The 18th annual meeting of the Society of Urologic Oncology presented an agenda covering a broad spectrum of topics in genitourinary cancers, including a significant amount of emerging data on renal cell carcinoma. These findings offer an intriguing picture of how the field is evolving in many directions, from prognostic factors, genomic analysis and biomarkers to surveillance protocols, surgical outcomes and emerging data on pathology. There is much more to discover in this report. The posters are worth reviewing to obtain a sense of where investigative work is likely to present results with potential impact on the standard of care, or, at the least, will point toward directions to be explored at future scientific sessions.
Basic and Translational Research
Xu et al (Poster #31) studied the role of sphingosine kinase 1 (SphK1) in cell lines and patient specimens (including plasma) at the RNA and protein level. In additional functional and preclinical therapeutics studies were performed. The authors identified SphK1 upregulation as a poor prognostic factors in patients with RCC. In addition, SphK1 overexpression could result in RCC progression thru the Akt/mTOR pathway, and is a potential regulator of HIF pathways. In addition, the use of a SphK1 inhibitor resulted in improvement of sunitinib efficacy in preclinical models.
Lokeshwar et al (Poster #32) performed miR profiling on 54 tumor samples and 59 controls. They noted that a combination of altered 3 miRs (miR-21, miR-142-5p, and miR194) was associated with worse survival outcomes. In addition, these markers were validated using 311 patients from the kidney cancer TCGA.
Wu et al (Poster #33) used a next-generation sequencing panel of 23 known and potential RCC predisposition genes to study germline mutations in 190 Chinese patients with RCC diagnosis under the age of 45 years. They noted that 9.5% of patients had germline mutations in 10 of the genes, including 12 patients with mutations in known RCC genes (BAP1, VHL, FH, PBRM1, TSC1/2, FLCN).
Ghanaat et al (Poster #156) studied 281 patients with non-metastatic RCC who underwent surgery, and had genomic analysis of VHL, PBRM1, SETD2, BAP1, and KDM5C done. 33 patients developed metastatic disease at median follow up of 9 years. This more recent cohort was used to validate the 2008 MSKCC nomogram to predict metastatic disease in patients who undergo definitive surgery. The authors noted that the nomogram is still valid and accurate in this more recent patient population, and that KDM5C mutation status was still significant when incorporated into this nomogram.
Sanchez et al (Poster #163) used flow cytometry to study tumor microenvironment (TME) in 48 patients who underwent renal surgery. The authors noted that total CD8+ T-cell population was not associated with poor oncologic features, however the rate of resident CD8+ T-cells (CD8a+CD49a+CD103-) was associated with advanced stage at diagnosis.
Bhindi et al (Poster #53) evaluated Bim expression in peritumoral lymphocytes in 525 patients with metastatic clear cell RCC who underwent radical nephrectomy (169 patients had synchronous metastases), and found that high Bim expression was associated with worse CSS and OS in this cohort.
Lane et al (Poster #159) conducted a pilot study of measuring urine biomarkers using an ELISA multiplex assay in patients undergoing surgery (20 partial, and 2 radical nephrectomy). They performed selective ureteral catheterization of the operated kidney and foley catheter drainage to measure the biomarkers selectively. The authors noted that some biomarker levels are affected by blood contamination during resection, as well as induction of anesthesia per se. These results are important to account for confounders in future studies looking at the correlation of urinary biomarkers with surgical and renal functional parameters.
Pruthi et al (Poster #50) performed a radiogenomic study correlating image “roughness” as calculated from CT scans, with miR expression in 19 patients with clear cell, chromophobe and papillary RCC. They found that miR-10a, miR-10b, and miR-100 levels were inversely correlated with image roughness, while miR-21/miR-10b ratio was positively correlated with image roughness and could potentially differentiate RCC subtype.
Desai et al (Poster #157) studied the role of preoperative MRI in characterizing the tumor-parenchyma interface in 43 patients with a small renal mass who underwent robotic partial nephrectomy. All tumors had a visible pseudocapsule on MRI. 76.7% of the described pseudocapsules were circumferential, while 18.6% were fragmented and 4.7% were invasive. A pseudocapsule was identified in all tumor specimens on histologic evaluation. The authors noted that the presence of a fragmented or invasive pseudocapsule on preoperative MRI was associated with a higher i-Cap score.
Outcomes Research – Non-metastatic
Petros et al (Poster #39) studied conditional survival a cohort of 272 patients enrolled in a prospective active surveillance protocol for small renal mass. They noted that patients who reached the 2-year landmark had an improved likelihood of survival to 5 years. Multivariable analysis revealed that eGFR, Charlson Comorbidity Index, and tumor size of 3-4 cm were predictive of overall survival at baseline and at the 2-year landmark. Interestingly, patients with tumor size of 3-4 cm were at a higher risk of non-RCC death.
