Postop RT Study 'Very Likely' to Change Breast Cancer Practice

Kate Johnson

December 16, 2013

SAN ANTONIO — The majority of older breast cancer patients treated with breast-conserving surgery and adjuvant endocrine therapy can safely skip radiotherapy (RT) with no compromise to their survival or local control of the disease, according to results from the Postoperative Radiotherapy in Minimum-Risk Elderly (PRIME II) trial.

The mean age of the 1326 study participants was just over 70 years. "Older patients now represent an increasing proportion of patients we see in the clinic — over 50%," lead investigator Ian Kunkler, MD, said during a press conference here at the 36th Annual San Antonio Breast Cancer Symposium (SABCS).

"They often have a relatively benign natural history, and radiotherapy may represent overtreatment," said Dr. Kunkler, who is professor of clinical oncology at the Edinburgh Cancer Research Center, University of Edinburgh, Scotland.

Although current guidelines from the National Comprehensive Cancer Network allow omission of RT in women 70 years and older, "postoperative RT remains the standard of care in older women after wide local excision and endocrine therapy," Dr. Kunkler told Medscape Medical News.

Another major trial also found that the addition of RT provided negligible benefits but failed to change practice, he noted.

The CALGB 9343 trial randomized women 70 years and older with T1 estrogen-receptor (ER)-positive breast cancer to RT or no RT (N Engl J Med. 2004;351:971-977). The 5-year local or regional recurrence risk was lower in the RT group than in the non-RT group (1% vs 4%), but there was no difference in overall survival, he reported.

"However, a subsequent survey of 12,925 women in Medicare who fulfilled the criteria of the CALGB trial showed only a 3.0% to 3.7% reduction in the receipt of RT, suggesting the trial had not changed practice," he said (J Clin Oncol. 2012;30:1601-1607).

Dr. Kunkler predicted that PRIME II is "very likely" to change practice because it shows that the absolute benefit RT is even smaller.

The PRIME II results strengthen the data from the CALGB trial, said Kent Osborne, MD, codirector of SABCS and director of the Dan L. Duncan Cancer Center and Lester Sue Smith Breast Center at Baylor College of Medicine in Houston. He was not involved in the study.

"This is the second study that addresses this question, and it included a slightly younger age group," he told Medscape Medical News.

"When I was in training 40 years ago, we were in the era of more is better. Everybody thought that more treatment, more surgery, more radiation, high-dose chemotherapy, and bone marrow transplant would be better. That's turning out, as we've evolved over the last 3 decades, not to be the case," Dr. Osborne explained.

Recurrence Difference But No Impact on Survival

In PRIME II, all the patients with early-stage disease were treated with breast-conserving surgery and endocrine therapy (9% in the neoadjuvant setting), and were considered "low risk" for recurrence.

"Around 85% [of tumors] were T1, and a smaller proportion were T2 (11% to 12%), up to 3 cm, " said Dr. Kunkler. "Forty percent of tumors were grade 1, the majority (55%) were grade 2, and a very small proportion (between 3% and 4%) of patients had grade 3 histology."

The 5-year local recurrence rate was lower in the 658 patients randomized to whole-breast irradiation than in the 668 randomized to no RT (1.3% vs 4.1%; P = .002), and there was no difference in overall survival (93.2% vs 94.8%; P = .24).

The higher recurrence rate in the non-RT population in PRIME II "does not translate into a survival detriment, so even if a few more patients have a breast recurrence, they can be salvaged at that time with another lumpectomy and radiation or with mastectomy," Dr. Osborne explained.

Table. Outcomes in the RT and Non-RT Groups

Outcomes RT Group, % Non-RT Group, %
Regional recurrence 0.5 1.5
Distant recurrence 0.5 1.0
Contralateral breast cancer rates 0.7 1.5
New nonbreast cancer rates 3.7 4.8


On multivariate analysis of factors that might predict risk for local recurrence — such as tumor size, margin status, use of RT, age, grade, presence of lymphovascular invasion, and ER status — only use of radiotherapy (P = .001) and ER status (P = .02) were statistically significant.

ER Status Is Key to Treatment Consideration

For the 1196 ER-positive patients, "the absolute benefits of radiotherapy are relatively small," although statistically significant (P = .003). The reduction from 3.2% to 0.8% suggests that omission of RT in this group "appears a reasonable option," noted Dr. Kunkler. "It's a matter of discussion between the physician and the patient as to whether that very modest benefit is worth the potential risks of complications of radiotherapy and the burden of undergoing treatment."

However, in the 117 ER-negative patients, "more than 20% of the events occurred in the nonirradiated group (0.0% vs 11.1%; P = 0.015), suggesting that radiotherapy should not be omitted in this group," he said.

The implications of this study "have broad generalizability to a large and growing number of patients," Dr. Kunkler added.

"Probably 60% to 70% of women older than 65 fall into this category," he explained. More than 50% of patients presenting with early breast cancer are elderly women, and increasing proportions are presenting through breast screening programs, meaning their tumors are "quite small," with a relatively small proportion in the ER-negative category, he said.

The study was funded by the Chief Scientist Office. Dr. Kunkler has disclosed no relevant financial relationships.

36th Annual San Antonio Breast Cancer Symposium (SABCS): Abstract S2-01. Presented December 11, 2013.


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