Some data from a randomized, prospective trial of surgery vs. radiation therapy

We should emphasize immediately that the available data from the trial discussed below are not exactly compelling. For whatever reasons, the trial didn’t enroll enough patients to allow any conclusions about the relative effectiveness to the two forms of treatment.

Between 1996 and 2001, Lennernäs et al. enrolled Swedish patients with a broad spectrum of localized or locally advanced prostate cancer (clinical stage T1b-T3aN0M0 and PSA ≤ 50 ng/ml) who agreed to be randomized to one or other of two forms of treatment:

  • 6 months of androgen deprivation therapy (ADT) and an open radical prostatectomy or
  • 6 months of ADT and a combination of high-dose rate brachytherapy (2 × 10 Gy) and external beam radiotherapy (25 × 2 Gy)

It is not clear from the abstract of the paper whether the 6 months of ADT was all given prior to the other treatment (i.e., as neoadjuvant ADT) or before and after the other treatment (i.e., as neoadjuvant and adjuvant ADT). All patients were asked to complete standard questionnaires related to health-related quality of life (HRQoL) and all relevant symptoms (e.g., urinary, bowel, and sexual side effects) were investigated prospectively prior to randomization as well as at 12 and 24 months after randomization.

The authors report the following results:

  • 89 men were enrolled into the trial.
  • 8/89 men (9 percent) died of prostate cancer (but the total follow-up period is not available).
  • Overall survival during the follow-up period was 76 percent.
  • There were no discernible differences in HRQoL or complications between the two groups.
  • There was a statistically significant improvement in emotional functioning over time in both groups of patients.
  • There was a significant decrease in social functioning over time in both groups.
  • Financial difficulties increased over time in both groups.

As indicated above,

It was not possible to draw any conclusion on the efficacy of the two treatments due to insufficient power of the study.

One can ask all sorts of questions about this study:

  • Why were so few patients enrolled?
  • Exactly how broad was the spectrum of patients being enrolled?
  • Why did all the patients get ADT?
  • Why are the results are only being published 13 years after the last patient was enrolled?

At this point in time, however, all we can reasonably conclude from this study is that aggressive treatment of localized/locally advanced prostate cancer tends to have significant impact on patients over time, probably regardless of the type of treatment. This is not exactly a revelation.

The full text of the paper (which we have not seen) may provide answers to some of the above questions, but it probably does not enlighten us further with regard to any differences between patients’ short- or long-term outcomes. It may well be that a much larger study had originally been planned, but the investigators had difficulty getting patients to accept randomization (always a problem here in the USA with studies of this type). Or it may be that this was only ever intended as a pilot study for a larger initiative.

One Response

  1. I think all of these types of comparative studies of initial treatment will be difficult to recruit for. Most patients I’ve met form distinct opinions about which kind of treatment they want for themselves. In fact, as a patient advocate, I encourage them to read sites like this one in order to form their own preferences. Also, the very fact that the trial is being run under ethical guidelines may encourage patients to look at an option that he had written off before. In Scandinavia, there is a randomized comparison trial (NCT02102477) of surgery ± a/sRT vs EBRT + ADT for locally advanced patients. It just started in 2014. We’ll have to see how well it recruits.

    Another such randomized comparative trial — the PACE study — was cancelled last year. It sought to randomize favorable risk men to surgery or SBRT, and if surgery was refused or otherwise contraindicated, to SBRT or IMRT. I think the surgery/radiation divide may be too wide to cross. The CEASAR study in the US gets around the randomization problem by establishing registries for all patients treated at six sites. Because registries are population-based and not samples, they avoid the selection bias inherent in non-randomized samples. They are starting with the states of New Jersey and Louisiana, tertiary care facilities in Atlanta and Los Angeles and the CAPSURE database. The goal would be to someday have a national registry.

    Within the radiation category there are a few randomized trials comparing various fractionation schemes for external beam radiation. This is facilitated by the fact that radiation oncologists who do SBRT also do IMRT. But even within a category, we run into problems owing to specialization. A urologist proficient at open surgery may not be proficient at robotic surgery, and vice versa. Randomized patients would be sent to different surgeons who may have different proficiencies. In a study of, say, HDR vs LDR brachytherapy, the centers that do one often are not proficient in both.

    On top of those considerations, there are problems with how long such studies must run to demonstrate an oncological or toxicity advantage, and the large costs involved in long-term maintenance of the database. While randomized clinical trials are desirable, I think we will have to make our decisions without benefit of them, at least for a very long time.

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