Long-term outcomes after RP as first-line therapy for men with cT3 disease at time of diagnosis

We have no data from randomized trials on the relative effectiveness of surgery compared to radiation therapy in the treatment of men initially diagnosed with clinical stage T3NxM0 prostate cancer. However, we do now have data from > 800 men treated with radical prostatectomy (RP) and followed for up to 23 years at the Mayo Clinic.

Mitchell et al. conducted a retrospective analysis of data on the thousands of men treated by radical prostatectomy at the Mayo Clinic between 1987 and 1997. Based on that analysis, they offer the following information:

  • 843 men were treated by first-line radical prostatectomy alone after a diagnosis of clinical stage T3NxM0 disease.
  • Average (median) post-surgical follow-up was 14.3 years (range 0.1 to 23.5 years).
  • 223/843 patients (26.5 percent) were found to have pathological T2N0M0 disease post-surgery.
  • At an estimated follow-up of 20 years (based on Kaplan-Meier methodology)
    • Local recurrence-free survival for all patients was 76 percent.
    • Systemic progression-free survival for all patients was 72 percent.
    • Prostate cancer-specific survival for all men 81 percent.
  • On multivariate analysis, an increased risk for prostate cancer-specific mortality was evident in men with
    • Higher pathological Gleason scores (hazard ratio [HR] = 1.8)
    • Non-diploid chromatin content (HR = 1.8)
    • Positive surgical margins (HR = 2.1)
    • Seminal vesicle invasion (HR = 2.1)
  • A more recent year of surgery was associated with a decreased risk of cancer-specific mortality (HR = 0.88).

Mitchell et al. conclude that:

  • “RP affords accurate pathological staging and may be associated with durable cancer control for cT3 prostate cancer, with 20 years of follow-up.”
  • “RP as part of a multimodal treatment strategy therefore remains a viable treatment option for patients with cT3 tumors.”

However, they are also careful to note that external beam radiation therapy in combination with androgen deprivation therapy offers 10-year progression-free survival among about 88 percent of men when given as first-line therapy for men initially diagnosed with cT3 disease. The combination of radiation therapy and ADT may well (therefore) be the most appropriate form of treatment for older men initially diagnosed with cT3 disease.

The bottom line is that for those men with what may be the earliest stages of cT3 disease on diagnosis (and who may therefore turn out to have pT2 disease post-surgery) — and particularly for younger men who may be able to recover well after radical prostatectomy — surgery is still a very appropriate form of first-line treatment that can always be followed later with adjuvant or salvage radiation therapy (with or without ADT, as necessary). Careful patient selection and a thorough discussion of the risks and benefits of such an approach are clearly key factors in the application of such a clinical strategy.

4 Responses

  1. More bad science. Thanks.

    The Mayo doesn’t do radiation therapy? They couldn’t have done a randomized, prospective trial over the last 10 years of this controversy?

    This report, based on observational data, should not have been accepted for publication. It adds no new information, in my opinion.

  2. Dear Dr. Kelly:

    I don’t think you can blame the Mayo Clinic alone for the failure to carry out a randomized trial of surgery vs. radiation therapy in the first-line treatment of prostate cancer. A major attempt to carry out such a trial was implemented some years ago, but physicians (including urologists and radiation oncologists) across the country were unwilling to enroll men in this trial, and their patients were also unwilling to be randomized to such a trial.

    The data offered by the above study are what they are. The failure to be able to carry out a high-quality randomized trial in the USA appears to be a cultural issue that involves all relevant participants. The ongoing ProtecT study in the UK may help to resolve the unanswered question about the relative merits of surgery vs. radiation therapy vs. active surveillance in early stage prostate cancer … but it still won’t address the issues related to the appropriate first-line treatment of clinical stage T3 disease.

  3. Let’s face it. Departments of Urology and Radiation Oncology are business enterprises with the intent to be profitable. When more of our Centers of Excellence are using staff models with employed, salaried urologists and radiation oncologists, we’ll probably see these studies launched in the U.S.

    I don’t think we can blame the patients in this dilemma. They typically are not told the truth about the paucity of real outcome data. We all know that patients not seeking second opinions with RT or medical oncologists are more likely to do what their urologist recommends.

    Of course, one of the treatment arms should include expectant management. The option of active surveillance with curative intent was not born in the U.S. It couldn’t have been.

  4. I would think that any doctor — urologist or radiation oncologist — that wasn’t in business to be profitable wasted a fair amount of money through medical school. Surgery is not our evil, prostate cancer is. Active surveillance has been a tough nut to chew on in the medical community and I understand why. But it’s not a one size fits all solution. If there’s anything better out there for this type of patient it’s simple — prove it. FYI, my last PSA after 6 years with AJCC2002 pT3b prostate cancer is undetectable. … Can anyone let me know why I shouldn’t be happy with that?

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