New Guideline: No Single Formula for Postmastectomy RT

Kristin Jenkins

September 20, 2016

There is no one-size-fits-all formula for physicians to determine which patients with breast cancer are the best candidates for postmastectomy radiotherapy (PMRT), according to the authors of a new joint clinical practice guideline update.

Instead, the new guideline will help clinicians make more informed decisions and move toward more individualized patient care, say expert panel members from the American Society of Clinical Oncology (ASCO), the American Society for Radiation Oncology (ASTRO), and the Society of Surgical Oncology (SSO) who developed the update.

The guideline report was published online September 19 in the Journal of Clinical Oncology and Practical Radiation Oncology .

We still don't have a single, validated formula that can determine who needs PMRT. Dr Stephen B. Edge

"We still don't have a single, validated formula that can determine who needs PMRT, but we hope that the research evidence summarized in this guideline update will help doctors and patients make more informed decisions," said Stephen B. Edge, MD, cochair and ASCO expert panel representative, in a press release.

"We also hope that this publication will spur more research into patient and tumor characteristics that predict risk of recurrence after mastectomy," he added.

Dr Edge is vice president of healthcare outcomes and policy and a professor of oncology in the departments of surgical oncology and cancer prevention and control at Roswell Park Cancer Institute in Buffalo, New York. He is also professor of surgery at the University at Buffalo.

Reduction of Recurrence Risk

For the guideline update, the multidisciplinary expert panel reviewed the literature published between January 2001 and July 2015, including a meta-analysis of 22 clinical trials published in 2014. They also looked at studies not yet published.

The update was reviewed by the ASCO Health Services Research Committee members and the ASCO Board of Directors, as well as seven outside reviewers.

The document notes that evidence summarized from randomized clinical trials to July 2015 confirms that PMRT reduces the risks for local recurrence, any recurrence, and breast cancer mortality for patients with T1/2 breast cancer with one to three positive axillary nodes.

However, some patients are likely to have such a low risk for recurrence that the absolute benefit of PMRT is outweighed by its potential toxicities, the panel says.

Hence, the panel recommends routine use of PMRT for patients with four or more positive axillary lymph nodes, citing insufficient evidence to make recommendations for the use of PMRT in most patients with T1/2 tumors with one to three positive nodes.

Not all patients with positive nodes need PMRT, confirms Monica Morrow, MD, the SSO expert panel representative and chief of the breast service at Memorial Sloan Kettering Cancer Center in New York.

"Multiple factors which influence the risk of local recurrence, as well as factors which increase the risk of complications of PMRT and competing causes of death, should be considered," she said in an interview.

Dr Morrow noted that studies of nodal RT in patients undergoing lumpectomy show improvements in disease-free survival, but not overall survival, "so the benefits of PMRT may also be relatively small."

"The best candidates for PMRT include patients with heavier disease burdens — more nodal  metastases, cancer growing outside the wall of the node, larger tumors in the breast, lymphovascular invasion — as well as characteristics associated with higher risks of local recurrence: younger age, triple-negative cancer. A patient likely to have limited benefit, for example, would be one with a single involved node, smaller primary tumor, that was ER [estrogen receptor] positive," she told Medscape Medical News.

"In an era of personalized medicine, we want to be sure that we offer the right care to the right patients," said Abram Recht, MD, cochair of the panel and ASCO expert panel representative.

Thanks to advances in systemic therapy, fewer women need radiation therapy after a mastectomy Dr Abram Recht

"Thanks to advances in systemic therapy, fewer women need radiation therapy after a mastectomy," he noted in a statement. "This means we can be more selective when recommending this treatment to our patients." 

Dr Recht is professor of radiation oncology at Harvard Medical School as well as deputy chief and senior radiation oncologist of radiation therapy at Beth Israel Deaconess Medical Center in Boston, Massachusetts.

Decision Requires Significant Clinical Judgment

Because the decision to recommend PMRT requires significant clinical judgment, the panel agreed clinicians first consider factors that decrease the risk for recurrence, attenuate the benefit of reduced breast cancer–specific mortality, and/or increase risk for complications resulting from PMRT.

They recommended the routine use of PMRT in patients with T3 tumors with positive axillary nodes and in patients with operable stage III tumors.

When clinicians and patients elect to omit axillary dissection after a positive sentinel node biopsy, these patients should receive PMRT, the panel said, adding, "only if there is already sufficient information to justify its use without needing to know additional axillary nodes are involved."

The extent of radiation fields for PMRT remains controversial, but treatment of the chest wall — the site with greatest recurrence risk — "is mandatory," the panelists said.

Radiotherapy should generally be administered to both the internal mammary nodes and the supraclavicular-axillary apical nodes in addition to the chest wall or reconstructed breast, the panel said.

The panel agreed that most patients given neoadjuvant systemic therapy should receive PMRT but added that there was insufficient evidence to determine whether it should be included in all patients.

Axillary radiotherapy should not be given routinely in patients undergoing complete or level I/II axillary dissection.

There was insufficient data to determine the optimal sequencing of chemotherapy, tamoxifen, and PMRT, although the panel agreed that chemotherapy should be started soon after surgery, not after PMRT.

In patients undergoing prolonged chemotherapy, the panel could not reach consensus on whether it was better to deliver all chemotherapy before PMRT or to give concurrent chemoradiotherapy. They did, however, suggest that doxorubicin (Adriamycin; Pfizer) not be administered concurrently with PMRT.

There was insufficient evidence to make recommendations about the integration of PMRT and reconstructive surgery.

Although the panel agreed that the risk for serious toxicity with current radiotherapy techniques is low, there was not enough follow-up evidence to rule out very late cardiac toxicities.

Critical next steps include the identification of subsets of women who will benefit from PMRT as well as those who will not, Dr Morrow said. 

"Molecular profiling to predict the risk of distant recurrence has allowed us to decrease the use of chemotherapy, and it appears that profiles associated with a low risk of distant recurrence may also be associated with a low risk of local recurrence and hence limited benefit from PMRT. The development of gene signatures to identify subgroups more precisely would be extremely helpful," she added.

No study funding was reported. No relevant financial relationships have been disclosed.

J Clin Oncol Published online September 19, 2106. Abstract

Prac Rad Oncol. Published online September 19, 2016. Abstract

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