Is surgery appropriate for men with Gleason 8-10 disease?

It is well known that a Gleason score of 8-10 at the time of diagnosis is predictive of less good long-term outcomes in the treatment of prostate cancer. However, it is also well known that many men who present with early stage prostate cancer and a Gleason score of 8-10 do very well following radical surgery.

A Spanish group (Rioja Zuazu et al.) have now presented data from their series of > 750 radical prostatectomy patients treated between 1990 and 2004. Of these patients, 108 had Gleason scores of 8-10 at time of biopsy.

The median PSA of these 750+ patients at time of diagnosis was 12 ng/ml and 50 percent of them were clinical stage T2. What Rioja Zuazu et al. have done is to compare the outcomes of the group of 108 patients with Gleason 8-10 with the rest and, within the Gleason 8-10 group, analyze which variables were associated with progression and progression-free survival.

Their results can be summarized as follows:

  • Mortality data
    • 62.7 percent (490/781) of their patients are still alive and free of biochemical progression
    • 24.8 percent (194/781) are alive with biochemical progression
    • 2.9 percent (23/781) have died of prostate cancer specifically
    • 1.9 percent (15/781) have died of other causes
    • 7.6 percent (59/781) have been lost to follow-up
  • Biochemical progression data for the whole series (781 patients)
    • A clinical Gleason score 8-10 alone is a statistically significant influence factor biochemical progression
    • Progression-free survival of patients with Gleason 8-10 disease was 56 ± 5 percent at 3 years and 35 ± 7 percent at 5 years (significantly worse than the rest of the group; p < 0.0001)
    • Even in multivariate analysis, a biopsy Gleason score of 8-10 was an independent prognostic factor for biochemical disease progression (as were the clinical stage, the PSA level, and the size of tumor on the biopsy).
  • Biochemical progression data for the Gleason score 8-10 group alone
    • Influence factors on progression-free survival were PSA level and pathological (post-surgical) stage 
    • Patients with pT2 disease had a significantly better progression-free survival than those with pT3 disease at 3 years (80 ± 6 vs. 54 ± 13 percent) and at 5 years (40 ± 7 and 27 ± 7 percent). 
    • Gleason 8-10 patients with a PSA < 11 ng/ml have better 3-year (74 ± 7 vs. 30 ± 22 percent ) and 5-year (40 ± 7 vs. 26 ± 7 percent) progression-free survival than those with a PSA level >11 ng/ml

The authors conclude that a biopsy Gleason score of 8-10 is a negative independent prognostic factor on progression-free survival (which is nothing new). However, they also conclude that prognosis for these patients is better if they present with a pre-surgical PSA level < 11 ng/ml and are found to have a pathological stage of pT2 post surgery.

What is also of considerable interest to The “New” Prostate Cancer InfoLink, however, are the outcomes of surgical treatment alone for men with early stage prostate cancer and a Gleason score of 8-10.

Rioja Zuazu et al. have shown that in this group of men, even when the pre-surgical PSA level is < 11 ng/ml and the pathologic stage is pT2, the 5-year survival based on surgery alone is only 40 ± 7 percent. We therefore have three questions:

  • What is the appropriate adjuvant therapy for men with Gleason 8-10 prostate cancer, pathological stage pT2, and PSA < 11 ng/ml who have been surgically treated, or should they receive expectant management?
  • Can we differentiate between the 60 percent of men in this group who will have biochemical progression within 5 years and those who won’t, and should they be treated differently?
  • What is the appropriate adjuvant treatment for men with Gleason score 8-10 and a PSA > 11 ng/ml and those with a Gleason score of 8-10 and a pathological stage of pT3 post surgery?

It is clear that better guidelines need to be put in place for these men. Adjuvant radiation or adjuvant hormone therapy (or both) may not be the best strategy. Should most of these men be placed on clinical trials?

24 Responses

  1. Last August I had a radical prostectamy for a Gleason 10 prostate cancer. I am 69; the PSA at surgery was 7.3 ng/ml and the clinical stage was T2.

    My PSA after surgery was 0.2; so then I did 42 weeks of radiation therapy. After 4 months my PSA was 1.8, so I did 2 bone scans and an MRI — all negative.

    I started hormone therapy. After just 4 weeks, my PSA is 1.0, and I am continuing to take Casodex. My oncologist says there are cancer cells floating in my blood but no metastases. Is there any way to kill these cells before they metastasize?

    Thank you, Charles

  2. Dear Charles:

    I am very sorry to hear about your situation, and I fully understand your concern. The problem, however, is that — even though there are no signs of actual metastasis on the bone scans and the MRI — it is very highly likely that you already have micrometastatic disease. What this means is that between the cancer cells circulating in your blood and the Gleason 10 disease, you probably have very tiny metastases that have already formed, and that these are simply too small to be visible on any currently available type of imaging test.

    The critical issue is going to be how you continue to respond to the hormone therapy and whether your oncologist can help you to identify trials of newer, investigational drugs that you might be able to participate in. Another possibility is to talk to your doctor about early use of chemotherapy with docetaxel (Taxotere) to see if it can knock back the cancer cells that are already circulating. This could perhaps also have impact on your long-term risk for severe progression.

