As Dr. Mulders notes, the paradigm for treating kidney cancer has shifted from the Robson open radical nephrectomy with lymph node dissection for all renal masses, to robotic-assisted laparoscopic partial nephrectomy, to focal therapy (cryotherapy, RFA) and surveillance for many renal masses. Secondary to incidental findings of renal masses, there have been a stage migration to more stage I (small renal masses) tumors over the last two decades. Dr. Mulders says that based on the EAU Renal cell carcinoma guidelines, localized RCCs are best managed by nephron-sparing surgery when technically feasible. However, the current evidence base has significant limitations due to studies of low methodological quality marked by a high risk of bias.
Imperative indications for partial nephrectomy include a (functional) solitary kidney, conditions with a high risk of impairment of renal function, and bilateral tumors. So, what are the issues? (i) Partial nephrectomy has a relatively high complication rate, (ii) oncological outcomes may be compromised by recurrences (local or systemic), multifocality, or new onset of a tumor in the contralateral kidney, (iii) renal function and survival, and (iv) age and comorbidity. One of the main components of PADUA risk calculators for potential complications for partial nephrectomy is tumor size. Positive surgical margins for robotic partial nephrectomy are 0-7%, and may be as high as 18% for imperative indications. There are several factors influencing positive surgical margin rates:
The relationship between positive surgical margins and cancer recurrence are controversial. It may be associated with an increased risk of cancer recurrence, especially in highly malignant tumors. However, the majority of patients do not experience tumor recurrence (local or distant) and the influence on survival is limited (intermediate follow-up data).
The AXIPAN study was a phase II trial to evaluate the ability of neoadjuvant axitinib to reduce the size of T2 RCC for shifting from a radical nephrectomy to a partial nephrectomy indication1. Patients with cTaN0NxM0 ccRCC considered not suitable for partial nephrectomy were enrolled to receive axitinib 5mg twice daily for 2-6 months before surgery. Among 18 patients enrolled, the median tumor size was 76.5 mm. After axitinib neoadjuvant treatment, 16 tumors decreased in diameter, with a median size reduction of 17% (64.0 vs 76.5 mm; p < 0.001). The primary outcome of partial nephrectomy for a tumor <7 cm was considered achieved in 12 patients. Five patients had grade 3 adverse events and five patients experienced Clavien III-V post-surgery complications. At 2-year follow-up, six patients had metastatic progression, and two had a recurrence.
In the only phase III, level I study comparing radical and partial nephrectomy2, despite equivocal oncologic results, nephron-sparing surgery was significantly less effective than radical nephrectomy in terms of overall survival (HR 1.50, 95%CI 1.03-2.16). However, in patients without chronic kidney disease prior to surgery, radical nephrectomy is a significant risk factor for the development of kidney disease, which may be associated with substantial comorbidity and even death3. An updated renal function analysis of EORTC 309044 found that over a median follow-up of 6.7 years, eGFR <60 was reached by 85.7% with radical nephrectomy and 64.7% with nephron-sparing surgery, with a difference of 21.0%.
Dr. Mulders then posed the question: what else influences the line between partial and total nephrectomy?
- Expert opinion and skills in the laparoscopic era
- Absolute versus relative indications for partial nephrectomy
- The attachment of Gerota’s fascia
- Histology of the tumor
Presented by: Peter Mulders, MD, Professor, Chair of Urology, Radboud University Medical Centre, Nijmegen, the Netherlands
Written by: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, Twitter: @zklaassen_md, at the 16th Meeting of the European Section of Oncological Urology, #ESOU19, January 18-20, 2019, Prague, Czech Republic
- Lebacle C, Bensalah K, Bernhard JC, et al. Evaluation of axitinib to downstage cT2a renal tumours and allow partial nephrectomy: A phase II study. BJU Int 2018 Oct 5 [Epub ahead of print].
- Van Poppel H, Da Pozzo L, Albrecht W, et al. A prospective, randomised EORTC intergroup phase 3 study comparing the oncologic outcome of elective nephron-sparing surgery and radical nephrectomy for low-stage renal cell carcinoma. Eur Urol 2011 Apr;59(4):543-552.
- Huang WC, Levey AS, Serio AM, et al. Chronic kidney disease after nephrectomy in patients with renal cortical tumours: a retrospective cohort study. Lancet Oncol 2006 Sep;7(9):735-740.
- Scosyrev E, Messing EM, Sylvester R, et al. Renal function after nephron-sparing surgery versus radical nephrectomy: results from EORTC randomized trial 30904. Eur Urol 2014 Feb;65(2):372-377.
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