Search Results (7)

Background/Objectives: Metastatic renal cell carcinoma (mRCC) is a heterogeneous disease requiring precise risk stratification for optimal treatment selection. The International Metastatic RCC Database Consortium (IMDC) model classifies patients into favorable-, intermediate-, and poor-risk groups; however, emerging evidence suggests that the favorable-risk category encompasses patients with distinct prognoses. This study aims to evaluate whether subclassifying favorable-risk mRCC into “very favorable” and “favorable” subgroups improves prognostic accuracy and informs treatment strategies. Methods: This retrospective cohort study analyzed 189 patients diagnosed with mRCC at a single tertiary center between 2017 and 2023. Based on IMDC criteria, 75 patients were classified as favorable risk and included in the final analysis. These patients were further stratified into very favorable (n = 29) and favorable (n = 46) groups based on time from diagnosis to systemic therapy, Karnofsky performance status, and presence of metastases at specific sites. Kaplan–Meier analysis and Cox proportional hazards regression models were used to assess progression-free survival (PFS) and overall survival (OS). Results: Patients in the very favorable group demonstrated significantly longer median PFS (22.8 vs. 13.8 months, HR: 0.55, p = 0.020) and OS (74.4 vs. 42.7 months, HR: 0.38, p = 0.013) compared to the favorable group. In multivariate analysis, very-favorable-risk classification remained an independent prognostic factor for OS (p = 0.014) but not for PFS (p = 0.071). Conclusions: Stratifying favorable-risk mRCC patients into very favorable and favorable subgroups enhances prognostic assessment, potentially guiding more tailored treatment strategies. These findings highlight the need for refined risk models to improve personalized management in mRCC. Full article

According to the current guidelines, watchful waiting (WW) is a feasible option for patients with good or intermediate prognosis renal-cell carcinoma (RCC). However, some patients rapidly progress during WW, requiring the initiation of treatment. Here, we explore whether we can identify those patients using circulating cell-free DNA (cfDNA) methylation. We first defined a panel of RCC-specific circulating methylation markers by intersecting differentially methylated regions from a publicly available dataset with known RCC methylation markers from the literature. The resulting RCC-specific methylation marker panel of 22 markers was subsequently evaluated for an association with rapid progression by methylated DNA sequencing (MeD-seq) in serum from 10 HBDs and 34 RCC patients with a good or intermediate prognosis starting WW in the IMPACT-RCC study. Patients with an elevated RCC-specific methylation score compared to HBDs had a shorter progression-free survival (PFS, p = 0.018), but not a shorter WW-time (p = 0.15). Cox proportional hazards regression showed that only the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria were significantly associated with WW time (HR 2.01, p = 0.01), whereas only our RCC-specific methylation score (HR 4.45, p = 0.02) was significantly associated with PFS. The results of this study suggest that cfDNA methylation is predictive of PFS but not WW. Full article

Although high body mass index (BMI) was reported to associate with a better prognosis for metastatic renal cell cancer (mRCC) patients receiving anti-vascular endothelial growth factor (anti-VEGF) therapy, it is an imperfect proxy for the body composition, especially in Asian patients with a lower BMI. The role of visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and perirenal fat thickness (PRFT) in mRCC patients was still unknown. Therefore, a multicenter retrospective study of 358 Chinese mRCC patients receiving anti-VEGF therapy was conducted and their body composition was measured via computed tomography. We parameterized VAT, SAT and PRFT according to their median value and BMI according to Chinese criteria (overweight: BMI ≥ 24). We found VAT, SAT, and PRFT (all p < 0.05) but not BMI, significantly associated with overall survival (OS) and progression-free survival (PFS). Multivariate Cox analysis identified PRFT was the independent predictor of OS and PFS, and IMDC expanded with PRFT showed the highest C-index in predicting OS (OS:0.71) compared with VAT, SAT, and BMI. PRFT could increase the area under the curve of the traditional International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model in OS (70.54% increase to 74.71%) and PFS (72.22% increase to 75.03%). PRFT was introduced to improve the IMDC model and PRFT-modified IMDC demonstrated higher AIC in predicting OS and PFS compared with the traditional IMDC model. Gene sequencing analysis (n = 6) revealed that patients with high PRFT had increased angiogenesis gene signatures (NES = 1.46, p = 0.04) which might explain why better drug response to anti-VEGF therapy in mRCC patients with high PRFT. The main limitation is retrospective design. This study suggests body composition, especially PRFT, is significantly associated with prognosis in Chinese mRCC patients receiving anti-VEGF therapy. PRFT-modified IMDC model proposed in this study has better clinical predictive value. Full article

Systemic therapy for metastatic renal cell carcinoma has continuously evolved over the last two decades. Significant improvements in overall survival and quality of life of patients with advanced disease have been observed. With the approval of combination therapies with PD(L)-1 immune checkpoint inhibitors (ICI) as first-line therapy in 2019, the previous standard VEGFR-TKI monotherapy has been replaced as the primary treatment option. In addition to immunotherapy with nivolumab and ipilimumab, three VEGFR-TKI/ICI combinations are now approved. Therapy selection should be preceded by risk stratification using defined criteria from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC). Clinical parameters, as well as detailed patient counseling on differences in the efficacy profile (response rate, long-term progression-free survival), potential side effects, and impact on quality of life, are of key importance in the individual treatment decision. Full article

