Better survival associated with higher doses of EBRT in higher-risk patients


It has been getting increasingly clear that elevated doses of radiation to the prostate result in better prostate cancer-specific survival for men treated with first-line radiotherapy for localized prostate cancer. Newly-published data from a series patients with 9 years of follow-up continues to emphasize this trend towards better prostate cancer-specific survival.

Kuban et al. have reported on data from 301 patients initially diagnosed with clinical stage T1b-T3 disease. These patients were randomized to receive first-line treatment with external beam radiation therapy (EBRT) to either 70 Gy or 78 Gy in total. The objective of the paper is to report on long-term treatment failure patterns and survival in this randomized radiotherapy dose escalation trial.

The basic results of this study demonstrate that:

  • Patients treated to only 70 Gy who had pretreatment PSA levels >10 ng/ml or high-risk disease had (a) higher rates of biochemical and clinical failures and (b) a higher risk for prostate cancer-specific mortality than comparable patients treated to 78 Gy.
  • Patients treated to only 70 Gy who were < 70 years of age at the time of treatment died of prostate cancer nearly three times more frequently than of other causes, whereas those treated to 78 Gy died of other causes more frequently.
  • Patients treated to only 70 Gy who were ≥ age 70 years of age died of prostate cancer as often as other causes, whereas those receiving 78 Gy never died of prostate cancer within 10 years of follow-up.
  • Factors predicting for prostate cancer-specific mortality were:
    • A pretreatment PSA level >10.5 ng/ml
    • A Gleason score of 9 or 10
    • Prostate cancer recurrence within 2.6 years of initial radiation
    • A PSA doubling time of < 3.6 months at the time of prostate cancer recurrence.

The authors conclude that  for patients with localized prostate cancer who elect to receive external beam radiation therapy, a dose of 78 Gy (as compared to a dose of 70 Gy) decreases risk for biochemical and clinical failure and risk for  prostate cancer-specific mortality in patients with a pretreatment PSA >10 ng/ml or high-risk disease.

Doses of 80 Gy and higher are now commonplace in the treatment of localized prostate cancer using image-guided and intensity-modulated radiation therapy systems. The combination of such high doses of radiation therapy with methods to accurately target radiation with great accuracy (using fiducial markers, the Calypso system, and other evolving technologies that allow for small movements of the prostate even during a specific treatment session) have made it possible to deliver such elevated doses of radiation with enormous accuracy and much greater safety that was the case in the early to mid 1990s.

While the lack of well-structured trials designed to make direct comparisons of external beam radiation therapy to other forms of first-line therapy makes it impossible to determine if there is a “best” form of first-line therapy, it is reasonable to state that modern external beam radiation therapy is now capable of achieving very high levels of 10-year recurrence-free and overall survival.

8 Responses

  1. Aloha,

    With higher doses come higher risks of side effects. Don’t remember just what my dose was, but I think it was closer to 90 Gy. The better survival rate at 10 years is good news. My quality of life has been very poor. Without good pain meds, I’ve become afraid of going to the toilet, both #1 and #2. It is difficult to cope with these problems. I am alive.

    Joe

  2. Higher radiation doses without highly accurate radiation delivery protocols are a significant issue and can come with significant problems like those Joe mentions. That is why recent advances in the accuracy of delivery of radiation very specifically to the target tissues are so valuable, along with the evolving use of drugs like amifostine to help to prevent side effects of radiation.

  3. I can vouch for the benefits of the higher radiation dose. In 2004, at age 74, I was treated for prostate cancer (PSA 5.1, Gleason 9) with 38 sessions of IMRT (plus androgen blockade). The total dose was 80 Gy. Six years later, my PSA is low at 0.20 and steady. I have no serious residual side effects. I do urinate a little more frequently, but only once at night. No bowel problems that might not come with old age anyway and very tolerable.

    The only serious thing that happened, over the last 3 years, was two separate episodes of blood in my urine. Each was a one-time occurrence. They ran a lot of tests to rule out metastasis or a new cancer: all negative. My doctors decided that what happened was that small blood vessels in the area had been weakened by the radiation and finally broke. There have been no further complications and I feel fine.

