Radiation Dose Escalation Most Effective for Intermediate Prostate Cancer
Last Updated: 2009-12-10 19:38:47 -0400 (Reuters Health)
The newer technologies, including intensity-modulated radiotherapy, brachytherapy, and brachytherapy plus external beam radiation therapy, have all replaced conventional-dose 3D-conformal radiotherapy at Mayo Clinic
Lead investigator Dr. William W. Wong, a radiation oncologist at the Scottsdale-based clinic, told Reuters Health that most reports comparing these radiation modalities are outdated due to rapidly advancing technology. "The goal for us is to keep updating our data when new techniques are used so that we can find out whether there is improvement in treatment outcome and toxicity profile," Dr. Wong said.
The study included 853 patients with localized prostate cancer treated over an 11-year period with conventional-dose 3D-conformal radiotherapy (270 patients), high-dose intensity-modulated radiotherapy (314 patients), brachytherapy (225 patients) or external beam brachytherapy plus a brachytherapy boost (44 patients).
The intensity-modulated radiotherapy, brachytherapy and external beam brachytherapy plus brachytherapy protocols all had considerably greater biologically equivalent radiation doses than conventional-dose 3D-conformal radiotherapy.
Dr. Wong's group used biochemical control rates as the primary outcome measure and also looked at the effect of T classification, PSA level, Gleason score, perineural invasion, androgen deprivation therapy and risk grouping (low, intermediate or high) on patient outcome.
Overall 5-year biochemical control rates with conventional-dose 3D-conformal radiotherapy (74%) were significantly lower than rates with intensity-modulated radiotherapy (87%), brachytherapy (94%) and external beam brachytherapy plus brachytherapy (94%).
But if patients were in a clinically low-risk group, the radiation modality was not important to biochemical control (p = 0.22). The analysis of high-risk patients was complicated by the small numbers in this group; researchers could only say that intensity-modulated radiotherapy (74%) was significantly more effective in achieving biochemical control than 3D-conformal radiotherapy (49%), p=0.027.
The large group of intermediate-risk patients yielded the most clear-cut results. While 3D-conformal radiotherapy was associated with a 74% rate of biochemical control in intermediate patients, all the higher dose modalities led to significantly better control rates (intensity-modulated radiotherapy 88%, brachytherapy 94%, brachytherapy plus external beam radiation therapy 94%; p<0.0001).
In both univariate and multivariate analyses, biochemical control was significantly influenced by radiation modality, T classification, Gleason score, PSA level and perineural invasion. Risk classification was only assessed in univariate analysis and was significant.
The report also characterizes the incidence of gastrointestinal and genitourinary complications in the various radiation modalities. While no Grade 5 or 4 toxicities occurred (deaths or major surgeries and hospitalizations), there were some Grade 3 toxicities that lowered quality of life, such as urethral structure, incontinence and chronic pain.
Intensity-modulated radiotherapy and 3D-conformal radiotherapy shared similar rates of GI toxicities, but for GU toxicity, intensity-modulated radiotherapy was significantly more likely to cause early (49%) and late (27%) Grade 2 complications.
Also of note, acute and late GU toxicities were more common with brachytherapy or brachytherapy plus external beam brachytherapy compared to intensity-modulated radiotherapy and 3D-conformal radiotherapy.
For example, late Grade 3 GU complications were seen in 18% of brachytherapy and brachytherapy plus external beam brachytherapy patients compared with 5% of intensity-modulated radiotherapy and 3D-conformal radiotherapy patients. Late GI toxicities are also more frequent with brachytherapy plus external beam brachytherapy compared with all other modalities.
Other groups have found that androgen deprivation therapy appeared to improve outcomes when used in combination with external beam brachytherapy. In Dr. Wong's population, androgen deprivation therapy had no effect.
Dr. Wong noted that prior androgen deprivation therapy plus external beam brachytherapy studies used lower radiation doses and that the higher doses his group uses for intensity-modulated radiotherapy and brachytherapy may wash out the treatment effect of androgen deprivation therapy.
"A randomized prospective trial is needed to define the benefits of adjuvant androgen deprivation therapy and high-dose irradiation compared with high-dose irradiation alone," he said.
Cancer 2009:115:5596-5606.
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