This is part four of a four-part series on the PSA test in an attempt to demystify the most feared blood marker in men.
Part four: PSA after prostate cancer treatment
PSA rising after prostate cancer treatment is a bombshell to a man’s psyche.
A 63-year-old patient, one year after prostate cancer surgery, see’s me at the clinic for his recent diagnosis of recurrence PSA. (His PSA begins to rise after being undetectable for one year) He looks at me strangely. I ask him – what’s wrong? He responds, “ I thought I didn’t have ever to worry this S@#T again since I had it taken out. I expect my PSA to be zero forever, no? I’m confused” – he says.
Why is PSA still Measured after Prostate Cancer Treatment?
That freaking blood marker causes everything from anxiety to depression, even after prostate cancer treatment.
Here’s the deal; men who undergo medical treatment of prostate cancer like prostate removal or radiation, unfortunately, believe they are “home-free” after their treatment.
If this were true, why are patients required to return to their urologist every 3 to 6 months for a PSA test after surgery or radiation?
Men after prostatectomy or radiation even more so need to make lifestyle changes to reduce their risk of prostate cancer recurrence.
Here are two reason’s why:
1. Up to 40% of men experience biochemical recurrence (PSA recurrence) after initial treatment. (Freedland et al. 2007)
2. Men treated initially with Radiation Therapy (RT) have a higher chance of getting secondary bladder cancer or rectal cancer (Nieder et al. 2008)
Secondary cancers after initial cancer treatment should not be a surprise after this New York Times article highlighted this critical point.
What’s Considered biochemical recurrence (BCR) or PSA recurrence mean?
After surgical prostate removal (prostatectomy) – PSA recurrence is defined by a PSA of 0.2ng/ml to 0.4ng/ml within 6 to 13 weeks after the surgery.
Ultra-sensitive PSA assays have recently improved detection levels down to 0.01 ng/mL and may lead to better treatment outcomes through the earlier adoption of salvage radiation therapy following RP
After Radiation therapy (RT) for prostate cancer – PSA recurrence is more difficult to determine as PSA initially increase’s (known as PSA bounce) after RT and does not reach its lowest level for up to 18 months. There is no consensus on the definition of treatment failure, but most agree that the lowest PSA value after RT (referred to as the PSA nadir) plus 2 is the cut-off.
For example, let’s say Mr. Doe completed is RT today. His PSA before treatment is, say, 4.5ng/ml. His PSA may continue to go to whatever, say, 6.0 ( I’m making these numbers up) for another year or so (PSA bounce) before it begins to drop steadily. Two years later his name goes down to 2.5 (the nadir). Once his PSA reaches 4.5ng/ml (plus 2.0) that would be considered a PSA recurrence after RT.
Are you with me?
For men who undergo RT as primary treatment for prostate cancer, the most common treatment after PSA recurrence is cryotherapy (freezing the prostate).
Cryotherapy in this patient population can induce close to 100% impotence but not worsen urinary incontinence.
Men on Active Surveillance also are monitored primarily by PSA value and subsequent prostate biopsies. There’s no biochemical or PSA recurrence here since there is no treatment. The typical protocol for men on active surveillance for prostate cancer is biopsy once a year for up to two to three years to assure there has been no cancer progression. However, the physician may not be aware that in the latest research, they’d consider a follow-up biopsy every two years for active surveillance patients, not once a year. Biopsy every other year is indeed a viable approach for men not needing immediate medical treatment for prostate cancer based on research.
A final note on active surveillance for prostate cancer: Up to 33% of patients on active surveillance (AS) eventually fall out of surveillance and undergo definitive treatment after 2–5 years because of initial understaging or disease progression. Understaging means that the initial biopsy may have missed more aggressive prostate cancer with a Gleason 7 or higher.
I suggest a ProActive Surveillance approach in men on active surveillance for prostate cancer with the goal of the disease not to ever progress and reduce the risk of all-cause mortality.
Lastly, the use of PSA after focal therapy for prostate cancer is not well defined. Focal therapy, which includes cryotherapy, focal laser ablation and high-intensity focused ultrasound (HIFU) is a form of treatment for prostate cancer somewhere in between active surveillance and radical therapy. With focal therapy, the goal is to ablate (destroy) only the tumor and maybe about 1cm around it. PSA does not go down to zero after focal therapy since there is still prostate tissue intact and likely inflammation as well from the procedure. However, the PSA value does tend to decrease by 30% to 60% after focal therapy. A rapid increase in PSA after nadir can indicate biochemical recurrence and may require a biopsy.
Though not preferred by the surgeon, radical prostatectomy is an option after focal therapy if prostate cancer recurs.
PSA Doubling Time and other tests to determine Prostate Cancer Prognosis
In general, to determine a risk of aggressivity of prostate cancer, all pretreatment values are essential after PSA recurrence including, pretreatment PSA, tumor stage (T-stage), including Gleason score, surgical margin status, and lymph node status.
After prostate cancer treatment, PSA doubling time (PSADT) likely has the most prognostic value – this is the amount of time it takes for PSA value to double.
Let me give you another example.
Say my PSA today is 2.5ngml and it goes up to 5.0ng/ml in 6 months. The PSADT is six months.
In general, the longer the PSADT after PSA recurrence, the less likelihood of prostate cancer to be deadly.
As of late, genetic testing like Decipher® can help predict the possibility of metastasis from prostate cancer only after a prostatectomy. The Decipher® test only examines the prostate gland after it is removed surgically; thus, this test is not valuable after other type treatments like radiation.
Another element of prognostic importance is the time when PSA recurs after treatment.
For example, I have patients who have PSA recurrence ten to fifteen years after their prostatectomy. These patients will likely not succumb to prostate cancer.
Now, you don’t want to get your PSA test less than every three months to determine PSADT. Three PSA measurements obtained three months apart is considered a reliable foundation for calculation of PSADT.
Generally, the longer the PSADT, the better.
One study of 8,669 patients with prostate cancer treated with surgery (5,918 patients) or radiation (2,751 patients) found that a PSADT of less than three months was significantly associated with prostate cancer-specific mortality
Again, prostate cancer is an opportunity for nutritional and lifestyle changes that can reduce the possibility of succumbing to the disease.
Does Biochemical Recurrence (PSA recurrence) mean I will die from prostate cancer?
All-in-all the odds of dying from prostate cancer, even after PSA recurrence are better than almost any other cancer after relapse. Your chances of living longer with quality are particularly in your favor if a favorable lifestyle is adopted which reduces the risk of prostate and overall mortality.
Average time from PSA recurrence to prostate cancer death is 16 years (Freeland et al. 2007), if one’s fate is indeed from this disease. Most men with PSA recurrence, however, die of other causes than from prostate cancer, i.e., heart disease.
Importantly, PSA increase after prostatectomy may be due to benign, non-cancerous prostate tissue left behind after surgery (Djavan et al., 2005).
Only a small group of men die from biochemical recurrence (PSA recurrence) after prostate cancer. One study looked at over six hundred men for about sixteen years after prostate cancer treatment and noticed a tiny number succumbed to their disease after BCR. Based on the conclusion of this study, the odds of you living after BCR are in your favor.
So, stop sweating the PSA so much. I see men with high anxiety provoked when going for their PSA test.
I am reminded of an old Jewish phrase, “Don’t’ die while you are still alive.”
However, we all need a kick in the behind to do more of the things that help us live our best life. And the PSA test helps with that.
When does Androgen Deprivation Therapy after Prostate Cancer Recurrence?
The term Androgen Deprivation Therapy (also known as hormone therapy) refers to treatments meant to eliminate testosterone production by surgical removal of the testicles or chemically castrate the patient with drugs such as Leuprolide ( there are many others.)
The negative impact on quality of life in men on ADT can be significant, including hot flashes, bone loss, increased fracture risk, sexual dysfunction, loss of libido, memory loss, increased fat deposition, loss of muscle mass and other metabolic changes (increases in cholesterol and insulin resistance) that may increase risk for heart disease.
Lastly, not everybody with BCR (PSA recurrence) needs treatment. A man with a detectable and low PSA level of 0.05ng/ml after RP may have a persistently detectable PSA without significant change for a long time. Such a patient is unlikely to progress and suffer prostate cancer-related death because as Djavan et al. showed, there can be benign prostate tissue left behind.
Key Takeaway Points on PSA Screening after Prostate Cancer Diagnosis
• Biochemical recurrence (PSA increase) after prostate treatment is more common than people think.
• PSA recurrence is not necessarily a death sentence
• PSA doubling time is valuable to determine prognosis
• Pre-treatment values are also helpful
• Genetic testing only after prostatectomy is useful in determining prognosis
• PSA recurrence is a reminder to stay the course and improve your nutrition and lifestyle so that you can live your best life despite prostate cancer recurrence.
Every prostate cancer recurrence situation is different, and the treatment approach should be individualized.
Learn what food and meals work best for prostate cancer at the live event CaPLESS Eats.
CaPLESS Eats clears up the confusion on what to eat for prostate cancer.
My last 4 Blog Posts
Nieder AM, Porter MP, Soloway MS. Radiation therapy for prostate cancer increases subsequent risk of bladder and rectal cancer: a population-based cohort study. J Urol. 2008 Nov;180(5):2005-9;
Djavan B., Milani S., Fong Y. K. (2005). Benign positive margins after radical prostatectomy means a poor prognosis – pro. Urology 65, 218–220.
Freedland S. J., Humphreys E. B., Mangold L. A., Eisenberger M., Dorey F. J., Walsh P. C., Partin A. W. (2005). Risk of prostate cancer-specific mortality following biochemical recurrence after radical prostatectomy. JAMA 294, 433–439.