Monday, April 7, 2014

Positive Surgical Margins after Partial Nephrectomy: Cause for Concern?

A positive surgical margin implies that cancer is left behind at the time of surgery.  For many cancer surgeries, including prostate and bladder cancer, positive surgical margins are a surrogate for quality of surgery and have implications for additional treatments and cancer survival.  For some cancers, including renal cell cancer (RCC), the implications of a positive surgical margin are less clearly defined.  In this blog, Mohamad E. Allaf, Director of Minimally-Invasive and Robotic Surgery, reviews the data regarding positive surgical margins following partial nephrectomy for the treatment of renal cancer.

Defining Positive Surgical Margins in the Context of the Evolution of Nephron-Sparing Surgery

As kidney surgery evolved from radical to partial nephrectomy (PN), and then from open to minimally-invasive surgery, the definition of a safe margin also evolved. Initially definitions decreased from strict size criteria (i.e. 5mm)[1,2] to any tumor-free margin regardless of size,[2,3] and now consideration of tumor enucleation when possible.  Enucleation is defined by incision of the renal parenchyma within a few millimeters of the tumor, and removal of the tumor by blunt dissection of the plane between the capsule of the tumor  and the healthy renal tissue.[4]  Minervini and colleagues examined oncologic outcomes after standard PN and simple enucleation.  They found a lower rate of positive surgical margins in the patients undergoing enucleation compared to PN (0.2% vs 3.4%) but no difference in recurrence-free or cancer-specific survival.  Interestingly, patients with high-grade disease (Fuhrman Grade 4) who underwent enucleation had worse cancer-specific survival (CSS) compared to those undergoing PN.  Despite these reports , there is still a widespread belief among urologists that enucleation is unsafe with a high risk of incomplete tumor excision, especially for larger lesions.[5]

Rates and Predictors of Positive Surgical Margins

Positive surgical margins have been reported in 0.7-10% of PN series.[6,7]  There are surgical considerations and tumor characteristics that are related positive margins.  Surgical considerations included impaired intraoperative visibility and poor orientation; and can be modified by surgeon experience, intraoperative ultrasound or better clamping techniques.  Tumor characteristics include tumor size, location and invasion;[6] however, due to the relatively low rate of positive surgical margins, parsing out which characteristics are most important remains controversial.


Implications of Positive Surgical Margins

In the case of a positive surgical margins, some surgeons will advocate re-resection or salvage radical nephrectomy.  However, the nephrectomy specimen will only have viable tumor in 6.9% to 15% of cases.[8,9]  The historic CSS after PN is 95% or better.  Several retrospective studies, including one by Besalah and colleagues, fail to demonstrate a difference in survival for patients with positive surgical margins.[10]  A recent large, multi-center study investigated 943 patients undergoing robotic PN; these authors found a low positive surgical margin rate (2.2%), but a higher rate of recurrence and metastases in the patients with positive margins.[11]


Summary


  • Positive surgical margins after partial nephrectomy for renal cell carcinoma are rare.
  • A positive surgical margin may reflect difficulties with a technical aspect of surgery or imply adverse tumor biology.
  • The data regarding recurrence and survival for patients with a positive surgical margin is inconclusive; however the strongest data suggests that: 
    • patients with positive surgical margins are at higher risk for recurrence.
    • this is more evident in patients with high-grade cancer.
    • long-term cancer-specific survival is not affected by margin status.


Recommendations from Dr. Allaf

A "gross" positive margin, meaning a positive margin noticed at the time of initial partial nephrectomy, should be addressed.  This could involve taking additional tumor or completion nephrectomy.

A "microscopic" positive margin, a margin noted by the pathologist under the microscope after the tumor has been removed, warrants careful consideration.  Sometimes the surgeon is certain that all tumor was removed at the time of surgery and can alleviate patient anxiety (frozen margins at the time of surgery can be helpful here).  Regardless, these patients warrant a careful period of active surveillance.  For patients with high-grade or high-stage tumors this should involve frequent imaging and early consideration of a re-operative intervention.

 
Mohamad E. Allaf, M.D. 
Associate Professor of Urology, Oncology, and Biomedical Engineering
Johns Hopkins Medical Institutions
Director, Minimally Invasive and Robotic Surgery
Johns Hopkins Hospital






[1] Li Q-L, Guan H-W, Zhang Q-P et al. Optimal margin in nephron-sparing surgery for renal cell carcinoma 4 cm or less. Eur Urol. 2003; 44: 448.
[2] Castilla EA, Liou LS, Abrahams NA et al. Prognostic importance of resection margin width after nephron-sparing surgery for renal cell carcinoma. Urology. 2002; 60: 993.
[3] Timsit MO, Bazin JP, Thiounn N, et al: Prospective study of safety margins in partial nephrectomy: intraoperative assessment and contribution of frozen section analysis. Urology. 2006; 67: 923.
[4] Minervini A, Ficarra V, Rocco F, et al. Simple enucleation is equivalent to traditional partial nephrectomy for renal cell carcinoma: results of a nonrandomized, retrospective, comparative study. J Urol. 185:1604-1610
[5] Touijer K, Jacqmin D, Kavoussi LR et al. The expanding role of partial nephrectomy: a critical analysis of indications, results, and complications. Eur Urol. 2010; 57: 214.
[6] AnI, Finelli A, Alibhai SMH, et al. Prevalence and impact on survival of positive surgical margins in partial nephrectomy for renal cell carcinoma: a population-based study. BJU Int. 2013;111: E300–E305.
[7] Marszalek M, Carini M, Chlosta P et al. Positive surgical margins after nephron-sparing surgery. Eur Urol. 2012; 61: 757.
[8] Raz O,Mendlovic S, Shilo Y, et al. Positive surgical margins with renal cell carcinoma have a limited influence on long-term oncological outcomes of nephron sparing surgery. Urology. 2010;75:277–80.
[9] Sundaram V, Figenshau RS, Roytman TM, et al. Positive margin during partial nephrectomy: does cancer remain in the renal remnant? Urology. 2011;77:1400–3.
[10] Besalah K, Pantuck AJ, Rioux-Leclercq N, Thuret R, et al. Positive surgical margin appears to have negligible impact on survival of renal cell carcinomas treated by nephron-sparing surgery. Eur Urol. 2010;57:466-473.
[11] Khalifeh A, Kaouk JH, Bhayani S, et al. Positive surgical margins in robot-assisted partial nephrectomy: a multi-institutional analysis of oncologic outcomes (leave no tumor behind). J Urol. 2013;190:1674-1679.

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