In a Phase I/II dose-escalation study of the use of intensity-modulated radiation therapy (IMRT) to treat prostate and pelvic nodes in patients with prostate cancer, Ferreira et al.1 treated patients with 70 to 74 Gy to the prostate and dose-escalating pelvic lymph node-IMRT at doses of 50 Gy (Cohort 1), 55 Gy (Cohort 2), and 60 Gy (Cohort 3) in 35 to 37 fractions. Additionally, two hypofractionated cohorts received 60 Gy to the prostate and 47 Gy to pelvic lymph nodes in 20 fractions over four weeks (Cohort 4) and five weeks (Cohort 5). Among 447 patients over a median 90 month follow-up, the two-year rates of grade 2+ bowel/bladder toxicity were as follows, suggesting adequate tolerability:
- Cohort 1, 8.3%/4.2% (95% CI 2.2%-29.4%/0.6%-26.1%)
- Cohort 2, 8.9%/5.9% (95% CI 4.1%-18.7%/2.3%-15.0%)
- Cohort 3, 13.2%/2.9% (95% CI 8.6%-20.2%/1.1%-7.7%)
- Cohort 4, 16.4%/4.8% (95% CI 9.2%-28.4%/1.6%-14.3%)
- Cohort 5, 12.2%/7.3% (95% CI 7.6%-19.5%/3.9%-13.6%)
The PIVOTAL trial published last year2 also showed the tolerability of radiotherapy in this setting. In this trial, 124 patients with locally advanced, high-risk prostate cancer were randomized between prostate-only IMRT (74 Gy/37 fractions) and prostate and pelvic lymph node IMRT (74 Gy/37 fractions to prostate, 60 Gy/37 fractions to pelvis). At week 18, G2+ lower GI toxicity-free rates were 96.7% (90% confidence interval [CI], 90.0-99.4) for the prostate only group and 95.2% (90% CI, 88.0-98.7) for the prostate and pelvic lymph node group. At two years, the cumulative proportion of RTOG G2+ GI toxicity was 16.9% (95% CI, 8.9%-30.9%) for the prostate only group and 24.0% (95% CI, 8.4%-57.9%) for the prostate and pelvic lymph node group.
As Dr. van As mentioned at the outset of his talk, IMRT to the pelvic lymph node in this disease space works. The Phase I/II dose-escalation study of IMRT by Ferreira et al.1 noted that over a median follow-up of 90 months, five-year failure-free survival was 71% and the pelvic control rate was 94%. Regarding sites of recurrence, this included local (10%), pelvic lymph nodes (6%), non-pelvic lymph nodes (9%), and other distant metastasis (23%).
Data from the STAMPEDE trial also provides insights into efficacy.3 Among 721 men with newly diagnosed M0 disease, time to failure-free survival was worse in patients with N+ disease (hazard ratio [HR] 2.02, 95% CI 1.46-2.81) than in those with N0 disease. Additionally, failure-free survival outcomes favored the planned use of radiotherapy for patients with both N0 M0 (HR 0.33, 95% CI 0.18-0.61) and N+M0 disease (HR 0.48, 95% CI 0.29-0.79).
Dr. van As concluded that radiotherapy is safe and effective, and is the treatment of choice for pelvic lymph nodes.
Presented by: Nicholas van As, MBBCH, MRCP, FRCR, MD, Medical Director and Consultant Clinical Oncologist, The Royal Marsden NHS Foundation Trust, London, United Kingdom
Written by: Zachary Klaassen, MD, MSc, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, Augusta, Georgia, Twitter: @zklaassen_md at the Virtual 2020 EAU Annual Meeting #EAU20, July 17-19, 2020
1. Ferreira, Miguel Reis, Atia Khan, Karen Thomas, Lesley Truelove, Helen McNair, Annie Gao, Chris C. Parker et al. "Phase 1/2 dose-escalation study of the use of intensity modulated radiation therapy to treat the prostate and pelvic nodes in patients with prostate cancer." International Journal of Radiation Oncology* Biology* Physics 99, no. 5 (2017): 1234-1242.
2. Dearnaley, David, Clare L. Griffin, Rebecca Lewis, Philip Mayles, Helen Mayles, Olivia F. Naismith, Victoria Harris et al. "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)." International Journal of Radiation Oncology* Biology* Physics 103, no. 3 (2019): 605-617.
3. James, Nicholas D., Melissa R. Spears, Noel W. Clarke, David P. Dearnaley, Malcolm D. Mason, Christopher C. Parker, Alastair WS Ritchie et al. "Failure-free survival and radiotherapy in patients with newly diagnosed nonmetastatic prostate cancer: data from patients in the control arm of the STAMPEDE trial." JAMA oncology 2, no. 3 (2016): 348-357.