Wednesday, April 20, 2011

High Risk Prostate Cancer After Prostatectomy: Radiate or Wait?

The findings of a pathology report after a radical prostatectomy can be critical in determining outcomes for men with prostate cancer.  In these reports, pathologists describe key aspects of the prostate cancer including how aggressive it looks under the microscope and if it has spread outside of the boundaries of the prostate.  The pathologist also comments on whether the cancer was removed in its entirety or whether the surgeon cut across the cancer at one or more sites.  This information is not only critical in determining prognosis but, also, in determining if and when the patient may need supplemental radiation therapy.  In this post I will describe the “high risk” pathologic features and explain the necessity and timing of radiation therapy for men who have one or more of these features on their pathology report.

High Risk Pathologic Features

Upon reviewing the pathology report after a prostatectomy for prostate cancer, four characteristics are critical to determine about the prostate specimen that was removed:

  1. Extracapsular Extension(ECE):  The prostate is normally covered on all of its surfaces by a lining called the capsule.  The pathology report will state if this capsule is intact and whether any cancer appears to be extending beyond it.  If prostate cancer has already spread beyond the capsule at the time of surgery, chances are higher that some cancer moved beyond the prostate and was left behind.

  1. Seminal Vesicle Invasion:  The seminal vesicles are a pair of glands that are situated above and behind the prostate gland.  They are responsible for producing part of the semen that is ejaculated during sex.  Occasionally, prostate cancer spreads from the prostate to the seminal vesicles.  This invasion is considered a poor prognostic sign.  Involvement of the seminal vesicles is often associated with metastatic and/or locally recurrent prostate cancer after prostatectomy.

  1. Positive Margins:   When the pathologist reviews a prostatectomy specimen, a key feature that he looks for is the status of the margins.  The pathologist looks at all of the cut surfaces and determines whether any prostate cancer is seen at these surfaces.  Sometimes a positive margin cannot be avoided due to prostate cancer that extends well beyond the boundaries of the prostate.  In other cases, the margin is positive due to technical errors during surgery in which parts of the prostate (and cancer) were left behind.  In either case, positive surgical margins often result in a higher rate of local recurrence of prostate cancer.  Of note, not all positive margins are considered high risk.  I will explore this topic in a future post.

  1. Gleason Score: As mentioned in numerous prior posts, the Gleason score is a measure of how aggressive prostate cancer looks under the microscope.  Higher Gleason scores( greater than 7) are associated with a higher chance of local and distant recurrence after surgery and of an overall worse prognosis.

The presence of these adverse factors on a prostate biopsy portends a much higher chance of recurrent cancer.  Studies have demonstrated that 40-50% of men with combinations of these factors will have PSA relapse.  This statistic is important because up to a third of men with PSA recurrence will develop metastatic disease within 8 years and 17% of these men will die of prostate cancer within 15 years.  The increased risk posed by these adverse pathologic factors led to the question of whether men with such features would benefit from immediate radiation therapy after prostatectomy.

Adjuvant Radiation Therapy

Numerous studies have been performed to determine whether patients with high risk pathologic factors would benefit from radiation therapy immediately after prostatectomy.  Called adjuvant radiation therapy, this type of treatment is usually instituted starting approximately 3-4 months following prostatectomy.  One of the biggest studies evaluating adjuvant radiation therapy after prostatectomy was conducted by the Southwest Oncology Group (SWOG) and published in 2009.  The study evaluated 425 men determined to have the adverse pathologic factors noted above after radical prostatectomy.  In this study, half of the men were randomly assigned to undergo adjuvant radiation therapy and half were assigned to observation.  For those men undergoing observation, initiation of treatment (with radiation, hormonal therapy, or both) was usually stimulated by a rising PSA and was done at the discretion of the treating doctor. 

The SWOG study yielded some very impressive results supporting adjuvant radiation therapy.  The study demonstrated that men treated with adjuvant radiation therapy were only half as likely to have a PSA recurrence as compared to those men simply followed with observation.  After over 12 years of follow up, this translated into a 38% decreased risk of metastatic disease.  In addition, the implementation of adjuvant radiation therapy resulted in an approximately 8% higher chance of survival (74% vs 66%) at 10 years after treatment.

