Saturday, April 2, 2011

PSA Recurrence After Prostatectomy: The Good, The Bad, and the Ugly

A major milestone in the prostate cancer journey is obtaining a PSA level after treatment.  If a man has surgery, a procedure in which the entire prostate gland is removed, the expected result is a permanently undetectable PSA.  Because a successful surgery should remove all remnants of the cancer as well as the benign elements of the prostate, there should be nothing left to produce the dreaded PSA.  Patients derive a tremendous amount of satisfaction and relief in hearing that there PSA is undetectable, an unambiguous sign that their prostate cancer is gone.  For some men, however, the news is not as great.  At some point after surgery, 15-40% of  men hear the dreaded news that their PSA is not undetectable and that, most likely, there cancer has returned.  What many patients do not know is that not all PSA recurrences are created equal.  Some types of recurrences are much more worrisome than others and require very different treatment approaches.  In this post I will try to define PSA recurrence and attempt to differentiate the different types of recurrences.

Defining a PSA recurrence seems pretty obvious at first glance.  After all, PSA after prostatectomy should be 0.  Any other number is considered a PSA recurrence. In reality, things are not that simple.  First, we have to differentiate PSA recurrence from PSA persistence.  A first PSA test obtained 1-3 months after prostatectomy should be 0.  However, any PSA value other than 0 is not considered a PSA recurrence at this time.  The reason for this is that the PSA has not recurred but, rather, has persisted. Although this difference in terminology may seem like nothing more than semantics, it makes a tremendous difference in terms of prognosis and understanding the status of the prostate cancer.  Patient who have a persistent PSA after prostatectomy almost always have metastatic disease.  While imaging tests like a bone scan or CT scan may be negative, a persistent PSA indicates that some cancer cells are lurking somewhere in the body that are simply too small to identify on imaging tests.  These cells are then labeled micrometastatic disease.  Unfortunately, patients in this situation can no longer be considered curable.  Instead, they often get palliative hormonal therapy which, fortunately, can often keep those few micrometastatic cancer cells from significantly growing for many years. These patients may also qualify for clinical trials.

Unlike PSA persistence, PSA recurrence occurs when a postoperative PSA at first goes to 0 and then begins to rise after some period of time.  However, at least technically speaking, not all rises in PSA have been considered recurrences.  Historically, a PSA rise to 0.4 after surgery has been considered a recurrence.  Rises in PSA lower than this have been considered insignificant, possible due to some left over benign prostate tissue.  More recently, the value of 0.2 has been chosen.  Although these definitions seem pretty arbitrary they actually have significance because they determine when the patient has recurrent cancer and, in turn, when they should start salvage therapy.  With the advent of ultrasensitive PSA, much lower PSA values have been recorded and some doctors have initiated salvage therapy at PSA levels significantly lower than 0.2.

As I mentioned earlier in this post, a PSA recurrence has different implications on the status of prostate cancer and subsequent prognosis depending on several factors:

1)      Time from Surgery: Many studies have demonstrated that the longer the time between surgery and PSA recurrence, the less chance that the recurrent cancer is aggressive and likely to spread.  The consensus seems to be that 3 years appears to be a critical cut off point.  One study demonstrated that for men with otherwise good risk factors, those that had a PSA recurrence more than 3 years after surgery had a 13% greater chance of surviving their prostate cancer 15 years later as compared to those men with a PSA recurrence within 3 years of surgery( 94% versus 81% survival at 15 years).

2)      Gleason Score of Prostate Cancer:  The Gleason score is a measure of how aggressive the cells of prostate cancer look under the microscope.  It generally ranges from 6-10, with higher scores being associated with more aggressive cancer.  Men with Gleason scores above 7 who have a PSA recurrence after prostatectomy are at higher risk for metastasis and death from prostate cancer.  For example, a study demonstrated that men with recurrence of a Gleason 8 or higher prostate cancer within 3 years of prostatectomy had a 19% higher chance of surviving their prostate cancer within 15 years than those men with a recurrence of Gleason 6 or 7 prostate cancer within 3 years of prostatectomy( 62% versus 81% survival at 15 years).

