Adrenal vein sampling versus CT scan to determine treatment in primary aldosteronism: an outcome-based randomised diagnostic trial.

BACKGROUND: The distinction between unilateral aldosterone-producing adenoma or bilateral adrenal hyperplasia as causes of primary aldosteronism is usually made by adrenal CT or by adrenal vein sampling (AVS). Whether CT or AVS represents the best test for diagnosis remains unknown. We aimed to compare the outcome of CT-based management with AVS-based management for patients with primary aldosteronism. METHODS: In a randomised controlled trial, we randomly assigned patients with aldosteronism to undergo either adrenal CT or AVS to determine the presence of aldosterone-producing adenoma (with subsequent treatment consisting of adrenalectomy) or bilateral adrenal hyperplasia (subsequent treatment with mineralocorticoid receptor antagonists). The primary endpoint was the intensity of drug treatment for obtaining target blood pressure after 1 year of follow-up, in the intention-to-diagnose population. Intensity of drug treatment was expressed as daily defined doses. Key secondary endpoints included biochemical outcome in patients who received adrenalectomy, health-related quality of life, cost-effectiveness, and adverse events. This trial is registered with ClinicalTrials.gov, number NCT01096654. FINDINGS: We recruited 200 patients between July 6, 2010, and May 30, 2013. Of the 184 patients that completed follow-up, 92 received CT-based treatment (46 adrenalectomy and 46 mineralocorticoid receptor antagonist) and 92 received AVS-based treatment (46 adrenalectomy and 46 mineralocorticoid receptor antagonist). We found no differences in the intensity of antihypertensive medication required to control blood pressure between patients with CT-based treatment and those with AVS-based treatment (median daily defined doses 3·0 [IQR 1·0-5·0] vs 3·0 [1·1-5·9], p=0·52; median number of drugs 2 [IQR 1-3] vs 2 [1-3], p=0·87). Target blood pressure was reached in 39 (42%) patients and 41 (45%) patients, respectively (p=0·82). On secondary endpoints we found no differences in health-related quality of life (median RAND-36 physical scores 52·7 [IQR 43·9-56·8] vs 53·2 [44·0-56·8], p=0·83; RAND-36 mental scores 49·8 [43·1-54·6] vs 52·7 [44·9-55·5], p=0·17) for CT-based and AVS-based treatment. Biochemically, 37 (80%) of patients with CT-based adrenalectomy and 41 (89%) of those with AVS-based adrenalectomy had resolved hyperaldosteronism (p=0·25). A non-significant mean difference of 0·05 (95% CI -0·04 to 0·13) in quality-adjusted life-years (QALYs) was found to the advantage of the AVS group, associated with a significant increase in mean health-care costs of €2285 per patient (95% CI 1323-3248). At a willingness-to-pay value of €30 000 per QALY, the probability that AVS compared with CT constitutes an efficient use of health-care resources in the diagnostic work-up of patients with primary aldosteronism is less than 0·2. There was no difference in adverse events between groups (159 events of which nine were serious vs 187 events of which 12 were serious) for CT-based and AVS-based treatment. INTERPRETATION: Treatment of primary aldosteronism based on CT or AVS did not show significant differences in intensity of antihypertensive medication or clinical benefits for patients after 1 year of follow-up. This finding challenges the current recommendation to perform AVS in all patients with primary aldosteronism. FUNDING: Netherlands Organisation for Health Research and Development-Medical Sciences, Institute of Cardiology, Warsaw.

Indium-111-labeled girentuximab immunoSPECT as a diagnostic tool in clear cell renal cell carcinoma.

