BJUI. Solitary, isolated metastatic disease to the kidney: Memorial Sloan-Kettering Cancer Center experience

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1 ; 2010 Urological Oncology SOLITARY, ISOLATED METASTATIC DISEASE TO THE KIDNEY ADAMY ET AL. BJUI Solitary, isolated metastatic disease to the kidney: Memorial Sloan-Kettering Cancer Center experience Ari Adamy, Christian Von Bodman, Tarek Ghoneim, Ricardo L. Favaretto, Melanie Bernstein and Paul Russo Urology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA Accepted for publication 12 August 2010 Study Type Therapy (case series) Level of Evidence 4 OBJECTIVE To analyse the clinical characteristics and outcomes of patients who underwent nephrectomy for solitary, isolated metastatic disease to the kidney. What s known on the subject? and What does the study add? Usually malignant disease involving the kidneys is characterized by bilateral and multiple lesions in association with widespread dissemination of the primary tumour. Metastasis to the kidney as a solitary, isolated renal mass is an extremely rare event and little is known about its characteristics and outcomes. Our study shows that kidney involvement by other tumours can occur as isolated solitary lesions and the kidney can be the first and only site of metastatic involvement. Of the 14 patients included in the study, 8 were alive at the last follow-up and 4 without evidence of disease after nephrectomy. In this highly selected group of patients nephrectomy can be offered as a therapeutic option. PATIENTS AND METHODS From July 1989 to July 2009, we identified 13 patients who underwent nephrectomy for solitary metastasis to the kidney. Patients demographics, intra-operative variables and outcomes are reported. RESULTS The median age at nephrectomy was 52 years (range 33 79). Eleven patients (85%) had an incidentally discovered renal mass, whereas two patients (15%) presented with gross haematuria. Median time from initial surgery at the primary site to development of metastatic disease to the kidney was 63 months (range 9 136). No patient had evidence of disease at other sites at the time of nephrectomy. In seven patients (54%), the kidney was the first site of recurrence. The most common primary site was the lung in five patients (38%), followed by the colon in two (15%), chest wall in two (15%) and bone, brain, breast and salivary gland in one patient each (8%). Of the 14 procedures performed, eight (57%) were partial nephrectomy (PN) and six (43%) were radical nephrectomy (RN). Four patients died after progression from the primary tumour, all within 2 years of nephrectomy. One patient with a primary chondrosarcoma had no evidence of disease at last follow-up and died from other causes 50 months after nephrectomy. The median follow-up for the eight patients who were alive at last follow-up was 30 months after nephrectomy. Four of these patients had no evidence of disease and four patients were alive with metastatic disease. CONCLUSION Kidney involvement by metastatic disease can occur as isolated solitary lesions. Some patients will also have the kidney as the first and only site of metastatic involvement. The presence of an isolated renal metastasis should not be considered an end-stage disease, and nephrectomy can be offered for highly selected patients as a therapeutic option. KEYWORDS kidney neoplasm, metastasis, nephrectomy, lung neoplasm, colonic neoplasm INTRODUCTION With improvements in cancer screening, therapy and supportive care, an increase in the number of cancer survivors has been seen in the United States [1]. This increase in the number of cancer survivors, coupled with the widespread use of non-invasive imaging techniques, will lead to an increase in the number of patients with a renal mass diagnosed during surveillance for non-renal malignancies. Rabbani et al. [2] showed that approximately 27% of patients with renal cell carcinoma (RCC) have another primary cancer, most of these cancers being antecedent or synchronous. Although the renal mass will more commonly be a renal primary tumour, a small proportion of patients will present with metastatic disease involving the kidney [3]. Metastasis to the kidney is not an uncommon event, being present in 7% to 12% of patients with cancer at post-mortem examination [4,5]. These data include microscopic metastasis below the threshold of computerized tomography (CT) scan detection; the diagnosis in the clinical setting is less frequent [6]. Usually such metastases are multiple, small and bilateral [5,7]. The majority of patients with renal involvement by other tumours also have widely metastatic disease to other organs [8]. The presence of solitary renal metastasis without evidence of a disseminated non-renal , doi: /j x x

