Toxicity and Patient-Reported Outcomes of a Phase 2 Randomized Trial of Prostate and Pelvic Lymph Node Versus Prostate only Radiotherapy in Advanced Localised Prostate Cancer (PIVOTAL).
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Embargo End Date
ICR Authors
Authors
Dearnaley, D
Griffin, CL
Lewis, R
Mayles, P
Mayles, H
Naismith, OF
Harris, V
Scrase, CD
Staffurth, J
Syndikus, I
Zarkar, A
Ford, DR
Rimmer, YL
Horan, G
Khoo, V
Frew, J
Venkitaraman, R
Hall, E
Griffin, CL
Lewis, R
Mayles, P
Mayles, H
Naismith, OF
Harris, V
Scrase, CD
Staffurth, J
Syndikus, I
Zarkar, A
Ford, DR
Rimmer, YL
Horan, G
Khoo, V
Frew, J
Venkitaraman, R
Hall, E
Document Type
Journal Article
Date
2019-03-01
Date Accepted
2018-10-05
Abstract
PURPOSE: To establish the toxicity profile of high-dose pelvic lymph node intensity-modulated radiation therapy (IMRT) and to assess whether it is safely deliverable at multiple centers. METHODS AND MATERIALS: In this phase 2 noncomparative multicenter trial, 124 patients with locally advanced, high-risk prostate cancer were randomized between prostate-only IMRT (PO) (74 Gy/37 fractions) and prostate and pelvic lymph node IMRT (P&P; 74 Gy/37 fractions to prostate, 60 Gy/37 fractions to pelvis). The primary endpoint was acute lower gastrointestinal (GI) Radiation Therapy Oncology Group (RTOG) toxicity at week 18, aiming to exclude a grade 2 or greater (G2+) toxicity-free rate of 80% in the P&P group. Key secondary endpoints included patient-reported outcomes and late toxicity. RESULTS: One hundred twenty-four participants were randomized (62 PO, 62 P&P) from May 2011 to March 2013. Median follow-up was 37.6 months (interquartile range [IQR], 35.4-38.9 months). Participants had a median age of 69 years (IQR, 64-74 years) and median diagnostic prostate-specific androgen level of 21.6 ng/mL (IQR, 11.8-35.1 ng/mL). At week 18, G2+ lower GI toxicity-free rates were 59 of 61 (96.7%; 90% confidence interval [CI], 90.0-99.4) for the PO group and 59 of 62 (95.2%; 90% CI, 88.0-98.7) for the P&P group. Patients in both groups reported similarly low Inflammatory Bowel Disease Questionnaire symptoms and Vaizey incontinence scores. The largest difference occurred at week 6 with 4 of 61 (7%) and 16 of 61 (26%) PO and P&P patients, respectively, experiencing G2+ toxicity. At 2 years, the cumulative proportion of RTOG G2+ GI toxicity was 16.9% (95% CI, 8.9%-30.9%) for the PO group and 24.0% (95% CI, 8.4%-57.9%) for the P&P group; in addition, RTOG G2+ bladder toxicity was 5.1% (95% CI, 1.7%-14.9%) for the PO group and 5.6% (95% CI, 1.8%-16.7%) for the P&P group. CONCLUSIONS: PIVOTAL demonstrated that high-dose pelvic lymph node IMRT can be delivered at multiple centers with a modest side effect profile. Although safety data from the present study are encouraging, the impact of P&P IMRT on disease control remains to be established.
Citation
International journal of radiation oncology, biology, physics, 2019, 103 (3), pp. 605 - 617
Source Title
Publisher
ELSEVIER SCIENCE INC
ISSN
0360-3016
eISSN
1879-355X
Collections
Research Team
Clinical Trials & Statistics Unit
ICR-CTSU Urology and Head and Neck Trials Team
Clinical Academic Radiotherapy (Dearnaley)
ICR-CTSU Urology and Head and Neck Trials Team
Clinical Academic Radiotherapy (Dearnaley)