1. Case description
This is the case of a young patient with a large solid mass of the right kidney suggestive of renal cell carcinoma (RCC) and multiple lesions that are highly suspicious for metastases in regional lymph nodes, both adrenal glands, both lungs, and pancreas. He has no symptoms associated with either primary tumour or distant metastases. He has no major comorbidities, his performance status is very good, and his preference is for maximal treatment.
The first point is whether this patient could benefit from cytoreductive nephrectomy (CN). According to current European Association of Urology (EAU) guidelines , CN for metastatic RCC (mRCC) is recommended in patients with good performance status, large primary tumours, and low metastatic volume.
Although the level of evidence for recommending CN plus immunotherapy compared with immunotherapy alone is high, the role of CN in the era of targeted therapies utilising tyrosine kinase inhibitors (TKIs) and anti–vascular endothelial growth factor antibodies is not well defined. In a large retrospective study of the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) including 1658 synchronous mRCC patients treated with either CN and targeted therapy or targeted therapy alone, Heng et al.  showed that CN is beneficial for most patients even after adjusting for the known prognostic factors (haemoglobin below the lower normal limit; corrected calcium, neutrophils, and platelets above the upper normal limits; Karnofsky performance status <80%; and time from diagnosis to treatment <1 yr). Patients with estimated survival times <12 mo or with four or more IMDC risk factors may not benefit from CN. Our patient had none of the IMDC prognostic factors; therefore, based on this study, he would be a good candidate for CN.
The second question is whether metastasectomy should be performed immediately in this patient. According to current EAU guidelines , no recommendations can be given about who to treat and how to treat the metastases; rather, the decision must be made individually considering performance status, risk profiles, patient preference, and alternative techniques to achieve local control. This recommendation is based on the findings of a recent systematic review on local treatments (including both surgery and radiation therapy) of metastases in RCC patients . The authors of this paper observed that patients treated with complete metastasectomy had better survival and symptom control than those treated with either incomplete or no metastasectomy, but they concluded that these findings should be interpreted with caution due to the high risk of bias and confounding across the evaluated studies.
Our patient had multiple subcentimetre nodules in both lungs. In a retrospective study of 382 patients with RCC and indeterminate pulmonary nodules on preoperative chest computed tomography scan, nodule size <1 cm was not associated with distant metastases or cancer-specific death . Our patient also had three small pancreatic lesions. Metastases to the pancreas do not seem to confer a dismal prognosis in the setting of advanced RCC. In a recent retrospective multicentre study of 103 RCC patients with synchronous or metachronous metastases to the pancreas and resected primary tumour , overall survival was relatively long, with a median of 132 mo, and was not improved by surgical resection of the pancreas in comparison with targeted therapy with TKIs. At multivariable analysis, Memorial Sloan Kettering Cancer Center risk group was the only independent prognostic factor, thus aggressive therapy to these two locations in our patient does not seem to be justified.
The third and crucial point is bilateral adrenal involvement adjunct to other metastatic sites. This scenario is particularly challenging because any attempt at maximising local oncological control (ie, adrenalectomy) must be weighed against the risk of adrenal insufficiency with the need for life-long mineralocorticoid and glucocorticoid replacement therapy. Because synchronous bilateral adrenal metastases from RCC are extremely rare, no standard approach is accepted. A recent nonsystematic review of published case reports  concluded that bilateral adrenalectomy still has to be considered the first option from an oncologic standpoint; however, partial adrenalectomy with intraoperative frozen sections should be attempted, at least unilaterally, whenever possible, especially in case of smaller lesions. In our case, only unilateral (ie, right) adrenalectomy was performed. This was decided because the complexity of surgery would have increased if an additional left adrenalectomy had been performed at the same time. Moreover, the risk of perioperative complications would have increased, with potential damage to the contralateral kidney. Finally, adrenals were not the only site of metastatic spread.
3. Treatment strategy
We discussed the following therapeutic options after surgery. One option was no immediate treatment, with intervention at the time of radiologic or symptomatic progression. In a small retrospective study including 58 asymptomatic or minimally symptomatic mRCC patients in whom targeted therapy was deliberately postponed , more than half could be observed with no active treatment for >12 mo without detrimental effect on the response to subsequent therapy. Predictive factors for rapid progression were Karnofsky performance status <100%, liver metastases, and time from diagnosis to active monitoring <1 yr. The other option was immediate targeted therapy with TKIs. If disease stabilisation were to be obtained, treatment of metastatic sites could be discussed.
Our patient underwent a radiologic restaging 2 mo postoperatively. All metastatic lesions were unchanged except for the left adrenal mass, which had increased to 6 cm. He is currently under treatment with sunitinib. At the latest follow-up visit, he is asymptomatic and his adrenal function is preserved.
Conflicts of interest
The authors have nothing to disclose.
-  B. Ljungberg, K. Bensalah, S. Canfield, et al. EAU guidelines on renal cell carcinoma: 2014 update. Eur Urol. 2015;67:913-924 Crossref
-  D.Y. Heng, J.C. Wells, B.I. Rini, et al. Cytoreductive nephrectomy in patients with synchronous metastases from renal cell carcinoma: results from the International Metastatic Renal Cell Carcinoma Database Consortium. Eur Urol. 2014;66:704-710 Crossref
-  S. Dabestani, L. Marconi, F. Hofmann, et al. Local treatments for metastases of renal cell carcinoma: a systematic review. Lancet Oncol. 2014;15:e549-e561 Crossref
-  R. Mano, E. Vertosick, A.I. Sankin, et al. Subcentimeter pulmonary nodules are not associated with disease progression in patients with renal cell carcinoma. J Urol. 2015;193:776-782 Crossref
-  M. Santoni, A. Conti, S. Partelli, et al. Surgical resection does not improve survival in patients with renal metastases to the pancreas in the era of tyrosine kinase inhibitors. Ann Surg Oncol. 2015;22:2094-2100 Crossref
-  H. Öztürk. Bilateral synchronous adrenal metastases of renal cell carcinoma: A case report and review of the literature. Oncol Lett. 2015;9:1897-1901
-  I. Park, J.L. Lee, J.H. Ahn, et al. Active surveillance for metastatic or recurrent renal cell carcinoma. J Cancer Res Clin Oncol. 2014;140:1421-1428 Crossref
a Urology Unit, Academic Medical Centre Hospital “Santa Maria della Misericordia,” Udine, Italy
b Department of Experimental and Clinical Medical Sciences, University of Udine, Udine, Italy
Corresponding author. Urology Unit, Academic Medical Centre Hospital “Santa Maria della Misericordia,” Piazzale Santa Maria della Misericordia 15, IT-33100 Udine, Italy. Tel.: +390432552931; Fax: +390432552930.
© 2015 European Association of Urology, Published by Elsevier B.V.