2 SOLITARY, ISOLATED METASTATIC DISEASE TO THE KIDNEY malignancy is rare and the role of nephrectomy in patients with such disease is not established [9]. To better understand the role of nephrectomy in these rare patients, we review our institution s experience with nephrectomy in patients with solitary, isolated metastatic disease to the kidney. PATIENTS AND METHODS Patients Characteristic (n = 13) Age at surgery, years (range) 52 (33 79) Male gender (%) 7 (54) Presentation (%) Incidental 11 (85) Local (haematuria) 2 (15) Procedure* (%) Partial nephrectomy 8 (57) Radical nephrectomy 6 (43) Site of primary malignancy (%) Lung 5 (38) Colon 2 (15) Chest wall 2 (15) Salivary gland 1 (8) Bone 1 (8) Breast 1 (8) Brain 1 (8) Side of involvement (%) Right 5 (38) Left 7 (54) Bilateral 1 (8) Time to kidney metastasis, months (range) 63 (9 136) Kidney as the initial site of metastasis (%) 7 (54) Presence of other metastases during follow-up (%) 9 (69) From July 1989 to July 2009, 3472 patients underwent either a partial (PN) or radical nephrectomy (RN) at Memorial Sloan- Kettering Cancer Center. After Institutional Review Board approval, we searched our TABLE 1 Patient characteristics *One patient had two procedures, a partial and a radical nephrectomy. prospectively collected renal cancer database, identifying 13 patients with solitary, isolated metastasis to the kidney. Only nephrectomies done for distant metastatic disease were included in the study. Patients who underwent nephrectomy for direct tumour extension from a primary malignancy and patients with kidney involvement by lymphoma were excluded. In three patients, a preoperative biopsy was done before nephrectomy, confirming the diagnosis of metastasis to the kidney. In all patients, the kidney was the only site of disease and nephrectomy was performed as a metastasectomy. Patient demographic data were collected and relevant operative, radiographical and pathological variables were reviewed. Variables collected from the database included age, gender, clinical presentation, laterality, procedure performed, tumour histology, tumour size and follow-up details. Descriptive statistics were compiled for all preoperative and postoperative variables. RESULTS PATIENT CHARACTERISTICS The characteristics of all patients who underwent nephrectomy for an isolated metastatic disease to kidney are summarized in Tables 1 and 2. The median age at TABLE 2 Characteristics of patients with isolated, solitary metastatic disease to kidney Age/ gender Primary site Histology Presentation Procedure Kidney as initial site Tumour diameter (cm) Time to kidney mets (m) 1 74/F Colon Adenocarcinoma Incidental PN + RN No DOD 2 50/F Chest wall Mesenchymal chondrosarcoma Incidental PN No DOC 3 38/M Chest wall Epithelioid leiomyosarcoma Incidental PN No DOD 4 46/F Colon Adenocarcinoma Incidental PN No AWD 5 68/M Lung Adenocarcinoma Haematuria RN Yes DOD 6 70/M Lung Adenocarcinoma Incidental PN Yes AWD 7 56/M Lung Squamous cell carcinoma Haematuria RN Yes NED 8 48/M Salivary gland Adenoid cystic carcinoma Incidental PN No NED 9 52/M Lung Squamous cell carcinoma Incidental RN Yes NED 10 64/F Breast Lobular carcinoma Incidental PN Yes NED 11 33/M Bone (femur) Spindle cell sarcoma Incidental RN No DOD 12 40/M Brain Hemangiopericytoma Incidental PN Yes AWD 13 79/F Lung Adenocarcinoma Incidental RN Yes AWD FU (m) Last status Mets, metastasis; FU, follow-up; PN, partial nephrectomy; RN, radical nephrectomy; DOC, death from other causes; DOD, dead of disease; AWD, alive with disease; NED, no evidence of disease

3 ADAMY ET AL. FIG. 1. Images from a 48-year-old male with an incidental diagnosis of a left renal mass. The patient had a previous history of an adenoid cystic carcinoma originated in the salivary gland. An axial contrast-enhanced computerized tomography (CT) image demonstrates a 4.1-cm low attenuation solid enhancing left renal lesion. The mass does not enhance to the same extent as renal parenchyma. FIG. 2. Images of a 33-year-old male with a history of a spindle cell sarcoma that originated in the distal femur. During a follow-up CT scan the patients was diagnosed with an incidental right renal mass. Axial contrast-enhanced computerized tomography (CT) image shows a 6.4-cm renal mass in the central portion of the right kidney. The mass mildly enhances with intravenous contrast imaging (A). An 8-min delayed image demonstrates that the mass is outside of the renal pelvis, compressing the renal collecting system (B). TABLE 3 Pathological findings after nephrectomy for isolated, solitary metastatic disease to kidney Patients Characteristic (n = 13) Median tumour diameter, cm 4.5 (1 7) (range) Histology (%) Adenocarcinoma Lung 3 (23) Colon 2 (15) Squamous cell carcinoma (lung) 2 (15) Chondrosarcoma (chest wall) 1 (8) Leiomyosarcoma (chest wall) 1 (8) Adenoid cystic carcinoma 1 (8) High-grade sarcoma (bone) 1 (8) Lobular carcinoma (breast) 1 (8) Haemangiopericytoma (brain) 1 (8) nephrectomy was 52 years (range 33 79). Seven patients (54%) were males and six (46%) were females. Eleven patients (85%) had an incidentally discovered renal mass during routine imaging follow-up, whereas two patients (15%) presented with gross haematuria. In both patients who presented with haematuria the lung was the primary site of disease and had the shortest time from primary tumour operation to nephrectomy (9 and 15 months after initial treatment). One of the incidentally detected patients with colorectal carcinoma as the primary malignancy had an elevation in the carcinoembryonic antigen which prompted investigation using abdominal imaging. Median time from the initial surgery at the primary site to development of metastatic disease to the kidney was 63 months (range months). Renal masses were located in the right kidney in five patients (38%), left kidney in seven (54%) and both kidneys in one (8%). Six patients (46%) had a previous history of metastatic disease resected at other sites prior to renal mass diagnosis, and in seven patients (54%) the kidney was the first site of disease relapse. No patient had evidence of disease at other sites at the time of nephrectomy (Figs 1,2). PRIMARY MALIGNANCIES The most common primary site was the lung in five patients (38%), followed by the colon in two (15%), chest wall in two (15%) and bone, brain, breast and salivary gland in one patient each (8%). The kidney was the first site of metastasis in all patients with lung primary cancer, in the patient with breast cancer and in the patient with brain haemangiopericytoma. The remaining patients had a history of surgically resected metastatic disease at other sites before the diagnosis of kidney metastasis. TREATMENT AND PATHOLOGICAL CHARACTERISTICS Fourteen procedures were performed in 13 patients. One patient with bilateral renal masses in the preoperative imaging underwent a right PN and then a left RN. This patient had a history of primary colorectal cancer and a resection of lung metastasis. She underwent a kidney biopsy confirming metastatic disease to the kidney and received chemotherapy prior to nephrectomy without a good response. Of the 14 procedures performed, eight (57%) were PN and six (43%) were RN. Six patients (46%) underwent a nephrectomy because the renal lesion resembled a renal cortical tumour. In seven patients (54%), the initial suspicion was of metastasis and the nephrectomy was performed because the kidney was the only site involved with disease. Of these seven patients, three underwent kidney biopsy prior to nephrectomy confirming the initial suspicion. The histological findings are summarized in Tables 2 and 3. The median tumour diameter was 4.5 cm (range 1 7). The most common histological subtype was lung adenocarcinoma in three patients (23%), followed by lung squamous cell carcinoma and colon adenocarcinoma in two patients each (15%). ONCOLOGICAL OUTCOMES Four patients died after progression from the primary tumour. One with primary colon cancer, one with lung cancer, one with leiomyosarcoma and one with osteosarcoma died 20, 19, 15 and 10 months after nephrectomy, respectively. One patient with a

4 SOLITARY, ISOLATED METASTATIC DISEASE TO THE KIDNEY primary chondrosarcoma had no evidence of disease at last follow-up and died from other causes 50 months after nephrectomy. The remaining eight patients were alive after a median follow-up of 30 months after the kidney operation. Four of these patients have no evidence of disease at 5, 17, 36 and 39 months after nephrectomy, including two patients with a primary lung cancer, a patient with breast cancer and a patient with adenoid cystic carcinoma originating in a salivary gland. Two patients with lung cancer, one patient with colon cancer and one patient with haemangiopericytoma of the brain are alive with metastatic disease at 9, 27, 33 and 36 months after nephrectomy, respectively. DISCUSSION In the present study, we report a series of patients who underwent nephrectomy for solitary, isolated metastatic disease to the kidney. This situation is extremely rare; usually malignant disease involving the kidney is characterized by bilateral and multiple lesions in association with widespread dissemination of the primary tumour [9]. All patients in our cohort had the kidney as the only site of metastasis at the time of nephrectomy. Also, 54% of them had the kidney as the first site of metastatic spread. For this reason, the presence of a solitary renal mass in the