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 Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 3  |  Issue : 2  |  Page : 36-39

Lung metastasectomy in renal cell carcinoma: Evaluation of 20 cases


Department of Thoracic Surgery, School of Medicine, Gazi University, Ankara, Turkey

Date of Web Publication15-Apr-2019

Correspondence Address:
Aynur Bas
Department of Thoracic Surgery, School of Medicine, Gazi University, Besevler, Ankara 06500
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/njct.njct_10_18

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  Abstract 


Aim: About 90% of kidney cancers are renal cell carcinoma (RCC), and one-third of them are metastatic at the time of diagnosis. Most RCC metastases are to the lung. In this article, we present the results of a series of pulmonary metastasectomies for RCC in our institute. Materials and Methods: Twenty cases who underwent pulmonary metastasectomy for RCC between 2007 and 2017 were retrospectively reviewed. Patients were classified according to the age, sex, smoking history, duration of disease-free survival, number of metastatic lesions, median survival time, survival time after metastasectomy, type of surgery, and whether they received immunotherapy. Results: Fifteen of the patients were male and five were female. The mean age was 60-year-old (range: 28–86-year-old). Nineteen of the 20 patients had a history of nephrectomy. The median disease-free survival time was found to be 16.5 months while the median survival time after nephrectomy was 43.3 months. The number of detected metastatic lesions ranged from one to eight, and the location of the majority of them was intraparenchymal. Survival time after metastasectomy was found to be 20.6 months. Surgical approaches included bilateral metastasectomy through median sternotomy, unilateral wedge resection, and lobectomy through video-assisted thoracoscopic surgery or thoracotomy. Conclusion: The results of a combination of pulmonary metastasectomy and immunotherapy treatment were found to be better than immunotherapy or surgery alone. However, further study is needed with a larger series to support this argument.

Keywords: Lung, metastasectomy, metastasis, renal cell carcinoma


How to cite this article:
Bas A, Gökçe A, Turk MS, Sayan M, Çelik A, Kurul &C, Taştepe A&. Lung metastasectomy in renal cell carcinoma: Evaluation of 20 cases. Niger J Cardiovasc Thorac Surg 2018;3:36-9

How to cite this URL:
Bas A, Gökçe A, Turk MS, Sayan M, Çelik A, Kurul &C, Taştepe A&. Lung metastasectomy in renal cell carcinoma: Evaluation of 20 cases. Niger J Cardiovasc Thorac Surg [serial online] 2018 [cited 2019 Sep 18];3:36-9. Available from: http://www.nigjourcvtsurg.org/text.asp?2018/3/2/36/256251




  Introduction Top


Kidney cancers account for approximately 2%–3% of all cancers. They are most commonly seen in the sixth and seventh decades of life, and the male-to-female ratio is 1.5:1. Etiological factors include smoking, obesity, hypertension, and antihypertensive treatment.[1],[2],[3],[4],[5] The most common type of renal cancer is renal cell carcinoma (RCC). The great majority of RCC metastases are to the lung, and approximately one-third of the patients with RCC have pulmonary metastasis at the time of diagnosis. According to the literature, the mean survival time of metastatic patients was reported to be 10–12 months, and the 2-year survival rate was 18%–20%.[6] Surgical removal of isolated metastatic nodules located in the lung is controversial. However, some authors recommend surgical excision for metastatic RCC to confirm pulmonary metastasis, improve surveillance, and exclude primary lung cancers.[7],[8],[9],[10] In this study, 20 cases with RCC metastasis who underwent surgery in our clinic between 2007 and 2017 were analyzed and compared with the literature.


  Materials and Methods Top


All medical records of 20 patients who underwent surgery due to metastatic pulmonary disease of RCC between 2007 and 2017 in the Gazi University, Department of Thoracic Surgery were analyzed retrospectively. Patients were classified according to the age, sex, smoking history, duration of disease-free survival, number of metastatic lesions, median survival time, survival time after metastasectomy, type of surgery, and whether they received immunotherapy. The preoperative evaluation of the patients was performed by physical examination, routine blood tests, electrocardiography, pulmonary function tests, and thoracic computed tomography. Statistical analysis was performed using IBM SPSS Statistics 20 (Armonk, New York, US) at a 95% security level. Survival analysis was performed using the Kaplan–Meier method.