    If I was wearing your shoes, I would go for a second opinion to a major specialty prostate cancer where I could be seen by a medical oncologist who is significantly involved in trials of the very latest drugs that are in development. You may be eligible for trials of some of these drugs, and these may give you the best shot at gaining control over your disease progression.

  3. Hi,

    I am just, trying to get some information.

    I had robotic surgery for Gleason 8 prostate cancer. I was told I may need some help to be able to consider sex, after. But Viagra has no effect, and much worse than that problem, is the problem that when I even try on any level, after the build up, when the point of release, should happen. I am in undescribable pain, each and every time. I was told that I would not be able to produce semen; however, no-one mentioned anything about unbearable pain.

    Hoping for some information.

  4. Anthony: If you join our social network, we can see if we can find other men who may have had similar experiences who might be able to help you get through this.

  5. Hi.

    My husband, who is now 59, had a radical prostatectomy in 2006. Biopsy showed he had Gleason 10, clinical stage T3a.

    He received radiation soon after; he had a recurrence within 2 years; he went on hormone treatment immediately and stayed on for 1 year.

    His PSA remains undetectable to this day (May 17, 2012) without the help of hormones or chemotherapy.

    Never give up hope!

  6. Hi. Your husband is a very lucky man. He will survive!!


  7. Hi.

    Standing by for clinical trial of enzalutamide (MDV3100); also, cabozantinib (XL-184) has shown unprecedented results in men with bone metastasis.


  8. Thank you Charles! Good luck to you also.


  9. My husband is 56 and had his prostate removed. His Gleason factor was 8. He has had check-ups every year. His PSA level after surgery was 1.0. He had a test 4 weeks later and the reading is now 2.0. He has had an MRI and a bone scan, which showed nothing. The operation was successful and now they are discussing whether to have radiation therapy or hormone therapy. He feels fine. Has taken to drinking pomegranate juice and eating them. Your thoughts on what will happen next.

  10. Lorraine:

    If you join our social network, we can discuss all this in detail. The fact that the bone and MRI scans were negative is unsurprising. The fact that the PSA is rising means your husband has residual disease. If this residual disease is confined to the so-called “prostate bed” and nearby tissues, then a combination of radiation and hormone therapy may still be applied with curative intent. The fact that he feels fine is good, but it doesn’t mean he has no cancer.

  11. Good day.

    My father has been diagnosed this year with a Gleason score of 8 and his PSA is 7.73. He is 66 years old.

    He hasn’t (yet) had any scans of other parts of his body for metastases; he will do that in October 2012.

    His doctors gave him androgen deprivation therapy (with Dipherelina 11.25 mg) for 3 months. His last ultrasound showed his prostate volume was 43 x 59 mm. For the past 10 years he has had therapy with antibiotics and herbal drugs for prostate problems. Analysis of his blood and urine are all good even now.

    My questions are: Is this good therapy; is it serious in this stage; and can radical prostatectomy be done to a man with these results?

    Thank you for your time and hope for an answer.

  12. Dear Vlada:

    We strongly suggest that you click here to join our social network, where we can discuss your father’s situation in more detail.

    What I can tell you on the basis of the information you have provided so far is that radical prostatectomy is potentially possible, but it may not be the most appropriate form of treatment for your father because of his age. When you join the social network we can talk more about about radiation therapy and other options as opposed to radical prostatectomy.

  13. Hi.

    If the cancer is confined to the prostate, remove it! If it has left the prostate he will have bone metastasis, dont go there! I did. Don’t wait, take action now!


  14. My partner has just been diagnosed with Gleason 8 prostate cancer with a PSA of 20. We are both in a dreadful state of worry as he has to have an MRI of his prostate and bone scans to see if the cancer has spread to other parts of his body. We are so frustrated by the length of time it is all taking. My partner is aged 66 years.

    It is now some 7 weeks since he first went to his GP and 5 weeks since his biopsy. Yesterday (October 10, 2012) he had a MRI on his prostate and we have to wait another week for a bone scan; then there’s another wait for the results of these and what line of treatment has been decided on by the consultants. Is this normal to have to wait so long? I am sure we are not alone with this situation but it feels like hell!


  15. Dear Cyndi:

    It is my understanding that there is considerable variation from region to region in the UK in the time it takes someone like your partner to be “moved through the system.” You are right, your partner has high-risk prostate cancer; he should be moved through the system much faster. Obviously I have no idea where you live, but if I was you or your partner (and I used to live in the UK), I would have raised a stink by now.

    Having said that, there is a strong likelihood that your partner’s bone scan will be negative but that the MRI will show extension of the cancer at least into the seminal vesicles and perhaps through the capsule of the prostate (so-called extracapsular disease). If you join our social network, we can work with you to go into more individual detail.