While the SWOG study made a strong argument for starting radiation therapy after prostatectomy for those men with high risk pathologic features, it also created some doubt.  The study had several limitations, one of the most important of which was that not all men in the observation arm actually got radiation after a PSA recurrence.  In fact, only 33% of patients who had a PSA recurrence underwent such delayed or salvage radiation therapy at the time of recurrence. This problem begged the question of whether adjuvant radiation therapy is really necessary or if, in fact, radiation therapy could be delayed until PSA recurrence is noted.

Salvage Radiotherapy

While no notable  prospective studies have been completed which directly compare adjuvant to salvage radiation therapy in men with pathologically high risk prostate cancer, numerous studies have evaluated salvage therapy in isolation.  A very widely cited study performed in 2007 retrospectively evaluated the outcomes of salvage radiation therapy in 500 patients with adverse pathologic factors after prostatectomy for prostate cancer.  The study demonstrated that men undergoing radiation therapy shortly AFTER PSA RECURRENCE demonstrated some good outcomes.  For example, the study reported that men with positive margins and a Gleason score less than or equal to 7 had a 61% chance of no progression after a PSA recurrence if salvage radiation was instituted at a PSA level less than or equal to 2.  In addition, the study demonstrated that, if implemented at a recurrent PSA level less than or equal to 0.5, salvage therapy resulted in no signs of disease in 48% of all men treated.

While also not perfect, this study led many urologists to question the need for immediate or adjuvant radiation therapy for patients with adverse pathologic findings on prostatectomy specimens.  Given the fact that the SWOG study determined that adjuvant therapy yielded a survival benefit in only 1 in12 men treated, many urologists argued that it would be more prudent to wait until PSA recurrence to begin radiation therapy. This argument was strengthened by the fact that radiation therapy is, of course, not without its own risks and side effects.  Studies have demonstrated that radiation can lead to injury to the rectum and bladder, occasionally causing diarrhea, blood in the urine and/or stool, urinary frequency and urgency, and pain.  In addition, radiation may cause scar tissue in the urethra tube.  Some have argued that radiation therapy administered soon after prostatectomy can also lead to decreased urinary control although studies have not shown this to be true.  As a result, common practice today is to closely monitor men with high risk pathologic features after prostatectomy and to give salvage radiation therapy upon the first signs of PSA recurrence.

While the policy of administering salvage radiation therapy for men with high risk pathologic features has been relatively successful, it really leaves the question of whether SOME men are losing some survival benefit by not getting adjuvant radiation therapy.  A study published last year by a very respected radiation oncologist ( Anthony D’Amico, MD) and urologist( Judd Moul, MD) tried to answer this question through a retrospective evaluation of over 1600 men undergoing radical prostatectomy for high risk prostate cancer at Duke University.  The study classified men with adverse pathologic features into those with T3 disease( extracapsular extension{ECE} or positive seminal vesicles), Gleason score 8-10, and positive margins. The study then compared men that underwent immediate adjuvant radiation with those that underwent salvage radiation only after PSA recurrence.  The study found that for those men who had only one adverse feature (for example a positive margin but with no ECE or seminal vesicle involvement and Gleason score less than or equal to 7), only 18% of the 587 men observed after prostatectomy demonstrated a PSA recurrence after 8 years of follow up.  Of these men that had a PSA recurrence AND got salvage radiation therapy at the time of recurrence, NONE died from prostate cancer after 9 years of follow up.  The study concluded that while men with multiple adverse pathologic factors should be considered for adjuvant therapy, those with a single adverse factor can reserve radiation therapy for a PSA recurrence, avoiding unnecessary radiation in 80% of cases without any increased risk of death from prostate cancer in the long term.

As you can see, deciding what to do about high risk pathologic features after prostatectomy can be very controversial.  Reviewing the pathology report with your urologist after surgery is critical.  Identifying high risk features in the report can help you determine your overall risk for recurrence and help guide you toward appropriate supplemental therapy if and when it is indicated.

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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


  1. I had my RP performed last March. Initial PSA was surgery path report showed I was a Gleason 6, 2 positive margins (7mm & 14mm), microscopic bladder neck involvement (margins clear), lymph nodes clear, SV clear, approx, 28% total gland involvement.. As of today all my PSA's have been undetectable.

    Surgeon says I was in the "gray area" for I day at a test at a time...I was 43 when diagnosed...a young man with what I "thought" was an old man's disease.

  2. If ECE is found on endorectal MRI, is RT over RP suggested??

  3. This is Gleason 7 (3+4). Nodes appear normal, SV appears normal on MRI as well.

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