Background
Succinate dehydrogenase type B (SDHB) mutation carriers are at risk of phaeochromocytoma and paraganglioma from a young age. It is widely recommended that patients enter a lifelong screening program to detect tumours, as metastatic disease is associated with high mortality.
Objective
The purpose of this study was to describe screen-detected tumours in SDHB mutation carriers enrolled in a screening-program, to assess predictors of disease diagnosis, and to compare outcomes in screen-detected tumours to probands.
Methods
This was a multi-centre study of clinical data collected by both retrospective and ongoing prospective follow-up in genetics clinics at Royal North Shore Hospital (RNSH), Prince of Wales Hospital (PoWH) and the Royal Hobart Hospital (RHH). Probands were defined as the first individual in a family to be diagnosed with a genetic condition after presenting with a tumour. Annual clinical assessment of catecholaminergic symptoms, blood pressure and biochemical measurements of plasma metanephrines or urinary catecholamines were included in the surveillance protocols of all three centres. RNSH and PoWH followed the Cancer Institute NSW guidelines for two yearly MRI base of skull to coccyx imaging surveillance (https://www.eviq.org.au) while RHH surveillance consisted of second yearly imaging with ultrasounds neck and abdominal and after age 18 with four yearly fluorodeoxyglucose (18F) positron emission tomography/computed tomography (18F-FDG PET/CT).
Results
182 SDHB mutation carriers from 59 families undergoing routine surveillance were assessed. Median age at first surveillance was 33 years (range 1 to 81 years). There were 33 probands and 149 non-probands. Median duration of follow up was 6.0 ± 0.4 years. Tumours were detected in 30 of 149 (20%) non-probands undergoing screening (age range 9-76 y). Male gender and young age were associated with detection of tumours. Patients with screen-detected tumours were less likely to be associated with metastatic disease compared to probands. Estimated 10-year metastasis-free survival was 66% for probands and 84% for non-probands with screen-detected tumours (p=0.0268). Screen-detected tumours were smaller than those in probands (median 28 ± 4.2 mm versus 45 ± 8.3 mm respectively, p=0.004). Tumour size 40mm was associated with progression to metastatic disease (OR 16.0, 95% CI 2.3-177.5, p=0.003). Patients with screen-detected tumours had lower mortality compared to probands: 10-year overall survival was 79% for probands and 100% for non-probands (p=0.0286).
Conclusion
This is the largest Australian study to describe screen-detected tumours and outcomes for SDHB mutation carriers in a surveillance program. Patients with screen-detected tumours had smaller tumours, reduced risk of metastatic disease and lower mortality compared to probands. Tumour size 40mm was associated with increased risk of metastatic progression. Our results suggest that SDHB mutation carriers should undertake surveillance to improve clinical outcomes.