Pruthi et al (Poster #49) reviewed the outcomes of active surveillance of 106 patients with 140 renal cystic lesions deemed to be Bosniak 2F or higher. Patients had a median follow up of 46 months, with a median of 7 abdominal scans performed. Bosniak 3 cysts were divided into 3s (enhancing septation) and 3n (nodularity present). The authors found that Bosniak 3s were more likely to regress, Bosniak 3n were more likely to progress, with no difference in growth rates between Bosniak 4 and non-Bosniak 4 cysts, and no development of metastatic disease in any of the patients on surveillance.
Westerman et al (Poster #42) used a large RCC cohort to study 158 patients with cystic clear cell RCC. These patients were noted to be younger, have more cystic features on imaging, did not present with metastatic disease, and had no sarcomatoid dedifferentiation and only 1% rate of coagulative tumor necrosis, when compared with non-cystic RCC. Only 1 of the 158 patients with cystic RCC died of RCC (median follow up of survivors was 10.5 years), highlighting the favorable prognosis of this group of patients.
Bhindi et al (Poster #54) characterized a large cohort of patients with RCC treated with surgery into indolent versus aggressive, instead of the more commonly used terminology of benign versus malignant. Indolent tumors consisted of low-grade clear cell RCC, low-grade papillary RCC, low-grade translocation-associated RCC, any chromophobe, clear cell papillary, mucinous tubular and spindle cell, tubulocystic, and SDH-B deficient RCC. The authors noted that the 10-year CSS of patients with indolent malignant tumors was 96%, compared to 82% for those with aggressive tumors. In addition, they calculated the risk of malignancy and aggressiveness based on tumor size and sex. They noted that with increasing tumor size, the probability of malignancy reaches 90% at around 4cm, and plateaus afterwards, while the risk of aggressiveness continues to increase with larger tumor sizes. Not surprisingly, for any particular size, the risk of aggressive histology was higher in males than in females.
Hamilton et al (Poster #37) used a multi-institutional cohort of 2640 patients with non-metastatic RCC to analyze the nuances in staging pT3a patients. They noted that those patients who were considered cT1 and were upstaged at surgery to pT3a had similar outcomes to patients with pT2 disease, and those patients with cT2 upstaged to pT3a were more in line with cT3a upstaged to pT3a. The authors are suggesting a modification to the TNM staging system based on these data, after appropriate confirmatory studies are done.
Reddy et al (Poster #168) used a similar cohort of patients to compare outcomes of patients who underwent radical nephrectomy or partial nephrectomy, and were upstaged at surgery to pT3a, and noted that patients who underwent partial nephrectomy were at a higher risk of positive surgical margin, lower risk of blood transfusion, and lower risk of GFR<60. There were no differences in complication rates or oncologic outcomes when comparing upstaged pT3a patients who underwent radical nephrectomy versus partial nephrectomy.
Isharwal et al (Poster #148) studied the impact of preoperative comorbidities on recovery of renal function after partial nephrectomy using 405 patients from a single institution. The authors showed that the primary determinant of renal functional recovery was parenchymal preservation, followed by ischemia characteristics (cold versus warm, duration), and was independent of comorbidities.
Klinger et al (Poster #158) used a cohort of 336 patients from an international collaboration to study the correlation of preoperative assessment of volume preservation (PAVP) and surgeon postoperative assessment of volume preservation (SAVP) with postoperative renal functional outcomes in patients undergoing partial nephrectomy. The authors noted that PAVP and SAVP were moderately correlated with each other, and that they were correlated with postoperative GFR.
Ingham et al (Poster #153) studied the effect of aspirin on outcomes of over 10,000 patients undergoing partial nephrectomy using the Premier Hospital Database. 774 patients were noted to be taking aspirin. Patients on aspirin undergoing minimally invasive partial nephrectomy were less likely to need a blood transfusion. Patients on aspirin were more likely to experience a major cardiovascular event regardless of surgical approach.
Baiocco et al (Poster #161 and Poster #162) evaluated the role of multiplex partial nephrectomy MPN (partial nephrectomy for 3 or more tumors) in solitary kidneys, and compared outcomes with patients undergoing standard partial nephrectomy (SPN). The authors noted that patients who underwent MPN had more blood loss, more blood transfusions, longer hospital stay, higher rate of Clavien grade 3 complications, more need for permanent hemodialysis, and higher local recurrence rates. In addition, the outcomes were not statistically different in patients undergoing repeat MPN abd those patients under- going initial MPN.
