically about their approach to managing mHSPC before and during the pandemic. RESULTS: Overall there were 50/119 (42%) respondents. Most were male (65%), from Ontario (35%), practicing in academic centers (71%), with 45% reporting their practices focused primarily on genitourinary malignancies and one other tumor site. The majority were in practice 1 to 5 years (34%). Overall 65% indicated their practice patterns had changed since the pandemic, with 51% offering more ARATs and less docetaxel chemotherapy. In low volume mHSPC, the use of ARATs increased from 73% to 79%, while the use of docetaxel remained unaltered at 2%. In high volume disease, the use of ARATs increased from 63% to 84%, while the use of docetaxel decreased from 37% to 14%. Use of granulocyte colony stimulating factor (G-CSF) with docetaxel chemotherapy increased by 35%. Post-pandemic, 45% reported they intend to maintain these changes. Only 18% reported they had prostate cancer patients test positive for COVID-19, and all patients recovered. CONCLUSION: Management of patients with mHSPC in Canada has changed during the pandemic, with increased uptake of ARATs and reduced use of docetaxel, a trend expected to continue beyond the pandemic. How this trend will impact uptake of triplet therapy (ADT + ARAT + Docetaxel), downstream treatment choices and overall outcomes remains to be seen.

Outcomes for International Metastatic Renal Cell Carcinoma Database Consortium Prognostic Groups in Contemporary First-line Combination Therapies for Metastatic Renal Cell Carcinoma.

BACKGROUND: The combination of immuno-oncology (IO) agents ipilimumab and nivolumab (IPI-NIVO) and vascular endothelial growth factor targeted therapies (VEGF-TT) combined with IO (IO-VEGF) are current standard of care first-line treatments for metastatic renal cell carcinoma (mRCC). OBJECTIVE: To establish real-world clinical benchmarks for IO combination therapies based on the International mRCC Database Consortium (IMDC) criteria. DESIGN, SETTING, AND PARTICIPANTS: Patients with mRCC who received first-line IPI-NIVO, IO-VEGF, or VEGF-TT from 2002 to 2021 were identified using the IMDC database and stratified according to IMDC risk groups. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Overall survival (OS), time to next treatment (TTNT), and treatment duration (TD) were calculated using the Kaplan-Meier method and compared between IMDC risk groups within each treatment cohort by the log-rank test. The overall response rate (ORR) was calculated by physician assessment of the best overall response. The primary outcome was OS at 18 mo. RESULTS AND LIMITATIONS: In total, 728 patients received IPI-NIVO, 282 IO-VEGF, and 7163 VEGF-TT. The median follow-up times for patients remaining alive were 14.3 mo for IPI-NIVO, 14.9 mo IO-VEGF, and 34.4 mo for VEGF-TT. OS at 18 mo for favorable, intermediate, and poor risk was, respectively, 90%, 78%, and 50% for those receiving IPI-NIVO; 93%, 83%, and 74% for IO-VEGF; and 84%, 64%, and 28% for VEGF-TT. ORRs in favorable-, intermediate-, and poor-risk groups were 41.3%, 40.6%, and 33.0% for those receiving IPI-NIVO; 60.3%, 56.8%, and 40.9% for IO-VEGF; and 39.3%, 33.5%, and 20.9% for VEGF-TT, respectively. The IMDC model stratified patients into statistically distinct risk groups for the three endpoints of OS, TTNT, and TD within each treatment cohort. Limitations of this study were the retrospective design and short follow-up. CONCLUSIONS: This study demonstrated that the IMDC model continues to risk stratify patients with mRCC treated with contemporary first-line IO combination therapies and provided real-world survival benchmarks. PATIENT SUMMARY: The International Metastatic Renal Cell Carcinoma Database Consortium model continues to stratify patients with metastatic renal cell carcinoma receiving modern combination treatments in the real-world setting.

Evaluating the impact of early identification of asymptomatic brain metastases in metastatic renal cell carcinoma.

