Does Delaying Adjuvant Chemotherapy for Non-small Cell Lung Cancer Affect Survival?

Abstract & Commentary

By Gary R. Shapiro, MD, Medical Director, Cancer Center of Western Wisconsin, New Richmond, Wisconsin. Dr. Shapiro reports no financial relationships relevant to this field of study.

Synopsis: One-third of non-small cell lung cancer patients treated with adjuvant chemotherapy start it more than 10 weeks after surgery. Although the time interval between surgery and initiation of adjuvant chemotherapy impacts survival in colorectal and breast cancers, delaying adjuvant chemotherapy does not appear to be associated with inferior survival in non-small cell lung cancer.

Source: Booth CM, et al. Time to adjuvant chemotherapy and survival in non-small cell lung cancer. Cancer 2013;119:1243-1250.

This analysis, a sub-study of a population-based, retrospective cohort study of early-stage non-small cell lung cancer (NSCLC) in the Canadian province of Ontario, linked physician billing codes for chemotherapy to the Ontario Cancer Registry to describe the effect of delaying the initiation of adjuvant chemotherapy to more than 10 weeks. Although the optimal time for initiating adjuvant chemotherapy for NSCLC is unknown, the authors chose 10 weeks based on contemporary NSCLC adjuvant trials that required chemotherapy to be started no more than 8-9 weeks after surgery. In addition to cancer-related factors like histology and stage, Booth and his colleagues analyzed the role that comorbidity, socioeconomic status, age, gender, and region of residence had on overall survival (determined from date of diagnosis).

Among the 15,164 patients diagnosed with NSCLC in the province of Ontario during 2004-2006, 22% underwent surgical resection (pneumonectomy, lobectomy, or segmentectomy), of whom 31% (1032) went on to receive adjuvant chemotherapy. The median time to initiating the adjuvant chemotherapy was 8 weeks (range 1-16 weeks), and 67% of patients started within 10 weeks of surgery. Male gender, higher stage of disease, greater comorbidity, and more extensive surgery were independently associated with inferior survival. However, there was no significant difference in 4-year overall survival between patients who started adjuvant chemotherapy within 1-10 weeks after surgery and those who started 11-16 weeks after surgery (64% vs 61%, P = 0.758). Patients’ region of residence was the only factor that was a significant predictor of delayed adjuvant chemotherapy; though male gender, higher stage of disease, greater comorbidity, and more extensive surgery were all independently associated with inferior survival.

Commentary

Since it captures the overwhelming majority (98%) of all incident cases of cancer in Ontario, the Ontario Cancer Registry accurately reflects the “real life” world of community oncology. However, the authors of the current study are correct to point out that their analysis may be limited by the lack of information in the registry dealing with cancer-specific survival. Nevertheless, these are the first published data to provide insight into the optimal time of initiating adjuvant chemotherapy for NSCLC, an important contribution given the fact that one-third of patients in the Ontario population began chemotherapy more than 10 weeks after surgery.

Most oncologists like to start adjuvant chemotherapy for breast, colon, or lung cancer 3-4 weeks after surgery. They usually accept delays for up to 8-10 weeks, but hesitate to initiate adjuvant treatment beyond the 12-week mark due to lack of data regarding efficacy.

That the Ontario Cancer Registry analysis found no association between the time to starting adjuvant chemotherapy for NSCLC and survival is in marked contrast to the abundant literature dealing with breast and colon cancer that has established the importance of beginning adjuvant chemotherapy sooner rather than later. Indeed, overall survival and disease-free survival are both decreased with as little as a 4-week delay in starting postoperative adjuvant chemotherapy in patients with breast1 and colon2 cancer. For those with colon cancer, each 4-week delay results in a 12% increase in the risk of death.3

It is of course possible that the biology of NSCLC differs from that of breast and colon cancer, but a more likely explanation for this difference is the magnitude of efficacy between adjuvant chemotherapy for breast or colon cancer and NSCLC. The Booth analysis did include an assessment of the effect that the timing of adjuvant chemotherapy may have had on chemotherapy-related mortality, and found no association.

Despite its limitations, including the lack of data regarding chemotherapy delays of more than 16 weeks, this study provides important information to assist oncologists and patients as they weigh the burdens and benefits of adjuvant chemotherapy for early-stage NSCLC. Until further research is available, it provides comfort to the many patients who find themselves dealing with these questions more than 10 weeks after they have had surgery.

References

1. Biagi JJ, et al. J Clin Oncol 2011;29(15 suppl):1128-1139.

2. Des Guetz G, et al. Eur J Cancer 2010;46:1049-1055.

3. Biagi JJ, et al. JAMA 2011;305:2335-2342.