Background: The association between Lynch syndrome (LS) and a higher risk of upper tract urothelial carcinoma is well established, but its effect on the risk of bladder and kidney cancers remains controversial. This review aimed to compare the relative risk (RR) of bladder and kidney cancer in confirmed LS germline mutation carriers compared to the general population. Methods: Medline, Embase, Cochrane Central, and Google Scholar were searched on 14 July 2022 for studies published in English that reported on the rates of urological cancer in adults with confirmed LS germline mutation. The quality of included studies was assessed using Cochrane’s tool to evaluate risk of bias in cohort studies. Random effects meta-analysis estimated the pooled relative risk of bladder and kidney cancer in LS carriers compared to the general population. The quality of the overall evidence was evaluated using GRADE. Results: Of the 1839 records identified, 5 studies involving 7120 participants from 3 continents were included. Overall, LS carriers had a statistically significantly higher RR of developing bladder cancer (RR: 7.48, 95% CI: 3.70, 15.13) and kidney cancer (RR: 3.97, 95% CI: 1.23, 12.81) compared to unaffected participants (p < 0.01). The quality of the evidence was assessed as “low” due to the inclusion of cohort studies, the substantial heterogeneity, and moderate-to-high risk of bias. Conclusion: Lynch syndrome is associated with a significant increase in the relative risk of kidney and bladder cancer. Clinicians should adopt a lower threshold for germline mutation genetic testing in individuals who present with bladder cancer. Further studies evaluating the role and cost-effectiveness of novel urine-based laboratory tests are needed. High-quality studies in histologically proven renal cell carcinoma and their underlying germline mutations are necessary to strengthen the association with LS.

Background: The maximum standardised uptake value (SUV_max) can potentially be affected by the uptake period during PSMA PET imaging. The optimal image acquisition period for 2-(3-{1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (¹⁸F-DCFPyL)PSMA PET/CT is yet to be established. This study aims to evaluate the effect of the uptake period on the SUV_max in diagnosing localised, clinically significant prostate cancer using ¹⁸F-DCFPyL-PSMA PET/CT. Methods: Sixty biopsy-naive men with one or more PI-RADS 4 or 5 lesions of at least 10 mm on multiparametric MRI (mpMRI) were enrolled to undergo ¹⁸F-DCFPyL-PSMA PET/CT. SUV_max was prospectively measured following an uptake period of 60, 90 and 120 min post injection of ¹⁸F-DCFPyL-PSMA radiotracer. Concordance with biopsy results or final histopathology was recorded. Results: Mean absolute differences in SUV_max at 60 vs. 90, 60 vs. 120, and 90 vs. 120 min uptake periods were 3.23 (SD 4.76), 4.53 (SD 7.33), and 3.24 (SD 4.56), respectively. This represents a statistically significant systematic increase in SUV_max (p-value < 0.001) with increasing uptake period. The interval between the uptake period of 60 vs. 120 min represented the largest SUV_max change of 29.98%. Conclusions: The SUV_max is a dynamic variable significantly affected by uptake period. Our study supports image acquisition at 120 min following injection of ¹⁸F-DCFPyL radiotracer. Further studies are needed to determine if this acquisition period can be applied to other Fluorine-18 based PSMA radiotracers.

A 63-year-old woman with multiple endocrine neoplasia type 2A (MEN2A) presented with recurrent spells of headaches, sweats and palpitations decades after right adrenalectomy for phaeochromocytoma, and total thyroidectomy for medullary thyroid cancer. She was hypertensive and in sinus rhythm. DOTA-TATE positron-emission tomography (PET) demonstrated a 12mm enhancing left adrenal incidentaloma. 24 hours urine catecholamines, and multiple plasma metanephrine and normetanephrine measurements were all within normal reference ranges. Based on her symptoms and imaging findings, left adrenalectomy was performed and found a 40 mm phaeochromocytoma. Her symptoms have since completely resolved and plasma metanephrine is now undetectable MEN2-associated phaeochromocytomas are often bilateral and may be metachronous. Patients at high risk of phaeochromocytoma who develop symptoms of catecholamine excess should be carefully evaluated even if plasma or urinary metanephrines are within the normal reference range. Biochemical reference ranges for metanephrines need to be adjusted accordingly in patients who have had prior unilateral total adrenalectomy.