Management of renal cell carcinoma with solitary metastasis
© Thyavihally et al. 2005
Received: 20 December 2004
Accepted: 20 July 2005
Published: 20 July 2005
Distant metastasis are common in Renal cell carcinoma (RCC) nearly one forth of the patients have metastasis at presentation while another 50% develop metastasis during the follow-up. A small percentage of these are solitary metastasis. We describe survival after surgical excision or radiotherapy of solitary metastatic lesion from renal cell carcinoma
Patients and methods
Between 1988–2001, 43 patients with solitary metastasis to different sites from renal cell carcinoma underwent either surgical excision or radiotherapy were analyzed. The solitary nature of the lesions was confirmed by investigations. All patients have had radical nephrectomy for the primary lesion. Survival analysis was carried out by Kaplan Meier Method.
All solitary metastatic lesions were treated with intent of cure either by excision or radiotherapy. Of these, 13 patients had solitary metastasis at the time of presentation in whom 3-year overall median survival was 26 months. The survival of those who developed solitary metastases during follow-up after nephrectomy for primary was 45 months. The patients with long interval between diagnosis and development of metastasis, early stage and low grade of the primary tumor had better prognosis.
Complete resection of either synchronous or metachronous solitary metastases from renal cell carcinoma is justified and can contribute to a long-term survival in this select group of patients.
Nearly 20–25% of patients with renal cell carcinoma (RCC) have distant metastasis at presentation. Another 50% develop metastasis or local recurrence during follow-up after the treatment of the primary . RCC can recur at any time after nephrectomy and usually metastasizes via venous and lymphatic routes. Frequent sites of metastasis include the lung parenchyma (50% to 60%),  bone (30% to 40%),  liver (30% to 40%), and brain (5%) . Other rare sites of metastasis include pancreas [5, 6], adrenal gland [7, 8], parotid gland , maxilla, pharynx etc. Even with early-stage disease, late metastases can occur after complete resection. However, after the development of metastasis the prognosis is often poor, as non-operative modalities for advanced renal carcinoma have failed to improve survival significantly. The average survival of metastatic RCC is about 4 months and only 10% of these survive for one year. Chemotherapy, hormonal therapy, and radiotherapy have generally proved ineffective for primary lesion or metastatic deposits, but an improved survival is seen with the use of immunotherapy with either interleukins or interferon [10, 11]. There is a small subset of patients where solitary metastasis is present either at the time of presentation or develops during follow-up after nephrectomy these patients have a better survival. An autopsy series showed that 8 to 11% of the patients with metachronous metastases have a solitary lesion . With the introduction of immunotherapy or immunochemotherapy for advanced renal cell carcinoma, survival has improved for a subset of patients. Surgical resection of the renal tumor and solitary metastases if present is still the treatment of choice for these lesions . By modern perioperative management, even extended resections of metastatic lesions can be performed with limited morbidity and mortality . The present study reports the result of retrospective analysis of the records of 43 patients treated for solitary synchronous or metachronous metastases from renal cell carcinoma.
Patients and methods
Between 1988 and 2001, 1863 patients of RCC were treated of these 43 cases had solitary metastasis to different sites. Thirteen patients had synchronous solitary metastsis, whereas 30 patients developed solitary metastasis during follow-up after the treatment of the primary in a metachronous fashion. The location and extent of the metastatic disease was evaluated by various diagnostic methods, which include chest radiograph, isotope bone scan, liver function tests, and serum alkaline phophatase. All patients underwent either ultrasound (USG) or computerized tomography (CT) of abdomen to rule out local recurrence. The patients with lymph node metastasis were excluded from the analysis. An attempt was made to obtain histological proof of the metastatic lesion either by fine needle aspiration cytology (FNAC) or USG/CT guided biopsy. The analysis was performed separately for patients with synchronous and metachronous metastatic lesions. Survival analysis was calculated by using Kaplan-Meier test and survival was compared using Log-rank test.