  16. I am 73 years old and a retired radiologist. For 3 years my PSA has been rising.

    When my PSA was 2 ng/ml, I had a TRUS biopsy which was negative for cancer but showed one core of PIN. One year later my PSA was 2.9. Another TRUS biopsy was negative and a PCA3 test was also negative. Another year later my PSA went to 4.9 ng/ml but went down to 3.9 ng/ml on a repeat test, probably due to sex. I went to the Mayo Clinic and at 6 months follow-up my PSA was the same, but after another 6 months follow-up the PSA was up to 7.4 ng/ml. A transperineal biopsy with 16 cores were negative.

    My prostate is only 30-35 g. After another 6-month follow-up peroiod my PSA went to 10 ng/ml and another 4 months later a 28-core transperineal biopsy was positive, with one core showing Gleason 6 disease and three showing Gleason 8 disease in 75% to 95% of each core. A CT of the abdomen and pelvis with oral and IV contrast and a bone scan were negative. During the last two biopsies the urologist did not see any abnormality in my prostate or my seminal vesicles. DREs were always normal. I have opted to have a robot-assisted radical prostatectomy for pathological staging. If there is no obvious extension beyond the prostate, follow-up PSA values will determine any need for adjuvant therapy.

    Thank you very much for any comments or suggestions since I will have the prostatectomy on December 4, 7 weeks post-biopsy.

  17. Dear Dr. Unite:

    Clearly you have had a challenging personal case of prostate cancer that was difficult to diagnose. Having said that, I am always concerned about the overall outcomes (as opposed to just the oncologic outcomes) of men of your age who undergo surgery, because these can be problematic.

    At the end of the day, the appropriateness of surgery for a man of 73 years with Gleason 8 disease is clearly a matter for individual discussion and agreement between the patient and the treating physician, and as a physician yourself you are far better informed than most patients who would be faced with such a decision. My only advice would be that you need to make absolutely sure you have had a very straightforward conversation with your surgeon about the risks for long-term (albeit perhaps minor) incontinence as well as the risks for positive surgical margins. Have you also looked at the projections for your oncologic outcomes based on the data in the Kattan pre-treatment nomogram? You do have a significant risk for extracapsular extension and for seminal vesicle invasion.

  18. Hello,

    my dad, age 74, has been just diagnosed with prostate cancer, Gleason 8 (3+5), PSA before biopsy 7,4 ng/ml. Localization: 15% of the sample on one side, and 70% on the other. Unfortunately, I have no additional information at the time.

    My dad just came back from his doctor who had informed him that there is no need to worry at all and the prognosis is fine. He had been prescribed a Lucrin Depot to be served (by injection) next 6 months without any surgery needed.

    However, considering his age and high level of Gleason factor, I am still worried and would like to know your opinion about the doctor’s proceedings. Shouldn’t there be additional examination accomplished, like MRI or bone scan?

    I do not want to worry my dad unnecessarily but do not want to underestimate the risk neither.

    Thank you very much for your opinion.

  19. Dear Martina:

    It would be best if you were to join our social network, where we can discuss the details of your father’s diagnosis and treatment more easily.

    The Lucrin treatment should reduce your father’s PSA to a very low level quite quickly and keep it there for a very extended period of time. However, you could certainly consider taking you father to a center that specializes in the treatment of locally advanced prostate cancer to get a second opinion. Because of the Gleason score of 3 + 5, your father does have an aggressive form of prostate cancer, and radiation therapy might be appropriate in combination with the Lucrin. Surgery is probably not a good idea in a man of his age, however, unless he is in phenomenally good physical condition.

  20. Gleason score 3 + 5 = 8. Doctor recommends hormone and radiation therapy, does not recommend surgery due in part to a 4-cm aneurism in my belly area. PSA is 12.

    Surgery or therapy?

  21. Dear CK:

    If you want to join our social network, we can discuss your case in detail. However, we would need a lot more information, and we are in no position to be able to comment on whether your abdominal aneurysm makes surgery inappropriate. Many patients find it helpful to get a second opinion from another specialist when they are uncomfortable with the first opinion.

  22. What is the role of strontium and biphosphanates in delaying bones metastasis .

  23. What is the role of new genetic tests on prostate tissue both from the view of prognosis and targeted therapy?

  24. Dear Eion:

    Your question about genetic tests is a very complex question that would take pages and pages to respond to accurately. The best brief answer is that we really don’t know yet because it depends on the test, the result, and the precise clinical situation of the patient.

    Your question about the roles of bisphosphonates and strontium in the treatment of prostate cancer is easier to deal with:

    — Bisphosphonates like zoledronate (Zometa) are used in men with advanced prostate cancer (including metastatic prostate cancer) who are being treated with androgen deprivation therapy (ADT, also known as “hormone” therapy) to help to maintain bone strength and prevent fractures and other skeletal-related events or SREs.

    — Radioactive strontium-89 chloride was the first injectable, systemic form of radiation therapy used to prevent pain in men with metastatic prostate cancer. Its use is now generally considered to be of historic interest only (at least in Europe and America) because a much newer drug known as radium-223 (Xofigo) appears to be at least as effective in prevention of pain, provides a small overall survival benefit, and appears to have fewer side effects too.

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