3)      PSA Doubling Time: The PSA doubling time appears pretty self explanatory.  The term refers to the time it takes for the PSA to double in value.  To calculate this number you need a few PSA values spread at least 3 months apart.  You also need to use a fairly complex formula to get the exact value.  For our purposes, a rough, eyeball assessment will do just fine.  For example, by looking at a series of PSA values we can roughly estimate if the PSA is doubling every month, every 6 months, or every year, etc... Studies have demonstrated that PSA doubling time is one of the most important prognostic factors used to evaluate a PSA recurrence after prostatectomy.  Let’s look at an example:  If a man has a PSA recurrence more than 3 years after prostatectomy for a Gleason 6 prostate cancer and his PSA doubling time is more than 15 months, his chance of surviving the prostate cancer at 15 years is 94%.  If that exact same man has a PSA doubling time of less than 3 months, however, his chance of surviving prostate cancer at 15 years is only 19%.  As you can see, the importance of the PSA doubling time cannot be overstated.


These 3 factors are vital in evaluating a man with a PSA recurrence after prostatectomy not only to determine prognosis but, also, to figure out what future treatment needs to be undertaken, if any.  A man with a PSA recurrence more than 3 years after prostatectomy for a Gleason 6-7 prostate cancer and a PSA doubling time of greater than 15 months has a 94% chance of surviving his prostate cancer at 15 years.  In contrast, a man with a PSA recurrence less than or equal to 3 years after prostatectomy for a Gleason 8-10 prostate cancer and a doubling time of less than 3 months have <1 % chance of surviving for that same period of time.  As you can imagine, most men find their situation somewhere in between these two extreme scenarios. 

Men with favorable factors most likely have a local recurrence of the cancer in the part of the pelvis where the prostate was located.  This type of recurrence tends to move more slowly and can be cured with radiation therapy with some success.  Some men, depending on their overall health and age, may not even need any treatment for this type of low risk recurrence.  Men with high risk factors, in contrast, most likely have metastatic disease.  This type of recurrence is usually more aggressive and not responsive to local therapy.  Instead, men with this type of PSA recurrence are usually treated with palliative hormonal therapy to try to control rather than cure the recurrent cancer.  Others may opt for clinical trials to try novel treatments to battle the more aggressive cancer.

The take home message of this post is to NOT treat all PSA recurrences the same.  While a PSA recurrence is obviously disappointing and frightening it is not always as bad as you might think.  Many recurrences are very manageable and still offer the possibility of cure. Some recurrences may not even need to be treated.   Men with PSA recurrence should discuss their specific risk factors with their urologist in determining an appropriate treatment course. 

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This blog is not a medical practice and cannot provide specific medical advice. This information should never be used to replace or discount the medical advice you receive from your physician.

25 comments:

  1. You wrote: "a study demonstrated that men with recurrence of a Gleason 8 or higher prostate cancer within 3 years of prostatectomy had a 19% higher chance of surviving their prostate cancer within 15 years than those men with a recurrence of Gleason 6 or 7 prostate cancer within 3 years of prostatectomy..." I think you meant LOWER, not higher. (higher Gleason = lower survival).

    What do you think of the ultra-sensitive test, post RP? I know some reputable centers, such as Hopkins, do not tend to recommend it, presumably because of the anxiety it can cause. But other docs seem to think it is useful because it can show early signs of recurrance, allowing for earlier salvage treatments? What do you think? Do you routinely use ultra-sensitive psa?

    Also, what you do think of adjuvant versus salvage RT? How does a patient decide whether to wait for evidence of recurrance or do adjuvant RT? Seems some recent studies have suggested better outcomes with ART.

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  2. Correction:

    Gleason Score of Prostate Cancer: The Gleason score is a measure of how aggressive the cells of prostate cancer look under the microscope. It generally ranges from 6-10, with higher scores being associated with more aggressive cancer. Men with Gleason scores above 7 who have a PSA recurrence after prostatectomy are at higher risk for metastasis and death from prostate cancer. For example, a study demonstrated that men with recurrence of a Gleason 8 or higher prostate cancer within 3 years of prostatectomy had a 19% LOWER chance of surviving their prostate cancer within 15 years than those men with a recurrence of Gleason 6 or 7 prostate cancer within 3 years of prostatectomy( 62% versus 81% survival at 15 years).

    Men with recurrence of Gleason 8 cancer have a LOWER chance of surviving than men with Gleason 6-7 prostate cancer.

    Sorry if there was confusion.

