Michael R Folkert1, Michael J Zelefsky2, Raquibul Hannan3, Neil B Desai3, Yair Lotan4, Aaron M Laine5, D W Nathan Kim3, Sarah Hardee Neufeld3, Brad Hornberger4, Marisa A Kollmeier2, Sean McBride2, Chul Ahn6, Claus Roehrborn4, Robert D Timmerman3. 1. Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas. Electronic address: michaelr.folkert@utsouthwestern.edu. 2. Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York. 3. Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas. 4. Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas. 5. Center for Cancer and Blood Disorders, Weatherford, Texas. 6. Department of Biostatistics, University of Texas Southwestern Medical Center, Dallas, Texas.
Abstract
PURPOSE: High-dose SABR for prostate cancer offers the radiobiologic potency of the most intensified radiation therapy regimens but was associated with >90% rates of ulceration of the anterior rectal wall on endoscopic assessment; this infrequently progressed to severe rectal toxicity in prior prospective series. A multi-institutional phase 2 prospective trial was conducted to assess whether placement of a perirectal hydrogel spacer would reduce acute periprostatic rectal ulcer events after high-dose (>40 Gy) SABR. METHODS AND MATERIALS: Eligible patients included men with stage ≤T2c localized grade group 1 to 3 prostate cancer, a prostate-specific antigen (PSA) level ≤15 ng/mL, American Urological Association Symptom Index = AUA-SI scores ≤18, and a gland volume ≤80 cm3. Patients underwent perirectal hydrogel spacer placement, followed by SABR of 45 Gy in 5 fractions every other day to the prostate only. Androgen deprivation was not allowed except for cytoreduction. The rectal wall was directly assessed by serial anoscopy during follow-up to determine whether the spacer would reduce acute periprostatic rectal ulcer events from >90% to <70% within 9 months of treatment. RESULTS: Forty-four men were enrolled and 43 were eligible for protocol analysis. The median follow-up for surviving patients was 48 months. Acute periprostatic ulcers were observed in 6 of 42 patients (14.3%; 95% confidence interval, 6.0%-27%; P < .001) at a median of 2.9 months posttreatment (range, 1.7-5.6 months). All ulcers (grade 1, 5 ulcers; grade 2, 1 ulcer) resolved on repeat anoscopy within 8 months of incidence. There were no grade ≥3 late gastrointestinal toxicities; the incidence of late grade-2 gastrointestinal toxicities was 14.3%, with a prevalence at 3 years of 0%. No toxicities greater than grade 3 occurred in any domain. Four-year freedom from biochemical failure was 93.8% (95% CI, 85.2%-100.0%). CONCLUSIONS: Temporary hydrogel spacer placement before high-dose SABR treatment for localized prostate cancer and use of strict dose constraints are associated with a significant reduction in the incidence of rectal ulcer events compared with prior phase 1/2 trial results.
PURPOSE: High-dose SABR for prostate cancer offers the radiobiologic potency of the most intensified radiation therapy regimens but was associated with >90% rates of ulceration of the anterior rectal wall on endoscopic assessment; this infrequently progressed to severe rectal toxicity in prior prospective series. A multi-institutional phase 2 prospective trial was conducted to assess whether placement of a perirectal hydrogel spacer would reduce acute periprostatic rectal ulcer events after high-dose (>40 Gy) SABR. METHODS AND MATERIALS: Eligible patients included men with stage ≤T2c localized grade group 1 to 3 prostate cancer, a prostate-specific antigen (PSA) level ≤15 ng/mL, American Urological Association Symptom Index = AUA-SI scores ≤18, and a gland volume ≤80 cm3. Patients underwent perirectal hydrogel spacer placement, followed by SABR of 45 Gy in 5 fractions every other day to the prostate only. Androgen deprivation was not allowed except for cytoreduction. The rectal wall was directly assessed by serial anoscopy during follow-up to determine whether the spacer would reduce acute periprostatic rectal ulcer events from >90% to <70% within 9 months of treatment. RESULTS: Forty-four men were enrolled and 43 were eligible for protocol analysis. The median follow-up for surviving patients was 48 months. Acute periprostatic ulcers were observed in 6 of 42 patients (14.3%; 95% confidence interval, 6.0%-27%; P < .001) at a median of 2.9 months posttreatment (range, 1.7-5.6 months). All ulcers (grade 1, 5 ulcers; grade 2, 1 ulcer) resolved on repeat anoscopy within 8 months of incidence. There were no grade ≥3 late gastrointestinal toxicities; the incidence of late grade-2 gastrointestinal toxicities was 14.3%, with a prevalence at 3 years of 0%. No toxicities greater than grade 3 occurred in any domain. Four-year freedom from biochemical failure was 93.8% (95% CI, 85.2%-100.0%). CONCLUSIONS: Temporary hydrogel spacer placement before high-dose SABR treatment for localized prostate cancer and use of strict dose constraints are associated with a significant reduction in the incidence of rectal ulcer events compared with prior phase 1/2 trial results.
Authors: Raquibul Hannan; Samer Salamekh; Neil B Desai; Aurelie Garant; Michael R Folkert; Daniel N Costa; Samantha Mannala; Chul Ahn; Osama Mohamad; Aaron Laine; Dong W Nathan Kim; Tamara Dickinson; Ganesh V Raj; Rajal B Shah; Jing Wang; Xun Jia; Hak Choy; Claus G Roehrborn; Yair Lotan; Robert D Timmerman Journal: Int J Radiat Oncol Biol Phys Date: 2021-11-11 Impact factor: 8.013
Authors: Lily Chen; Bhavani S Gannavarapu; Neil B Desai; Michael R Folkert; Michael Dohopolski; Ang Gao; Chul Ahn; Jeffrey Cadeddu; Aditya Bagrodia; Solomon Woldu; Ganesh V Raj; Claus Roehrborn; Yair Lotan; Robert D Timmerman; Aurelie Garant; Raquibul Hannan Journal: Front Oncol Date: 2022-02-21 Impact factor: 6.244
Authors: Michael C Repka; Michael Creswell; Jonathan W Lischalk; Michael Carrasquilla; Matthew Forsthoefel; Jacqueline Lee; Siyuan Lei; Nima Aghdam; Shaan Kataria; Olusola Obayomi-Davies; Brian T Collins; Simeng Suy; Ryan A Hankins; Sean P Collins Journal: Front Oncol Date: 2022-03-31 Impact factor: 6.244