A high-tech form of radiotherapy that shapes radiation beams to tumours can dramatically improve outcomes for patients with prostate cancer, long-term clinical trial results show. As many as 71% of patients with prostate cancer were alive and disease free five years after treatment with intensity-modulated radiation therapy (IMRT). Researchers also found that IMRT – which is highly focused on the tumour and spares nearby normal tissues – was a safe treatment. Only between 8% and 16% of patients experienced bowel or bladder toxicity.
The trial, led by a team at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust, was one of the first ever studies of IMRT, which is designed to be much more precise than traditional forms of radiotherapy.
When the trial began, many of these patients were considered incurable and giving radiotherapy to this region of the body had been considered too risky for fear that the side-effects to the bowel would be too severe.
The pioneering study was funded by the ICR and The Royal Marsden, with additional support from Cancer Research UK.
The trial found that IMRT could safely be given to the pelvis to help stop the spread of the disease. After an average of 8.5 years of follow-up, overall survival was 87% and the level of side-effects was manageable.
Between the years 2000 and 2010, 447 male patients with prostate cancer took part in the study to test whether this new method of radiotherapy could safely treat the lymph nodes of the pelvis, a common site for prostate cancer to spread.
The study has already changed clinical practice, with IMRT becoming the standard of care at major cancer centres in the UK, although it is not universally available.
IMRT, which was developed by researchers at the ICR and The Royal Marsden, works by changing the shape of a radiation beam so it is sculpted to closely fit a patient's tumour, reducing the amount of radiation affecting healthy tissue.
Because there is less radiation affecting healthy tissue, clinicians are able to increase the amount of radiation given to the cancer cells, potentially making the treatment more effective.
The latest study establishes the safety of giving IMRT to the pelvic lymph nodes. Further work is still needed to fully determine the effectiveness of the treatment and in which patients its benefits will offset the low but expected adverse effects.
Revolutionary radiotherapy technique
Study leader Professor David Dearnaley, professor of uro-oncology at the ICR, and consultant clinical oncologist at The Royal Marsden NHS Foundation Trust, said: “Our trial was one of the first of this revolutionary radiotherapy technique, which was pioneered by colleagues here at the ICR and The Royal Marsden. These long-term results demonstrate that using IMRT to target the pelvic lymph nodes is safe and effective for men with prostate cancer.
“This technique has already proven to be a game changer for men with prostate cancer and the work done here has already been carried forward into later-stage phase II and phase III trials. I’m excited to see this treatment become available to every man with prostate cancer who could benefit from it.
“Between treating the first ever patients on this trial, and those we treat today, there has been a complete revolution in using this technique. When we first started it took 45 minutes to provide treatment; today it only takes two or three minutes. It's been a giant leap forward for radiotherapy treatment.”
Professor Paul Workman, CEO of the ICR, said: “Radiotherapy is often seen as perhaps old-fashioned and crude compared with other cancer treatments – but nothing could be further from the truth. Radiotherapy today has been enhanced far beyond recognition since its first use over a century ago, and is now a highly precise, incredibly sophisticated treatment. It’s great to see this long-term evidence of the degree to which precision radiotherapy has transformed outcomes for men with prostate cancer.”
Professor David Cunningham, director of the NIHR Biomedical Research Centre at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, London, said: “Radiotherapy is a very important component of effective treatment for patients with many different types for cancer, and the results of this research mean we can deliver this treatment with less adverse effects on the normal, surrounding tissues and organs and is a real advance for patients with prostate cancer.”
Purpose: To investigate the feasibility of dose escalation and hypofractionation of pelvic lymph node intensity modulated radiation therapy (PLN-IMRT) in prostate cancer (PCa).
Methods and Materials: In a phase 1/2 study, patients with advanced localized PCa were sequentially treated with 70 to 74 Gy to the prostate and dose-escalating PLN-IMRT at doses of 50 Gy (cohort 1), 55 Gy (cohort 2), and 60 Gy (cohort 3) in 35 to 37 fractions. Two hypofractionated cohorts received 60 Gy to the prostate and 47 Gy to PLN in 20 fractions over 4 weeks (cohort 4) and 5 weeks (cohort 5). All patients received long-course androgen deprivation therapy. Primary outcome was late Radiation Therapy Oncology Group toxicity at 2 years after radiation therapy for all cohorts. Secondary outcomes were acute and late toxicity using other clinician/patient-reported instruments and treatment efficacy.
Results: Between August 9, 2000, and June 9, 2010, 447 patients were enrolled. Median follow-up was 90 months. The 2-year rates of grade 2+ bowel/bladder toxicity were as follows: cohort 1, 8.3%/4.2% (95% confidence interval 2.2%-29.4%/0.6%-26.1%); cohort 2, 8.9%/5.9% (4.1%-18.7%/2.3%-15.0%); cohort 3, 13.2%/2.9% (8.6%-20.2%/1.1%-7.7%); cohort 4, 16.4%/4.8% (9.2%-28.4%/1.6%-14.3%); cohort 5, 12.2%/7.3% (7.6%-19.5%/3.9%-13.6%). Prevalence of bowel and bladder toxicity seemed to be stable over time. Other scales mirrored these results. The biochemical/clinical failure–free rate was 71% (66%-75%) at 5 years for the whole group, with pelvic lymph node control in 94% of patients.
Conclusions: This study shows the safety and tolerability of PLN-IMRT. Ongoing and planned phase 3 studies will need to demonstrate an increase in efficacy using PLN-IMRT to offset the small increase in bowel side effects compared with prostate-only IMRT.
Miguel Reis Ferreira, Atia Khan, Karen Thomas, Lesley Truelove, Helen McNair, Annie Gao, Chris C Parker, Robert Huddart, Margaret Bidmead, Ros Eeles, Vincent Khoo, Nicholas J van As, Vibeke N Hansen, David P Dearnaley
[link url="https://www.icr.ac.uk/news-archive/pioneering-precision-radiotherapy-boosts-prostate-cancer-survival"]Institute of Cancer Research material[/link]
[link url="http://www.redjournal.org/article/S0360-3016(17)33655-6/fulltext"]International Journal of Radiation, Biolog, Physics abstract[/link]