What is the efficacy of external beam radiotherapy compared with other treatments for local control for locally advanced disease?

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What is the efficacy of external beam radiotherapy compared with other treatments for local control for locally advanced disease?

External beam radiotherapy compared with other treatments for local control

The management of locally advanced prostate cancer has long been controversial. For patients with a reasonable life expectancy, radiotherapy has traditionally been utilised. More recently, hormonal therapy combined with radiotherapy has been shown to improve outcomes. ADT alone has traditionally been used for locally advanced disease in patients with a poor performance status and/or significant co-morbidities predicting a short life expectancy. Locally uncontrolled disease can be a morbid situation for patients, however, and may cause symptoms related to obstruction, renal impairment, bleeding and pain.

Prior to 2006 (the cut-off date for inclusion of trials for this analysis), there were only three randomised trials comparing radiotherapy with alternative treatment approaches for locally advanced prostate cancer. These all asked different questions, contained small numbers of patients (between 73 and 151 patients), used old techniques, and provided conflicting results.

There was a suggestion of improved survival of radiotherapy over orchidectomy in one study of 151 patients[1][2] but at a cost of increased toxicity. Another study of 73 patients[3] suggested that radiotherapy compared with observation did not delay the first onset of metastases but no long-term follow-up with survival was given. A third study of 95 patients[4] suggested an improvement in progression-free survival with surgery and hormones versus low-dose radiotherapy plus hormones, but at the cost of increased toxicity in the surgery group. Long-term follow-up of the Akakura study published since 2006[5] has demonstrated similar results with a non-significant trend for improved disease-free survival but at increased toxicity.

Based on randomised trial evidence, it is not possible to quantify the degree of benefit provided by radiotherapy alone for locally advanced prostate cancer and that the role of surgery or hormonal therapy alone in this group of patients remains to be defined. However, as detailed in the section on the Role of brachytherapy, the totality of data supports the use of androgen deprivation and radiotherapy over radiotherapy alone. The degree of benefit of adding radiotherapy to androgen deprivation was uncertain until a landmark Scandinavian trial was published in The Lancet in January 2009.87 This randomised 875 men with high-risk prostate cancer to hormonal therapy alone (three months of combined androgen blockade followed by indefinite flutamide) or to the same hormonal therapy combined with radiation (3D conformal radiotherapy to prostate and seminal vesicles to dose of 70Gy). Of the cohort 78% had T3 disease and 40% had a PSA>20. With a median follow-up of 7.6 years, there was a 10% improvement in overall survival with the radiotherapy arm (70.4% versus 60.6%). Prostate-specific mortality (for T3 and PSA>20 subgroups as well as the entire cohort) and biochemical control were also improved with the addition of radiotherapy but at the cost of slightly higher rates of urinary, bowel and sexual problems at five years.

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Evidence summary and recommendations

Evidence summary Level References
There are only three randomised trials comparing radiotherapy with alternative treatment approaches for locally advanced prostate cancer. These all asked different questions, contained small numbers of patients, used old techniques, and provided conflicting results. The current body of evidence does not exclude a clinically important benefit with the use of radiotherapy in locally advanced prostate cancer. II, III-1 [1], [2], [3], [4], [5], [6]
Evidence-based recommendationQuestion mark transparent.png Grade
Based on randomised trial evidence, it is not possible to quantify the degree of benefit

provided by radiotherapy alone for locally advanced prostate cancer. The role of surgery or hormonal therapy alone in this group of patients remains to be defined.

D


Evidence-based recommendationQuestion mark transparent.png Grade
Radiation in addition to hormone therapy improves survival and is recommended.
B


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References

  1. 1.0 1.1 Aro J, Haapiainen R, Kajanti M, Rannikko S, Alfthan O. Comparison of endocrine and radiation therapy in locally advanced prostatic cancer. Eur Urol 1988;15(3-4):182-6 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/3063541.
  2. 2.0 2.1 Aro J, Haapiainen R, Kajanti M, Rannikko S, Alfthan O. Orchiectomy, estrogen therapy and radiotherapy in locally advanced (T3-4 M0) prostatic cancer. Scand J Urol Nephrol Suppl 1988;110:103-7 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/3187397.
  3. 3.0 3.1 Paulson DF, Hodge GB Jr, Hinshaw W. Radiation therapy versus delayed androgen deprivation for stage C carcinoma of the prostate. J Urol 1984 May;131(5):901-2 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/6423840.
  4. 4.0 4.1 Akakura K, Isaka S, Akimoto S, Ito H, Okada K, Hachiya T, et al. Long-term results of a randomized trial for the treatment of Stages B2 and C prostate cancer: radical prostatectomy versus external beam radiation therapy with a common endocrine therapy in both modalities. Urology 1999 Aug;54(2):313-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/10443731.
  5. 5.0 5.1 Akakura K, Suzuki H, Ichikawa T, Fujimoto H, Maeda O, et al. A randomized trial comparing radical prostatectomy plus endocrine therapy versus external beam radiotherapy plus endocrine therapy for locally advanced prostate cancer: results at median follow-up of 102 months. Japanese Study Group for Locally Advanced Prostate Cancer,. Jpn J Clin Oncol 2006 Dec;36(12):789-93 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17082219.
  6. Isaka S, Shimazaki J, Akimoto S, Okada K, Yoshida O, Arai Y, et al. A prospective randomized trial for treating stages B2 and C prostate cancer: radical surgery or irradiation with neoadjuvant endocrine therapy. Jpn J Clin Oncol 1994 Aug;24(4):218-23 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/8072201.

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Appendices