Rectal Sparing Via Hydrogel Spacer For Dose-Escalated Hypofractionated Radiation Course In High Risk Localized Prostate Cancer: Analysis Of Dosimetric and Toxicity Outcomes

Pasquale Gambardella1, Stefano Arcangeli2, Alessia Monaco2, Cristina Caruso2, Michele Cianciulli2, Genoveva Boboc2, Maria Cristina Pressello3, Vittorio Donato2
  • 1 Azienda Ospedaliera San Camillo-Forlanini - U.O. Urologia (Roma)
  • 2 Azienda Ospedaliera San Camillo-Forlanini - U.O. Radioterapia (Roma)
  • 3 Azienda Ospedaliera San Camillo-Forlanini - U.O. Fisica Medica (Roma)


Radiation dose-escalation is a major issue in prostate cancer, since there is growing evidence that cure rates indicated by biochemical disease-free survival and prostate cancer-specific survival depend on the radiation dose to the target [1]. However, increased radiation dose to the rectum results in dose – limiting toxicity [2]. The aim of this study is to evaluate the contribution of an injection of an absorbable synthetic polyethylene glycol (PEG) hydrogel for temporarily separating the rectum and prostate during a dose-escalated hypofractionated course of radiotherapy (RT) for high – risk prostate cancer (PCa) in order to decrease the rectal radiation-induced toxicity.

Methods and results

Eight patients with high risk, localized PCa underwent a dose-escalated hypofractionated radiation schedule of 16 fractions of 3.5 Gy for a total dose of 56 Gy to prostate and seminal vesicles, considered isoeffective to 80 Gy with conventional fractionation with regard to tumor control (a/b value of 1.5 Gy) and administered with Helical Tomotherapy (HT). All patients were simulated before and after a transperineal injection of a spacer in order to increase the distance between the prostate and the rectal wall. MRI scans were used for anatomical assessment of rectal separation. HT plans were generated on both scans for dosimetric comparisons. Procedure adverse events and acute GI toxicity according to RTOG were documented. The hydrogel placement in the Denonvillier space was successfully obtained in all patients without complications, with a median gel thickness at midgland of 11 mm (range, 6-16 mm). Dosimetric comparisons between preinjection and postinjection plans showed a statistically significant reductions (p<0.005) in rectal dose across high dose levels, resulting in a maximum reduction in rectal volume receiving 90% and 75% of the prescription dose of 19.6 Gy (35%) and 15.68 Gy (28%), respectively. No significant dose reductions were seen at low rectal dose levels. After a median follow up of 6 months (range 3 to 12 months), no patients experienced RTOG grade ≥ 2 rectal toxicity and two patients were classified as having RTOG grade 1 rectal toxicity in the last week of radiotherapy, completely resolved within 40 days.


Despite advanced treatment delivery and a more favourable therapeutic ratio, that can be exploited by a hypofractionated approach, dose escalation leads to increased side effects [3-5]. As a consequence up to 20% of the patients develop acute and chronic grade ≥ 2 rectal toxicity after dose-escalated RT, either normo or hypofractionated [6-8]. A method of reducing the amount of rectum treated to higher dose levels would be expected to result in reduction of the rate of rectal toxicity. The current study shows that the decrease in high rectal dose levels obtained by the use of a hydrogel spacer is associated with negligible acute GI toxicity and allows dose-escalated hypofractionated radiotherapy. Longer follow-up is warranted to assess late toxicity and define which patients might benefit from this approach.


1. Viani GA, Stefano EJ, Afonso SL: Higher-than-conventional radiation doses in localized prostate cancer treatment: a meta-analysis of randomized, controlled trials. Int J Radiat Oncol Biol Phys 2009, 74(5):1405–1418.
2. Kuban D, Pollack A, Huang E, Levy L, Dong L, Starkschall G, Rosen I: Hazards of dose escalation in prostate cancer radiotherapy. Int J Radiat Oncol Biol Phys 2003, 57(5):1260–1268
3. Al-Mamgani A, van Putten WL, Heemsbergen WD, van Leenders GJ, Slot A, Dielwart MF, Incrocci L, Lebesque JV: Update of Dutch multicenter dose escalation trial of radiotherapy for localized prostate cancer. Int J Radiat Oncol Biol Phys 2008, 72(4):980–988
4. Dearnaley DP, Sydes MR, Graham JD, Aird EG, Bottomley D, Cowan RA, Huddart RA, Jose CC, Matthews JH, Millar J, et al: Escalated-dose versus standard-dose conformal radiotherapy in prostate cancer: first results from the MRC RT01 randomised controlled trial. Lancet Oncol 2007, 8(6):475–487
5. Syndikus I, Morgan RC, Sydes MR, Graham JD, Dearnaley DP: Late gastrointestinal toxicity after dose-escalated conformal radiotherapy for early prostate cancer: results from the UK Medical Research Council RT01 trial (ISRCTN47772397). Int J Radiat Oncol Biol Phys 2010, 77(3):773–783.
6. Al-Mamgani A, Heemsbergen WD, Peeters ST, Lebesque JV: Role of intensity modulated radiotherapy in reducing toxicity in dose escalation for localized prostate cancer. Int J Radiat Oncol Biol Phys 2009, 73(3):685–691.
7. Zelefsky MJ, Levin EJ, Hunt M, Yamada Y, Shippy AM, Jackson A, Amols HI: Incidence of late rectal and urinary toxicities after three-dimensional conformal radiotherapy and intensity-modulated radiotherapy for localized prostate cancer. Int J Radiat Oncol Biol Phys 2008, 70(4):1124–1129
8. Arcangeli S, Strigari L, Gomellini S, et al. Updated Results and Patterns of Failure in a Randomized
Hypofractionation Trial for High-risk Prostate Cancer. Int J Radiation Oncol Biol Phys 2012, 84 (5): 1172-1178