  Results Top


Fifteen of the patients were male and five were female. The mean age was 60-year-old (range: 28–86-year-old). The average smoking history was 25 pack/years. Nineteen of the 20 patients had a history of nephrectomy. Based on pathological staging, 75% of the cases were diagnosed as Stage 3–4, and 15% as Stage 1–2 [Table 1]. Synchronous metastasis was present in five patients. Recurrence developed in only two patients, and they underwent reoperation. Unilateral metastasectomy was performed in 75% of the patients. A mean of 3.35 (range: 1–8) lesions was removed during the procedure, and 81.7% of them were reported as metastases. In the pathology reports, resection materials from two patients were reported as RCC metastasis as well as adenocarcinoma and mucoepidermoid carcinoma [Table 2]. Both of our patients had been diagnosed during operation by frozen section procedure, and after that, we performed mediastinal lymph node dissection and anatomic resection (segmentectomy). One of them was diagnosed pathologically with Stage 1A3, (T1cNoMo) adenocarcinoma; the other one was diagnosed with Stage 3A (T2aN2Mo) mucoepidermoid carcinoma.
Table 1: Histopathological type and staging

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Table 2: Features of pulmonary surgery

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The overall median survival time was 43.3 months after RCC diagnosis in the kidney, but it was 20.6 months after diagnosis of pulmonary metastasis. The mean duration of disease-free interval was found to be 16.5 months. It was found that 52% of the patients received immunotherapy. While the median survival time of patients who received immunotherapy was 26 months, it was only 15 months in the other group [Figure 1]. The 1-, 3-, and 5-year survival rates were calculated as 69%, 52%, and 17%, respectively [Figure 2].
Figure 1: Survival time of patients undergoing pulmonary metastasectomy whether they received immunotherapy.

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Figure 2: 1-, 3- and 5-year survival rates of patients undergoing pulmonary metastasectomy.

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  Discussion Top


The feasibility and success of the pulmonary metastasectomy procedure depend on several factors that include the location of nodules, number of metastases, residual lung reserve, and medical condition of the patient. Good prognostic factors include a lack of intrapulmonary and mediastinal lymph node involvement, number of metastases fewer than seven, disease-free survival >2 years, possibility of complete resection, and absence of metachronous tumor.[8] Except in cases of solitary pulmonary metastasis, the role of surgery in RCC metastasis is still debated due to effective systemic treatment options, such as immunotherapy. However, resection of pulmonary metastases is associated with higher survival rates, and the results are better than for other anatomical regions. Hoffman et al. suggested that pulmonary metastasectomy can be performed if the number of metastatic lesions is fewer than six and there are good medical conditions.[7] The prognosis of patients with unresectable metastatic RCC is very poor. Mean survival times were reported to range from 6 to 10 months, and 5-year survival rates were reported to range from 5% to 10% in various studies.[8],[9],[10] Oddsson et al. reported a 5-year survival rate of 29% in patients undergoing pulmonary metastasectomy.[11] The 5-year survival rate after pulmonary metastasectomy for RCC was reported as 20%–50% in various studies in the literature.[12] In our series, the survival rates at 1, 3, and 5 years were 69%, 52%, and 17%, respectively. This result was evaluated as an appropriate survival rate when compared to management without surgery for metastatic diseases. Longer median survival times and increased 5-year survival rates were reported after pulmonary metastasectomy for RCC in selected patient groups in various studies[13],[14],[15],[16] [Table 3].
Table 3: Survival rates of variable studies after pulmonary metastasectomy

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Approximately one-third of patients with RCC have pulmonary metastasis at the time of diagnosis, and pulmonary metastasis eventually develops in about half of the remaining patients.[17] The rate of synchronous metastasis was found to be 25% in our series. Recurrence was seen in 10% of patients, and metastasectomy was repeated in these patients. It is thought that reoperation is effective for recurrent pulmonary metastases. Cerfolio et al. reported that the survival rate of these patients was similar to nonrecurrent patients.[18]