(1). Background: Immunohistochemical (IHC) evaluation of programmed death-1 (PD-1) and its ligand (PD-L1) is being used to evaluate advanced malignancies with potential response to immune checkpoint inhibitors. We evaluated both plasma and tissue expression of PD-1 and PD-L1 in the same cohort of patients, including non-metastatic and metastatic clear cell renal cell carcinoma (CCRCC). Concomitant plasma and tissue expression of PD-1 and PD-L1 was evaluated with emphasis on diagnostic and prognostic implications. (2) Methods: we analyzed PD-1 and PD-L1 IHC expression in tumor tissues and soluble forms (sPD-1 and sPD-L1) in plasma from 89 patients with CCRCC, of which 23 were metastatic and 16 received systemic therapy. The primary endpoint was evaluation of overall survival using Kaplan-Meier analysis and the Cox regression model. Plasma samples from healthy volunteers were also evaluated. (3) Results: Interestingly, sPD-1 and sPD-L1 levels were lower in cancer patients than in controls. sPD-1 and sPD-L1 levels and their counterpart tissue expression both at the tumor center and infiltrating front were not associated. Higher expression of both PD-1 and PD-L1 were associated with tumor grade, necrosis and tumor size. PD-1 was associated to tumor stage (pT) and PD-L1 to metastases. sPD-1 and sPD-L1 were not associated with clinico-pathological parameters, although both were higher in patients with synchronous metastases compared to metachronous ones and sPD-L1 was also higher for metastatic patients compared to non-metastatic patients. sPD-1 was also associated with the International Metastatic Renal Cell Cancer Database Consortium (IMDC) prognostic groups in metastatic CCRCC and also to the Morphology, Attenuation, Size and Structure (MASS) response criteria in metastatic patients treated with systemic therapy, mainly tyrosine-kinase inhibitors. Regarding prognosis, PD-L1 immunostaining at the tumor center with and without the tumor front was associated with worse survival, and so was sPD-L1 at a cut-off >793 ng/mL. Combination of positivity at both the tissue and plasma level increased the level of significance to predict prognosis. (4) Conclusions: Our findings corroborate the role of PD-L1 IHC to evaluate prognosis in CCRCC and present novel data on the usefulness of plasma sPD-L1 as a promising biomarker of survival in this neoplasia. Full article

With 15 drugs currently approved for the treatment of metastatic renal cell carcinoma (mRCC) and even more combination regimens with immunotherapy on the horizon, there remains a distinct lack of molecular biomarkers for therapeutic efficacy. Our study reports on real-world clinical outcomes of mRCC patients from a tertiary academic medical center treated with empirically selected standard-of-care therapy. We utilized the Stanford Renal Cell Carcinoma Database (RCCD) to report on various outcome measures, including overall survival (OS) and the median number of lines of targeted therapies received from the time of metastatic diagnosis. We found that most metastatic patients did not survive long enough to attempt even half of the available targeted therapies. We also noted that patients who failed to receive a clinical benefit within the first two lines of therapy could still go on to experience clinical benefit in later lines of therapy. The term, “clinical benefit” was assigned to a line of therapy if a patient remained on drug treatment for three months or longer. Moreover, patients with clinical benefit in at least one line of therapy experienced significantly longer OS compared to those who did not have clinical benefit in at least one line of therapy. Developing biomarkers that identify patients who will receive clinical benefit in individual lines of therapy is one potential strategy for achieving rational drug sequencing in mRCC. Full article

Objectives: In the present study, we explored the real-world efficacy of the immuno-oncology checkpoint inhibitor nivolumab and the tyrosine kinase inhibitor cabozantinib in the second-line setting. Methods: Using the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) dataset, a retrospective analysis of patients with metastatic renal cell carcinoma (MRCC) treated with nivolumab or cabozantinib in the second line after prior therapy targeted to the vascular endothelial growth factor receptor (VEGFR) was performed. Baseline characteristics and imdc risk factors were collected. Overall survival (OS) and time to treatment failure (TTF) were calculated using Kaplan–Meier curves. Overall response rates (ORRS) were determined for each therapy. Multivariable Cox regression analysis was performed to determine survival differences between cabozantinib and nivolumab treatment. Results: The analysis included 225 patients treated with nivolumab and 53 treated with cabozantinib. No significant difference in median OS was observed: 22.10 months [95% confidence interval (CI): 17.18 months to not reached] with nivolumab and 23.70 months (95% CI: 15.52 months to not reached) with cabozantinib (p = 0.61). The TTF was also similar at 6.90 months (95% CI: 4.60 months to 9.20 months) with nivolumab and 7.39 months (95% CI: 5.52 months to 12.85 months) with cabozantinib (p = 0.20). The adjusted hazard ratio (HR) for nivolumab compared with cabozantinib was 1.30 (95% CI: 0.73 to 2.3), p = 0.38. When adjusted by IMDC criteria and age, the HR was 1.32 (95% CI: 0.74 to 2.38), p = 0.35. Conclusions: Real-world IMDC data indicate comparable OS and TTF for nivolumab and cabozantinib. Both agents are reasonable therapeutic options for patients progressing after initial first-line VEGFR-targeted therapy. Full article