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Lobectomy best prolongs lives of early stage lung cancer patients

Patients with early stage lung cancer live longer when they receive a lobectomy – the most common type of operation for the disease – rather than a less extensive operation or radiation treatment, according to a University of California study.

"Our data suggest that the more aggressively we treat early lung cancer, the better the outcome," said lead author Dr Alex Bryant, of the School of Medicine at the University of California – San Diego. "This study is one of the best-powered and detailed analyses to date and suggests that lobectomy is still the preferred treatment of this disease for most patients."

Using the Veterans Affairs Informatics and Computing Infrastructure (VINCI), Bryant, Dr James D Murphy, and colleagues identified patients who were diagnosed with early stage non-small cell lung cancer (NSCLC) between 2006 and 2015, and who were treated with either surgery or radiation. In all, 4,069 patients were included: 73% (2,986) underwent lobectomy, 16% (634) received a sub-lobar resection, and 11% (449) received stereotactic body radiation therapy (SBRT). Lobectomy is the removal of an entire lobe of the lung; sub-lobar resection is a less extensive operation that includes wedge and segmental resections; SBRT delivers very high doses of radiation over a short period of time (typically 1-2 weeks), precisely targeting the tumour.

The researchers described VINCI as an "extremely rich source of health information" from which they were able to gather detailed data related to a large, nationwide group of veterans. The database includes patient-specific data related to preoperative pulmonary function, smoking history, and tumour staging. Factors such as these are often not available and have not been consistently addressed in previous studies, which sets this study apart, according to Bryant.

In their analyses, the researchers found that the 5-year incidence of cancer death was lowest in the lobectomy group at 23%, with the sub-lobar group at 32%, and SBRT patients at 45%. SBRT also was associated with a 45% increased risk of cancer death compared with lobectomy.

Surgery, though, was not without risks. The study showed that both surgical groups had higher immediate mortality compared to radiation due to operative risks. The 30-day mortality was 1.9% for lobectomy, 1.7% for sub-lobar resection, and 0.5% for SBRT.

But as time went on and with longer follow-up, the surgery groups demonstrated superiority to SBRT, with long-term survival favouring surgery, especially lobectomy, over radiation. The 5-year overall survival rate for lobectomy patients was 70%, followed by the sub-lobar resection group at 56%, and SBRT at 44%.

"Our data suggest that the higher operative risks of surgery are more than offset by improved survival in the months and years after treatment, particularly for lobectomy," said Bryant.

The study also showed that the use of SBRT increased throughout the study period, accounting for 2% of all treatments in 2006 and 19% in 2015. Bryant explained that for patients who are too sick to tolerate a major operation like lobectomy, SBRT makes sense and has become an increasingly common option. Less extensive surgeries, such as sub-lobar resections, also remain a possibility, but there are ongoing concerns about a higher risk of tumour recurrences, he said. As a result, lobectomy remains the standard treatment for early lung cancer in patients who can tolerate a major surgical procedure.

"The public should be aware that lung cancer – even when caught at a very early stage – is a serious diagnosis and deserves aggressive treatment," said Bryant.

Lung cancer is the leading cause of cancer death, with more people dying of lung cancer than of colon, breast, and prostate cancers combined. NSCLC is the most common type of lung cancer, accounting for 80% to 85% of all lung cancer diagnoses, according to the American Cancer Society (ACS). ACS estimates that more than 222,500 Americans will be diagnosed with lung cancer this year, and more than 155,000 lung cancer patients will die. About 14% of all new cancers are lung cancers.

Background: Stereotactic body radiation therapy (SBRT) has been proposed as a potential alternative to surgery for early lung cancer, although we lack well-powered prospective randomized data comparing these treatments, and existing studies suffer from incomplete information on confounders that can bias results. Here, we evaluated the comparative effectiveness of surgery and SBRT in lung cancer treatment using a large extensively detailed database from the Veteran’s Affairs system.
Methods: We identified veterans with biopsy-proven clinical stage I non-small cell lung cancer diagnosed between 2006 and 2015 from within the Veteran’s Affairs Informatics and Computing Infrastructure. We compared cancer-specific survival among patients receiving lobectomy, sublobar resection, or SBRT using univariable and multivariable competing risk analyses. Multivariable analyses adjusted for confounders including preoperative pulmonary function, smoking status, comorbidity, and staging workup procedures.
Results: In all, 4,069 patients were included (449 SBRT, 2,986 lobectomy, 634 sublobar resection). Unadjusted analysis found higher immediate postprocedural mortality in the surgery groups compared with the SBRT group. The multivariable analysis considering long-term survival found higher cancer-specific mortality for SBRT compared with lobectomy (subdistribution hazard ratio 1.45, 95% confidence interval: 1.09 to 1.94, p = 0.01), although no survival difference between SBRT and sublobar resection (subdistribution hazard ratio 1.25, 95% confidence interval: 0.93 to 1.68, p = 0.15).
Conclusions: Among a large cohort of early stage lung cancer patients, we found that lobectomy had improved survival compared with SBRT, although we found no survival difference between sublobar resection and SBRT. Despite these findings, the potential for unmeasured confounding remains and prospective randomized trials are needed to better compare these treatment modalities.

AK Bryant, RC Mundt, AP Sandhu, JJ Urbanic, AB Sharabi, S Gupta, MD Daly, JD Murphy

[link url="https://www.sciencedaily.com/releases/2017/11/171130122808.htm"]Elsevier material[/link]
[link url="http://www.annalsthoracicsurgery.org/article/S0003-4975(17)31099-8/fulltext"]Annals of Thoracic Surgery abstract[/link]

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