Moderate Hypofractionated Protracted Radiation Therapy and Dose Escalation for Prostate Cancer: Do Dose and Overall Treatment Time Matter?

81 Background: Dose-escalated radiotherapy for localised prostate cancer improves disease control but at the expense of increased overall treatment time and late toxicity. Given the low alpha-beta ratio for prostate cancer, treatment with hypofractionation should be biologically advantageous. Intensity-modulated radiotherapy (IMRT) allows dose escalation with hypofractionation, while achieving acceptable levels of toxicity. We report our 7 year late toxicity data in patients treated with two such regimens within the Hypofractionated Dose Escalation utilising Intensity-modulated Radiotherapy in Carcinoma of the Prostate (HIPRO) study. Methods: Sixty men, median age 75 years (50-87), with localised adenocarcinoma of prostate (T1-3NOMO) and either Gleason score ≥7 or PSA 20-50ng/L received 57Gy in 19 fractions (n=30) or 60Gy in 20 fractions (n=30) using 5-field inverse-planned IMRT. All patients received neoadjuvant hormone therapy, continuing for up to 6 months after treatment. Late toxicity was assessed at 7 years follow-up using RTOG criteria and LENT/SOMA questionnaire. Results: Forty-four (73%) patients were alive at 7 years. Nine patients (21%) reported RTOG grade 1 bowel or bladder toxicity; there was no grade 2 toxicity or above and no difference between the fractionation schedules. LENT/SOMA questionnaires were returned by 31/44 patients. Mean and median scores were less than one for bowel and urinary symptoms. When compared with pre-treatment, the proportion of patients with significant (maximum LENT/SOMA ≥2) urinary symptoms remained similar (75% vs. 76%), problems with sexual function had decreased (84% vs. 98%) but bowel symptoms increased (62% vs. 25%). At 5 years, overall survival was 83% and 74% and cause-specific survival was 83% and 84% in the 57Gy and 60Gy groups respectively. Conclusions: Dose-escalated hypofractionated IMRT for prostate cancer appears well tolerated with acceptable levels of late toxicity. Studies to assess long term disease control with these regimens are on-going. No significant financial relationships to disclose.

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Radiation therapy dose and androgen deprivation therapy in localized prostate cancer: a meta-regression of 5-year outcomes in phase III randomized controlled trials

Prostate Cancer and Prostatic Diseases ◽

10.1038/s41391-021-00432-2 ◽

2021 ◽

Author(s):

Tommy Jiang ◽

Daniela Markovic ◽

Jay Patel ◽

Jesus E. Juarez ◽

Ting Martin Ma ◽

...

Keyword(s):

Prostate Cancer ◽

Radiation Therapy ◽

Androgen Deprivation Therapy ◽

Dose Escalation ◽

Low Dose ◽

Androgen Deprivation ◽

Phase Iii ◽

Localized Prostate Cancer ◽

Treatment Intensification ◽

Meta Regression

Abstract Background While multiple randomized trials have evaluated the benefit of radiation therapy (RT) dose escalation and the use and prolongation of androgen deprivation therapy (ADT) in the treatment of prostate cancer, few studies have evaluated the relative benefit of either form of treatment intensification with each other. Many trials have included treatment strategies that incorporate either high or low dose RT, or short-term or long-term ADT (STADT or LTADT), in one or more trial arms. We sought to compare different forms of treatment intensification of RT in the context of localized prostate cancer. Methods Using preferred reporting items for systemic reviews and meta-analyses (PRISMA) guidelines, we collected over 40 phases III clinical trials comparing different forms of RT for localized prostate cancer. We performed a meta-regression of 40 individual trials with 21,429 total patients to allow a comparison of the rates and cumulative proportions of 5-year overall survival (OS), prostate cancer-specific mortality (PCSM), and distant metastasis (DM) for each treatment arm of every trial. Results Dose-escalation either in the absence or presence of STADT failed to significantly improve any 5-year outcome. In contrast, adding LTADT to low dose RT significantly improved 5-year PCSM (Odds ratio [OR] 0.34, 95% confidence interval [CI] 0.22–0.54, p < 0.001) and DM (OR 0.35, 95% CI 0.20–0.63. p < 0.001) over low dose RT alone. Adding STADT also significantly improved 5-year PCSM over low dose RT alone (OR 0.55, 95% CI 0.41–0.75, p < 0.001). Conclusion While limited by between-study heterogeneity and a lack of individual patient data, this meta-analysis suggests that adding ADT, versus increasing RT dose alone, offers a more consistent improvement in clinical endpoints.

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