    Prostate Doc

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  3. I do not use ultrasensitive PSA as I feel that it does not provide much more than stress. I think treating recurrent cancer within normal PSA parameters should lead to good success. I believe that adjuvant versus salvage RT is a complicated decision but, for my patients, I usually wait at least until they regain continence prior to initiating XRT.

    Prostate Doc

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  4. I was diagnosed in June, 2010 after two negative biopsies..On the third 12 core biopsy, one core showed Gleason 9, two cores G-6, one core G-7..I had robotic surgery on Sept 3, 2010. Positive margin, positive vesicle, (1) negative nodes. My PSA never went lower than 0.9 I guess you call that "persistent", first time I have heard that term..My docs (3 or 4 of them) all agreed my cancer was probably still localized and SRT was worth doing. Two radiation oncologists insisted I also be put on HT for two years as part of the salvage treatment..I completed 40 RT sessions, 72Gy on Feb 10, 2011. PSA at that time was undetectable. So SOMETHING is working...

    You seem to think persistent PSA after surgery almost guarantees distant metastasis and my radiation treatment was little more than a transfer of wealth...Taking another Eligard shot is NOT something I'm looking forward to, a recent study suggests that 6 months works almost as well as a year and I'm tempted to just coast along for a while and see how my PSA behaves..My R-doc does not like that idea at all.

    What do YOU think??

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  5. Fairwind: unfortunately I cannot comment on specific cases. However, generally speaking, the presence of prostate cancer in the seminal vesicle is associated with distant metastasis in 50% of cases. Nonetheless, studies have shown some benefit of radiation for men with seminal vesicle disease, albeit in those men whose postoperative PSA comes down to 0 after surgery. Hormonal therapy has been demonstrated by numerous studies to be beneficial in conjunction with radiation therapy in tackling locally advanced prostate cancer. European studies favor 2 years whereas recent US studies have advocated 6 months. All depends on who you want to believe. I hope that helps.

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  6. Should I be concerned if my psa went from undetectable @3months post surgery to 0.06 @6 months post prostatectomy ? I had a Gleason score of 6 and cancer was encapsulated within the prostate post pathology. Any action that is generally recommended at this point? Next steps?

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  7. BT: While I cannot comment on specific cases, I can say that the ultrasensitive PSA that was used to identify your PSA of 0.06 is a mixed blessing. While it sometimes does identify prostate cancer recurrence early, it can also identify benign prostate tissue that may have been left behind. As such, most urologists do not classify a prostate cancer as recurrent until a PSA is > 0.2. Most will wait until at least this value before proceeding to salvage therapy. That being said, some will jump on salvage therapies with lower PSAs in men with high risk cancer.

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  8. My psa post surgery has maintained at <0.05 for the past 2 1/2 years, until my last test where it measured 0.06. Does this rise indicate the presence of cancer?

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  9. Tom: While I cannot comment on individual cases, I can make the following comments. PSA detected at a value less than 0.1 is considered ultrasensitive PSA. This PSA is a mixed blessing because, although it can pick up recurrent prostate cancer very early, it can also detect the presence of left over benign prostate tissue that is completely insignificant. That is why many urologists use the normal PSA with a threshold of detection of 0.1. In addition, cancer recurrence is defined as a PSA level of 0.2 or 0.4, depending on who you want to believe. Values lower than these are technically not indicative of a cancer recurrence. That being said, some urologists turn to ultrasensitive PSA for patients with very high risk disease because they want to jump on the slightest hint of recurrence. That is why, as I mention in the post, it is so important to keep in mind other factors like stage, Gleason score, tine from surgery, margins, etc. Your urologist should be able to put all of your information together to give you a more clear idea of what the chances of recurrent cancer are for you in the context of this new, albeit tiny, rise in PSA. Hope that helps.

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  10. My husband had radical prostrate surgery in 2004 - the cancer had penetrated the prostate wall and was in the pelvic tissue. His gleason score was 8. In 2010 his PSA went to .2 and over the last two years it has climbed to .9. It was a one year doubling time. They just found a 1.1 centimeter mass in the area of the prostrate where his original surgery had been. Is there a way to determine a prognosis based upon this information?

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  11. My brother is 58 years. RAdical Prostatectomy 7 years ago due to agressive adenocarcinome (seminal vesicle +).Submitted to local radiotherapy and than hormonal therapy due to PSA increase (<2.0). In the last 2 years, radiotherapy (2x) for a vertebral metastasis and, recently, for a rib. Unfortenately, the last scintigraphy showed a new vertebral metastasis (L1). Is it safe to go for a new radiotherapy cycle? Does chemotherapy has a role in this phase? Is there any new therapy to try in a multicenter study? Thanks a lot.

