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A meta-analysis of long-term follow-up of high dose vs conventional dose in external beam radiotherapy of prostate cancer, "Beyond the Abstract," by Zan Hou, Guangjun Li, and Sen Bai

BERKELEY, CA (UroToday.com) - Prostate cancer is the most common cancer in older men in the US, the UK, and Western Europe.[1] External beam radiation therapy (EBRT) is a radical treatment method for localized and locally advanced prostate cancer (T1-4N0-1M0). The National Comprehensive Cancer Network（NCCN) recommends that three-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiation therapy (IMRT) should be used to treat localized and locally advanced prostate cancer. In the past two decades, many nonrandomized clinical trials[2, 3, 4, 5] have suggested that dose escalation in EBRT can bring excellent clinical outcomes, with acceptable toxicity. Nonetheless, the relationship between outcomes such as overall survival (OS) and prostate cancer-specific survival (PCSS) in the randomized controlled trials is still unclear. Therefore, in order to find out their relationships, we conducted a meta-analysis that assessed whether HDRT is superior to CDRT in long-term follow-up.

Six randomized controlled trials with a total population of 2 822 men were included. In terms of 10-year efficacy relative to conventional-dose radiotherapy, high-dose radiotherapy was associated with almost an equivalent OS and PCSS, but a significant decrease in the BF. In terms of toxicity, HDRT significantly increased the late Grade 2 or higher (G ≥ 2) gastrointestinal（GI）toxicity and late G ≥ 2 genitourinary (GU) toxicity. Thus, we came to a conclusion that dose escalation in 3D-CRT should be discreetly used in the treatment of prostate cancer due to the increase of late toxicities.

The emergence of IMRT, image guided radiation therapy (IGRT) and adaptive radiation therapy (ART) guarantee a dose escalation of prostate cancer, while reducing the toxicity of normal tissues. Jeff et al.[6] compared the toxic effects of 3D-CRT and IMRT and found that for both bladder and rectum, the volumes receiving 65, 70, and 75 Gy were significantly lower with IMRT (all P < 0.0001). IMRT is associated with a significant reduction in acute Grade ≥ 2 GI/GU toxicity and late Grade ≥ 2 GI toxicity. Krauss et al.[7] reported a 10-year result of off-line ART which is similar to Jeff et al.

In conclusion, IMRT, IGRT, and ART technologies seem to be safer and more effective. With the use of these technologies, the dose of prostate cancer can even increase to more than 80 Gy.[8] Certainly, more randomized controlled trials are needed to verify that whether these technologies are suitable for a dose escalation in the treatment of prostate cancer.

References:

  1. Cancer Research UK Prostate cancer statistics – key facts (2011) Available from: http://www.cancerresearchuk.org/about-cancer/type/prostate-cancer/
  2. Michalski, J ; Winter, K ; Roach, M. et al. (2012) Clinical Outcome of Patients Treated With 3D Conformal Radiation Therapy (3D-CRT) for Prostate Cancer on RTOG 9406. Int J Radiat Oncol Biol Phys Vol.83(3), pp.E363-E370
  3. Spratt, Daniel E.; Pei, Xin; Yamada, Josh et al. (2013)Long-term Survival and Toxicity in Patients Treated With High-Dose Intensity Modulated Radiation Therapy for Localized Prostate Cancer. Int J Radiat Oncol Biol Phys, March 1, Vol.85(3), p.686(7)
  4. Goldner G. Bombosch V. Geinitz H. et al. (2009) Moderate risk-adapted dose escalation with three-dimensional conformal radiotherapy of localized prostate cancer from 70 to 74 Gy: FFFirst report on 5-year morbidity and biochemical control from a prospective Austrian-German multicenter phase II trial. Strahlentherapie und Onkologie, Vol.185(2), pp.94-100
  5. D'Ambrosio D.J. Pollack A. Harris E.E.R. et al. (2008)Assessment of External Beam Radiation Technology for Dose Escalation and Normal Tissue Protection in the Treatment of Prostate Cancer，Int J Radiat Oncol Biol Phys, Vol.70(3), pp.671-677
  6. Jeff M. Michalski, MD, Yan Yan, MD, MS, Deborah Watkins-Bruner, PhD et al. (2013) Preliminary Toxicity Analysis of 3-Dimensional Conformal Radiation Therapy Versus Intensity Modulated Radiation Therapy on the High-Dose Arm of the Radiation Therapy Oncology Group 0126 Prostate Cancer Trial. Int J Radiat Oncol Biol Phys, Vol.87(5), pp.932-938
  7. Krauss DJ, Yan D, Gustafson GS et al. (2013) Results of image-guided, dose-escalated radiation therapy for localized prostate cancer: 10-year results using an off-line, adaptive technique. Int J Radiat Oncol Biol Phys 87(2):S354–S355-
  8. Daniel E. Spratt, MD, Xin Pei, PhD, Josh Yamada, MD et al. (2013) Long-term Survival and Toxicity in Patients Treated With High-Dose Intensity Modulated Radiation Therapy for Localized Prostate Cancer. Int J Radiat Oncol Biol Phys, Vol.85(3), p.686(7)

Written by:
Zan Hou, Guangjun Li, and Sen Bai as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.

West China Hospital Cancer Center, Sichuan University, Chengdu, People's Republic of China

High dose versus conventional dose in external beam radiotherapy of prostate cancer: A meta-analysis of long-term follow-up - Abstract

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