The Relationship Between PSA and Total Testosterone Levels in Men with Prostate Cancer - Beyond the Abstract

Rates of low serum testosterone (T) and prostate cancer (PC) increase with age, both impacting the health and quality of life of older men.1 Low T may impact men’s overall health, with increased risks of lower bone mineral density, pre-diabetes/diabetes, metabolic syndrome, and major adverse cardiovascular events.1,2 PC is an androgen-dependent cancer,3 likewise, so is prostate-specific antigen (PSA) production.4 There is likely a threshold level of serum T required for optimal PSA production, consistent with the previously described “saturation model” for T stimulation of the androgen receptor.1


For the last 30 years, PSA testing has been the cornerstone of PC screening, playing a critical role in diagnosing and monitoring men with PC. Studies have shown that the prevalence of PC increases in men with low T.3,5  Low serum total T level has been shown to be associated with a higher stage and higher PC grade. It is also worth noting that low T levels are also associated with an increased likelihood of extra-prostatic extension, positive surgical margins, and biochemical recurrence for patients treated with RP.6,7 Despite that, no society guideline includes serum T level measurement as an integral part of the screening for prostate cancer.

The present study aimed to evaluate the relationship between T and PSA in patients diagnosed with PC, finding that a low PSA level (<2 ng/ml) is a predictor of low T levels (50% of such men had total T levels <300 ng/dl), especially in patients with higher grade PC. These results suggest that clinicians should give consideration to measuring serum T levels when men with prostate cancer have low PSA values.

Given that PSA production is T-dependent and following on from the study’s findings, the question can be raised: should all PSA levels be indexed to a patient’s T values. If treatment decisions are to be made based on PSA values (prostate biopsy, definitive therapy, adjuvant therapy), should not the clinician be in possession of the most accurate PSA level? In that case, knowing that the patient is T replete would be an important consideration.

Written by: Jose M. Flores MD, MHA, John P. Mulhall, MD, MSc, FECSM, FACS, Sexual & Reproductive Medicine Program, Urology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

References:

  1. Kaplan AL, Hu JC, Morgentaler A, Mulhall JP, Schulman CC, Montorsi F. Testosterone Therapy in Men With Prostate Cancer. Eur Urol. 2016;69: 894-903.
  2. Mulhall JP, Trost LW, Brannigan RE, et al. Evaluation and Management of Testosterone Deficiency: AUA Guideline. J Urology. 2018;200: 423-32.
  3. Ahlering TE, My Huynh L, Towe M, et al. Testosterone replacement therapy reduces biochemical recurrence after radical prostatectomy. BJU Int. 2020;126: 91-96.
  4. Evans MJ. Measuring oncogenic signaling pathways in cancer with PET: an emerging paradigm from studies in castration-resistant prostate cancer. Cancer Discov. 2012;2: 985-94.
  5. Sarkar RR, Patel SH, Parsons JK, et al. Testosterone therapy does not increase the risks of prostate cancer recurrence or death after definitive treatment for localized disease. Prostate Cancer Prostatic Dis. 2020.
  6. Isom-Batz G, Bianco FJ, Jr., Kattan MW, Mulhall JP, Lilja H, Eastham JA. Testosterone as a predictor of pathological stage in clinically localized prostate cancer. J Urol. 2005;173: 1935-7.
  7. Ferro M, Lucarelli G, Bruzzese D, et al. Low serum total testosterone level as a predictor of upstaging and upgrading in low-risk prostate cancer patients meeting the inclusion criteria for active surveillance. Oncotarget. 2017;8: 18424-34.

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