Incidence of synchronous and metachronous adrenal metastases following tumor nephrectomy in renal cell cancer patients: a retrospective bi-center analysis

Since the introduction of the radical nephrectomy approach for malignant kidney disease by Robson including removal of the adrenal gland more than half a century ago, this approach has been adopted towards organ- and nephron-sparing procedures (O'Malley et al. 2009).

The incidence of synchronous metastasis into the ipsilateral adrenal gland has been reported to be 2-10% (Robey and Schellhammer 1986;Winter et al. 1990). Although in advanced local disease a relevant number of patients diagnosed with renal cell cancer (RCC) are metastasized at the time of diagnosis (Hock et al. 2002), metachronous adrenal metastasis is a rare event. However, in general, metastasis to the adrenal gland is the second most common tumorous lesion in the adrenal glands after benign adrenocortical adenomas. In the case of metastatic RCC (mRCC) the incidence is from 7% to 23% in autopsy series (Wunderlich et al. 1999).

In a recent study Weight et al. demonstrated that patients do not have a benefit either in improved cancer-specific survival or in risk reduction of metachronous adrenal metastasis by performing simultaneous adrenalectomy. The authors reported synchronous ipsilateral tumor involvement of 2.2% (n=88) and a metachronous metastasis to the adrenal gland in 3.7% (n=147) after initial surgery (Weight et al. 2011). The latter finding was confirmed by other investigators, who concluded that in case of unsuspicious imaging, low tumor stage, and normal palpation during surgery the adrenal gland can be left in situ (Kobayashi et al. 2003;Kuczyk et al. 2002;Kuczyk et al. 2005). Since radiographic investigations have improved during the last decades, accounting for an increase of small adrenal lesions, it might be debatable that in case of positive radiological findings additional surgery seems to be necessary. We therefore analyzed retrospectively in a bi-center study model the number of positive pathological results (i.e. metastasis) in the adrenal gland after a tumor nephrectomy in a large cohort of patients with simultaneous adrenalectomy and with metachronous adrenalectomy due to a suspicious radiological finding in computer tomography (CT) and positron emission tomography (PET-CT) or magnetic resonance imaging (MRI). The main aim of this study is to discuss the aspects of simultaneous biopsy during radical nephrectomy surgery in case of RCC and the need of resection of a suspicious lesion in the adrenal gland in follow-up CT scans of patients with RCC history.

A routine ipsilateral adrenalectomy is not recommended in radical nephrectomy (Levy et al. 1998;Kuczyk, Munch et al. Munch et al. 2002) when no suspicious result is detected in imaging modalities or intraoperative findings are suspicious for tumor spread. In an earlier study we found that only a minority of RCC patients (1%) present with a solitary adrenal metastasis without other metastatic sites at the time of diagnosis (Kuczyk, Wegener et al. 2005). In cases where adrenal metastases originating from RCC were found, an advanced and disseminating disease could be found in approx. 96% (Wunderlich, Schlichter et al. 1999;Winter, Miersch et al. Miersch et al. 1990). Kobayashi et al. demonstrated in a retrospective study that there is no statistically significant difference in disease-specific survival in patients undergoing ipsilateral simultaneous adrenalectomy and patients with adrenal-sparing radical nephrectomy because of RCC (Kobayashi, Nakamura et al. 2003). We also noted a low incidence (5.3%) of synchronous adrenal metastasis. Interestingly we observed that, to our knowledge for the first time, regarding a suspicious lesion in the adrenal gland in follow-up CT scans a histological positivity (i.e. metastasis) of 100% could be found. The mean time to the development of a metachronous metastasis was 52.3 months. Both PET-CT coupled with CT or MRI are the diagnostics of choice in case of suspected adrenal lesions and in case of suspicious findings a preoperative hormonal evaluation is recommended (Sancho et al. 2012). In experienced hands a minimal invasive approach especially to patients with contralateral metachronous metastasis after previous radical nephrectomy is a feasible option (Rane et al. 2011;Abel et al. 2011).

This study supports the known results that synchronous metastasis is a rare event in RCC patients. Hence in case of suspicious lesions in follow-up imaging after adrenal-sparing radical nephrectomy a metastasis is very likely and a surgical resection should be performed. In case of advanced tumor disease at the time of diagnosis it should be discussed if in case of uncertain imaging prior to surgery (Tsui et al. 2000), an intra-operative biopsy could be helpful in deciding whether a simultaneous adrenalectomy should be performed. Otherwise postoperative hormonal dysfunction and necessity of hormonal replacement can be the result, particularly with regard to the risk of metachronous metastasis. Regarding long-term intervals to metastasis, frequent patient follow-up should be recommended. Our study suffers from bias in patient selection and retrospective data collection, which constitute study limitations. However, the presented data suggest the need of a routine and time-controlled follow-up of the patient and in case of a suspicious lesions in either CT- or MRI scan, the necessity of a surgical resection should be discussed. A prospective study with a long-term follow-up is needed to further elucidate this aspect.

Synchronous adrenalectomy is not routinely recommended with nephrectomy. In case of pre-operative suspicious imaging an intraoperative frozen section and investigations by the surgeon should be performed. In case of metachronous tumor growth within the adrenal gland, PET-CT/CT or MRI should be performed. In radiological positive cases, a surgical resection of this lesion due to its high probability of malignancy should be discussed.

Furthermore, frequent follow-ups of RCC patients should be recommended due to the long mean time of the development of a metachronous metastasis of approximately 52 months.