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Staging locally advanced breast cancer patients with ¹⁸F-labeled fluorodeoxyglucose (FDG) PET-CT detected more distant metastases -- and thus reduced the number of patients who received combined modality therapy -- compared with conventional staging, a randomized trial showed.

Among 369 patients, 23% of those in the PET-CT group were upstaged from stage IIB or III to stage IV breast cancer compared with 11% of those who underwent conventional staging -- consisting of bone scan and CT of the chest/abdomen and pelvis -- for an absolute difference of 12.3% (95% CI 3.9-19.9, P=0.002), reported Mark N. Levine, MD, MSc, of McMaster University in Hamilton, Ontario, and colleagues.

This led to a change in treatment for 81.3% of the 43 upstaged PET-CT patients and 95.2% of the 21 upstaged conventionally scanned patients, they noted in the .

Moreover, 81% of those in the PET-CT group ended up receiving combined modality treatment versus 89.2% of the conventionally staged patients -- an absolute difference of 8.2% (95% CI 0.1-15.4, P=0.03).

"In women with LABC [locally advanced breast cancer], staging defines disease extent and guides therapy," Levine and colleagues wrote. "More than twice as many patients were upstaged with PET-CT compared with conventional staging. The implications are that patients who are upstaged to stage IV would avoid the toxicity and adverse impact of aggressive combined modality therapy on quality of life when the disease is incurable."

In an analysis of different patient subsets, the investigators found that among patients without inflammatory breast cancer, 23% of 168 PET-CT patients were upstaged compared with 10% of 168 in the conventional group, while among 33 patients with inflammatory breast cancer, upstaging occurred at the same frequency in both groups.

PET-CT was more sensitive in detecting asymptomatic stage IV disease in patients with estrogen receptor (ER)-positive disease (relative risk [RR] 2.8, 95% CI 1.4-5.5). It was also more sensitive -- but less so -- for upstaging ER-negative (RR 1.6, 95% CI 0.6-4.6) and HER2-positive (RR 1.6, 95% CI 0.6-3.8) cancers.

In an , Lajos Pusztai, MD, DPhil, of the Yale School of Medicine in New Haven, Connecticut, said that like all good trials, this one resulted in several unanswered questions.

"The thorniest unanswered question of all is if foregoing multimodality therapy with curative intent in patients who have no clear evidence of distant metastases on conventional imaging but have apparent disease on FDG PET-CT might not decrease recurrence-free survival and even overall survival," Pusztai wrote. "It is possible that we are denying some patients with limited metastatic disease the potential for cure."

While, in general, metastatic breast cancer is not curable, long-term follow-up data from patients at MD Anderson Cancer Center and in other retrospective studies showed "a small but not zero likelihood of survival without progression at 10 years in those with [metastatic breast cancer] and no prior systemic therapy," he noted. "The critical questions become who are those patients, and can we identify them?"

While using FDG PET-CT for the systemic staging of locally advanced breast cancer increases the diagnosis of de novo oligometastatic stage IV breast cancer, Pusztai observed that the optimal management of this type of cancer "remains uncertain."

In explaining the rationale behind the trial, Levine and colleagues pointed out that staging of locally advanced breast cancer is traditionally performed using anatomic-based imaging methods such as chest radiograph, liver ultrasound, or CT for lung and liver metastases, and bone scintigraphy for skeletal metastases.

However, reports have suggested that ¹⁸F-labeled FDG PET-CT can be beneficial compared with other imaging tests in detecting asymptomatic distant metastases in women with newly diagnosed breast cancer, and that the detection rate increases with stage.

Thus, Levine and colleagues conducted what they said was the only addressing the utility of PET-CT for locally advanced breast cancer.

The trial was conduced from December 2016 to April 2022 across six centers in Ontario. Included patients (mean age 53 years) had histological evidence of invasive ductal carcinoma of the breast and a TNM stage of III or IIb (T3N0, but not T2N1).

In 2009, an prioritized comparative effectiveness research for PET-CT in staging cancer patients, Levine and team noted, suggesting that their trial "can be considered as comparative effectiveness research."

On the basis of the results of the trial, the Ontario Ministry of Health now funds PET-CT for the staging of patients with clinical stage IIb (T3N0) and stage III breast cancer, they said.

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