Patient and tumor characteristics- synchronous solitary metastasis
Total No. of patients
38–69 years (mean = 57)
Site of metastasis
Bone-6, Lung-3, Liver-2, Brain-1, Opposite adrenal-1
Pathological stage of primary
pT1–3, pT2–6, pT3–4
Grade I-1, Grade II-4, Grade III-5, Grade IV-3
Patient and tumor characteristics- metachronous solitary metastasis
Total No. of patients
34–75 Years (Mean 54)
3–33 months (Mean 16)
Site of metastasis
Bone-13, Lung-6, Liver-3, Brain-2, Parotid-1, Maxilla-1, Pharyngeal wall-1, Gall bladder-1, Opposite adrenal-1, Soft tissue shoulder-1.
Histology of primary
Conventional Clear cell carcinoma -25
Pathological stage of primary
pT1–9, pT2–13, pT3–8
Grade I-5, Grade II-12, Grade III-7, Grade IV-6
RCC is known for its varied presentation and its propensity to metastasize by way of both venous and lymphatic routes. Ritchie and deKernion  found that 23% of patients with RCC present initially with metastatic disease and 25% develop metastatic disease within 5 years of nephrectomy. RCC can, however, metastasize to virtually any organ, including the thyroid, pancreas, skeletal muscle, and skin or underlying soft tissue.
Despite the early promising results with immunotherapy, a complete response occurs in less than 15% and is rarely durable, emphasizing that metastatic disease best treated with complete resection of the primary and metastatic lesions where possible. Solitary metastases are identified at the time of diagnosis of renal cell carcinoma in 2% to 4% of patients. Depending on the location of the solitary metastasis, radical nephrectomy  with excision of the solitary metastatic lesion has been advocated, with 20% to 30% 5-year survival rates being reported.
Barney in 1961  did nephrectomy and lobectomy for lung metastasis and patient survived for 23 years. This influenced many workers to perform excision of solitary metastasis. Middleton  reviewed the literature and concluded that the survival after surgical excision of solitary metastatic lesions was 45% at 3-years and 34% at 5-years. Tolia and Whitmore , Morrow et al , and Jett et al  also reported similar 5-year survival after the treatment of solitary metastatic tumors. Skinner et al  reported a 29% 5-year survival in a series of 41 patients in whom one or two metastases were excised surgically in addition to nephrectomy. In our series, the 3 and 5-year post metastatectomy survival was 58% and 35% respectively in metachronous group of patients whereas 3-year survival was 20% in the synchronous group, the higher survival could be due to number of patients being loss to follow-up and hence censored from the survival analysis.
Middleton  found significant difference in survival between synchronous and metachronous solitary metastases, synchronous group being the worst. O'Dea et al  and Rafla  also agreed that the patients with synchronous solitary metastasis have poor survival when compared to patients who develop metastasis after removal the primary tumor. Although the site of metastasis was not significant in many reports we found patients with lung and bone metastases fared much better (median 62 months) than with liver and brain metastases (median 22 months). This could be due to the fact that not all patients with brain metastasis had undergone surgical resection, and more use of adjuvant treatment in patients with lung or bone metastasis.
Most metachronous metastases are identified in the first or second year after nephrectomy. Tally et al  Skinner et al  and Tongaonkar et al  found that survival in metachronous metastases which appeared before one year after the nephrectomy was poor (median overall survival 33 months) when compared to one in whom metastases appeared after one year (median overall survival 55 months). Our results also suggests that over all survival in patients with disease free interval less than one year was 31 months when compared to 63 months in those disease free intervals was more than one year.
We also noted significant difference in the survival among patients of different primary tumor stage and Fuhrman's nuclear grading with early stage and low grade having better survival. Thus, the groups of patients who do better with solitary metastasis excision are those with disease free interval of more than one year, low primary tumor stage, low grade and those with bone and pulmonary parenchymal metastasis. However, the effect of treatment modality and adjuvant immunotherapy can not be calculated due to smaller number of cases in the present series.
A small subset of patients with a solitary metastasis from renal cell carcinoma and good general condition may benefit from nephrectomy and resection/radiotherapy of the metastatic lesion. Surgical excision can locally control the tumor, and relieve pain. Patients with disease free interval of more than one year before development of solitary metastasis, early primary tumor stage, low-grade and patients with bone and pulmonary parenchymal metastasis appear to have better survival. We believe that the relatively prolonged survival of these small cohort of patients with solitary metastatic lesions from RCC justify aggressive surgical excision involving multispecialty specialists with long-term survival, however, prospective studies are needed before this can be recommended as standard practice.
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