Objective To validate models currently used to predict metastatic renal cell carcinoma (mRCC) outcomes in a cohort of patients undergoing cytoreductive nephrectomy (CN). Patients and methods A total of 10 RCC prognostic models (International Metastatic RCC Database Consortium [IMDC]; Memorial Sloan Kettering Cancer Center [MSKCC]; Culp; Leibovich; University of California at Los Angeles Integrated Staging System [UISS]; Stage, Size, Grade, and Necrosis [SSIGN]; Yaycioglu; Karakiewicz; Cindolo; and Margulis) were chosen based on clinical relevance and use in clinical trial design. Model validation was performed using patients who underwent CN at a single institution between 2005 and 2017, and model discrimination (ability to select patients at risk of death) was assessed. Concordance indices (c‐index) were calculated and compared with originally published c‐indices. Results A total of 515 CN patients were stratified according to the prognostic models. A total of 387 (75%) died over the study period, with estimated 3‐year survival of 46.1% (95% confidence interval [CI] 41.6–50.4%). All models’ discriminatory capacity underperformed when compared to the originally published c‐indices. The c‐indices ranged from 0.53 (95% CI 0.50–0.56) for the Cindolo model to 0.61 (95% CI 0.58–0.64) for the Leibovich model. The MSKCC and IMDC models performed poorly with c‐indices of 0.55 and 0.56, respectively. Conclusion Currently used prognostic models have limited discriminatory capacity when applied to a modern cohort of patients undergoing CN. They are inadequate for risk stratification and randomisation in prospective clinical trials of untreated patients with mRCC. Caution should be used when using these models for clinical decision making.
Scientific understanding of how the immune microenvironment interacts with renal cell carcinoma (RCC) has substantially increased over the last decade as a result of research investigations and applying immunotherapies, which modulate how the immune system targets and eliminates RCC tumor cells. Clinically, immune checkpoint inhibitor therapy (ICI) has revolutionized the treatment of advanced clear cell RCC because of improved outcomes compared to targeted molecular therapies. From an immunologic perspective, RCC is particularly interesting because tumors are known to be highly inflamed, but the mechanisms underlying the inflammation of the tumor immune microenvironment are atypical and not well described. While technological advances in gene sequencing and cellular imaging have enabled precise characterization of RCC immune cell phenotypes, multiple theories have been suggested regarding the functional significance of immune infiltration in RCC progression. The purpose of this review is to describe the general concepts of the anti-tumor immune response and to provide a detailed summary of the current understanding of the immune response to RCC tumor development and progression. This article describes immune cell phenotypes that have been reported in the RCC microenvironment and discusses the application of RCC immunophenotyping to predict response to ICI therapy and patient survival.
Objectives To evaluate the ability of magnetic resonance imaging (MRI)‐targeted biopsy combined with systematic biopsy (MRI‐biopsy) to reduce negative biopsies and detect clinically significant prostate cancer compared to systematic biopsy (SB) alone in the confirmatory biopsy setting using matched cohorts. Patients and Methods Patients were identified from an active surveillance database who had a previously positive transrectal ultrasonography‐guided SB followed by a confirmatory biopsy at a single institution between 2006 and 2019. Patients were divided into two cohorts based on confirmatory biopsy technique: SB alone or MRI‐biopsy (which included MRI‐targeted and systematic biopsies). Cohorts were then matched on age, prostate‐specific antigen (PSA) level, number of positive cores on initial biopsy and initial biopsy Gleason grade group (GG). Logistic regression was performed to identify associations with confirmatory biopsy upgrading. Results After matching, 514 patients were identified (257 per cohort). PSA, prostate volume and PSA density prior to initial biopsy, in addition to total number of initial biopsy positive cores and GG, were similar between the matched cohorts. After confirmatory biopsy, 118/257 patients (45.9%) in the MRI‐biopsy cohort were upgraded compared to 46/257 patients (17.9%) in the SB cohort (P < 0.001). The rate of negative confirmatory biopsy was 32/257 (12.5%) compared to 97/257 (37.7%) in the MRI‐biopsy and SB cohorts, respectively (P < 0.001). Confirmatory MRI‐biopsy was associated with greater odds of confirmatory biopsy upgrade from GG 1 to ≥GG 2 compared to SB alone (odds ratio 3.62, 95% confidence interval 1.97–6.63; P < 0.001). Conclusion The addition of MRI‐targeted biopsies to SB in the confirmatory biopsy setting among men with previously detected prostate cancer resulted in fewer negative confirmatory biopsies and detection of more clinically significant prostate cancer compared to SB alone.
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