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ESOU18

ESOU18: Treatment Modalities for Intermediate Risk Prostate Cancer - Hypofractionation Radiotherapy

Amsterdam, The Netherlands (UroToday.com) The significant role of dose-escalation in the radiation treatment (RT) of localized prostate cancer (PC) is well established. Nevertheless, when delivered at conventional fractionation (CF, 1.8-2 Gy/fraction), the prolonged treatment time of high-dose RT (7-8 weeks) can lead to a high number of hospital visits. In the linear quadratic model, describing the relationship between cell survival and total radiation dose/dose per fraction, the response of both normal and neoplastic tissue to fraction size is described by the VVV ratio. For most tumors, this ratio is generally high, in the range of 8-10 Gy. In contrast, several studies have demonstrated a much lower ratio (not greater than 1.5 Gy) for PC, leading to a strong rationale for hypofractionation in the radiation treatment of PC. The delivery of fewer radiotherapy fractions, each of a higher dose than that used in CF, was assumed to result in a similar biological dose delivered, without increasing the risk of gastrointestinal (GI) and genitourinary (GU) toxicity. The results of several randomized phase III trials comparing CF and hypofractionation have recently been published. Two of these studies, also enrolled patients with intermediate risk PC (IRPC) and have shown no difference between CF and hypofractionation. [1,2] 

Despite these encouraging but preliminary results, the safety and oncological adequacy of stereotactic body radiation therapy (SBRT) in the management of IRPC needs to be confirmed by ongoing phase III trials. Meanwhile, the preliminary results of an ongoing phase III study comparing moderate hypofractionation with SBRT indicate equivalent and overall mild patient-reported changes in bowel and sexual domains. However, an apparently worse deterioration in urinary symptoms is seen in patients treated with moderate hypofractionation.[3] 

Another challenging issue is that of the feasibility of and indications for prophylactic whole pelvic nodal irradiation in the context of hypofractionation[4], in patients with moderate/high risk of lymph node involvement. Several series have reported the feasibility and clinical efficacy of a simultaneous integrated boost (SIB) intensity modulated radiation therapy (IMRT) approach in which both the prostate (± seminal vesicles), and pelvic lymph-nodes can be safely irradiated with daily doses in the range of 2.5-3.2 and 1.8-2 Gy, respectively. [4] 

Lastly, it is important to note that androgen deprivation therapy, which was differently prescribed in all the above mentioned trials, (usually being at the discretion of the referring radiation oncologist), did not seem to significantly improve clinical outcome. In a recent retrospective analysis of over 19,000 patients with favorable IRPC, treated with modern dose-escalated radiotherapy at conventional fractionation ± ADT, no benefit whatsoever emerged from the combined-modality (ADT+RT) treatment. [5] Therefore, it is safe to assume, that in the near future, patients with IRPC treated with moderate or extreme hypofractionation, could be spared the additional costs and morbidity of ADT.

Speaker: Cesare Cozzarini, MD Department of Radiation Oncology San Raffaele Scientific Institute Milan, Italy. 

Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre @GoldbergHanan at The 15th Meeting of the EAU Section of Oncological Urology ESOU18 - January 26-28, 2018 - Amsterdam, The Netherlands

References:

  1. Pollack A, Walker G, Horwitz EM, et al. Randomized trial of hypofractionated external-beam radiotherapy for prostate cancer. J Clin Oncol 2013, 31:3860-3868. 
  2. Incrocci L, Wortel RC, Alemayehu WC et al. Hypofractionated versus conventionally fractionated radiotherapy for patients with localized prostate cancer (HYPRO): final efficacy results from a randomised, multicentre, open-label, phase 3 trial. Lancet Oncol 2016, 17:1061- 1069.
  3. Johnson SB, Soulos PR, Shafman TD, et al. Patient-reported quality of life after stereotactic body radiation therapy versus moderate hypofractionation for clinically localized prostate cancer. Radiother Oncol 2016, 121:294-298. 
  4. Kaidar-Person O, Roach M 3rd, Créhange G. Whole-pelvic nodal radiation therapy in the context of hypofractionation for high-risk prostate cancer patients: a step forward. Int J Radiat Oncol Biol Phys 2013, 86:600-605. 
  5. Falchook AD, Basak R, Mohiuddin JJ, Chen RC. Evaluation of the effectiveness of adding androgen deprivation to modern dose-escalated radiotherapy for men with favorable intermediate-risk prostate cancer. Cancer, 2016 122:2341-2349