2022 WUOF/SIU International Consultation on Urological Diseases: Genetics and Tumor Microenvironment of Renal Cell Carcinoma.

Renal cell carcinoma is a diverse group of diseases that can be distinguished by distinct histopathologic and genomic features. In this comprehensive review, we highlight recent advancements in our understanding of the genetic and microenvironmental hallmarks of kidney cancer. We begin with clear cell renal cell carcinoma (ccRCC), the most common subtype of this disease. We review the chromosomal and genetic alterations that drive initiation and progression of ccRCC, which has recently been shown to follow multiple highly conserved evolutionary trajectories that in turn impact disease progression and prognosis. We also review the diverse genetic events that define the many recently recognized rare subtypes within non-clear cell RCC. Finally, we discuss our evolving understanding of the ccRCC microenvironment, which has been revolutionized by recent bulk and single-cell transcriptomic analyses, suggesting potential biomarkers for guiding systemic therapy in the management of advanced ccRCC.

Immune checkpoint blockade in renal cell carcinoma.

Immune checkpoint blockade (ICB) is the foundation of current first-line therapies in patients with metastatic renal cell carcinoma (mRCC) with the potential for eliciting long-lasting remissions. With the expanding arsenal of ICB-based therapies, biomarkers of response are urgently needed to guide optimal therapeutic selection. We review the data behind ICB therapy in RCC, emerging biomarkers of response, and the evolving role of surgery in patients with mRCC.

Clinicopathologic features associated with survival after cytoreductive nephrectomy for nonclear cell renal cell carcinoma.

OBJECTIVES: To report the overall survival (OS) outcomes of patients with nonclear cell renal cell carcinoma (nccRCC) treated at our institution with a cytoreductive nephrectomy (CN) and better understand the clinical and pathological characteristics of the patients that respond best. MATERIAL AND METHODS: We queried our prospectively maintained database for patients who underwent CN for nccRCC between 1989 and 2018. Histology was reviewed by an expert genitourinary pathologist, and nccRCC tumors were subdivided into papillary, unclassified, chromophobe, and other histology. Baseline clinicopathology, treatments, and survival outcomes were recorded. Preoperative hematological parameters including the neutrophil-to-lymphocyte ratio (NLR) were analyzed. Significant univariate predictors of OS were tested in a multivariate model. RESULTS: There were 100 nccRCC patients treated with CN. Median age was 61 years (IQR: 48-69) and 65% were male. There were 79 patient deaths with a median OS of 13.7 months (10.8-27.2). Estimated 2- and 5-year survival was 40.1% and 12.2%, respectively. Median follow-up of survivors was 13 months (IQR: 3-30). On multivariate analysis, increasing NLR (hazard ratio [HR] 1.27; 95% confidence interval [CI] 1.14-1.40, P < 0.001) and sarcomatoid features (HR 2.18; 95% CI 1.19-3.97, P = 0.014) conferred worse OS and the presence of papillary features were a favorable prognostic feature (HR 0.37; 95% CI 0.21-0.65, P < 0.001). CONCLUSIONS: OS outcomes in patients with nccRCC who underwent a CN are consistently modest throughout the study period. Patients with papillary features and a lower preoperative NLR may be better candidates for a CN.

Characterizing recurrent and lethal small renal masses in clear cell renal cell carcinoma using recurrent somatic mutations.

INTRODUCTION: Small renal masses (SRMs) with evidence of clear cell renal cell carcinoma (ccRCC) are understudied. Current algorithms for the management of SRMs include surgical resection, ablation, and active surveillance. We sought to identify genomic biomarkers that could potentially refine the management of ccRCC in SRMs, especially in patients being evaluated for active surveillance. METHODS: We identified patients who had SRMs (4cm or less) at time of surgery, had sequencing performed on their primary tumor and had a diagnosis of ccRCC. Patients were selected from 3 publicly available cohorts, The Cancer Genome Atlas (n = 110), University of Tokyo (n = 37), The International Cancer Genome Consortium (n = 31), and from our own institutional prospective database (n = 25). Among this cohort we analyzed mutations present in at least 5% of tumors, assessing for the enrichment of mutations and progression-free survival using the composite endpoint of recurrence or death of disease. Analysis was adjusted for multiple testing. A Cox regression model was used to assess clinical variables with significant mutations. RESULTS: In total, 203 patients were available for analysis. Median follow-up was 43.1 months among survivors. Mutations in VHL, PBRM1, SETD2, BAP1, KDM5C, and MTOR were present in more than 5% of tumors. Twenty-three patients (11.3%) had recurrence or died of their disease. Mutations in KDM5C were associated with inferior survival from either recurrence or death from disease, adjusted P 0.033. CONCLUSIONS: We identified mutations in SRMs in ccRCC that are associated with recurrence and lethality. The strongest association was seen in those with KDM5C mutations. Use of these genomic biomarkers may improve stratification of patients with SRMs and for those who may be appropriate for active surveillance. Prospective evaluation of these markers is needed.

