Articles

Maxwell Sandberg, Gregory Russell, Dana Feldman, Mitchell Hayes, Reuben Ben David, Justin Miller, Kartik Patel, Brejjette Aljabi, Seok-Soon Byun, Oscar Rodriguez Faba, Donato Cannoletta, Tatiana Letowski, Gustavo Villoldo, Patricio Garcia Marchinena, Thiago Mourao, Gaetano Ciancio, Charles C. Peyton, Rafael Zanotti, Steven Chang, Philippe E. Spiess, Reza Mehrazin, Diego Abreu, Stenio de Cassio Zequi, Alejandro Rodriguez.

Abstract

The primary objective of this study was to assess the utility of using systemic therapy for patients with renal cell carcinoma with tumor thrombus (RCC-TT) in the setting of both metastatic (mRCC-TT) and non-mRCC-TT disease.

Purpose

The role of systemic therapy in the management of these renal cell carcinoma with a tumor thrombus (RCCC-TT) patients is poorly understood. In this multi-institutional analysis, we study preoperative systemic therapy for non-metastatic and metastatic patients as well as postoperative systemic therapy. We find preoperative systemic therapy for metastatic RCC-TT patients was associated with a prolonged overall and cancer-specific survival.

Methods

This was a multi-institutional retrospective analysis from 1999-present, and every patient underwent radical nephrectomy with tumor thrombectomy (RN-TT) plus/minus systemic therapy. Systemic therapy was defined as chemotherapy, immunotherapy, targeted therapy, or any combination administered ≤12 months from RN-TT. Overall survival (OS), cancer-specific survival (CSS), and metastasis-free survival (MFS) were studied. We examined the effect of preoperative systemic therapy before RN-TT for non-mRCC-TT, preoperative systemic therapy before RN-TT for mRCC-TT, and postoperative systemic therapy after RN-TT.

Results

A total of 206 patients were nonmetastatic before RN-TT, and 146 (70.9%) did not receive systemic therapy and 60 (29.1%) did. There was no difference in OS and CSS (p > .05), but MFS was significantly better in the no systemic therapy group (Median not reached; 80 months 50.6% of the cohort did not experience metastatic event vs. 13 months; p < .0001). 117 patients had mRCC-TT before RN-TT, and of these, 84 (71.2%) received preoperative systemic therapy and 33 (28.2%) did not receive systemic therapy before surgery. Median OS was 24 months in the systemic therapy group and 5.7 months in the non-systemic therapy group.

Maxwell Sandberg, Rachel Vancavage, Claudia Marie-Costa, Emily Ye, Mitchell Hayes, Justin Miller, Reuben Ben David, Kartik Patel, Kimberly Waggener, Brejjette Aljabi, SeokSoon Byun, Patricio García Marchiñena, Thiago Mourao, Charles Peyton, Reza Mehrazin, Philippe Spiess, Rafael Zanotti, Steven Chang, Stenio de Casio Zequi, Diego Abreu, Alejandro Rodriguez.

Summary

Purpose

With multi-institutional collaboration, the purpose of this study was to analyze geographical differences of renal cell carcinoma with tumor thrombus between patients in North America, Central/South America, and South Korea.

Materials and methods

Patients with renal cell carcinoma and a tumor thrombus who underwent nephrectomy plus thrombectomy were retrospectively analyzed. Patients were from North America, Central/South America, and South Korea. All comparisons were done based on the region where a patient had their surgery and follow-up. Chi-squared test, analysis of variance, Kaplan-Meier survival with log-rank test, and Cox regression analysis were used.

Results

A total of 478 patients were included, 212 from North America, 209 from Central/South America, and 57 from South Korea. Of note, thrombus level was different using the Neves classification system between regions (p < 0.001), with a greater thrombus level in Central/South America. Surgical approach differed, with laparoscopic cases done most often in Central/South America and robotic in North America (p < 0.001). Tumor grade was lowest in South Korea (p < 0.001) and stage (p < 0.001) greatest in Central/South America. Overall survival was greater in South Korea compared to Central/South America (p = 0.026). Cancer-specific survival was greater in South Korea relative to North America and Central/South America (p = 0.026).

Conclusions:

Patients from North America, Central/South America, and South Korea diagnosed with renal cell carcinoma and tumor thrombus do not present the same and have different outcomes peri-/post-operatively. This includes important variables which have impacts on patient morbidity and mortality. Considering increased efforts on health equity in urology, the causes of these differences call for further investigation.

Keywords

Renal cell carcinoma; Thrombus; Continental; Equity; Disparities.

