Focal Boosted IMRT Treatment of Prostate Cancer to 84 Gy in 28 Fractions: Preliminary Clinical Outcomes and Dosimetry

Abstract

The FLAME trial reported that focal boosting of prostate tumor to 95 Gy in 35 fractions improves biochemical control. However, this treatment is not commonly used in the United States. We investigated a focally boosted treatment of 84 Gy in 28 fractions (EQD2 108 Gy, BED 252 Gy). Between 2019-2022, men with unfavorable intermediate risk (uIR) and high risk (HR) prostate cancer were enrolled on a prospective registry and received a novel IMRT regimen. The dose levels were 84 Gy to the gross tumor volume (GTV) as defined on mpMRI (T2W and ADC) with no added margin, 70 Gy to the prostate and proximal seminal vesicles, and optional 50.4 Gy to elective pelvic lymph nodes (all 28 fractions). Patients received fiducial markers and hydrogel spacer. The treatment planning goal was to cover 95% of the GTV at 84 Gy, and also meet the target and normal tissue dosimetry criteria of the hypofractionated treatment arm of NRG-GU005. VMAT was used for treatment delivery. ADT was given at the discretion of the treating physician. A total of 20 men were included in the study, 2 (10%) uIR and 18 (90%) HR. 9 (45%) tumors were GS 7, 7 (35%) were GS 8, and 4 (20%) were GS 9. There were 13 (65%) stage cT1, 4 (20%) cT2 and 3 (15%) cT3. One (5%) patient received short term ADT, 18 (95%) long term ADT, and 1 (5%) refused ADT. 18 (90%) men received elective nodal radiation. The mean baseline PSA was 25.1 (range 4.2-73.4). The median baseline IPSS score was 11.1 (IQR 4.5-12), and 4 patients had severe baseline urinary symptoms (IPSS ≥20). The mean baseline prostate volume was 57.4 cc (range 26.8-198.3). The mean volume of the 84 Gy boost target was 7.1 cc (range 2.3-15.0) and the mean proportion of the prostate boosted was 14.8% (range 2% - 47%). There were 10 (50%) men with 1 boost target, 6 (30%) with two, 3 (15%) with three, and 1 (5%) had 4 boost targets. Targets were located in peripheral zone (85%), transition zone (30%), and central zone (5%). Patients met all per-protocol normal tissue criteria of NRG-GU005, except for bladder D0.03cc. The mean±SD (Gy) rectum D15%, D25%, and D30% were 51±5, 45±5, 42±4. The mean±SD (Gy) bladder D0.03cc, D30%, D50% were 79±4, 50±8, 38±10. At a median follow up time of 21.3 months (range 7.1-38.2), no patients have developed biochemical progression, local recurrence, distant progression, or death from prostate cancer. One patient died at 18 months from metastatic colorectal cancer, unrelated to prostate cancer treatment. Acute grade 1-2 GU toxicity occurred in 13 (65%) patients, and acute grade 1-2 GI toxicity occurred in 4 (20%) patients. No patients developed grade 3+ acute or late GU or GI toxicity. Two patients required temporary foley catheter for obstruction during RT, and both had IPSS >20 at baseline. The patient who refused ADT had a PSA bounce of magnitude 2.2 ng/mL at 14 months, PSA values declined without additional treatment. A novel 28-fraction focal boosted IMRT treatment is feasible and has an acceptable early toxicity profile. Oncologic results are promising but require longer follow up.