In our study, the average number of nodules removed was 3.35 (range: 1–8), and the average number of metastatic nodules removed was 2.70 (range: 1–8). The most important determining factor for long-term survival is complete resection. It has been reported in the literature that when complete resection is performed in the presence of isolated lung metastasis of RCC, longer survival is achieved compared to incomplete resection.[12] On the contrary, Steinbach et al. reported that complete resection was not important and that longer survival was obtained compared to unresectable pulmonary metastasis even if incomplete resection was performed.[19] This suggestion demonstrates that even if it is performed incompletely, surgery can decrease the tumor burden and increase the effects of systemic treatment by activating the immune system. Adjuvant interferon (IFN)-alpha therapy added following surgery can significantly improve the survival time.[20] In our study, median survival time from primary RCC diagnosis was 43.3 months, disease-free survival time was 16.5 months, and median survival time after metastasectomy was 20.6 months. Yamashita et al. found that patients who underwent metastasis surgery had a longer survival time (26 months) compared to the nonoperated group.[21] In our study, patients who underwent metastasectomy were classified by whether or not they received immunotherapy. The median survival time of patients who received immunotherapy was 26 months while it was 15 months for those who did not receive it. We determined that the duration of median survival increased when immunotherapy was added to metastasectomy. Flanigan et al. reported that the median survival time of patients with RCC treated with IFN alone was 8.1 months, but it was 11.1 months in patients treated with INF following nephrectomy.[22] This result can be interpreted that as the tumor burden decreases, the median survival time increases. In recent years, angiogenesis inhibitor drugs have been used for targeted therapy. In a study by Motzer et al., the median progression-free survival was found to be 11 months in patients with low- and intermediate-risk metastatic RCC treated with sunitinib, and 5 months in patients treated with IFN-alpha.[23] When a peripheral nodule is detected in a patient with extrapulmonary malignancy, there is no definitive criterion for determining whether it is a primary malignant tumor or metastatic nodule based on its radiological appearance. However, Park et al. detected 59 ground-glass opacity nodules on thoracic computed tomography in 34 patients with extrapulmonary malignancies. They found that 67% of them were malignant, and all of them were primary lung cancer. No metastatic nodule featuring ground-glass opacity was detected in the study. Based on this result, they indicated that when nodules with ground-glass opacity are detected in patients who have extrapulmonary malignancy, these nodules tend to be primary lung cancer.[24] van Bodegom et al. found that the incidence of concurrent malignancy development in different organs was generally 1.7%–3.9%.[25] Sarihan et al. stated that the incidence of synchronous or metachronous second primary lung cancers was 0.46%.[26] When a pulmonary nodule is detected in a patient with extrapulmonary cancer, it should not be considered to be a probable metastasis. For planning of proper treatment and accurate prediction of prognosis, the appropriate diagnostic approach to the etiology of the nodule should be performed without delay.[27],[28] In our study, a second primary lung cancer was detected in 10% of all cases. This situation changed the operative approach and treatment modality.


  Conclusion Top


Surgical treatment should be considered in the presence of pulmonary metastasis in RCC patients since there is no effective adjuvant medical therapy, despite improved medical treatment modalities. The median survival time can be increased by surgical treatment in RCC patients with metachronous lung metastasis. It should be remembered that patients with extrapulmonary malignancy may have concurrent primary lung cancer, and interventions for histopathological tissue diagnosis should be made.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Russo P, O'Brien MF. Surgical intervention in patients with metastatic renal cancer: Metastasectomy and cytoreductive nephrectomy. Urol Clin North Am 2008;35:679-86.  Back to cited text no. 1
    
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European Network of Cancer Registries. Eurocim version 4.0 European İndices Database V2.3, 730 Entitiy Dictionary (2001). Lyon; 2001.  Back to cited text no. 2
    
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Pfannschmidt J, Hoffmann H, Muley T, Krysa S, Trainer C, Dienemann H, et al. Prognostic factors for survival after pulmonary resection of metastatic renal cell carcinoma. Ann Thorac Surg 2002;74:1653-7.  Back to cited text no. 8
    
