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Should mediastinal lymphadenectomy be performed during lung metastasectomy of renal cell carcinoma? "Beyond the Abstract," by Pierre-Emmanuel Falcoz, et al

BERKELEY, CA (UroToday.com) - Renal cell carcinoma (RCC) is an uncommon malignancy in adult patients, accounting for 3% of adult cancers.[1] Nearly half of these patients develop metastases during their lifetime.[2, 3, 4, 5] In the case of pulmonary metastases, surgery, when technically feasible, remains the best treatment, with a 5-year survival of up to 50%, whereas medical treatments lead to 5-year survival rate ranging from 3 to 11%.[3, 6, 7, 8, 9, 10, 11, 12, 13] Our previous study also reported that about 30% of patients suffer from lymph node involvement (LNI) (hilar or mediastinal) in the case of lung metastases.[14]

Regarding LNI, the completeness of carcinological resection and the pre-operative imaging results are two major concerns that need to be specifically addressed.

First, the published literature supports the idea that LNI is a significant, independent, prognostic factor that negatively impacts on survival.[14] However, only one study reported a survival gain in the case of mediastinal lymphadenectomy, although the p-value was not significant (HR= 0.66; Confidence Interval: 0.41 – 1.06, p=0.08).[15] In addition, this study suffered from a major bias. Indeed, the group of patients who underwent a mediastinal lymphadenectomy was analyzed from a prospective database and compared to a historical series composed of patients who did not benefit from a mediastinal lymphadenectomy. Therefore, one can wonder whether the survival gain is related to the patients’ status (presence of retroperitoneal nodal involvement in the historical series) or to a modification of adjuvant treatment (introduction of anti-angiogenic targeted therapies in the mediastinal lymphadenectomy group).

Consequently, based on the published literature on the impact of mediastinal lymphadenectomy on survival, one can only hypothesize that there is a probable benefit due to a complete carcinological resection. Indeed, not performing a total lymphadenectomy may leave neoplastic cells in place and expose patients to the risk of loco-regional and / or distant recurrence.

Second, the chest computerized tomography (CT) does not seem to be the most appropriate exam to evaluate LNI. Indeed, the CT sensitivity only reached 84% in the paper of Winter et al.[15] In another study, Kanzaki et al. attempted to exclude patients suspected of having LNI from surgery, based on pre-operative CT images.[16] However, they found a bit more than 10% of nodal involvement by histopathological analysis. Nevertheless, the authors did not report if they had performed radical lymphadenectomy or sampling. In the case of sampling, the number of patients having LNI could have thereby been greater as the histopathological status of nodes is not strictly related to their macroscopic aspect.

In conclusion, it seems that mediastinal lymphadenectomy should be performed to achieve a complete carcinological resection and decrease the risk of loco-regional and / or distant recurrence. Because of its poor sensitivity, CT should not be considered alone to select patients who may benefit from a mediastinal lymphadenectomy, and we strongly advocate that all patients with metastatic RCC should undergo a radical mediastinal lymphadenectomy. Patients suspected of having LNI, according to the pre-operative imaging, should not be excluded from surgery. They also may benefit from multimodal therapies such as new, targeted anti-angiogenic therapies.

References:

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  2. Kattan MW, Reuter V, Motzer RJ, Katz J, Russo P. A postoperative prognostic nomogram for renal cell carcinoma. J Urol 2001;166(1):63-67.
  3. Pantuck AJ, Zisman A, Belldegrun AS. The changing natural history of renal cell carcinoma. J Urol 2001;166(5):1611-1623.
  4. Sorbellini M, Kattan MW, Snyder ME et al. A postoperative prognostic nomogram predicting recurrence for patients with conventional clear cell renal cell carcinoma. J Urol 2005;173(1):48-51.
  5. Zisman A, Chao DH, Pantuck AJ et al. Unclassified renal cell carcinoma: Clinical features and prognostic impact of a new histological subtype. J Urol 2002;168(3):950-955.
  6. Cerfolio RJ, Allen MS, Deschamps C et al. Pulmonary resection of metastatic renal cell carcinoma. Ann Thorac Surg 1994;57(2):339-344.
  7. Eggener SE, Yossepowitch O, Kundu S, Motzer RJ, Russo P. Risk score and metastasectomy independently impact prognosis of patients with recurrent renal cell carcinoma. J Urol 2008;180(3):873-878; discussion 878.
  8. Fourquier P, Regnard JF, Rea S, Levi JF, Levasseur P. Lung metastases of renal cell carcinoma: Results of surgical resection. Eur J Cardiothorac Surg 1997;11(1):17-21.
  9. Jett JR, Hollinger CG, Zinsmeister AR, Pairolero PC. Pulmonary resection of metastatic renal cell carcinoma. Chest 1983;84(4):442-445.
  10. Kavolius JP, Mastorakos DP, Pavlovich C, Russo P, Burt ME, Brady MS. Resection of metastatic renal cell carcinoma. J Clin Oncol 1998;16(6):2261-2266.
  11. Kierney PC, van Heerden JA, Segura JW, Weaver AL. Surgeon's role in the management of solitary renal cell carcinoma metastases occurring subsequent to initial curative nephrectomy: An institutional review. Ann Surg Oncol 1994;1(4):345-352.
  12. Morrow CE, Vassilopoulos PP, Grage TB. Surgical resection for metastatic neoplasms of the lung: Experience at the University of Minnesota Hospitals. Cancer 1980;45(12):2981-2985.
  13. Pogrebniak HW, Haas G, Linehan WM, Rosenberg SA, Pass HI. Renal cell carcinoma: Resection of solitary and multiple metastases. Ann Thorac Surg 1992;54(1):33-38.
  14. Renaud S, Falcoz PE, Olland A, Massard G. Should mediastinal lymphadenectomy be performed during lung metastasectomy of renal cell carcinoma? Interact Cardiovasc Thorac Surg 2013;16(4):525-528.
  15. Winter H, Meimarakis G, Angele MK et al. Tumor infiltrated hilar and mediastinal lymph nodes are an independent prognostic factor for decreased survival after pulmonary metastasectomy in patients with renal cell carcinoma. J Urol 2010;184(5):1888-1894.
  16. Kanzaki R, Higashiyama M, Fujiwara A et al. Long-term results of surgical resection for pulmonary metastasis from renal cell carcinoma: A 25-year single-institution experience. Eur J Cardiothorac Surg 2011;39(2):167-172.

 

Written by:
Stéphane Renaud, Pierre-Emmanuel Falcoz,* Anne Olland and Gilbert Massard as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.

Department of Thoracic Surgery, Nouvel Hôpital Civil, Strasbourg University Hospital, Strasbourg, France
*Corresponding Author: Pr Pierre-Emmanuel Falcoz, Department of Thoracic Surgery, Nouvel Hôpital Civil, 1 Place de l’Hôpital, BP 426, 67091 Strasbourg Cedex, France. E-mail :

The authors would like to thank Linsey Cosbie for her editorial assistance.

Should mediastinal lymphadenectomy be performed during lung metastasectomy of renal cell carcinoma? - Abstract

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