Ryan et al (Poster #169) studied the effect of diabetes mellitus on outcomes in 3,041 patients with RCC treated with surgery. The authors noted that diabetes did not impact recurrence free survival in RCC, but only overall survival. They also noted that patients with stage I RCC, those who had radical nephrectomy in the setting of being diabetic had worse outcomes compared to those who had partial nephrectomy and those without diabetes, while diabetes was not associated with overall survival in patients with stage II-IV.
Ristau et al (Poster #151) studied the safety and effectiveness of partial nephrectomy in a cohort of patients with high-complexity tumors (RENAL nephrometry score 10-12) treated at 4 institutions. They did not note a difference in 30-day complications between partial nephrectomy and radical nephrectomy. On multivariable analysis, recurrence-free survival was higher for patients who underwent partial nephrectomy, while overall survival was not different, indicating a likely selection bias.
Gomella et al (Poster #155) studied the outcomes of nephrectomy and lymphadenectomy in 17 patients with hereditary leiomyomatosis and RCC with clinically positive nodes. Median number of nodes removed was 24, and median number of positive nodes was 4. Four patients (24%) were still disease free at time of last follow-up, while 9 patients (69%) had tumor recurrence within the lymphadenectomy template boundaries, pointing toward the need for more aggressive systemic therapy in this patient population.
Kaushik et al (Poster #142) used an open-source platform to study kidney cancer care disparities in South Texas (within the catchment area for University of Texas Health Science Center in San Antonio). The authors noted that kidney cancer incidence was significantly higher in Hispanics compared to Non-Hispanic Whites, in all ages groups over 20, with a strong male to female ratio.
Xia et al (Poster #43) used the NCDB to investigate the correlation between hospital volumes and outcomes of over 18,000 patients who underwent robotic assisted partial nephrectomy, and found that higher volume hospitals experience better outcomes (lower rate of conversion to open surgery, lower rate of hospital stay>3 days, and lower rate of positive surgical margins).
Outcomes Research – Metastatic
Peyton et al (Poster #38) used a cohort of 293 patients with metastatic RCC with IVC tumor thrombus to study the prognostic role of neutrophil-lymphocyte ratio (NLR). Patients with lower NLR experienced longer overall survival. They noted that NLR could substratify patients with intermediate risk MSKCC (but not good or poor risk patients) into 2 clearly different groups (OS of 24 months versus 12 months for those with low NLR versus high NLR, respectively).
Martin et al (Poster #146) used a cohort of patients with metastatic RCC with primary in place, enrolled on a phase 3 clinical trial of sunitinib versus sunitinib + AGS-003, to study chronic kidney disease after cytoreductive nephrectomy in patients with preoperative GFR over 60. Of the 371 patients, 45.5% developed stage 3 or worse chronic kidney disease on short-term follow-up. Factors that predicted this finding included age, hypertension, Charleson Comorbidity Index, history of renal stones, and presence of liver metastatic disease.
Xia et al (Poster #41) used the NCDB to evaluate patients with RCC with oligometastatic disease from 2010-2013 who underwent cytoreductive nephrectomy, in order to study the value of metastasectomy in this cohort. Of the 2395 patients in this study, 14.7% underwent a metastasectomy. Patients who underwent a metastasectomy were noted (while controlling for comorbidity) to have longer OS (HR=0.65, OS of 37.5 months versus 20.8 months in no-metastasectomy patients), and to receive targeted therapy less frequently (44.0% versus 56.1%).
Woldu et al (Poster #52) used the NCDB to study the effect of delay of receiving targeted therapy on outcomes of 2716 patients with metastatic clear cell RCC. They noted that a delay in receiving targeted therapy (divided in subgroups of less than 2 month, 2-3 months, 3-6 months, and over 6 months) was not associated with worse outcomes in this patient population, keeping in mind that selection bias was an important factor in this delay.
Xia et al (Poster #145) used the NCDB to study short-term outcomes after cytoreductive nephrectomy in relation to hospital volume. Hospitals with 8 or more cases per year were considered high-volume for the purpose of this study. Patients treated at high-volume hospitals experienced lower rates of 30-day and 90-day mortality, prolonged length of stay, and 30-day readmission. In addition, these outcomes were noted to improve more with higher numbers of surgeries performed within these centers.
Lenis et al (Poster #147) used the NCDB to study trends and effects of overall survival of surgery in patients with metastatic RCC and IVC tumor thrombus. The authors noted that patients with T3b and T3c potentiallywere less likely to undergo surgery than those with T3a disease. In this cohort, cytoreductive nephrectomy was associated with improved survival in patients with T3a and T3b, but not T3c disease. KCJ