Maxwell Sandberg, Gregory Russell, Jacob Malakismail, Mitchell Hayes, Reuben Ben David, Justin Miller, Kartik Patel, Brejjette Aljabi, Seok‐Soon Byun, Oscar Rodriguez Faba, Donato Cannoletta, Tatiana Letowski, Gustavo Villoldo, Patricio Garcia Marchinena, Thiago Mourao, Gaetano Ciancio, Charles C. Peyton, Rafael Zanotti, Philippe E. Spiess, Reza Mehrazin, Diego Abreu, Stenio de Cassio Zequi, Alejandro Rodriguez.

Abstract

The gold standard treatment for renal cell carcinoma with a tumor thrombus (RCC-TT) is radical nephrectomy with tumor thrombectomy (RN-TT). Operative approaches to this can be done open (ORN-TT), laparoscopic (LRN-TT), or robotic (RRN-TT). The purpose of this study was to compare overall survival (OS), cancer-specific survival (CSS), and metastasis-free survival (MFS) between open, laparoscopic, and robotic approaches to RN-TT using the Intercontinental Collaboration on Renal Cell Carcinoma (ICORCC) database. Patient records were reviewed from the ICORCC database. All patients included in the study underwent RN-TT for RCC-TT from 1999 to present. Tumor thrombus level was graded using the Neves classification system. Statistical analysis was carried out using analysis of variance, chi-squared test, and Kaplan–Meier survival curves with log-rank test to compare outcomes by surgical approach. A total of 392 patients were included. There were 308 ORN-TT, 61 LRN-TT, and 23 RRN-TT cases. On Kaplan–Meier analysis, OS and CSS were not significantly different by approach (p>0.05). MFS was significantly lower in RRN-TT patients (p=0.030). Operative time was the longest in ORN-TT, followed by LRN-TT, and RRN-TT the quickest (p=0.011). Blood transfusion rates were significantly lower in RRN-TT relative to ORNTT (p<0.001). Rates of lymph node dissection, soft tissue margin positivity, and cytoreductive surgery were alike (p>0.05). There is no definitive superiority of one operative approach compared to another. RRN-TT may result in worse MFS for patients, which calls for further investigation, but this is not certain. Ultimately, the risks, benefits, and resources the surgeon has at his/her disposal should all play in the final operative choice of RN-TT for the patient.

Keywords

Thrombus · Renal cell carcinoma · Robotic · Urology · Laparoscopic

Kosuke Takemura ^a,b, Satoru Yonekura ^c, Laura E. Downey ^a, Dimitris Evangelopoulos ^a, Daniel Y.C. Heng ^b

^a School of Public Health, Imperial College London, London, UK; ^b Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada; ^c Gustave Roussy Cancer Campus, Villejuif, France

Abstract

Context

Body mass index (BMI) is a useful tool for measuring body composition. It is unclear whether high BMI is a favourable indicator in patients with metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitors (ICIs).

Objective

To investigate the prognostic significance of BMI in patients with mRCC treated with ICIs in a systematic review and meta-analysis.

Evidence acquisition

Ovid MEDLINE, Embase, and Web of Science were systematically searched in July 2021, and meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.

Evidence synthesis

A total of 517 nonduplicate citations were screened by title and abstract, followed by full-text screening of 57 candidate articles to determine whether each study met the eligibility criteria. Overall, a total of 2281 patients from eight studies were included in the systematic review and meta-analysis. BMI levels were compared with overall survival (OS) and progression-free survival (PFS) in seven and three studies, respectively. Overweight/obese BMI was significantly associated with better OS compared to normal BMI (adjusted hazard ratio [aHR] 0.77, 95% confidence intervals [CI] 0.65–0.91; p = 0.002). A similar trend was observed for PFS (aHR 0.66, 95% CI 0.44–1.00; p = 0.050). There was no statistical heterogeneity or obvious publication bias among these studies.

Conclusions

This is the first systematic review and meta-analysis to evaluate the impact of BMI on survival outcomes of patients with mRCC treated with ICIs. To confirm the existence of the obesity paradox for patients with mRCC in the immuno-oncology era, high-quality clinical trials and basic research are warranted.

Patient summary

We reviewed published data on survival outcomes of 2281 patients with metastatic kidney cancer treated with immunotherapy drugs in relation to their body mass index (BMI). We found that higher BMI was associated with better survival when compared to normal BMI for this disease setting and treatment strategy.

Bi K, Xiao He M, Bakouny Z, et al.

Cancer Cell. 2021 May 10;39(5):649-661.e5.
DOI: 10.1016/j.ccell.2021.02.015.

