SAT-313 Persistently Elevated Testosterone Levels in Prostate Cancer Despite Androgen Deprivation Reveals Underlying hCG Secretion From Coexisting Urothelial Carcinoma

Abstract Disclosure: B. Peng: None. M. Salam: Eli Lilly & Company, Bayer, Inc., Neurocrine Biosciences Inc., MBX Biosciences, Inc., Crinetics Pharmaceuticals, Inc., Mylan. Introduction: Urothelial carcinoma is the most common type of bladder cancer in developed countries. There are primary reports of urothelial carcinoma causing ectopic hCG secretion, as well as urothelial carcinoma of the prostate, but few reports relating to the consequences on the hormonal axis. Here, we present a case of persistently elevated testosterone levels despite androgen deprivation therapy (ADT) due to ectopic hCG secretion in a patient with urothelial carcinoma and prostate cancer. Clinical Case: An 87-year-old male with coexisting hormone sensitive prostate adenocarcinoma and bladder cancer was found to have metastases to the lungs and lymph nodes. Lung metastases were presumed to be from prostate primary based on prostate-specific membrane antigen PET scans and elevated PSA levels. CT-guided lymph node biopsy showed metastatic urothelial carcinoma. He underwent ADT with GnRH modulators. Despite this treatment, testosterone levels remained high to high-normal (pre-ADT-Testosterone was 731 ng/dL, [193-740 ng/dL]; post-ADT-Testosterone ranged between 663-919 ng/dL), even though LH and FSH levels were appropriately suppressed. Further testing ruled out non-classical congenital adrenal hyperplasia and testicular germ-cell tumor. Due to the persistently and inappropriately elevated levels of testosterone, other endogenous sources of testosterone were examined, and he was found to have a grossly elevated hCG level (6476 IU/L, [<5 IU/L]) which suggested a tumor producing ectopic hCG. He was started on chemotherapy for the urothelial cancer, and hCG levels dropped significantly (nadir 36 IU/L) with suppression of testosterone levels (nadir <5 IU/L) while on ADT. hCG staining to the lymph node biopsy was negative. Unfortunately, his cancer eventually progressed, and the patient passed approximately a year and a half later. Conclusion: Although it is not entirely clear which cancer was the cause of his ectopic hCG expression, response of testosterone levels with bladder cancer chemotherapy suggests urothelial cancer as the source. To our knowledge, this is the second reported case of persistently elevated testosterone during ADT that was found to be from secretion of hCG in patients with urothelial carcinoma and prostate cancer. It is important for clinicians to recognize this possibility when evaluating elevated testosterone levels despite ADT. References: Gagliano-Jucá T, Hirsch MS, McGregor BA, Basaria S. Failure of Androgen-Deprivation Therapy Due to Ectopic hCG Secretion. N Engl J Med. 2023;388(7):660-662. Sołek J, Kalwas M, Sobczak M, Dębska-Szmich S, Kupnicki P, Jesionek-Kupnicka D. Urothelial carcinoma of the prostate with raised β-hCG levels: a case report. J Med Case Rep. 2022;16(1):238. Presentation: Saturday, July 12, 2025