BERKELEY, CA (UroToday.com) -
Adrenocortical cancer (ACC) is a very rare malignancy with a worldwide incidence of approximately 1 in 3 million of the population. Because of its rarity, the experience of individual surgeons with the management of ACC remains very limited. According to HES (Hospital Episodes Statistics) data, adrenalectomy for ACC is commonly done in hospitals were only one such case is treated annually as two or more such operations were undertaken in only seven hospitals in 1998 and in 11 hospitals in 2007. A recent paper described the experience gained in three large University centres in the UK over a decade with only 40 patients managed in Newcastle, Sheffield and Cardiff. Outside such recognized UK centres for endocrine surgery, the experience remains minimal since most adrenal surgery in the UK is performed by surgeons who undertake less than five cases per year. The worldwide situation in individual hospitals is likely to be similar. This extremely small number of patients reported from University hospitals is at odds with the data from the International Association of Cancer Registries that records 150 cases diagnosed yearly in the UK. Most patients are therefore either not operated or are operated by general surgeons who rarely perform adrenalectomy. This suspicion is reinforced by the fact that members of the British Association of Endocrine and Thyroid Surgeons (BAETS) have logged only 68 adrenalectomies for ACC (out of a total of 1 280 adrenalectomies performed between 2000-2005), while in the same period an estimated 900 patients should have been diagnosed/treated in the UK.
ACC represents one of the most aggressive human cancers, with an overall 5-year survival of only 30-40%.[6,7] Several national and pan-European structures have recently been established to improve the therapeutic options offered to patients with ACC and, in addition, to promote basic and clinical research in this field. The European Network for the Study of Adrenal Tumours (ENSAT) has taken a lead in promoting common European standards for diagnosis and therapy, data collection, and tumour banking for ACC. For the first time, patients with metastatic or unresectable ACC have been considered for entry in a prospective multicentre international randomized controlled trial comparing different cytotoxic chemotherapy regimes (FIRM-ACT). The very small number of patients treated even in large University hospitals hampers easy recruitment and it might be that many patients enrolled in trials and reported in medical/surgical trials are the most severe cases referred for treatment to tertiary referral centres.
Tumour invasion into the inferior vena cava (IVC) defines a small subgroup of patients with ACC who have additional therapeutic difficulties. The largest series of 15 patients with IVC invasion reported from Cochin Clinic (Paris, France) included a review of a further 106 cases reported in the literature over three decades and concluded that involvement of the IVC should not be considered a contraindication for surgery if complete resection of the primary tumour and its locoregional extension can be achieved. Our paper, the abstract for which recently appeared in UroToday, is based on a collaboration of members of the European Society of Endocrine Surgeons (ESES) involved in the care of patients with ACC. A standardised questionnaire agreed by the study initiators (Bruno Carnaille, Lille, France and Radu Mihai, Oxford, UK) was sent to ESES’ national representatives and cascaded to members of their national professional associations. As replies were received only from surgeons from 18 centres in nine countries, it remains likely that data is influenced by biased reporting. This dataset is also limited by the lack of a denominator as it remains unknown how many other patients with ACC presenting with IVC invasion did not undergo surgery and it is impossible to know whether surgeons who did not reply to our study were involved in the care of such patients.
In our study, from an initial cohort of 38 patients with ACC with IVC invasion, at the time of the study 12 patients were alive at 2-58 months after initial operation (median 16 months) with known metastatic disease (n=7) or with no signs of distant disease (n=5). To date, there have been limited data regarding the impact of large vessel extension on overall survival and recurrence-free survival in ACC. A previous literature review of 106 cases published by early 2000 reported an overall survival of 9 months. In a retrospective review of 57 patients undergoing ACC resection with curative intent over a decade at the Memorial Sloan Kettering Cancer Center, the 3-year overall survival with and without large vessel extension were 29% vs. 93% and 3-year recurrence-free-survival was 15% vs. 67%. In our cohort the median survival was 16 months, and these findings are in support of a proactive management of patients with extensive vascular invasion. Even more encouraging is that some patients reported in our series are alive without signs of metastatic disease over 1-year after their operation.
All patients in the series reported in our paper had open adrenalectomy, as the complex venous control precludes the use of a laparoscopic approach. Furthermore, the operations involved resection of surrounding viscera (i.e. nephrectomy / splenectomy/ distal pancreatectomy / liver resection) in two-thirds of patients. These findings confirm the general view that open adrenalectomy is the procedure of choice for patients with known or suspected malignant adrenal tumours and that good results obtained with laparoscopic procedures  are due to strict patient selection. Because of the increasing interest in laparoscopic and robotic adrenal surgery undertaken by surgeons with minimal/no previous exposure to patients with ACC, one should be very reserved in interpreting the favourable outcomes obtained by laparoscopic surgery in centres with large practice.
In summary, surgical treatment of adrenocortical cancer (ACC) remains poorly monitored, and it is likely that patients suffering from a condition with bleak prognosis continue to be treated in centres lacking the multidisciplinary support. Our paper highlights the possibility of obtaining reasonable survival with low morbidity when patients presenting with extreme local invasion (i.e. macroscopic extensive invasion into inferior vena cava) are treated in centres with appropriate facilities and experience that aim to set the benchmark for the care of patients with ACC.
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Radu Mihai, MD, PhD, FRCS and Consultant Endocrine Surgeon as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.