  4. Aloha Sitemaster,

    The dose delivered to the prostate (second month) was aimed using ultrasound each time a dose was administrated. It was also an IMRT machine. The first setup included the three tattoos which were made/positioned using a CAT scan. The first month doses were pelvic cavity. This is the time when the damage was done, based on the pain level reached during the third week. Was suppose to drink the same amount of water each time, but due to damage, I could not hold it as long. So the technique was up to date, just my internals seem to have been in the wrong place.

    Drugs to ease side affects were not discussed or offered.

    Joe

  5. Joe,

    You received photons (x-rays) where proton therapy was a better option. IMRT is like shooting you with an 0.22 in the bladder and rectum while using a 0.50 caliber in the prostate. Proton therapy has the “Bragg Effect” where the energy is delivered to the prostate not elsewhere.

    Using CT scans exposes you to between 400 and 900 times the power of a chest x-ray. MRI’s can give the same results.

    You have been medically abused by radiologists. Please talk this up so that no one else has to needlessly suffer what happened to you.

    BTW some radiologists own the equipment they use so they will not give you straight advise about it’s terrible effects.

  6. The relative merits of proton beam radiation therapy and other forms of radiation therapy to treat prostate cancer have been a source of controversy for 15+ years. Sadly, the simple fact is that we have failed to collect and publish high quality, comparative data that would allow a neutral observer to assess the relative clinical merits (including the adverse effects and the long-term clinical outcomes) of the various forms of radiation therapy used in the treatment of prostate cancer. Dogmatism does not help any patients who are newly diagnosed today, when there have been significant improvements in the delivery of differing types of radiation therapy than was the case when men like Joe were treated.

  7. Aloha Bob McCullough.

    It’s not quite that simple Bob. As the Sitemaster points out, plus the fact that with 12 of 12 cores showing prostate cancer, it was assumed that small amounts of prostate cancer (undetectable) had escaped the prostate, i.e. the pelvic cavity dose to try to neutralize these starting prostate cancer sites.

    OK, now for proton therapy. Protons entering the body have a much greater chance for damaging body cells than radiation due to the sheer size and energy potential of each proton compared to x-ray energy packets. As protons travel through a body, they leave a trail of damage and destruction before their energy is expended. With respect to an x-ray packet, which is adsorbed with fewer interactions, I would choose the x-ray. The difference between the two treatments is mainly in the delivery, like how many, how much energy, and how much collateral damage is acceptable. It is true that x-ray packets (wave or particle) will travel farther before interaction than protons, hence damage to the colon, rectum, and anus may be higher. But this is an aiming/delivery problem for both treatments.

    In my case the prostate was tucked up more into the bladder, hence more bladder damage.

    At this point, you can not say that one treatment is better than the other. If your prostate cancer is like one or two cores, very little collateral damage is produced, like a friend of mine. His life hardly skipped a beat during treatment with IMRT and many years after is just fine, i.e., no side effects.

    Like the Sitemaster says, we know so little, and in the end, we are swayed by how much publicity an owner of treatment equipment can deliver. Each case of prostate cancer is so different, the only thing they have in common is that it is prostate cancer!

    Reminds me of the battle between robots and just plain old surgery — it is all in the delivery capability of the doctor.

    Joe

  8. Joe,

    Look at the pix on Wikipedia. The charged particles are channeled to explode at a precise point using the Braggs’ peak control. Usually, 100 ton magnets aim the protons. Loma Linda, the University of Florida, et al. have been using this for over a decade. I am about to enter a clinical trial at the University of Florida for salvage radiation. It is much more precise than photon (IMRT) which is VERY important for prostate cancer. That is why I responded to your initial comment.

    As for open vs robot-assisted surgery, the former causes pints of blood loss and a much longer hospital stay, increased chance of infection, etc. It is done by older surgeons who have not learned the new techniques. Medicine is a fast-paced technology and many old timers can’t keep up. They use salesmenship to sell their outmoded techniques as if the technology hasn’t changed.

    Now, thanks to Dr Google, we patients can research and try to keep them honest.

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