BACKGROUND: Improved and more frequent radiologic evaluation has resulted in increased identification of renal masses of unknown origin, which frequently pose a diagnostic dilemma for urologists. OBJECTIVE: Carbonic anhydrase IX (CAIX) is an antigen ubiquitously expressed in clear cell renal cell carcinoma (ccRCC). The specific and high level of expression in ccRCC makes CAIX an excellent target for imaging ccRCC lesions. We present our experience with immuno-single-photon emission computed tomography (immunoSPECT) imaging with the indium-111 ((111)In)-labeled anti-CAIX antibody girentuximab in patients presenting with either a primary renal tumor or a history of ccRCC and lesions suspect for metastases during follow-up. DESIGN, SETTING, AND PARTICIPANTS: Twenty-nine patients received 100-200 MBq (111)In-labeled girentuximab. Whole-body and single photon emission computed tomography (SPECT) images were acquired after 4-7 d. INTERVENTION: Injection with (111)In-girentuximab and image acquisition after 4-7 d. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Accuracy of (111)In-girentuximab immunoSPECT. RESULTS AND LIMITATIONS: Distinct uptake of (111)In-girentuximab was seen in 16 of 22 patients presenting with a renal mass. All renal masses proven to be ccRCC after resection (n=15) were detected with (111)In-girentuximab. Suspect lesions of six patients showed no uptake of (111)In-girentuximab. In these patients, ccRCC was not found, nor progression occurred. Seven patients with a history of ccRCC and possible metastatic lesions on follow-up computed tomography scans were imaged with (111)In-girentuximab. In four of these patients, the lesions showed preferential uptake of (111)In-girentuximab and local or systemic treatment was initiated. In three other cases, no (111)In-girentuximab targeting was seen. During follow-up of these three patients, one showed progression, for which systemic treatment was started. In the two other patients, no progression occurred, suggesting a benign nature. CONCLUSIONS: (111)In-girentuximab immunoSPECT can be used to detect ccRCC lesions in patients with a primary renal mass and to clarify the nature of lesions suspect for metastases in patients with a history of ccRCC.

Phase 1 radioimmunotherapy study with lutetium 177-labeled anti-carbonic anhydrase IX monoclonal antibody girentuximab in patients with advanced renal cell carcinoma.

BACKGROUND: Patients with metastatic clear cell renal cell carcinoma (ccRCC) have a dismal prognosis. Therefore, new and less toxic treatments are needed. OBJECTIVE: We determined the maximum tolerated dose (MTD) and potential therapeutic efficacy of multiple infusions of lutetium 177 ((177)Lu)-girentuximab (cG250) on various dose levels in a phase 1 trial in patients with progressive metastasized ccRCC. DESIGN, SETTING, AND PARTICIPANTS: In this uncontrolled case series in 23 patients with progressive ccRCC metastases, cG250 accumulation was verified by diagnostic indium 111-cG250 imaging. Patients then received a high-activity dose of (177)Lu-cG250. INTERVENTION: Groups of three patients received (177)Lu-cG250, starting at a dose level of 1110 MBq/m(2)(177)Lu-cG250, with dose increments of 370 MBq/m(2) per group. In the absence of persistent toxicity, progressive disease, and accelerated blood clearance, patients were eligible for retreatment after 3 mo with 75% of the previous activity dose. Patients could receive a total of three treatment cycles. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Determination of the MTD was the primary and therapeutic efficacy was the secondary outcome measurement of the study. RESULTS AND LIMITATIONS: The MTD was 2405 MBq/m(2) because higher doses resulted in dose-limiting myelotoxicity. Some patients received second (13 of 23 [56%]) and third (4 of 23 [17%]) treatment cycles. Most patients (17 of 23 [74%]) demonstrated stable disease 3 mo after the first treatment, and one patient showed a partial response that lasted for 9 mo. Mean growth of target tumor lesions was reduced from 40.4% (95% confidence interval [CI], ± 17.0) during the last 3 mo before study entry to 5.5% (95% CI, ± 5.3; p<0.001) at 3 mo after the first treatment cycle. No major nonhematologic side effects were observed. CONCLUSIONS: (177)Lu-cG250 radioimmunotherapy in metastatic ccRCC patients is well tolerated at an activity dose level as high as 2405 MBq/m(2) (MTD). Radioimmunotherapy with (177)Lu-cG250 may stabilize previously progressive metastatic ccRCC.