Trial findings were published in the study, “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),” in the International Journal of Radiation Oncology*Biology*Physics.
While most men with newly diagnosed prostate cancer have localized disease, a significant proportion of them are at risk of their disease spreading to the lymph nodes in the pelvis. While the treatment of choice for these patients is androgen deprivation therapy and radiation to the prostate, studies in breast cancer patients suggest that radiation to the surrounding lymph nodes could increase survival outcomes.
However, this type of therapy can lead to side effects, such as gastrointestinal (GI) toxicity and incontinence, and whether this approach could be safely delivered to prostate cancer patients was not previously known.
“Radiotherapy to the pelvic lymph nodes using traditional methods can often result in unpleasant side-effects for the patient in the form of bladder and bowel problems,” David Dearnaley, MD, professor of uro-oncology at The Institute of Cancer Research, London, said in a press release.
“Radiotherapy technology has developed over recent years, meaning we can target doses to tumours more accurately and reduce the dose to surrounding tissue,” said lead investigator Emma Hall, PhD, deputy director of the Cancer Research UK-funded Clinical Trials and Statistics Unit at the institute.
“This is the first randomised controlled trial designed to assess whether or not modern radiotherapy methods can deliver a high dose to the pelvic lymph nodes without causing the patient to suffer toxic side-effects,” Hall added.
The Phase 2 trial (ISRCTN48709247), called PIVOTAL and conducted at multiple centers in the U.K., included 124 patients (median age 69 years) whose prostate cancer was at risk of spreading to the lymph nodes in the pelvis.
Participants were randomly assigned “intensity-modulated” radiotherapy (IMRT) — a kind of radiation therapy that delivers high doses of radiation in a very precise manner, minimizing damage to healthy tissues — to the prostate only or to the prostate and pelvic lymph nodes.
The primary goal of the trial was to assess the safety of IMRT by measuring lower GI acute toxicity, using the Radiation Therapy Oncology Group (RTOG) scoring criteria, at 18 weeks after the radiation treatment. Clinician assessment of acute toxicity was performed every two weeks, from the beginning of the treatment.
Secondary goals included biochemical recurrence — when prostate-specific antigen (PSA) levels rise, indicative of cancer recurrence — overall survival, disease-specific survival, disease spread to local lymph nodes or distant regions, and patient-reported outcomes.
Pelvic lymph node IMRT was considered safe if, after 18 weeks of treatment, fewer than 20% of patients experienced lower GI acute toxicity of grade 2 or higher.
By 18 weeks, these side effects were experienced by 3.3% of patients given radiation therapy to the prostate and by 4.8% of those who received radiation to the prostate and lymph nodes, supporting the treatment’s safety.
In addition, patients in both treatment groups reported similar quality of life, namely in bowel symptoms and incontinence, which was maintained throughout the two years of follow-up.
The proportion of patients experiencing biochemical remission was similar in both groups — 9.7% in the prostate only group and 11.2% in the lymph node group. Cancer recurrence in the prostate, lymph nodes, and in distant regions was also similar in both groups.
“We have shown that intensity-modulated radiotherapy is a smarter, kinder treatment for locally advanced prostate cancer that can be administered to the pelvic lymph nodes as well as the prostate without having a detrimental impact on a patient’s quality of life,” said Dearnaley, who is also a consultant clinical oncologist at The Royal Marsden NHS Foundation Trust.
“This type of radiotherapy can now be delivered at centres around the country and would be feasible as standard treatment on the [National Health System],” he added. “The next step for this treatment regime is to show it can improve survival, and trials to assess this are under way.”
Several Phase 3 trials are now studying the survival benefits of pelvic radiation therapy in prostate cancer patients, one in the U.K. (ISRCTN80146950), one in the U.S. (NCT01368588), and a third in France (NCT01952223).