absence of involvement of other sites should not preclude the suspicion of kidney involvement by metastatic disease. The time from treatment of primary tumour to diagnosis of renal metastasis can be variable. A previous study by Choyke et al. [8] showed a mean time to recurrence of 2.2 years, with nine patients recurring in the first year. In the present study, the median time to diagnosis of kidney metastasis was 63 months and two patients were diagnosed after 8 years. The difference can be explained by the fact that in the first study most of the patients had disseminated disease and in the present study all patients had the kidney as a solitary metastatic site at the time of nephrectomy. In studies of secondary malignancies of the kidney, the lung is by far the most common primary cancer, followed by the breast, gastrointestinal tract and melanoma [4 6,8]. In the present study, the lung was also the most common primary cancer. Although not present in our series, a male predominance is reported in other studies and the high proportion of lung cancer as the primary site is hypothesized to be the reason for this gender difference [6]. Only two patients presented with local symptoms, both with gross haematuria and a prior diagnosis of lung cancer. Interestingly, these two patients had the shortest time to recurrence in our series, 9 and 15 months after initial surgery. Previous studies have shown that most renal metastases, such as renal cortical tumours, are detected incidentally [7]. In the present study, we also found that solitary renal metastases were incidentally detected in the overwhelming majority of patients. Unfortunately, on the basis of radiological studies alone it is impossible to distinguish an incidental renal cortical tumour from a renal metastasis [7]. Yet, there are characteristics on CT scans which are more typical for a metastasis [10,11]. These include lesions that are multifocal, endophytic and either isodense or slightly low in attenuation relative to renal parenchyma on unenhanced CT examinations. Typically, these small tumours are hypovascular and are enhanced only slightly by intravenous contrast administration [10,11]. When analysing factors that predicted the presence of metastasis vs primary tumour in patients with a renal mass and previous history of other malignancy, Sánchez-Ortiz et al. [9] showed that progression of the initial tumour and absence of renal mass enhancement on CT scan were highly associated with the presence of kidney metastasis. In non-randomized studies of other types of cancer, surgical excision of isolated metastatic lesions has shown to improve survival. Some series analysing adrenalectomy for isolated metastatic disease from non-small cell lung cancer (NSCLC) have shown 5-year survival rates of around 25% [12,13]. In these previous studies, survival appears to be related to the disease-free interval. Patients with metachronous metastasis and experiencing recurrence more than 6 months after resection of the primary lung cancer had a better prognosis. Analysing patients who underwent adrenalectomy for isolated metastasis from different primary tumours, including NSCLC, RCC and colorectal cancer, Kim et al. [14] reported a 5-year actuarial survival of 24%, and survival was also related to the disease-free interval and whether the lesion was completely resected. Evidence of the potential effect that resection of metastatic disease can have on patient survival was also shown for brain metastasis from NSCLC, lung metastasis in RCC and liver metastasis in colorectal cancer, among others [15 18]. In general, the treatment of metastatic disease involving the kidney consists of systemic chemotherapy. The agent of choice is based on the histology of the primary tumour. Even with aggressive regimens, the results are usually poor. The role of nephrectomy in these patients is not established. Some case reports of nephrectomy for metastatic osteosarcoma have shown favourable results, whereas in other cases of colon and lung cancer the patients died soon after nephrectomy [19 21]. In the present study, surgical excision of metastasis to the kidney was performed in three different situations: in patients with an initial suspicion of a renal cortical tumour where the metastasis was a postoperative finding; in patients who had primary tumours that responded poorly to systemic therapy and the primary treatment was complete surgical excision of the lesions, such as sarcomas; and lastly, in patients with metastasis diagnosed in the preoperative period where nephrectomy was offered as a treatment option. Of the 13 patients analysed, eight were alive after a median follow-up of 30 months, and half of them were without evidence of disease. In