The PRIME trial of post-operative radiotherapy in elderly, low-risk breast cancer patients: Quality of life after five years

Well over a million cases of breast cancer are diagnosed worldwide each year. It is commonest in the elderly and its prevalence is increasing further as the population ages. Elderly breast cancer patients, however, have historically been excluded from clinical trials, with data from younger patients merely extrapolated into the upper age groups. There is still a need to establish a body of data to inform clinical practice and establish guidelines for treating breast cancer in women over 65.

Post-operative radiotherapy is generally assumed to reduce the risk of recurrence in low-risk breast cancer patients initially treated with surgery and systemic therapy. However, its effectiveness in older patients has been questioned. The PRIME trial (Post-operative Radiotherapy In Minimum-risk Elderly) was set up in 1997 to investigate the value and cost-effectiveness of whole breast radiotherapy (WBRT) in women over 65 with breast cancer estimated to be at minimal risk of recurrence after breast-sparing surgery and adjuvant endocrine therapy. The first report of this trial, published in 2007, showed no overall difference in quality of life between patients treated with and without radiotherapy up to 15 months after surgery. A new report by Linda Williams from the University of Edinburgh and colleagues from Edinburgh and Aberdeen updates the previous one with quality of life data on all enrolled patients up to five years after surgery [1].

The PRIME trial enrolled 255 patients from UK breast cancer clinics, with a mean age of 72.5. All were diagnosed with early breast cancer at low risk of recurrence and were randomised to receive either WBRT or no radiotherapy after the initial treatment. A detailed description of the trial design and early follow-up is given in the initial report [2]. Participants were then assessed after three and five years using postal questionnaires that were based on EORTC quality of life scales and the Hospital Anxiety and Depression scale and that included open-ended questions. Cost-effectiveness of the treatment regimens was estimated using quality-adjusted life years (QALYs) as derived for the five-year time period.

Over 94% of the enrolled patients completed the questionnaires at both the three-year and five-year time points. Twenty-nine of the participants (1%) died before the end of the five years, but only nine of the deaths (4/13 in the radiotherapy arm and 5/16 in the non-radiotherapy arm) were related to breast cancer. There were few significant reported differences in morbidity and overall quality of life, with patients in the radiotherapy arm reporting increased rates of breast problems and fatigue but lower rates of endocrine side effects and, interestingly, insomnia compared to those in the non-radiotherapy arm. Some treatment-related morbidity was reported throughout the five-year period in both arms, and patients reported anxiety about the return of their cancer throughout the period although this tended to decrease over time. Many patients reported some decline in physical and cognitive abilities over the five years, but this was no more than could be expected in an elderly and ageing population and was not considered to be cancer- or treatment-related. No significant conclusions about the optimal treatment could be derived from the cost-effectiveness analysis.

Williams and her colleagues concluded that adjuvant radiotherapy was well tolerated in elderly patients with breast cancer at low risk of recurrence, with patients who received radiotherapy observing no significant difference in overall quality of life after five years compared to those who did not. Further research is needed in particular to determine the cost-effectiveness of omitting radiotherapy in this patient group over the long term. A much larger trial in a similar patient group, PRIME II, is due to report later in 2011 and this may begin to address some of the outstanding issues.

References

[1] Williams, L.J., Kunkler, I.H., King, C.C., Jack, W., van der Pol, M. (2011) A randomised controlled trial of postoperative radiotherapy following breast-conserving surgery in a minimum-risk population: Quality of life at 5 years in the PRIME trial. Health Technol Assess 15(12). doi: 10.3310/hta15120

[2] Prescott, R.J., Kunkler, I.H., Williams, L.J., King, C.C., Jack, W., van der Pol, M., et al. (2007) A randomised controlled trial of postoperative radiotherapy following breast-conserving surgery in a minimum-risk older population: The PRIME trial. Health Technol Assess 11(31).