Abstract 481: Utility of hCG as a biomarker of treatment response in advanced urothelial cancer: A population based series at Akershus University Hospital, Norway
Authors: Puco Katarina , Bjerner Johan , Müller Stig , Lilleaasen Gunder M. , Husby Haldor , Røed-Undlien Mattias , Heinrich Daniel , Dahl Fredrik A. , Røe Oluf D. , Oldenburg Jan 
Published: July 2021

Abstract
Background
Treatment options in patients with advanced urothelial carcinoma (aUC) have improved significantly in the last decade, highlighting the need for adequate biomarkers. High tumor CGB5 mRNA, encoding Human Chorionic Gonadotrophin β (hCGβ) and elevated serum free hCGβ are related to poorly differentiated UC and correlated to poor prognosis. Hypothetically, hCG could be used as serum tumor marker in aUC patients.
Patients and methods
From December 2018 to November 2020, serum hCG levels were measured in 62 aUC patients referred to the oncology department, Akershus University Hospital. Median age 68 years, 42 male and 21 female. Total serum hCG (intact hCG + free hCGβ) was measured by electrochemiluminescence immunoassay “ECLIA”. In order to compensate for hypogonadism-related increases, hCG ≥ 50% above upper normal limit was considered as being elevated (hCG+), otherwise it was considered negative (hCG-). Further, hCG levels were defined as increasing (↑) or declining (↓) at treatment evaluation and follow up. Radiologically, patients had newly diagnosed disease (ND), progressive disease (PD) or non-PD (stable disease, partial or complete response) according to RECIST 1.1 at evaluation and follow up. hCG values were correlated with radiological findings at diagnosis, during and after treatment. Statistics by 2 x 2 contingency table and Chi Square (χ2) test.
Results
At least one hCG+ value was measured in 38 of 62 patients (61%), range 0.8 - 62,700 IU/L, and hCG was elevated in 22 of 43 patients (51%) with available hCG value at diagnosis, mean 15 IU/L (range 0.8 - 58). In total 213 hCG measurements could be correlated with concomitant CT or MR scans. At radiologic evaluation of ND & PD, hCG+/↑ and hCG -/↓ was found in 62 and 50 measurements, respectively. At non-PD, hCG -/↓ and hCG+/↑ was found in 94 and 7 measurements, respectively. For ND & PD versus non-PD, hCG showed a sensitivity and specificity of 55% and 93% respectively (95% CI 46-65% and 86-97%), positive and negative predictive value of 90% and 65% (95% CI 81-95% and 60-70%) and accuracy of 73% (95% CI 66-79%), χ2: p&lt;0.00001. Exclusion of the 24 patients without elevated hCG showed improved sensitivity 76% at the cost of lower specificity 82% (95% CI 65-85% and 66-92% respectively), positive and negative predictive value 90% and 63% (95% CI 82-95% and 52-72%) and accuracy of 78% (95% CI 70-86%), χ2: p&lt;0.00001.
Conclusions
Ectopic hCG production was observed in 61% of aUC patients with a strong and meaningful correlation between hCG changes and radiologic evaluation of treatment response. Intriguingly, hCG increase sometimes preceded radiologic PD, thus categorized as “false positive” until subsequent radiologic PD. hCG appears to be a promising tumor marker for biochemical treatment response evaluation in aUC patients.
Citation Format: Katarina Puco, Johan Bjerner, Stig Müller, Gunder M. Lilleaasen, Haldor Husby, Mattias Røed-Undlien, Daniel Heinrich, Fredrik A. Dahl, Oluf D. Røe, Jan Oldenburg. Utility of hCG as a biomarker of treatment response in advanced urothelial cancer: A population based series at Akershus University Hospital, Norway [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 481.