Volume-doubling Time May Help Distinguish Aggressive Cancer from Slow-growing Tumors

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Changes in the size of lung tumors over time, as measured by volume-doubling times on low-dose computed tomography, can be used to distinguish aggressive lung cancer from slow-growing or indolent tumors and reduce overdiagnosis that could result in overtreatment and unnecessary morbidity. Results from a retrospective estimation of volume-doubling times in a prospective low-dose computed tomography screening cohort also found that lung-cancer specific mortality was low among patients with slow-growing and indolent tumors. The study was published in the Annals of Internal Medicine.

The nonrandomized single-center Continuous Observation of Smoking Subjects (COSMOS) study recruited asymptomatic current or former heavy smokers (≥ 20 pack-years) aged 50 years and up who agreed to 5 consecutive years of low-dose computed tomography. Of the 5,203 enrolled participants, 4,122 presented for all five annual scans.

Of the 175 cases of primary lung cancer diagnosed, 55 were diagnosed at baseline (1.1% of the screened population) and 120 were incident cancers detected during subsequent screening rounds. Among those 120 cases, “the main focus of the study,” according to the authors, 19 (15.8%) were new (no nodule on previous scan) and fast-growing, with a median [volume-doubling time] of 52 days, and 101 (84.2%) had progressed from the year before, including 70 (58.3%) that were fast-growing and 31 (25.8%) that were slow-growing or indolent.

Major Results

The median volume-doubling time was 223 for fast-growing and 545 days for slow-growing or indolent cancer. “The median [volume-doubling times] for adenocarcinomas (303 days) was significantly longer than that for squamous cell carcinomas (77 days) and cases of small cell cancer (70 days),” the researchers reported.

“The main finding of our study is that [volume-doubling time] seems to be a plausible indicator of cancer aggressively in cases of incident cancer,” the authors wrote. Prognosis was highly favorable for cancers with a volume-doubling time of 200 or more days.

“Another important finding of our study was that early diagnosis and early treatment, even of fast-growing cancer resulted in good long-term survival for our patients, most of whom had stage I disease at diagnosis, However, good long-term survival must be balanced against the risk of invasive procedures for benign disease,” the authors added. In this study, 29 of the screened patients who had surgical biopsy had benign disease.

“Having identified potentially overdiagnosed lung cancer as slow-growing or indolent lesions, the problem of managing them remains,” the researchers continued. In this study, all nodules suspicious for cancer were treated with surgical resection. The authors acknowledged, however, that “standard resection (lobectomy with lymph node dissection) may be overtreatment for slow-growing or indolent lesions, most of which are minimally invasive adenocarcinomas,” and “a less-aggressive approach may be more appropriate.”

The authors concluded that the volume-doubling time analysis of cancers diagnosed after the initial screening “suggests that at least approximately 75% of detected cases were aggressive, downsizing the problem of overdiagnosis. Among the 25% of slow-growing or indolent cases, many are likely to have been overdiagnosed. To limit overtreatment in such cases, minimally invasive limited resection and nonsurgical treatments should be investigated prospectively.”

Veronesi G, et al: Ann Intern Med 157:776-784, 2012