Absorbable hydrogel spacer use in men undergoing prostate cancer radiotherapy: 12 month toxicity and proctoscopy results of a prospective multicenter phase II trial
© Uhl et al.; licensee BioMed Central Ltd. 2014
Received: 19 October 2013
Accepted: 15 April 2014
Published: 24 April 2014
Radiation therapy is one of the recommended treatment options for localized prostate cancer. In randomized trials, dose escalation was correlated with better biochemical control but also with higher rectal toxicity. A prospective multicenter phase II study was carried out to evaluate the safety, clinical and dosimetric effects of the hydrogel prostate-rectum spacer. Here we present the 12 months toxicity results of this trial.
Fifty two patients with localized prostate cancer received a transperineal PEG hydrogel injection between the prostate and rectum, and then received IMRT to a dose of 78 Gy. Gastrointestinal and genitourinary toxicity were recorded during treatment and at 3, 6 and 12 months following irradiation by using the RTOG/EORTC criteria. Additionally, proctoscopy was performed 12 months after treatment and the results were scored using the Vienna Rectoscopy Scale (VRS).
Of the patients treated 39.6% and 12.5% experienced acute Grade 1 and Grade 2 GI toxicity, respectively. There was no Grade 3 or Grade 4 acute GI toxicity experienced in the study. Only 4.3% showed late Grade 1 GI toxicity, and there was no late Grade 2 or greater GI toxicity experienced in the study. A total of 41.7%, 35.4% and 2.1% of the men experienced acute Grade 1, Grade 2 and Grade 3 GU toxicity, respectively. There was no Grade 4 acute GU toxicity experienced in the study. Late Grade 1 and Grade 2 GU toxicity was experienced in 17.0% and 2.1% of the patients, respectively. There was no late Grade 3 or greater GU toxicity experienced in the study. Seventy one percent of the patients had a VRS score of 0, and one patient (2%) had Grade 3 teleangiectasia. There was no evidence of ulceration, stricture or necrosis at 12 months.
The use of PEG spacer gel is a safe and effective method to spare the rectum from higher dose and toxicity.
Prostate cancer is the most common cancer in older men in the USA and Europe. The predicted 2013 prostate cancer death rate in Europe is 10.5/100.000 men. Despite treatment advances, prostate cancer still ranks third in cancer death, after lung and colon carcinoma. Furthermore, the incidence of new prostate cancer cases in 2010 was the highest of cancers among men in developed countries across the globe. Radiation therapy or prostatectomy are often the recommended treatment options for localized prostate cancer[3, 4]. In patients undergoing prostate radiotherapy biochemical control is improved with dose escalation. However, dose escalation can also increase rectal toxicity due to the prostate - rectum proximity. Although highly conformal techniques like imaged guided radiation therapy (IMRT) are able to improve dose sparing of the rectum wall, the dose to the anterior rectal wall remains high[6–8]. The dose escalation study of Kuban, et al., was able to demonstrate a direct relationship between the volume of treated rectum and rectal toxicity. The Heemsbergen et al. publication on 553 evaluable patients from the Dutch dose escalation trial demonstrated a correlation between the acute toxicity and frequency of late rectal toxicity. Several methods have been developed to create space between the prostate and rectum to allow for prostate dose escalation while reducing rectal wall irradiation[10–12]. One of these methods is a polyethylene glycol (PEG) hydrogel that is injected between the rectum and the prostate before treatment planning and remains stable over the treatment period. A prospective multicenter phase II study was carried out to evaluate the safety, clinical, and dosimetric effects of the hydrogel prostate-rectum spacer. Fifty-two men with localized prostate cancer were included in this trial[13, 14]. In February 2013 Uhl et al. published the initial clinical outcomes with acute toxicity results of the first 48 patients and late toxicity of the first 27 patients. Six patients (12%) experienced acute Grade 2 GI toxicity (no Grade 3 or 4 toxicity), while Grade 2 and Grade 3 GU toxicity was experienced in 17 (35%) and 1 (2%) of the patients, respectively. One year after the end of therapy no Grade 2 or higher GU/GI toxicity occurred. This publication presents the results from all patients following study completion, 12 months following completion of EBRT and includes results of planned proctoscopic evaluation.
As previously described 52 men with pathologically confirmed stage T1 or T2 prostate cancer were evaluated in this prospective, non-randomized, multi-center, single arm, open-label trial. The study included otherwise healthy patients with prostates < 80 cc, PSA ≤ 20 ng/mL, Gleason Score ≤ 6 or Gleason Score 7 with a grade 3 predominant pattern. Excluded were patients with metastatic disease, planned pelvic lymph node radiotherapy, prior prostate surgery, uncontrolled diabetes, chronic systemic corticosteroid therapy, prior prostate or pelvis radiation therapy, active bleeding disorder, historical or active inflammatory bowel disease, or a history of rectal or gastrointestinal surgery. Androgen deprivation therapy was not an exclusion criteria. Following local Ethics Committee approvals patients were enrolled at the University of Heidelberg (n = 21), University of Aachen (n = 20), NKI-AVL Nederlands Kanker Instituut Amsterdam (n = 7) and University of Geneva (n = 4).
Acute and late GI/GU toxicity (Maximum score)
GI toxicity scores (n %)
GU toxicity scores (n %)
Grade 1 or worse
Grade 2 or worse
The use of PEG spacer gel is a safe and effective method to spare the rectum from higher dose and toxicity. Due to fewer late side effects on the rectum, along with the potential of enabling hypofractionation and dose escalation, the hydrogel spacer may lead to lower costs for the healthcare system.
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