My albeit short career in medical research has haphazardly and ironically kept me focused on your friend and mine—the prostate. More specifically, I have been driven to look at the possible biochemical processes underlying prostate cancer as well as the physical science behind our contemporary treatments of this particular malady. As a result, I can discuss the biggest points regarding our current standard of care for prostate cancer in the U.S.
Prostate cancer is currently noted as having the third highest rate of mortality amongst all other cancers, where 1 in 4 men are likely to experience the disease in their lifetime.1 While there are clearly many contributing factors to development of the disease, a general lack of biochemical knowledge has made cancer screening one of our societies only first lines of defense; and our screening just isn’t that great. As you might know, males over the age of 50 are recommended to have PSA screenings, which seeks to identify the concentration of an antigen in the patient’s blood. It’s minimally invasive, and doesn’t pose a significant risk to patients, but the practice can have an astounding 75% false-positive rate. This means that for every four men who are told they have an irregularly elevated PSA level, only one ends up with a diagnosis for prostate cancer.2 The vilifying factor is that the majority of individuals who’s lab results demonstrate elevated PSA are then referred to have a prostate biopsy, which is an invasive and costly procedure that requires anesthetics. 3 out of 4 men who receive these biopsies do not need them.
Luckily, new diagnostic tools are in development and the overall prognosis for prostate cancer, if caught early (low-risk), is quite good. Because of a reliably evident drop in prostatic zinc concentrations prior to any other external symptoms, a great deal of research is underway to create effective imaging tools to screen men’s prostatic fluid.3 My own thesis project focused on developing a contrast agent to be used with standard MRI that chelates with zinc and measurably affects the intensity of generated images. This has been safely demonstrated in mouse models.4 Hopefully, the practice will soon emerge on a broader stage following further investigation. Likewise, with improvements to modern chemotherapy and radiation treatments, the 10-year post-treatment rate of patients having no evidence of disease has reached upwards of 95% for patients with low-risk diagnoses—especially within the population that receives high dose rate (HDR) brachytherapy, an option that limits temporary radiation to affected tissues.5 So I feel confident in saying that, while current practices for prostate cancer could be improved, the future of it’s diagnosis and treatment is looking optimistic.
(1) Siegel, R. L.; Miller, K. D.; Jemal, A. Cancer Statistics, 2018. CA. Cancer J. Clin.2018, 68(1), 7.
(2) Wolf, A. M.; Wender, R. C.; Etzioni, R. B.; Thompson, I. M.; Amico, A. Vd; Volk, R. J.; Brooks, D. D.; Dash, C.; Guessous, I.; Andrews, K.; et al. American Cancer Society Guideline for the Early Detection of Prostate Cancer Update 2010. Cancer Journal, The2010,60(2), 70.
(3) Costello, L. C.; Franklin, R. B. The Clinical Relevance of the Metabolism of Prostate Cancer; Zinc and Tumor Suppression: Connecting the Dots. Mol. Cancer2006, 5, 17.
(4) Clavijo Jordan, M. V.; Lo, S.-T.; Chen, S.; Preihs, C.; Chirayil, S.; Zhang, S.; Kapur, P.; Li, W.-H.; De Leon-Rodriguez, L. M.; Lubag, A. J. M.; et al. Zinc-Sensitive MRI Contrast Agent Detects Differential Release of Zn(II) Ions from the Healthy vs. Malignant Mouse Prostate. Proc. Natl. Acad. Sci.2016, 113(37), E5464.
(5) Hauswald, H.; Kamrava, M. R.; Fallon, J. M.; Wang, P.; Park, S.; Van, T. High-Dose-Rate Monotherapy for Localized Prostate Cancer : 10-Year Results. Int. J. Radiat. Oncol. Biol. Phys.2016,94(4), 667.
I had no idea that the false-positive rate for PSA screening was so high! At the practice I scribed for, many men were still under the impression that the yearly direct physical examination of the prostate was the reliable method to use, and the provider I worked with had to inform several patients that this was not at all reliable as a diagnostic tool. Moving forward, do you think that the screening guidelines will still include a PSA followed by something such as imaging? Or do you suspect that prostate cancer screening will become similar in nature to the regular imaging women receive for breast cancer screening?
ReplyDeleteTo answer your question, Andrew, there are several more cogs to the machinery that I didn't quite mention. On one hand, yes, I would expect that as new non-invasive, more accurate, and less costly screening techniques are developed, the PSA will be phased out as a screening method. However, PSA levels are also recorded over time, wherein a PSA kinetics analysis can be conducted to monitor the progression or regression of disease. Essentially, you can measure a man's PSA doubling-time for example, and this will help you determine the aggressiveness of a particular cancer. So while PSA may not be a good measure for a positive diagnosis, it can be useful for informing on a timeline for treatment and what treatment options may be available. For this reason, PSA will likely stick around, and it may continue to be collected from as early on as possible in a clinical environment to best enable a physician to treat their patients. Perhaps, if imaging can fill this role as well, PSA could be entirely replaced. Hopefully that helps.
ReplyDeleteOtherwise, because the prognosis is so much better for individuals who catch their disease early on in it's development, I would expect that whatever testing measure we choose would be pushed as early and as broadly as possible, similar to a female breast exam. It's notable, however, to point out that PSA levels have not shown any real correlation for biological disease amongst men below the current recommended age. If we actually can find something more accurate, like something that might measure zinc levels in vivo, then we might expect screenings to be pushed much earlier in a mans life-- maybe at 40 or even 30.