Abstract & Commentary
By William B. Ershler, MD
Synopsis: By examining a large series of patients who had PET/CT scans obtained within 2 months of diagnosis of metastatic breast cancer, it was discovered that site-specific SUV correlated with survival. This was most apparent and statistically significant when comparing survival for patients with bone metastases, although similar but not statistically significant data also were presented for patients with liver, lung, or lymph node involvement.
Source: Morris PG, et al. Standardized uptake value by positron emission tomography/computed tomography as a prognostic variable in metastatic breast cancer. Cancer 2012;118:5454-5462.
Metastatic breast cancer (MBC) remains a challenge. Approximately 20% of patients present with metastatic disease and one-third or more of those treated initially with local or regional disease will relapse at distant sites.1 The goal of cure remains elusive for patients with MBC and median overall survival (OS), although highly variable, is between 24 and 36 months.2
Although a number of factors have proven useful in estimating prognosis for those with metastatic disease, including patient age, disease-free interval, and site of recurrence, clinical course remains highly variable. In this context, investigators at Memorial Sloan Kettering Cancer Center in New York explored the hypothesis that data from positron emission tomography/computed tomography (PET/CT) could further refine prognostic capabilities for patients with MBC.
The authors performed a retrospective analysis examining the PET/CT-derived maximum standardized uptake value (SUVmax) obtained on newly diagnosed MBC patients. For inclusion in this analysis, PET/CT images had to be available within 60 days of diagnosis of MBC and the patients included were those evaluated at their institution over an 8-year period (2001-2008). Patients were excluded if they had received chemotherapy in the 30-day period before the PET/CT images were obtained. OS was determined by accessing medical records. Since there was variability within individuals in the SUV by site of metastatic disease, separate analyses were conducted by site (e.g., bone, lymph node, liver, lung). Patients were classified into tertiles (highest, intermediate, and lowest) based on SUVmax at each site. Thus, some patients who had lesions at multiple sites contributed to the analysis for each site. The relationship between SUVmax and OS were assessed using Cox regression analysis.
In total, 253 patients were identified, and their median age was 57 years (range, 27-90 years). Of these, 152 patients (60%) died, and the median follow-up for the entire group was 40 months. On univariate analysis, SUVmax tertile was strongly associated with overall survival in patients who had bone metastases (n = 141; hazard ratio [HR], 3.13; 95% confidence interval [CI], 1.79-5.48; P < 0.001). This effect was maintained on multivariate analysis (HR = 3.19; 95% CI, 1.64-6.20, P = 0.002) after correcting for known prognostic variables including tumor histology and grade, ER/PR/EGFR status, prior therapy, and disease-free interval.
A greater risk of death was associated with SUVmax tertile in patients who had metastases to the liver (n = 46; HR, 2.07; 95% CI, 0.90-4.76), lymph nodes (n = 149; HR, 1.1; 95% CI, 0.69-1.88), and lung (n = 62; HR, 2.2; 95% CI, 0.97-4.95), although these results were not significant (P = 0.18, P = 0.31, and P = 0.095, respectively).
PET/CT imaging has evolved to become an essential tool in cancer medicine, but its role in staging and management of breast cancer remains to be established. Although not commonly recommended in the staging of early breast cancer,3 PET/CT has been helpful when standard imaging studies are equivocal or suspicious, especially in the setting of locally advanced or metastatic disease.
In the current study performed exclusively in the metastatic diseases setting, it was found that the FDG PET/CT-derived SUV offered prognostic information; those with high levels of FDG uptake (i.e., high SUV) had shorter survival than those with low levels. This was particularly true when comparing patients with bone metastatic lesions for which the observation reached statistical significance, even when controlling for other prognostic factors. When comparing SUV for patients with liver and/ or lung lesions, the correlation was present, but not quite to the level of statistical significance. Thus, clinicians should be aware that the level of SUV within bone MBC lesions may be an indicator of more aggressive disease, although there is insufficient evidence to date to base treatment decisions on this alone. This was a large, carefully conducted study including a broad array of MBC patients and sufficient time to determine median survival, yet conclusions should be tempered by acknowledging that it was a retrospective observational analysis from a single institution. Nonetheless, in light of these data, we can hope that investigators will incorporate SUVmax in future randomized interventional studies to confirm the prognostic value of this measure and, of equal or even greater importance, to determine if a decline in SUVmax is a reliable biomarker for treatment response and improved progression-free and overall survival.
1. Stewart BW, Kleihues P, eds. World Cancer Report. Lyon, France: IARC Press; 2003.
2. Rosso S, et al. Up-to-date estimates of breast cancer survival for the years 2000-2004 in 11 European countries: The role of screening and a comparison with data from the United States. Eur J Cancer 2010; 46:3351-3357.
3. Podoloff DA, et al. NCCN task force report: Positron emission tomography (PET)/computed tomography (CT) scanning in cancer. J Natl Compr Canc Netw 2007; 5 Suppl 1:S1-22.