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  12. Nancy: While I cannot give specific advice on this blog, I can say the following. PSA recurrence over 5 years after prostatectomy and a 1 year doubling time are both fairly good prognostic indicators in the context of a PSA recurrence but, of course, certain other factors for every individual case need to be kept in mind. As for the mass in the area of the prostate, it really depends on whether this mass is prostate cancer or not. Sometimes masses in the prostate bed can be biopsied to determine this. OF course, your doctor can make the best determination of this as he/she knows your husband's details.

    Prostate Doc

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  13. MMO: While I cannot speak to the the safety of repeat radiation (more appropriate for a radiation oncologist to determine this), I can say that numerous treatments are available for metastatic prostate cancer including chemotherapy, hormonal therapy like Lupron and Casodex, novel hormonal therapy like Zytiga, and immunotherapy. You should have your brother discuss the options with his oncologist.

    Prostate Doc

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  14. Chuck

    Had prostatectomy 6/12/12 with grade 8 tumor. PSA results of 6/28 showed level of 0.270. Is this time frame too soon, and will a PSA test prior to 8/6/12 have any significance at all?

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  15. Chuck: While I cannot comment on individual cases, I can say that it is better to generally wait at least a month before checking PSA after prostatectomy as it takes a while for the PSA in the bloodstream to dissipate.

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  16. Post prostatectomy, if the seminal vesical pathology is postive, you say there is a 50% chance of distant metastasis. Do you know the most common location of that metastasis?

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  17. my friend had a gleeson score of 7, and underwent a prostatectomy, he was advised a PSA test in 2 weeks and the reading was 0.4, does this mean there is a recurrence ????

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  18. After prostectomy in combanation with long acting lupron my PSA was ,1 9 months after the lupron wore off, and PSA was .01, three months .02 three months .03 with a t2c glease score 10 a concern. PS I am in the Punch trial. 6 does of chemo pre op.

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  19. above should have been <1 after nine months with lupron

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  20. yes <1 after surgery, took nine months for lupron to where off. No I'm seeing rises after every three months, good or no so good?

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  21. I had a RP a year ago, (UK). Gleason score after surgery was 4 + 3 = 7, but I have read this is equivalent to an 8. The histology report said cancer cells were close to the margin and complete removal could not be guaranteed. Post op PSAs at 3 months, 6 months and 9 months were "less than 0.01" i.e. undetectable. Presumably this is the "ultrasensitive" test. PSA at 12 months is 0.02. What is the significance of this?

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  22. Doctor, you have said there are 3 factors impacting the chance of survival after 15 years that are used to determine prognosis and future treatment: recurrence timeline, Gleason scope, PSA doubling time. The stats you have provided are at the extremes of 1% - 94%. Where can I get granular statistical data on how these 3 factors combine to indicate survival rates at 15 years?
    Appreciate your response on this. Many thanks.

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  23. I had a radical prostectomy 12/2011 Gleason score 3+4 with focal 5. My first PSA value after three months was .03, six months later .1,six months later .7 and my last after 3 months was 1.1 Is that considered doubling and what does it signify.

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  24. I has seed implants in 1999. After a couple of years my psa dropped to .04 and it remained there for 10 years. It then increases to .07 and in 2 years, with psa's every 3 months it has increased to .93. I am consulting with my doctor and it is his staff that has take every psa for 14 years. He wants to wait until the psa rises a bit and see if he can see cancer with a mri, a newer hi-resolution mri.I calculate that the psa has increased 23 times in about 2 years and though the number is low the rate of increase is extremely rapid. What course of action would you advise. Steve in Seattle

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  25. I had a prostate RP in Jan. 2011. Gleason score 7 (3+4). My PSA has gone from 0.6 to 2.9 over 3 years. No doubling in less than 1 year. The doctor knows there is a piece of prostate tissue left on the rectum wall about 2cm long. He has taken 3 biopsies of that tissue in 3 years and all were negative. He wants to take another biopsy this year and maybe start radiation, or hormone therapy.

    My question is as follows: If we know prostate tissue is there, and we know PSA is produced by the tissue, and it so far shows no cancer, why should I get radiation treatments or hormone injections?

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