addition, one patient died due to other reasons 50 months after nephrectomy and at that time had no evidence of recurrent lesions. In the absence of any established results in this rare situation, the present study raises the possibility that nephrectomy could be associated with prolonged survival in this highly selected group of patients. There are several limitations of the present study. First, this is a case series report in which nephrectomy was done as a treatment option in patients with different primary tumours, limiting our conclusions. Also, all patients had the kidney as the only site of disease at the time of nephrectomy, and metastases were usually diagnosed after a long disease-free interval. For this reason, the results may be more related to the biology of the disease than to the treatment itself. More studies with a larger number of patients are needed to clarify the role of nephrectomy in this setting. In conclusion, kidney involvement by metastatic disease can occur as isolated solitary lesions. Some patients will have the

5 ADAMY ET AL. kidney as the first and only site of metastatic involvement. The presence of an isolated renal metastasis should not be considered an endstage disease and nephrectomy can be offered for a highly selected group of patients as a therapeutic option. ACKNOWLEDGEMENTS The study was supported by the Sidney Kimmel Center for Prostate and Urologic Cancers. CONFLICT OF INTEREST None declared. REFERENCES 1 Ng AK, Travis LB. Subsequent malignant neoplasms in cancer survivors. Cancer J 2008; 14: Rabbani F, Reuter VE, Katz J, Russo P. Second primary malignancies associated with renal cell carcinoma: influence of histologic type. Urology 2000; 56: Pagani JJ. Solid renal mass in the cancer patient: second primary renal cell carcinoma versus renal metastasis. J Comput Assist Tomogr 1983; 7: Abrams HL, Spiro R, Goldstein N. Metastases in carcinoma; analysis of 1000 autopsied cases. Cancer 1950; 3: Bracken RB, Chica G, Johnson DE, Luna M. Secondary renal neoplasms: an autopsy study. South Med J 1979; 72: Bates AW, Baithun SI. The significance of secondary neoplasms of the urinary and male genital tract. Virchows Arch 2002; 440: Pollack HM, Banner MP, Amendola MA. Other malignant neoplasms of the renal parenchyma. Semin Roentgenol 1987; 22: Choyke PL, White EM, Zeman RK, Jaffe MH, Clark LR. Renal metastases: clinicopathologic and radiologic correlation. Radiology 1987; 162: Sánchez-Ortiz RF, Madsen LT, Bermejo CE et al. A renal mass in the setting of a nonrenal malignancy: when is a renal tumor biopsy appropriate? Cancer 2004; 101: Bailey JE, Roubidoux MA, Dunnick NR. Secondary renal neoplasms. Abdom Imaging 1998; 23: Honda H, Coffman CE, Berbaum KS, Barloon TJ, Masuda K. CT analysis of metastatic neoplasms of the kidney. Comparison with primary renal cell carcinoma. Acta Radiol 1992; 33: Mercier O, Fadel E, de Perrot M et al. Surgical treatment of solitary adrenal metastasis from non-small cell lung cancer. J Thorac Cardiovasc Surg 2005; 130: Tanvetyanon T, Robinson LA, Schell MJ et al. Outcomes of adrenalectomy for isolated synchronous versus metachronous adrenal metastases in non-small-cell lung cancer: a systematic review and pooled analysis. J Clin Oncol 2008; 26: Kim SH, Brennan MF, Russo P, Burt ME, Coit DG. The role of surgery in the treatment of clinically isolated adrenal metastasis. Cancer 1998; 82: Mussi A, Pistolesi M, Lucchi M et al. Resection of single brain metastasis in non-small-cell lung cancer: prognostic factors. J Thorac Cardiovasc Surg 1996; 112: House MG, Ito H, Gonen M et al. Survival after hepatic resection for metastatic colorectal cancer: trends in outcomes for patients during two decades at a single institution. J Am Coll Surg 2010; 210: , Hofmann HS, Neef H, Krohe K, Andreev P, Silber RE. Prognostic factors and survival after pulmonary resection of metastatic renal cell carcinoma. Eur Urol 2005; 48: 77 81; discussion 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: 873 8; discussion Terlecki RP, Triest JA, Madan SK, Vaishampayan UN. Nephrectomy in the management of metastatic osteosarcoma. Clin Genitourin Cancer 2008; 6: Aksu G, Fayda M, Sakar B, Kapran Y. Colon cancer with isolated metastasis to the kidney at the time of initial diagnosis. Int J Gastrointest Cancer 2003; 34: Yoshino I, Yohena T, Kitajima M et al. Survival of non-small cell lung cancer patients with postoperative recurrence at distant organs. Ann Thorac Cardiovasc Surg 2001; 7: Correspondence: Paul Russo, Memorial Sloan- Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. russop@mskkcc.org Abbreviations: PN, partial nephrectomy; RN, radical nephrectomy; RCC, renal cell carcinoma; CT, computerized tomography; NSCLC, non-small cell lung cancer