What is the efficacy of external beam radiotherapy techniques for locally advanced disease?
Definitive external beam radiotherapy techniques for locally advanced disease
There are nine randomised controlled trials comparing various definitive external beam radiotherapy techniques that include men with locally advanced disease. These studies investigate:
- limited versus extended field radiotherapy (three trials)
- various dose regimens (four trials), and
- conformal versus conventional techniques (two trials).
Limited radiation fields refer to treating the prostate alone with or without the seminal vesicles, whereas extended field radiotherapy includes treating the whole pelvis and in some cases the paraaortic nodes. The dose regimen trials have used various techniques to explore dose-escalated radiotherapy to between 74 and 80Gy compared with the more traditional doses between 64 and 70Gy. 3D conformal radiotherapy refers to the practice of conforming the shape of radiation fields to the prostate (based on CT imaging) in order to reduce dose to critical surrounding tissues.
The studies are variously limited by lack of stratification for types of locally advanced disease, old definitions of locally advanced disease, small numbers, lack of standardisation of endocrine therapy, differences in nodal volumes irradiated, relatively short follow-up, lack of blinding and lack of quality-of-life endpoints. Efficacy outcomes for locally advanced disease are restricted to subgroup analyses and the only toxicity data reported is for entire cohorts of men with T1–4 disease. Overall there are low volumes of good-quality evidence available.
Notwithstanding the above limitations, the two subgroup analyses comparing limited with extended field radiotherapy and examining efficacy outcomes show no differences in efficacy in terms of survival, progression-free survival or metastases. In the entire cohorts of men with T1–4 disease there are no consistent differences in reported toxicity. Because of this, it is common practice in Australia to treat limited fields only. However treating the whole pelvis can be justified in selected high-risk patients as at least two of the randomised trials demonstrating the benefit of combining adjuvant ADT with radiotherapy have incorporated whole pelvis radiotherapy.
Studies of dose escalation consistently show improved efficacy in terms of freedom from biochemical or clinical failure for high-risk patients  including a subgroup of 60 T3 patients. This trend was statistically significant in two of the studies. Late rectal toxicity appears to be worse with higher doses. For other endpoints there appear to be inconsistent differences. Late rectal toxicity appears to be worse with higher doses. There is a potential for dose escalation to have a significant clinical impact by improving efficacy. Further evidence is required in this subgroup of patients.
Studies comparing conformal with conventional radiotherapy are not powered for differences inefficacy. There are inconsistent differences in acute and late toxicities, although the differences that exist all favour conformal radiotherapy. There is potential to have a significant clinical impact by reducing toxicity. Further evidence is required in this subgroup of patients.
Evolution in technologies has led to refinements in 3D conformal therapies with the introduction of Intensity modulated and image guided radiation treatments ( IMRT and IGRT) which allow for better targeting of the prostate and shielding of critical surrounding tissues. These techniques facilitate improved delivery of dose escalated external beam radiation therapy. The results of these newer methods of delivery of treatment will no doubt become available in due course. Furthermore, the role of shortened courses of 3D conformal radiation therapy (hypo-fractionated regimens with biologically equivalent doses) compared with the traditional long courses of conventionally fractionated 3D conformal treatments are also currently being investigated in randomised studies.
Evidence summary and recommendations
| There is no evidence to support the routine use of extended field radiotherapy for locally advanced prostate cancer. The role of whole pelvis radiotherapy has yet to be defined.
There is some evidence to support the increased efficacy for doseescalated external beam radiotherapy for biochemical and clinical relapse. These data have not yet translated into improved survival or a reduction in distant disease-free survival. There is some evidence that dose-escalation increases toxicity, however, the impact on quality of life is yet to be determined. It is uncertain whether an benefits of dose escalation can be generalised to patients receiving neoadjuvant and/or adjuvant endocrine therapy. There is evidence that conformal radiotherapy decreases toxicity compared with conventional radiotherapy
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When radiation therapy alone is used, limited field radiotherapy has similar efficacy and has less toxicity than whole pelvis and therefore is recommended. The role of whole pelvis radiation is yet to be defined.
Consideration should be given to dose escalation (74Gy or higher) if it can be delivered safely.
Patients with locally advanced prostate cancer should receive 3D conformal radiation to minimise toxicity.
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