MANAGEMENT OF SMALL RENAL TUMORS: Current Evidence FERRY SAFRIADI Department of Urology AMC Hasan Sadikin Hospital/Padjadjaran University 39TH ASMIUA, Surabaya 7-10 Nov 2016

DEFINITION Small renal masses (SRMs), as a clinical entitiy, are defined as enhancing tumors <4 cm in diameter, with image characteristics consistent with stage T1aN0M0 RCC. Gill IS, et al. Small renal mass. N Engl J Med 2013 Novick AC,,et al. American Urological Association, 2008 The assessment must exclude metastases, in which case the patient would be considered to have metastatic RCC with a small primary tumor (T1aN0M+).

EPIDEMIOLOGY Epidemiological studies indicate that SRMs account for nearly one-half of all newly diagnosed renal masses. The incidence of SRMs has increased with the widespread use of imaging. Mortality rates are not increasing, despite the rising incidence and increased treatment. Hollingsworth JM, et al.J Natl Cancer Inst 2006 Canadian Cancer Society’s Advisory Committee on Cancer Statistics; 2013 SRMs are frequent in the elderly and infirm, in whom the risk of treatment must be weighed against life expectancy and malignant potential of the tumor. Lane BR, et al. Cancer 2010

About 20% to 25% of SRMs are benign. Leveridge MJ, et al. Eur Urol 2011 Most studies have reported that the rates of malignant pathology, higher grade, higher pathological stage, growth and the risk of metastasis increase with tumor size. Pierorazio P, et. al. J Urol 2013

Percutaneous Renal Tumor Biopsy SMRs Diagnosis before treatment is important to tailor therapy based on tumor histology either in the localized or metastatic setting. Meta-analysis: Accuracy for malignancy diagnosis Overall median rate: 92% (80.6-96.8%) 99.1% 99.7% Marconi L, et al. Eur Urol 2016

93.2% 89.8% Marconi L, et al. Eur Urol 2016

Flow diagram to Renal Biopsy Kutikov A, et al. Eur Urol 2016

Non Surgical Options: ACTIVE SURVEILLANCE is defined as the initial monitoring of tumour size by serial abdominal imaging (US, CT, or MRI) with delayed intervention reserved for tumors showing clinical progression during follow-up. Volpe, A., et al. Cancer, 2004. Indications: Elderly patients and/or patients with extensive comorbidities precluding surgery. Abouassaly R, et al. J Urol.2008, Beisland C, et al. Eur Urol. 2009 Lamb GW, et al. Urology. 2004

Delayed Intervention and Surveillance for Small Renal Masses (DISSRM) registry  Patients who chose active surveillance were older, had worse ECOG scores, more comorbidities, smaller tumors, and more often multiple and bilateral lesions. OS primary intervention vs. AS 2 years : 98% and 96% 5 years : 92% and 75% (p=0.06) Pierorazio PM, et al. Eur Urol 2015

CRYOABLATION performed by using either a percutaneous or a laparoscopic -assisted approach. No significant difference in the overall complication rates between laparoscopic and percutaneous cryoablation. Sisul, D.M., et al. Urology, 2013 Kim E.H., et al. J Urol, 2013 .

High risk recurrence criteria: Larger tumors (> 3 High risk recurrence criteria: Larger tumors (> 3.5 cm) and those with irregular shape or infiltrative appearance. Campbell SC, et al. J Urol 2009 LCA PCA p Mean length of stay 2.1 ±0.5 3 < 0.01 OS 78.5 % 86.3 % CSS 99.3 % 99.2 % RFS 83.2 % Kim EH, et al. J Urol 2013

CRYOABLATION vs. PARTIAL NEPHRECTOMY cT1b PN vs. Cryo RFS: p = 0.019 CSS: p = 0.48 OS: p = 0.155 Pts with Cryoablation cT1b had a higher rate local cancer recurrence. Caputo PA, et al. Eur Urol 2016

RADIOFREQUENCY ABLATION (RFA) 5-yr Disease-free Survival 91.5% vs. 74.5% p=0.003 5-yr Recurrence-free Survival 96.1% vs. 91.9% p= 0.01 5 –yr Overall Survival 73.3% Psutka SP, et al. Eur Urol 2012

Comparison of Partial Nephrectomy and Percutaneous Ablation for cT1 Renal Masses Distant metastases–free survival rates at 3 yr for PN, RFA, Cryo 99%, 93% 100% Overall survival rates at 3 yr PN, RFA, and Cryo 95%, 82% ,88% Thompson RH, et al. Eur Urol 2015

Surgical Options For decades, Radical Nephrectomy (RN) has been the mainstay of treatment for all renal masses including clinical stage 1 tumors. The main concern with RN is the negative impact on renal function and association with CKD. Huang WC, et al. Lancet Oncol 2006 RN is currently greatly over-utilized for the management of clinical stage T1 renal masses, particularly stage T1a. Hollenbeck BK, et al. Urology 2006

Partial nephrectomy is unsuitable in some patients due to: 1. locally advanced tumor growth 2. partial resection is not feasible due to unfavourable tumor location 3. significant deterioration in patient health.

The 10-yr progression rates NSS 4.1% 10-yr OS rates NSS and RN 75.2% and 79.4% The 10-yr progression rates NSS 4.1% RN 3.3% Gray’s test p = 0.48 Van Poppel H, et al. Eur Urol 2011

Renal function issue (0.36 mg/dL; 95% CI, 0.23–0.48; P < 0.001) The increase in creatinine level was significantly smaller in the PN group when analyzing both treatment received. Dash A, et al. BJUI 2006

NCCN Guidelines Kidney Cancer 2017

SUMMARY Active Surveillance is a reasonable option to manage SRMs in elderly patients or patients with significant comorbidities who are not good surgical candidates. Ablative therapy is promising but it need accurate criteria to define treatment success. Surgical removal is the standard of care for small renal tumors. NSS achieves equivalent oncologic outcomes and better preservation of renal function compared with RN and is therefore the primary treatment choice whenever technically feasible.

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