Abstract

Immune checkpoint blockade (ICB) results in durable disease control in a subset of patients with advanced renal cell carcinoma (RCC), but mechanisms driving resistance are poorly understood. We characterize the single-cell transcriptomes of cancer and immune cells from metastatic RCC patients before or after ICB exposure. In responders, subsets of cytotoxic T cells express higher levels of co-inhibitory receptors and effector molecules. Macrophages from treated biopsies shift toward pro-inflammatory states in response to an interferon-rich microenvironment but also upregulate immunosuppressive markers. In cancer cells, we identify bifurcation into two subpopulations differing in angiogenic signaling and upregulation of immunosuppressive programs after ICB. Expression signatures for cancer cell subpopulations and immune evasion are associated with PBRM1 mutation and survival in primary and ICB-treated advanced RCC. Our findings demonstrate that ICB remodels the RCC microenvironment and modifies the interplay between cancer and immune cell populations critical for understanding response and resistance to ICB.

Araujo DV, Wells JC, Hansen AR, et al.

J Geriatr Oncol.2021 Mar 2;S1879-4068(21)00046-1.
DOI: 10.1016/j.jgo.2021.02.022.

Abstract

Objective

Older adults with metastatic renal cell carcinoma(mRCC) are underrepresented in immune-checkpoint inhibitor(ICI) registration trials. Here we compare the efficacy of ICI treatments in older vs. younger adults with mRCC.

Methods

Using the International mRCC Database Consortium(IMDC), patients treated with a PD(L)-1 based ICI were identified. Older adult was defined as ≥70-years at the time of treatment. Descriptive statistics were summarized in means, medians, and proportions. Effectiveness endpoints included overall survival (OS), time-to-treatment failure(TTF), time-to-next treatment(TNT), and overall response rate(ORR). Hazards ratios were adjusted(aHR) for IMDC risk factors, histology, line of treatment and older age.

Results

Of 1427 included patients, 397(28%) were older adults. ICI was used as 1st line(1 L) in 40%, 2nd line(2 L) in 49% and 3rd line(3 L) in 11% of patients. In univariable analysis, older adults had inferior OS compared to younger adults(25.1 m vs. 30.8 m, p < 0.01). There were no significant differences in TTF (6.9 m vs. 6.9 m, p = 0.4) or TNT(9.1 m vs 10 m, p = 0.3) between groups. In multivariable analyses, older age was not independently associated with worse OS(aHR = 1.02, p = 0.8), TTF(aHR = 0.95, p = 0.6) or TNT(aHR = 0.93, p = 0.5). Older adults had a lower ORR compared to younger adults(24% vs. 31%, p = 0.01), which was mainly driven by responses in 1 L(31% vs. 44%, p = 0.02) and not observed in 2 L/3 L.

Conclusions

After multivariable analyses, older adults with mRCC treated with ICI had no difference in OS, TTF or TNT when compared to younger adults. Our data support that chronological older age should not preclude patients from receiving ICI based therapies.

Laukhtina E, Pradere B, D’Andrea D, et al.

Transl Androl Urol.2021 Feb;10(2):609-619.
DOI: 10.21037/tau-20-1101.

Abstract

Background

Accurate identification of ideal candidates for cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) is an unmet need. We tested the association between preoperative value of systemic albumin to globulin ratio (AGR) and overall survival (OS) as well as cancer-specific survival (CSS) in mRCC patients treated with CN.

Methods

mRCC patients treated with CN were included. The overall population was therefore divided into two AGR groups using cut-off of 1.43 (low, <1.43 vs. high, ≥1.43). Univariable and multivariable Cox regression analyses tested the association between AGR and OS as well as CSS. The discrimination of the model was evaluated with the Harrel’s concordance index (C-index). The clinical value of the AGR was evaluated with decision curve analysis (DCA).

Results

Among 613 mRCC patients, 159 (26%) patients had an AGR <1.43. Median follow-up was 31 (IQR: 16-58) months. On univariable analysis, low preoperative serum AGR was significantly associated with both OS (HR: 1.55, 95% CI: 1.26-1.89, P<0.001) and CSS (HR: 1.55, 95% CI: 1.27-1.90, P<0.001). On multivariable analysis, AGR <1.43 was associated with worse OS (HR: 1.51, 95% CI: 1.23-1.85, P<0.001) and CSS (HR: 1.52, 95% CI: 1.24-1.86, P<0.001). The addition of AGR only minimally improved the discrimination of a base model that included established clinicopathologic features (C-index=0.640 vs. C-index=0.629). On DCA, the inclusion of AGR marginally improved the net benefit of the prognostic model. Low AGR remained independently associated with OS and CSS in the IMDC intermediate risk group (HR: 1.52, 95% CI: 1.16-1.99, P=0.002).

Conclusions

In our study, low AGR before CN was associated with worse OS and CSS, particularly in intermediate risk patients.