10-year data from RTOG 9910 endorses 8 weeks of neoadjuvant ADT prior to radiation


According to a report on Practice Update last Monday, some interesting data were presented at a plenary session at the annual meeting of the American Society for Radiation Oncology (ASTRO) based on 10-year follow-up of men in the RTOG 9910 trial.

The basic result of this trial at 10 years of follow-up seems to be that 8 weeks of neoadjuvant androgen deprivation therapy (ADT) prior to radiation (followed by 8 additional weeks of ADT during radiation) is just as effective as 28 weeks of neoadjuvant ADT prior to radiation (followed by 8 additional weeks of ADT during radiation) for treatment of men with intermediate-risk prostate cancer.

This trial enrolled nearly 1,500 patients with intermediate-risk prostate cancer between February 2000 and May 2004. The patients were all randomized to first-line therapy with one or other of two forms of treatment:

  • Arm A: Patients in this arm of the trial (n = 752) received 8 weeks of neoadjuvant ADT with an LHRH analog and a non-steroidal antiandrogen (bicalutamide or flutamide) and were then treated with radiation therapy of 70.2 Gy in 39 fractions with doses to the seminal vesicles and pelvic nodes as needed while also receiving 8 additional concurrent weeks of ADT using the same combination of an LHRH agonist and a non-steroidal antiandrogen.
  • Arm B: Patients in this arm of the trial (n = 737) received exactly the same form of treatment with just one exception. They were given 28 weeks of neoadjuvant ADT prior to initiation of radiation therapy as opposed to only 8 weeks.

Biochemical recurrence of prostate cancer was defined as a rise of at least a 2 ng/dl in a patient’s PSA level compared to their PSA nadir.

According to Dr. Thomas Pisansky, who is the prinicipal investigator for this trial, and who presented these data at the ASTRO meeting:

  • At a median follow-up of 8.7 years for all patients and 9.3 years for all survivors,
    • 3 percent of all patients had died from prostate cancer.
      • 30 prostate cancer-specific deaths occurred in Arm A.
      • 24 prostate cancer-specific deaths occurred in Arm B.
      • This difference was not statistically significant.
    • Biochemical failures occurred in 25.3 percent of all patients.
      • 192/752 patients (25.5 percent) in Arm A.
      • 185/737 patients (25.1 percent) in Arm B.
      • This difference was not statistically signifciant
  • 10-year prostate cancer-specific survival rates were virtually identical for the two arms of the trial.
    • 95 percent for men in Arm A.
    • 96 percent for men in Arm B.
  • 10-year biochemical recurrence rates were exactly the same at 27 percent in both arms of the trial.
  • There were no significant differences in either locoregional progression or distant metastases at 10 years.
    • 6 percent locoregional progression for men in  Arm A.
    • 4 percent locoregional progression for men in Arm B.
    • 6 percent rate of distant metastasis for men in Arm A.
    • 6 percent rate of distant metastasis for men in Arm B.
  • Late radiation toxicities of grade 2 or higher occurred in
    • 10 percent of patients in Arm A
    • 8 percent of patients in Arm B
  • Sexual adverse events of grade 2 or higher occurred in
    • 8 percent of patients in Arm A
    • 17 percent of patients in Arm B

Dr. Pisansky (a professor of radiation oncology at the Mayo Clinic in Rochester, MN) is quoted as stating that:

In 10-years of follow-up, the disease-specific survival of men treated in either fashion is extraordinarily high.

It’s quite clear to us: The recommendation is that the pre-radiotherapy neoadjuvant androgen suppression need last no longer than 8 weeks. When you combine the pre-radiotherapy with the concurrent radiotherapy/androgen suppression, it need last no more than 16 weeks.

7 Responses

  1. GOOD NEWS FOR US, AND ANOTHER MEDICAL COST REDUCER

    This is clearly good news for men with intermediate-risk cases, and also good news that will enable reducing the cost of health care by avoiding additional androgen deprivation therapy (ADT) that adds no value.

