10-year survival data from the RT01 trial of differing doses of 3D-CRT

According to a paper just published in Lancet Oncology today, the 10-year follow-up results of the RT01 trial carried out under the auspices of the British Medical Research Council have shown an overall survival of 71 percent in both arms of this trial of two types of external beam radiation therapy.

The RT01 trial started enrolling patients back in 1998, when three-dimensional, conformal-beam radiation therapy (3D-CRT) was still the “standard” form of external beam radiation therapy for treatment of prostate cancer, and newer treatments like intensity-modulated radiation therapy (IMRT) and proton beam radiation therapy — let alone stereotactic body radiation therapy (CyberKnife radiation) — were unheard of outside a very select group of cancer centers.

The trial was designed to compare the then standard control dose of 64 Gy in 32 fractions to an escalated dose of 74 Gy in 37 fractions. (Note that many patients getting IMRT for treatment of localized prostate cancer today are being treated with doses of more like 80 Gy.) Patients were enrolled between January 7, 1998 and December 20, 2001, and randomized to one of other arm of the trial. Preliminary results were reported by Dearnaley et al. in 2007 at 5 years of follow-up.

The RT01 trial was an international, open-label, randomized controlled, Phase III trial. All patients had histologically confirmed prostate cancer (clinical stage T1b-T3aN0M0) with a PSA of < 50 ng/ml at diagnosis. All patients also received neoadjuvant androgen deprivation therapy starting 3 to 6 months before the start of their radiotherapy, and continuing until the end of radiotherapy.

The core results of the trial at 10 years of follow-up are as follows:

  • 862 men were initially registered.
  • 843 men were subsequently assigned to either the escalated-dose group (n = 422) or to the control group (n = 421).
  • 236 deaths had occurred as of August 11, 2011: 118 in each group.
  • Average (median) follow-up was 10.0 years
  • Overall survival at 10 years was 71 percent in each group (hazard ratio [HR] = 0.99).
  • Biochemical progression or progressive disease occurred in 391 patients
    • 221/421 (57 percent) in the control group
    • 170/422 (43 percent) in the escalated-dose group
  • Biochemical progression-free survival at 10 years was
    • 43 percent in the control group
    • 55 percent in the escalated-dose group

The authors conclude that, at a median follow-up of 10 years,

escalated-dose conformal radiotherapy with neoadjuvant androgen deprivation therapy showed an advantage in biochemical progression-free survival, but this advantage did not translate into an improvement in overall survival. These efficacy data for escalated-dose treatment must be weighed against the increase in acute and late toxicities associated with the escalated dose and emphasize the importance of use of appropriate modern radiotherapy methods to reduce side-effects.

Additional information about the study is available in a media release from the Institute for Cancer Research, and data on the side effects of treatment observed in this study were also previously reported at 5 years of follow-up. According to the ICR media release,

Men who received the higher dose were more likely to have side-effects associated with radiotherapy, but few men had severe side-effects. Receiving the higher dose reduced the need for follow-up hormone treatment, which also carries a risk of side-effects.

This trial has obviously been outdated by the evolution in newer forms of radiation therapy since it was initially designed and patients were enrolled in the late 1990s and early 2000s. However, it is worth noting that, despite the inclusion of a significant number of very high-risk patients (with clinical stages up to T3a and PSA values up to 50 ng/ml), only 91 of the 236 deaths reported in the current paper were prostate cancer-specific, so the prostate cancer-specific mortality rate in this trial at 10 years of follow-up was 10.8 percent.

These 10-year outcome data from the RT01 trial epitomize one of the major problems in all historical, randomized, Phase III clinical trials designed to assess the relative benefits of differing treatments for relatively early stage prostate cancer: by the time we get really meaningful outcome data, at about 10 years of follow-up, the technological capabilities available have moved far beyond the technological methods that were being tested. Without sophisticated, long-term prostate cancer registries that can track such data over time according to standardized systems, we are never really going to be able to overcome this problem.

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