MSACL 2025 Abstract

Prostate Cancer: Are Male Testosterone Assays Fit For Purpose?

Jonathan S Atkins (1), Brian G Keevil (1), Laura Owen (2), Phillip Monaghan (3), Carol Evans (4), Mark Saunders (4), Thomas Morris (5), Rachel Marrington (6) and James M Hawley (1,7)
(1) Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK (2) Salford Royal Hospital, Northern Care Alliance NHS Foundation Trust, Salford, UK (3) The Christie Partnership, Christie NHS Foundation Trust, Manchester, UK (4) Department of Medical Biochemistry and Immunology, University Hospital of Wales, Cardiff, UK (5) St. Georges’ University Hospital NHS Foundation Trust, London, UK (6) Birmingham Quality (UK NEQAS), Birmingham, UK (7) Laboratory of Medical Science, Medical Research Council, London, UK

James Hawley, MS (Presenter) Wythenshawe Hospital

Presenter Bio: I work as a Principal Clinical Scientist at Wythenshawe Hospital, Manchester, UK and I'm also currently undertaking a PhD at the University of Birmingham, UK. I have over 7 years experience with LC-MS/MS and 10 years in clinical diagnostics. In my day-to-day role I develop new LC-MS/MS assays for routine clinical use and help troubleshoot our existing assays. My PhD is looking at using mass spectrometry in combination with machine learning to interrogate the steroid metabolome in order to improve the diagnosis of adrenal cortical carcinoma.

I started as a Senior Scientist at Wythenshawe Hospital, Manchester, UK in May 2013 and have not looked back since. I now have over 7 years’ experience of developing, validating, verifying and troubleshooting LC-MS/MS assays. In this time, I have acquired a keen interest in small molecule analysis; in particular, different forms of sample preparation and the accurate quantification of steroid hormones. At Wythenshawe I have developed many of our routine LC-MS/MS assays that have been assessed against ISO 15189 and I have been the first author on several LC-MS/MS themed articles in peer reviewed journals. In 2018 I moved from Senior to Principal Clinical Scientist, with that I now enjoy having greater responsibility for training junior members of staff and supervising LC-MS/MS based projects.

My experience with LC-MS/MS and clinical diagnostics has enabled me to develop a strong working network with many UK based scientists and clinicians; in addition I have also collaborated with laboratories based in Italy, Germany, South Africa and the United States.

My doctorate work focuses on combining tandem mass spectrometry with machine learning to help differentiate adrenal carcinomas from adenomas. This will ultimately improve patient outcome by either preventing unnecessary surgery or reducing the time to diagnosis.

Relevant Financial Disclosures (within past 24 months, reported on Mar 19, 2025) No relevant financial relationship(s) to disclose. Conflict mitigation NOT REQUIRED.

BACKGROUND:
Androgen-deprivation therapy (ADT) is recommended to treat advanced prostate cancer. Evidence suggests that lowering testosterone concentrations below 0.7 nmol/L (20 ng/dL) improves patient survival and reduces disease progression. To date, limited work has been undertaken to assess the performance of testosterone assays in this concentration range in males receiving ADT therapy.

DESIGN:
Surplus serum from males taking ADT was obtained prior to disposal from a tertiary cancer centre. Samples were anonymised and distributed to collaborating laboratories for testosterone analysis by 5 routine assays. Simultaneously, we collaborated with UK NEQAS to arrange a small survey to assess how male prostate cancer samples are processed in the UK.

RESULTS:
The UK NEQAS survey indicated that 4/64 laboratories in the UK routinely refer samples for LC-MS/MS analysis in ADT patients. We observed considerable variation across routine immunoassay platforms compared to LC-MS/MS. All routine immunoassays displayed a mean positive bias, this ranged from 0.12 to 0.75 nmol/L (3.5 to 21.6 ng/dL).

SUMMARY:
Despite the clinical importance of suppressing testosterone in ADT, our results suggest this is a cohort of patients that is often overlooked. The performance of many routine immunoassays in this low nanomolar range is sub-optimal for these patients.