Not long ago, I posted a blog on the ability of androgen deprivation therapy (ADT) to boost the effectiveness of radiation therapy for prostate cancer. This synergistic effect is very important for men with intermediate or higher risk cancer who can’t have (or don’t want) radical prostatectomy, since the greater the risk, the more likely cancer will recur. Adding ADT justifiably raises hopes for cure.

 

Monitoring treatment success

Hope can be a fragile thing. After a man is treated for prostate cancer he must monitor his PSA (prostate specific antigen) for the rest of his life, regardless of the treatment method. Initially, PSA drops dramatically from its pre-treatment level, and a protocol is established to periodically keep an eye it, usually with a yearly blood test. For example, after radical prostatectomy, PSA is expected to drop to a level of 0.1 ng/mL or below, which is defined as undetectable, and remain there for the rest of the patient’s life. A long-term undetectable PSA is associated with cure.

 

Following whole gland radiation, it usually takes 12 or more months for PSA to drop to its lowest point (nadir) because it takes time for radiation to damage cancer’s DNA to the point where each cell dies off or cannot reproduce itself; once nadir is reached, the hope is it will remain there. However, after radiation + ADT, nadir is reached very quickly, often at undetectable levels using the above definition. That’s how powerfully ADT helps.

 

Just as with prostatectomy, a persistently undetectable PSA after radiation + ADT is presumed to mean success. But unlike prostatectomy, there is no established PSA nadir following radiation therapy that has been universally associated with cure.[i] In any case, the first red flag for surgery or radiation failure will be a detectable or rising PSA, respectively. This is called biochemical recurrence (BR), meaning a suspicious biomarker that prostate cancer is back. Hopes may be dashed, since patients who develop BR have a poorer prognosis than those who don’t.

 

Very low PSA after radiation + ADT as an outcome predictor

I recently came across a June, 2019 published study[ii] out of Memorial Sloan Kettering that caught my interest. The team of researchers reviewed 2566 intermediate and high-risk prostate cancer patients who were treated with radiation plus ADT between 1990-2012. For 1275 patients, their pretreatment PSA was less than 20 ng/mL. The average follow-up period was 7.6?years. The purpose of the review was to analyze post-treatment PSA dynamics and correlate them with outcomes, including biochemical recurrence, metastasis (distant spread), death from prostate cancer, and death from any other cause.

 

I was surprised to learn that a very low PSA level – well below the “undetectable” level of 0.1 ng/mL—at a mere three months after treatment meant likely treatment failure and worse outcomes. In the language of the article title, this is an “early biochemical predictor of survival.”

 

Study finding

According to the authors, “A PSA value ?0.09?ng/mL early after [radiation therapy + ADT] completion is associated with significantly worse prognosis across all clinical outcomes…” including metastasis and death specifically due to prostate cancer. On the other hand, the news isn’t totally pessimistic. They also found that if the early (three month) PSA was reduced by 95% or more from the pretreatment level, the patient had less risk of BR and metastasis. The team concluded, “These findings may identify patients who require early aggressive systemic management for high-risk disease.”

 

To sum up, a PSA as low as 0.09 ng/mL three months after radiation plus ADT can be an indicator of recurrence and lower survival chances. While this may seem discouraging, it’s important to keep in mind that the cases that were reviewed involved intermediate to high risk prostate cancer, which is by definition more challenging to treat. It’s also important to embrace optimism, given the amazing advances that are occurring with improved chemotherapy, immunotherapies, gene therapy, and the kind of personalized targeted treatments that are part of a new branch of medicine called theranostics.

This all circles back to the importance of monitoring PSA after any prostate cancer treatment, even for low risk disease. Thanks to the ability to follow up a suspicious PSA with multiparametric MRI, we can now pinpoint recurrence when it is highly treatable with a good chance for success. This means that a rise in PSA should never be assumed to be bad news, because with today’s breakthroughs, there’s better news coming.

 

 

NOTE: This content is solely for purposes of information and does not substitute for diagnostic or medical advice. Talk to your doctor if you are experiencing pelvic pain, or have any other health concerns or questions of a personal medical nature.

References

[i] Barrett W, Hertzfeld K. Undetectable Prostate-Specific Antigen Level Following Prostate Brachytherapy: An Apples-to-Apples Comparison with Radical Prostatectomy. Urotoday Int J. 2010 Apr;3(2). doi:10.3834/uij.1944-5784.2010.04.16

[ii] Patel MA, Kollmeier M, McBride S, Gorovets D et al. Early biochemical predictors of survival in intermediate and high-risk prostate cancer treated with radiation and androgen deprivation therapy. Radiother Oncol. 2019 Jun 6;140:34-40.