BACKGROUND: Brain metastases (BM) in metastatic renal cell carcinoma (mRCC) have been reported to be present in up to 25% of patients diagnosed with mRCC. There is limited published literature evaluating the role of routine intra-cranial imaging for the screening of asymptomatic BM in mRCC. AIMS: To evaluate the potential utility of routine intra-cranial imaging, a retrospective cohort study was conducted to characterize the outcomes of mRCC patients who presented with asymptomatic BM, as compared to symptomatic BM. METHODS AND RESULTS: The Canadian Kidney Cancer Information System (CKCis) database was used to identify mRCC patients diagnosed with BM. This cohort was divided into two groups based on the presence or absence of BM symptoms. Details regarding patient demographics, disease characteristics, systemic treatments, BM characteristics and survival outcomes were extracted. Statistical analysis was through chi-square tests, analysis of variance, and Kaplan-Meier method to characterize survival outcomes. A p-value of <0.05 was considered statistically significant for all analyses. A total of 267 mRCC patients with BM were identified of which 106 (40%) presented with asymptomatic disease. The majority of patients presented with multiple (i.e., >1) BM (75%) with no significant differences noted in number of BM or BM-directed therapy received in symptomatic, as compared to asymptomatic BM patients. Median [95% confidence interval (CI)] overall survival (OS) from mRCC diagnosis was 42 months (95% CI: 32-62) for patients with asymptomatic BM, and 39 months (95% CI: 29-48) with symptomatic BM (p = 0.10). OS from time of BM diagnosis was 28 months (95% CI: 18-42) for the asymptomatic BM group, as compared to 13 months (95% CI: 10-21) in the symptomatic BM group (p = 0.04). CONCLUSIONS: Given a substantial proportion of patients may present with asymptomatic BM, limiting intra-cranial imaging to patients with symptomatic BM, may be associated with a missed opportunity for timely diagnosis and treatment. The utility of routine intra-cranial imaging in patients with renal cell carcinoma, warrants further prospective evaluation.

Accuracy of germ cell tumor histology and stage within a Canadian cancer registry.

INTRODUCTION: Cancer registries are the mainstay for Canadian population-based cancer statistics. Data are collected in provincial and territorial registries, including the Nova Scotia Cancer Registry (NS CR). The goal of this study was to determine the accuracy of NS CR data for germ cell tumors (GCT). METHODS: This analysis included all NS CR patients diagnosed with GCT from 2006-2015. The date and method of diagnosis, primary site, histology, and stage were recorded from the NS CR and compared to each patient's chart. Any discrepancies between the two sources were reviewed and reasons behind the discrepancies recorded. RESULTS: A total of 229 patients made up the study cohort. Using NS CR data, 57.6% had seminoma, 34.5% non-seminoma (NSG CT), and 7.9% other. Discrepancies in pathology were noted in 16 patients (7.0%). Using NS CR staging data (available in 185 cases), 71.9% had stage I, 12.4% stage II, 11.9% stage III, and 3.8% other. Discrepancies in stage were noted in 32 patients (17.3%) with NS CR data downstaging eight patients (4.3%) and upstaging 21 patients (11.4%). The site of the primary GCT was discrepant in 12 patients (5.2%). The date of diagnosis was accurate within one week for all patients except one. CONCLUSIONS: Higher-level NS CR data, such as date of diagnosis and overall pathological diagnosis, appear relatively accurate; however, there are inaccuracies in histological subtype and stage. This study raises awareness of these gaps and highlights key areas for improvement in educating registry personnel who interpret and enter data about the uniqueness of GCT pathology, staging, and interpretation of tumor markers.

Upfront Cytoreductive Nephrectomy for Metastatic Renal Cell Carcinoma Treated with Immune Checkpoint Inhibitors or Targeted Therapy: An Observational Study from the International Metastatic Renal Cell Carcinoma Database Consortium.

BACKGROUND: The role of upfront cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) in the era of immune checkpoint inhibitors is unclear. OBJECTIVE: To evaluate the relationship between upfront CN and clinical outcomes in the setting of mRCC treated with immune checkpoint inhibitors or targeted therapy. DESIGN, SETTING, AND PARTICIPANTS: Using the International Metastatic RCC Database Consortium, we retrospectively identified patients diagnosed with de novo mRCC treated with immune checkpoint inhibitors or targeted therapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Overall survival (OS) was compared between the two groups using the Kaplan-Meier method and multivariable Cox regressions adjusting for known prognostic factors. RESULTS AND LIMITATIONS: We identified a total of 4639 eligible patients with mRCC. Among the 4202 patients treated with targeted therapy and 437 patients treated with immune checkpoint inhibitors, 2326 (55%) and 234 (54%) patients received upfront CN prior to treatment start. In multivariable analyses, CN was associated with significantly better OS in both the immune checkpoint inhibitor-treated (hazard ratio [HR]: 0.61; 95% confidence interval [CI], 0.41-0.90, p = 0.013) and the targeted therapy treatment (HR: 0.72; 95% CI, 0.67-0.78, p < 0.001) group. There was no difference in OS benefit of CN between the immune checkpoint inhibitor and targeted therapy treatment groups (interaction p = 0.6). Limitations include selection of patients from large academic centers and the retrospective nature of the study. CONCLUSIONS: Upfront CN is associated with a significant OS benefit in selected patients treated by either immune checkpoint inhibitors or targeted therapy, and still has a role in selected patients in the era of immune checkpoint inhibitors. PATIENT SUMMARY: Before effective systemic therapies were available for metastatic kidney cancer, surgical removal of the primary (kidney) tumor was the mainstay of treatment. The role of removing the primary tumor has recently been called into question given that more effective systemic therapies have become available. In this study, we find that removal of the primary kidney tumor still has a benefit for selected patients treated with highly effective modern systemic therapies, including targeted therapies and immune checkpoint inhibitors.