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Shiono S, Yoshida J, Nishimura M, Nitadori J, Ishii G, Nishiwaki Y, et al. Late pulmonary metastasis of renal cell carcinoma resected 25 years after nephrectomy. Jpn J Clin Oncol 2004;34:46-9.  Back to cited text no. 10
    
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Oddsson SJ, Isaksson HJ, Jonsson E, Einarsson GV, Gudbjartsson T. Pulmonary resections for metastatic renal cell carcinoma in iceland. Laeknabladid 2008;94:377-81.  Back to cited text no. 11
    
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Alt AL, Boorjian SA, Lohse CM, Costello BA, Leibovich BC, Blute ML, et al. Survival after complete surgical resection of multiple metastases from renal cell carcinoma. Cancer 2011;117:2873-82.  Back to cited text no. 12
    
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Renaud S, Falcoz PE, Alifano M, Olland A, Magdeleinat P, Pagès O, et al. Systematic lymph node dissection in lung metastasectomy of renal cell carcinoma: An 18 years of experience. J Surg Oncol 2014;109:823-9.  Back to cited text no. 13
    
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Kim JJ, Park JK, Wang YP. Surgical resection of pulmonary metastasis from renal cell carcinoma. Korean J Thorac Cardiovasc Surg 2011;44:159-64.  Back to cited text no. 14
    
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Bandiera A, Melloni G, Freschi M, Giovanardi M, Carretta A, Borri A, et al. Prognostic factors and analysis of S100a4 protein in resected pulmonary metastases from renal cell carcinoma. World J Surg 2009;33:1414-20.  Back to cited text no. 15
    
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Meimarakis G, Angele M, Staehler M, Clevert DA, Crispin A, Rüttinger D, et al. Evaluation of a new prognostic score (Munich score) to predict long-term survival after resection of pulmonary renal cell carcinoma metastases. Am J Surg 2011;202:158-67.  Back to cited text no. 16
    
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Pastorino U, Buyse M, Friedel G, Ginsberg RJ, Girard P, Goldstraw P, et al. Long-term results of lung metastasectomy: Prognostic analyses based on 5206 cases. J Thorac Cardiovasc Surg 1997;113:37-49.  Back to cited text no. 17
    
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Cerfolio RJ, Allen MS, Deschamps C. Pulmonary resection of metastatic renal cancer. Am Thorac Surg 1994;57:739-45.  Back to cited text no. 18
    
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Steinbach F, Langbein S, Allhoff EP. Surgery of metastases in renal cell carcinoma. Urologe A 2000;39:362-6.  Back to cited text no. 19
    
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Rini BI, Campbell SC. The evolving role of surgery for advanced renal cell carcinoma in the era of molecular targeted therapy. J Urol 2007;177:1978-84.  Back to cited text no. 20
    
21.
Yamashita Y, Ariyoshi A, Hasuo K, Shirakusa T. Surgical treatment of renal cell carcinoma associated with pulmonary metastasis. Nihon Gan Chiryo Gakkai Shi 1989;24:759-64.  Back to cited text no. 21
    
22.
Flanigan RC, Salmon SE, Blumenstein BA, Bearman SI, Roy V, McGrath PC, et al. Nephrectomy followed by interferon alfa-2b compared with interferon alfa-2b alone for metastatic renal-cell cancer. N Engl J Med 2001;345:1655-9.  Back to cited text no. 22
    
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Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 2007;356:115-24.  Back to cited text no. 23
    
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Park CM, Goo JM, Kim TJ, Lee HJ, Lee KW, Lee CH, et al. Pulmonary nodular ground-glass opacities in patients with extrapulmonary cancers: What is their clinical significance and how can we determine whether they are malignant or benign lesions? Chest 2008;133:1402-9.  Back to cited text no. 24
    
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van Bodegom PC, Wagenaar SS, Corrin B, Baak JP, Berkel J, Vanderschueren RG, et al. Second primary lung cancer: Importance of long term follow up. Thorax 1989;44:788-93.  Back to cited text no. 25
    
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Quint LE, Park CH, Iannettoni MD. Solitary pulmonary nodules in patients with extrapulmonary neoplasms. Radiology 2000;217:257-61.  Back to cited text no. 27
    
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