ASCO GU 2018: Best of Journals: Kidney Cancer - Urology

San Francisco, CA ( Dr. Umberto Capitano, from San Raffaele University, presented the best publications on the surgical management of kidney cancer from 2017. His discussion focused on hospital outcome variations, the impact of pre-operative proteinuria on overall survival (OS) following kidney surgery, and the impact of lymphadenectomy (LND) on of kidney cancer survival. 

The impact of hospital surgical volume on postoperative mortality and complication rates have been established for several procedures, but this association has remained elusive in kidney cancer. The publication by Lawson et al. in European Urology, addressed the issues by proposing a Renal Cancer Quality Score (RC-QS) which included five quality indicators defined as the % of T1a tumors undergoing partial nephrectomy (PN), T1-T2 receiving laparoscopic or robotic surgery, margin status following PN for T1 renal masses, length of hospital stay (LOS) and 30-day unplanned re-admission. These 5-quality metrics were then tested using the National Cancer Database (NCDB), which included data on 1,100 reporting hospitals. The authors demonstrated RC-QS scores were significantly associated with hospital volume and type treatment center with higher volume and academic center achieving higher scores. Furthermore, the RC-QS score was associated with improved 30-day and 90-day mortality on multivariate modeling. The RC-QS scores provides a validated measure of quality standards in the surgical management kidney cancer patients, which should be used by medical centers as a guide to understand possible deficiencies and improve surgical care.

The role of proteinuria in the development of post-renal surgery CKD has been well established; however, its overall effect in overall survival remains to be determined. In the publication by Yang et al. in the Journal of Urology this question is addressed by performing a retrospective review of 1300 patients undergoing kidney surgery at the Mayo Clinic. The pre-operative level of proteinuria was stratified as mild (< 150 mg/24hrs), moderate (150-500 mg/24hrs) and severe (> 500 mg/24 hrs).   On multivariate analysis, controlling for known survival confounders (age, gender, symptoms, smoking, eGFR, ECOG, type of surgery, tumor size, T stage, and necrosis) presence of severe proteinuria has significantly associated with worse OS 1.61 (95% CI 1.26-2.07, p <0.001). The above study adds to the data available to better counsel patients on the risk associated with kidney surgery in the presence of significant proteinuria. The role of PN vs. RN in patients with severe proteinuria remains to be studied, but one would imagen that these patients would benefit from a nephron-sparing approach. 

Lastly, Dr. Capitano discusses the emerging evidence on the role of LND on patients with high-risk kidney cancer. The need for extensive lymphadenectomy in patients undergoing RN remains a subject of debate. Despite the fact that multiple prior studies have shown a survival benefit with a lymph node dissection performed at the time of nephrectomy, a recent randomized trial failed (EORTC 30881) to show a distinct advantage. Although this trial represents level I evidence, its generalizability is limited since the trial included a significant number of patients at low risk for nodal metastasis (81% of patients had grade 1 or 2 tumors, and 72% had organ-confined disease). 

More recently, a study by Gershman et al., controlling for non-random treatment allocation using a propensity score-based analysis, evaluated the impact on survival of lymphadenectomy (LND) on 1,797 patients with non-metastatic RCC who underwent RN with and without lymphadenectomy. On evaluation of their cohort the authors reported no survival advantage associated with lymphadenectomy (CSS: HR 1.14, p = 0.23). More importantly, the authors assessed the impact of LND in several risk group categories using increasing threshold probabilities for presence of pN1 disease, noting a lack of added improvement in any of the survival measures (recurrence-free, cancer-specific, and/or overall survival). In an effort to reconcile the conflicting data on the survival benefit of LND, Gershman et al., examined the natural progression of patients with completely resected N1MO RCC. In the cohort consisting of 138 patients, the 5-year metastases-free survival was only 16% with a median time to recurrence of 4.2 months. A small subset of patients (16/138) did achieve a durable response, and on evaluation of their tumor characteristics, these patients were noted to have more indolent tumor biology (lower stage and grade, and absence of necrosis and sarcomatoid differentiation). 

Taken together, in patients who are clinically N positive, these findings suggest that LND plays a more important role as a staging (diagnostic) rather than therapeutic tool. Practically, the decision to perform an LND should be taken with caution and considered in a select group of patients (younger, FH-papillary type 2 tumors, and those considered for adjuvant trials), given that the majority of patients will not benefit from the added procedure but may be subjected to the low but real risk of LND associated complications. In cases where regional lymph nodes appear involved, in the absence of compelling data, the current standard of care is regional lymphadenectomy, especially in the M0 population.

Presented by:  Umberto Capitano, MD, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute

Written by: Andres F. Correa, MD , Fox Chase Cancer Center, Philadelphia, PA at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA