Handling relapse after Prostate Cancer Treatment - 2

Defining biochemical recurrence

As you are probably aware, both normal prostate cells and prostate cancer cells manufacture PSA. That is why the PSA level should fall to undetectable levels in men treated with radical prostatectomy, in which the prostate is removed, but is not likely to drop to zero in men treated with radiation therapy, even when treatment is successful.

This is because after radiation therapy the prostate gland remains intact and can recover some function. This is also true if you received hormone therapy as part of your radiation treatment: As you recover, testosterone levels rise, and so does your PSA.

The real challenge is defining what constitutes a biochemical recurrence after a particular type of therapy.

There is no consensus on this issue, but the working guidelines are summarized in Table 2.

Table 2: Guidelines for determining biochemical recurrence
Initial therapy	PSA threshold	Comments
Radical prostatectomy	0.2 ng/ml on at least two successive tests	Some physicians continue to use a higher threshold of 0.4 ng/ml or greater
Radiation therapy (external beam or brachytherapy)	Three successive elevations in PSA compared to nadir (low point), regardless of actual reading, according to the American Society for Therapeutic Radiology and Oncology	Many oncologists use a working definition that biochemical recurrence has occurred if PSA levels are greater than 1–2 ng/ml 12 to 18 months following initial treatment. Ideally, post-treatment PSA levels should be less than 0.5 ng/ml, but this is rare; levels of 0.6–1.4 ng/ml may occur.
Neoadjuvant hormone therapy and radiation therapy	Unknown

Further muddying the water, it is not clear what PSA levels should be in men who have undergone neoadjuvant hormone therapy in addition to radiation therapy. Hormone therapy suppresses levels of testosterone; once the therapy is stopped, testosterone levels rise, and PSA generally increases rapidly until the hormonal environment stabilizes.

Moreover, some men who have undergone external beam radiation therapy or implantation of radioactive seeds (brachytherapy) experience a phenomenon known as PSA bounce, a temporary spike in PSA that does not necessarily indicate recurrence.

Studies offer varying conclusions about how common this phenomenon is, probably because they use different definitions of what constitutes a “bounce.” Until more is known, if you have had some form of radiation therapy for prostate cancer and experience a spike in your PSA level, it is wise to ask your physician whether this could be a PSA bounce.

A common challenge

Rising PSA after initial treatment often comes as a shock to the person affected, but it’s actually a common problem. Studies indicate that biochemical recurrence affects roughly 15%–30% of men initially thought to be curable with localized treatment of prostate cancer. Certainly if you find yourself in this situation, you are not alone.

For example, a study published in the Journal of Urology, which followed 3,478 men who underwent radical prostatectomy for prostate cancer, found that 32% were likely to suffer a biochemical recurrence within 10 years. (The study actually followed patients an average of a little more than five years, but used actuarial tables to predict outcome at 10 years.)

Another study, published in the Journal of the American Medical Association, examined the outcomes for 1,997 men who underwent radical prostatectomy and were followed for an average of a little more than five years, and found that 15% experienced biochemical recurrence in that time. (For further details about these studies, see “Biochemical recurrence after surgery,” below.)

Biochemical recurrence after surgery Pound CR, Partin AW, Eisenberger MA, et al. Natural History of Progression after PSA Elevation Following Radical Prostatectomy. Journal of the American Medical Association 1999;281:1591–7. PMID: 10235151. Roehl KA, Han M, Ramos CG, et al. Cancer Progression and Survival Rates Following Anatomical Radical Retropubic Prostatectomy in 3,478 Consecutive Patients: Long-Term Results. Journal of Urology 2004;172:910–14. PMID: 15310996.

Other studies indicate that a similar (or perhaps slightly higher) percentage of men treated with radiation therapy will experience a biochemical recurrence (see “Biochemical recurrence after radiation therapy,” below).

For example, a study of 1,449 men with prostate cancer treated with brachytherapy, published in the Journal of Urology, found that anywhere from 19% to 26% experienced biochemical recurrence within 12 years, depending on the definition of recurrence.

It should be noted that nearly half the men were also treated with either neoadjuvant hormone therapy or a combination of brachytherapy and external beam radiation therapy, which may have increased the success of treatment or delayed recurrence.

And a study comparing the outcomes of 393 men who received different doses of external beam radiation therapy for prostate cancer, published in the Journal of the American Medical Association, found that 19.6% of those who underwent high-dose radiation therapy experienced biochemical recurrence within five years, while 38.6% of those who underwent conventional-dose radiation therapy did.

Biochemical recurrence after radiation therapy Potters L, Morgenstern C, Calugara E, et al. 12-Year Outcomes Following Permanent Prostate Brachytherapy in Patients with Clinically Localized Prostate Cancer. Journal of Urology 2005;173:1562–6. PMID: 15821486. Zietman AL, DeSilvio ML, Slater JD, et al. Comparison of Conventional-Dose vs High-Dose Conformal Radiation Therapy in Clinically Localized Adenocarcinoma of the Prostate: A Randomized Controlled Trial. Journal of the American Medical Association 2005;294:1233–9. PMID: 16160131.

How to handle a relapse after treatment for prostate cancer - Part One

Marc B. Garnick, M.D., discusses what biochemical recurrence means and what your options are

“Am I going to die?”

This is the first question a patient usually asks me when a follow-up blood test reveals that his prostate-specific antigen (PSA) level has risen after he has already undergone treatment for prostate cancer (usually a radical prostatectomy or radiation therapy).

The fear is understandable: When PSA levels rise to a certain threshold after prostate cancer treatment, the patient has suffered what is known technically as a biochemical recurrence, sometimes also referred to as a biochemical relapse or stage D1.5 disease.

Whatever term is used, it means that prostate cancer remains within the prostate after radiation therapy, that it survived outside the excised area after radical prostatectomy, or that it has reappeared in metastatic form in other tissues and organs.

In most cases the cancer remains at a microscopic level, and many years will pass before any physical evidence of it is detectable on a clinical exam or any abnormalities are seen on a bone scan or CT scan.  That’s usually of small comfort to the patient whose PSA has risen. It’s emotionally traumatic to go through treatment for prostate cancer, thinking it is cured, and then learn that it might have come back.

For many men, it’s as if they’re dealing with another diagnosis of cancer, except this time it’s much worse because there is less likelihood of getting cured.

A man’s confidence and sense of safety may be shattered, especially because the popular misconception is that when prostate cancer recurs, it is deadly.  Which brings me back to my patient’s question: “Am I going to die?”  The simple answer is yes, eventually — we all do — but you may not die from prostate cancer. Of course, with prostate cancer, nothing is simple.

This may be one disease, but it can appear in multiple forms, so every diagnosis or recurrence requires individualized assessment and intervention. To start thinking about the salient issues, see “Four key questions.”

Four key questions

If your PSA rises after prostate cancer treatment, answering four key questions will help you and your doctor determine next steps:

   •   What were your risk characteristics, such as Gleason score, PSA, and cancer stage, at the time of diagnosis? (See Table 1.)

   •   What type of treatment did you have? That will help determine your next treatment options.

   •   How long has it been since you underwent initial therapy for prostate cancer? This helps indicate how aggressive follow-up treatment needs to be.

   •   How fast is your PSA rising, as determined from several evaluations?

In practical terms, biochemical recurrence means that you are now dealing with a chronic disease, like diabetes, so that your clinical monitoring will have to increase and you may need to choose or adjust treatment to meet new challenges.

 

Unfortunately, we don’t yet have sufficient research to provide clear guidance about when a second therapy (referred to as salvage therapy) should be considered after biochemical recurrence, and which type of salvage therapy is most effective in particular circumstances. (Salvage therapy is a terrible term, but I use it in this article because it is the standard name for follow-up therapy.)

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Table 1: Predictors of biochemical recurrence at time of diagnosis Although a number of clinical factors contribute to your risk of relapse after treatment, the parameters below provide a simpler assessment of your chances of biochemical recurrence, based on your clinical profile at the time of diagnosis. For more sophisticated estimates, based on specific risk factors, see Figures 1 through 3 ____________________________________________________________________________________________________________

Low risk (33% chance of biochemical recurrence within five years)

Gleason score less than or equal to 6 and PSA less than or equal to 10 ng/ml and Cancer stage T1c or T2a.

</></></> Intermediate risk
(50% chance of biochemical recurrence
within five years)
 
Gleason score of 7 (if 3+4)

and/or PSA greater than 10 but no greater
than 20 ng/ml

and/or Cancer stage T2b.
</></></> High risk
(85% chance of biochemical recurrence within
five years)
Gleason score of 7 (if 4+3), or 8 or more

and/or PSA greater than 20 ng/ml

and/or Cancer stage T2c or more
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For those who have already suffered a biochemical recurrence after being treated for prostate cancer — or dread each follow-up blood test because it might signal such a recurrence — the next article in this series explains what a rising PSA after treatment really means and what your treatment options are.