What’s known on the subject? and What does the study add?

Solitary adrenal metastasis from primary renal cell carcinoma is rare, particularly when occurring in the contralateral adrenal gland. Traditionally an open adrenalectomy has been the gold-standard treatment. This study introduces the use of a retroperitoneal laparoscopic approach and reports on the perioperative and oncological outcomes of four patients who underwent this technique.

Introduction

Renal cell carcinoma (RCC) is the seventh most diagnosed malignancy in Australia with approximately 4,000 new cases annually (1). RCC can be an aggressive cancer because 1 in 3 patients develop distant metastatic disease following curative-intent surgical extirpation (2). Common sites of RCC metastasis include the lymph nodes, liver, lung, brain, and bones (3). Metastasis to the adrenal glands following nephrectomy is uncommon, and contralateral adrenal metastatic disease is particularly rare. In autopsies of 400 patients who have undergone nephrectomy for RCC, only 2.5% of the patients were identified to have metastatic disease in the contralateral adrenal gland (4).

For benign adrenal disorders requiring adrenalectomy, laparoscopic surgery is now the gold standard and can be performed through transperitoneal or retroperitoneal approaches (5). An open approach is still advocated for malignant adrenal disease (6). The retroperitoneal laparoscopic approach is a new technique that has potential advantages of lower morbidity compared with both open and transperitoneal procedures. Studies have shown that the retroperitoneal approach, where intraperitoneal organs are avoided, results in reduced operating time, reduced blood loss, superior postoperative pain scores, and reduced length of stay (6-8). However, only a few studies have described the use of this retroperitoneal approach in performing adrenalectomy for solitary metastatic RCC in the adrenal gland.

At our center, a laparoscopic fellowship-trained urological surgeon performs on average 27 retroperitoneal laparoscopic upper tract cases per year over the last 11 years and performs laparoscopic adrenalectomy also through a retroperitoneal approach.

Materials and Methods

We reviewed a prospectively collected single-surgeon series of retroperitoneal laparoscopic upper tract cases and identified four patients undergoing laparoscopic retroperitoneal adrenalectomy for solitary adrenal metastasis from RCC between 2015 and 2020. Demographic, clinical, and histopathological data were retrospectively collected from electronic health records.

Ethics approval was obtained from the Hunter New England Human Research Ethics Committee in conjunction with the Central Coast Local Health District (2020/ETH02908).

Our technique for laparoscopic retroperitoneal adrenalectomy is similar to previous descriptions (9,10). The patient is placed in a lateral decubitus position with the operating table manipulated to maximize the distance between the 12^th rib and the iliac crest. A four-port retroperitoneal technique is used with an initial 1.5-cm skin incision made below the inferior edge of the tip of the 12^th rib, where the muscle and fascial layers are bluntly entered with finger dissection, to form a space for balloon insufflation under vision, creating the retroperitoneal working space using a Spacemaker^TM Pro Access Dissector System. The balloon is deflated, and a laparoscope is placed thereafter. Three other laparoscopic ports are then placed parallel inferiorly to the 12^th rib in line with the primary port site incision (Figure 1). A 10-mm Medtronic Endo Retract II is used, Gerota’s fascia is incised, and the perinephric fat is dissected around the adrenal gland in a “no-touch technique” of the adrenal gland. The adrenal vein is double clipped and then divided, and the adrenal gland is removed with a 10-mm Covidien Endocatch bag.

Results

The operative and histopathological features of the primary RCC removed for the patients with subsequent adrenal metastatic disease are summarized in Table 1. Three of the four patients had undergone laparoscopic radical nephrectomy, and one patient had an open partial nephrectomy. All were pathologically confirmed clear cell RCC with clear surgical margins.

The mean age of the four patients at initial nephrectomy was 61±10.8 years. The interval from nephrectomy to the diagnosis of adrenal metastasis was 52.6 (13.6-121.0) months, as outlined in Table 2. Three of the four patients were identified to have metastatic disease in the adrenal gland on the contralateral side to their initial nephrectomy.

All four patients were asymptomatic when metastatic diseases were identified by routine surveillance computer tomography. Figure 2 displays representative slices of the initial radiology of the solitary adrenal tumors identified in four patients.

All four patients underwent retroperitoneal laparoscopic adrenalectomy. Perioperative outcomes are described in Table 3. The mean age and body mass index of the patients was 70±6.2 years and 38.3±4.3 kg/m², respectively. The mean operating time was 140±8.7 min. The mean estimated blood loss was 163±124.4 mL, and no blood transfusions and open conversions were required. The mean hospital length of stay was 2.3±0.4 days. The procedures in three of the four patients were partly performed by a trainee.

Postoperative complications were classified based on the classification. Only one Clavien-Dindo grade 1 complication was recorded within the 90-day postoperative period. This involved superficial wound dehiscence at a laparoscopic port site that required a community nurse for wound care. Antibiotics were not prescribed. The wound was inspected 2 weeks postoperatively and had healed by secondary intention. No patients were reported to have had endocrine complications as a result of adrenalectomy during this period.

Table 4 lists the pathology of the excised adrenal glands. All tumors were consistent with metastatic clear cell RCC and International Society of Urologic Pathologists grade 3. All surgical margins were clear.

Oncological outcomes are summarized in Table 5. At the time of writing, three of the four patients are alive and remain disease-free. Two patients underwent adjuvant chemotherapy for suspected local recurrence identified on surveillance imaging. The patient who developed widespread metastatic disease approximately 20 months post-adrenalectomy died. This was discovered following a pathological fracture of the right femur. The patient underwent adjuvant chemotherapy and radiotherapy. From the time of diagnosis of the metastatic disease, the patient survived another 25 months before he died. The oncological outcomes of each patient are outlined in Table 5.