    NOTE RE SEXUAL ADVERSE EVENTS OF GRADE 2 OR HIGHER:

    As a 14th year veteran of intermittent ADT as my only therapy (plus supporting drugs and lifestyle tactics) up to April of this year, therapy which included 31 months of ADT during my first round that started at age 56, the difference in sexual adverse events is understandable but needs context. That relatively short ADT of 4 months in group A would be unlikely to have substantial sexual consequences, and those that did occur would tend to dissipate fairly soon after the ADT was discontinued.

    While the longer ADT in group B, 36 weeks total, would be expected to cause some substantial sexual effects in more men, as occurred, it is important to recognize that those effects should have reversed for all or almost all of these men, probably within a month or two.

    During my first three rounds of much longer ADT (31 months, 19 months, 19 months), I have substantially recovered by 3 months, and my understanding is that that recovery is typical for most of us on ADT. As always with ADT, employing countermeasures to lessen the impact of side effects helps with this type of side effect.

  2. SUCCESS RATES AND NOW OBSOLETE DOSE OF RADIATION

    While the “glass is half full” with about 75% success in avoiding biochemical failure, it is likely that considerably better results would be achieved today with typical doses of around 78 to 81 Gy instead of the dose of 70,2 Gy in 39 fractions.

    My own dose this spring was 78 Gy in 39 fractions delivered by TomoTherapy, including a pelvic boost and ADT well before, during, and still continuing for my high-risk case. (No mets per imaging staging with feraheme USPIO and Na18F PET/CT bone scan.)

  3. Well, I am pleased with this. In 2009 I had 3 months of Casodex and Zoladex, in that sequence. This was fully neo-adjuvant. After that, EBRT and HDR brachytherapy, with Zoladex concurrent and then adjuvant for 3 more years. Note though, that I am a high-risk patient.

  4. Would someone please identify what an intermediate-risk prostate cancer is? Is there a similar definition of low-risk prostate cancer and high-risk prostate cancer?

  5. Dear Barry:

    There are various slightly different definitions of “low-“, “intermediate-” and “high-risk” prostate cancer, but the classic ones are those initially defined by D’Amico et al. These classifications only apply to localized disease, i.e., there must be no evident indication of either positive lymph nodes or metastatic cancer. According to the original D’Amico classification:

    — A low-risk cancer is one defined by the patient having all of the following — a PSA level of less than 10 ng/ml; a Gleason score of 6 or less; and a clinical stage of T2a or lower.

    — An intermediate-risk cancer is one defined by any one of the following — a PSA level between 10 and 20 ng/ml; a Gleason score of 7; and a clinical stage of T2b/c.

    — A high-risk cancer is defined by any one of the following — a PSA level of 20 ng/ml or higher; a Gleason score of 8 or higher; and a clinical stage of T3 or T4.

  6. Thank you for answering my question.

  7. My father, through the VA Hospital in Milwaukee, WI, participated in this guinea pig trial (against my better judgment as his daughter).

    He died a horrible, slow, extremely painful death due to the high doses of radiation of these experiments he received to his pelvic area and developed secondary sarcoma cancer. The hospital did a biopsy of the sarcoma cancer (again against my gut feeling of not to do it) and the needle biopsy seeded the cancer cells and they floated to his lungs and within months he died the most horrible painful death — he suffocated to death.

    Were the clinical doctors in charge of this study at his death bed when he was in hospice thanking him for being their guinea pig? NO!! They were out recruiting other men to replace him.

    Due to my father consenting to this study, he died an early painful death and he never got to see his grandkids graduate high school or college. Men out there: don’t consent to any type of this study — our government is using you.

    Never in my life have I ever been so disgusted with the medical profession. I am sickened by this study you conducted and the true lack of up front consequences awaited my father.

    My dad had two tours in Korea defending our great country … and what does he get in return? The VA Hospital and government using him as a statistic for one of their little human experiments.

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