Prospective Evaluation of Unprocessed Core Needle Biopsy DNA and RNA Yield from Lung, Liver, and Kidney Tumors: Implications for Cancer Genomics.

CONTEXT: Targeted needle biopsies are increasingly performed for the genetic characterization of cancer. While the nucleic acid content of core needle biopsies after standard pathology processing (i.e., formalin fixation and paraffin embedding (FFPE)) has been previously reported, little is known about the potential yield for molecular analysis at the time of biopsy sample acquisition. OBJECTIVES: Our objective was to improve the understanding of DNA and RNA yields from commonly used core needle biopsy techniques prior to sample processing. METHODS: We performed 552 ex vivo 18 and 20G core biopsies in the lungs, liver, and kidneys. DNA and RNA were extracted from fresh-frozen core samples and quantified for statistical comparisons based on needle gauge, biopsy site, and tissue type. RESULTS: Median tumor DNA yields from all 18G and 20G samples were 5880 ng and 2710 ng, respectively. Median tumor RNA yields from all 18G and 20G samples were 1100 ng and 230 ng, respectively. A wide range of DNA and RNA quantities (1060-13,390 ng and 370-6280 ng, respectively) were acquired. Median DNA and RNA yields from 18G needles were significantly greater than those from 20G needles across all organs (p < 0.001). CONCLUSIONS: Core needle biopsy techniques for cancer diagnostics yield a broad range of DNA and RNA for molecular pathology, though quantities are greater than what has been reported for FFPE processed material. Since non-formalin-fixed DNA is advantageous for molecular studies, workflows that optimize core needle biopsy yield for molecular characterization should be explored.

Minimally invasive approaches to prostate cancer: a review of the current literature.

INTRODUCTION: While radical retropubic prostatectomy has been the gold standard surgical approach, the explosion of minimally invasive methods has led to the search for less invasive treatment options. We offer an overview of the evolution of laparoscopic radical prostatectomy (LRP) and robot-assisted laparoscopic prostatectomy (RALP) in terms of the landmark publications and recent head-to-head comparisons, and we review our own experience. MATERIALS AND METHODS: A Medline search was performed using the keywords prostate cancer, prostatectomy, laparoscopic, and robotic. All pertinent articles concerning localized prostate cancer were reviewed. The Montefiore experience consisted of a retrospective review of a prospectively maintained confidential database. RESULTS: Several laparoscopic and robotic series were identified including review articles of each modality as well as studies directly comparing the two. Both LRP and RALP compare very favorably with conventional open surgery in terms of safety and oncologic efficacy. Both minimally invasive approaches offer decreased blood loss, transfusion rate, and length of hospital stay when contrasted with open surgery. When compared directly, LRP and RALP offer similar surgical, oncologic, and functional outcomes. However, RALP likely requires a shorter learning curve. CONCLUSION: The use of minimally invasive techniques has revolutionized the surgical treatment of prostate cancer. Pure LRP has been shown to be feasible and reproducible. However, it has a steep learning curve and is difficult to learn. In contrast, RALP is easier to learn and is now the surgical treatment of choice in most centers of excellence in the United States. The superior optics with respect to visualization and magnification translates into a procedure that is equivalent, if not superior, with respect to perioperative parameters, oncologic outcomes, and functional outcomes to its open counterpart.

From proficiency to expert, when does the learning curve for robotic-assisted prostatectomies plateau? The Columbia University experience.

To describe our single-institution experience with our first 70 consecutive robotic-assisted laparoscopic prostatectomies (RLPs) with particular focus on effect of learning curve on operative time, length of stay and blood loss. We also report our short-term outcome data in this heterogeneous cohort of men with prostate cancer (PCa). We reviewed our institutional database for the first 70 consecutive RLPs performed by a single surgeon (DS) over a 21-month period (March 2003 to December 2004). Surgical, pathologic and postoperative outcomes were analyzed. In order to evaluate the impact of the surgeon's and institution's learning curve on outcomes, the cases were divided into quartiles and stratified accordingly to identify trends. Ninety-nine percent (69/70) of all procedures were successfully completed robotically. Mean blood loss, operative time and mean length of stay were 231 ml, 264 min and 1.9 days, respectively. At follow-up, 76% of all patients were fully continent (no pads) and 93% (62/67) had undetectable PSA. The most dramatic improvement in surgical outcomes was seen within the first quartile of cases; however a statistically significant improvement trend existed throughout the series. This included a downward trend in operative time (P < 0.00001), estimated blood loss (P < 0.00001), and length of hospital stay (P = 0.003). This trend continued when controlled for in a multivariate analysis. Our results compare favorably with other RLP series as well as conventional laparoscopic series. Proficiency is achieved within the first 20 cases; however surgical outcomes continue to improve for RLP throughout the first 70 cases and perhaps beyond.