Discussion

In this case series at our institution, solitary adrenal metastatic RCC recurrence post-radical nephrectomy was rarely encountered. This is consistent with the published literature, in which retroperitoneal laparoscopic adrenalectomy for solitary adrenal RCC recurrence has not been well described. A dataset of a small series showed the safety of this procedure. Of interest, in our case series, the recurrence in three of the four patients found in the contralateral adrenal gland reflects the unpredictability of the disease. The underlying pathophysiology of why the RCC spread to the contralateral adrenal gland is unknown. It may be due to the rich blood supply of the organ in conjunction with a possible affinity of the RCC cells to adrenal tissues (11).

The nature of metastatic RCC is varied. Metastatic burden heavily influences survival. The mean survival in patients with heavy metastatic burden is approximately 11 months (12). In patients with solitary metastasis, approximately 30% are alive at 5 years (12). The role of local therapy for an oligometastatic disease is unclear. Utsumi et al. (13) reported that surgery for adrenal RCC metastasis achieved a curative outcome in 1 of 3 patients.

Although surgical management of solitary adrenal tumors from metastatic RCC is advocated, there is no clear evidence on how this should be performed-open or laparoscopic, and if minimally invasive, transperitoneal or retroperitoneal. Traditionally, open adrenalectomy was recommended for the treatment of malignant adrenal lesions. To our knowledge, no studies have compared retroperitoneal versus transperitoneal laparoscopic surgery in the management of solitary adrenal RCC metastasis. Studies of retroperitoneal against transperitoneal laparoscopic renal surgery have shown improved perioperative outcomes including blood loss, length of stay, and postoperative complications (14). This is hypothesized as caused by the earlier exposure of the critical anatomical structures gained in a retroperitoneal approach and lower risk of injuring intraperitoneal organs plus avoidance of adhesions from previous intra-abdominal surgery.

Several studies have now demonstrated comparable oncological and survival outcomes of laparoscopic and open adrenalectomy for patients with adrenal tumors, though not specifically related to the retroperitoneal approach (15,16). In a meta-analysis comparing transperitoneal laparoscopic adrenalectomy with the retroperitoneal approach in the management of pheochromocytoma in 145 patients, Jiang et al. (16) found that that the retroperitoneal approach was superior (17). Patients who underwent retroperitoneal laparoscopic adrenalectomy were associated with shorter operating times, less intraoperative blood loss, and a shorter duration of stay in hospital. No difference was found in the postoperative complications between groups (16). Chai et al. (17) performed a systematic review comparing laparoscopic retroperitoneal, laparoscopic intraperitoneal, and robotic adrenalectomy for adrenal tumors, but not specifically for solitary adrenal RCC metastasis. The review suggested that the laparoscopic retroperitoneal approach was superior (17). In this study, the perioperative outcomes demonstrated that this technique is associated with minimal blood loss and short operating time and length of stay. To our knowledge, no studies have compared the oncological outcomes and survival of patients who have undergone laparoscopic retroperitoneal adrenalectomy with other approaches. Survival outcomes at 5 years following removal of a solitary adrenal metastasis from RCC varied between 14% and 38% (18). A systematic review comparing disease-free survival, local recurrence, and mortality between laparoscopic and open adrenalectomy for adrenocortical carcinoma found no difference in these outcomes (19).

Despite the rapid advancements in systemic chemotherapeutic therapies for metastatic RCC, reports of long-term disease-free survival for metastatic RCC are limited. Thus, the finding that 3 of 4 patients treated surgically for oligometastatic RCC remain recurrence-free at the time of this study is promising.

To our knowledge, this is the largest case series of laparoscopic retroperitoneal adrenalectomy for solitary RCC metastasis to the adrenal gland. Our case series reports perioperative and oncological outcomes over a median follow-up of 40 (20-53) months. This study shows the technique to be safe with disease-free survival comparable with published literature for other extirpative techniques.

Study Limitations

This retrospective case series study provides data on a rare clinical scenario managed by a surgical approach not widely utilized. This study does not answer what is the optimal management strategy for solitary RCC metastasis to the adrenal gland. Nor does it provide evidence for this technique over other surgical techniques in those electing for surgical intervention.

Although three of the cases were performed partly by trainees, the operating time, blood loss, low perioperative complication rate, length of stay, and absence of positive margins suggest that this is a reproducible technique even for metastatic disease in the adrenal gland. Ideally, larger, prospective randomized studies will need to be undertaken to evaluate and compare this technique against others-transperitoneal, open, and robot-assisted techniques. However, these studies are difficult to perform prospectively given the rare nature of isolated adrenal RCC metastasis.

Conclusion

In this study, we have shown that laparoscopic retroperitoneal adrenalectomy is a safe procedure for the management of solitary adrenal metastatic disease from RCC. Although this is a small series with no control arm, the oncological outcomes are encouraging. Thus, randomized trials are needed to assess the optimal management for solitary RCC metastasis to the adrenal gland, in which surgical technique is optimal.

Ethics

Ethics Committee Approval: Ethics approval was obtained from the Hunter New England Human Research Ethics Committee in conjunction with the Central Coast Local Health District (2020/ETH02908).

Informed Consent: Retrospective study.

Peer-review: Externally peer-reviewed.

Authorship Contributions

Surgical and Medical Practices: G.A., M.L.J., Concept: C.P., M.L.J., Design: C.P., M.L.J., Data Collection or Processing: C.P., M.L.J., Analysis or Interpretation: C.P., G.A., M.L.J., Literature Search: C.P., Writing: C.P., G.A., M.L.J.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declare that they have no relevant financial.