Numerous studies have documented the timeliness of diagnosis and treatment of lung cancer patients, the majority of which come from European Union member countries. In a systematic review of the literature, Olsson et al identified 49 studies in which at least one time-interval in lung cancer care was reported.16 Median times to diagnosis ranged from 8–60 days dependent upon the starting point in the patient journey; some studies began at the identification of symptoms while others started at the identification of a SPN on x-ray or CT. The US studies included in this systematic review were three, small, single center VA hospital chart reviews that reported a median time from CT to diagnosis of 45 days17 and median times from “consultation” to surgery of 82 days and 104 days.18,19 More recently, Miaga et al conducted a chart review of 265 veterans who underwent cancer resection from 2005 to 2015 to assess time intervals between nodule identification, diagnosis, and surgical resection; changes in nodule radiographic size over time; final pathologic staging; and reasons for delays in care.20 They reported a median time from nodule identification to resection of 98 days with an interquartile range of 66–139 days. Yorio and colleagues identified 482 lung cancer patients treated at three hospitals associated with the University of Texas (UT) Southwestern Medical Center and reported a median of 16 days from image to diagnosis with an interquartile range of 6–43 days.21 Nadpara et al used National Cancer Institute's (NCI) Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data files from years 2002–2007 and reported a median of 187 days with an interquartile range of 36–308 days from first recorded symptoms to diagnosis.22 The difficulty in using first recorded symptoms as the starting point in a patient journey is their lack of specificity. Cough, shortness of breath and chest pain were the most frequently reported symptoms prior to diagnosis in a Canadian study of lung cancer patients; symptoms common to a variety of disease states from asthma to cardiac disease.23 Our study focused on the time period from first identified SPN, CT image or qualifying biopsy to diagnosis and found a median of 13 days with an interquartile range of 2 to 46 days. However, we found that there are significant differences in the timeliness of diagnosis by cancer stage; stage 3 and 4 cancers being diagnosed more quickly than stage 1 or 2 cancers. In addition, there is a great deal of dispersion irrespective of clinical stage with some 5–20% of patients requiring more than 6 months to get a diagnosis.
While guidelines exist regarding the evaluation of individuals with pulmonary nodules and lung cancer there are few guidance documents recommending timelines for lung nodule identification to diagnosis. 24–26 The NHS has recently published a handbook recommending that the time from nodule identification to diagnosis should be no more than 28 days.27 Similar recommendations come from Canada and Norway28,29 In this study, approximately 75–80% of patients with stage 3 or 4 cancer were diagnosed within a 30-day period from nodule identification. The timeliness of diagnosis for those with stage 1 or 2 lung cancer was less with approximately 55–65% receiving a diagnosis within 30 days of nodule identification. These differences in timeliness of diagnosis by stage were statistically significant at the p < 0.001 level. This is likely attributable to the size and location of the more advanced tumors making biopsy access easier. In addition, differences in timeliness to lung cancer diagnosis between early stage and late stage tumors may have also been affected by a willingness on the part of the clinician or patient to "monitor" the lung nodule and obtain a repeat chest CT after a specific time interval following the index visit. Nonetheless, depending on tumor stage, some 25–45% of lung cancer patients exceeded these timing recommendations. The results from our study suggest that future guidelines on timeliness and quality of diagnosis should take into account clinical stage at presentation.
Among those patients with an SPN diagnosis but no evidence of lung cancer, follow-up procedures, the majority of which were referrals visits or additional chest x-rays, were performed on approximately 90% of this patient population. This contrasts with the findings of Pyenson et. al. who studied administrative claims data (i.e., MarketScan) and reported that only 36% received follow-up care.30 However, Pyenson and colleagues did not include chest imaging or E&M as part of their algorithm and these constituted 60–90% of follow-up in our study. The use of PET, non-surgical biopsy and surgical resection as follow-up measures were quite similar between our study and theirs (3.4% vs 3.6%, 2.9% vs 4.9%, 0.4% vs 1% respectively).
The distribution of biopsies among lung cancer patients in our study mirrored those of others 31–34. The pattern was slightly different for the SPN cohort in that approximately 70% of the biopsies were bronchoscopies compared to 48% in the lung cancer cohort. In addition, the biopsy rate was much lower in the SPN cohort relative to the lung cancer cohort (6% vs 79% respectively). Multiple biopsies were common in both groups occurring in 25% of the lung cancer group and in 35.5% of the SPN cohort. The frequency of multiple biopsies in the lung cancer cohort was lower in our study relative to others possibly attributable to the fact that we did not include biopsies performed after the diagnosis date (i.e., for staging purposes).32–34 Complications from biopsy procedures were rare in both patient cohorts with pneumothorax occurring in 4–5% of those undergoing CT guided biopsy attributable, in part, to the use of a conservative algoritm to insure an identified complication was the result of a specific procedure. (see Appendix 1 for codes).
Currently most lung cancer patients present with advanced disease. Our study is no different in that 69.2% of patients were diagnosed as stage 3 or 4. As screening is introduced more widely, the number of small nodules detected will increase, and most of these will be benign.35 Guidelines that use a one-timeline for all can create counter-productive incentives, leading to unnecessary biopsies and ignore the value of careful observation and follow-up of low probability nodules. Guidelines on timeliness of care should take into account clinical stage at diagnosis and a more nuanced approach should be applied. Finally, technological improvements in the ability to access and biopsy small nodules in peripheral locations will facilitate more aggressive management of the SPN without compromising patient safety.
This study is not without limitations. This is a retrospective study that is associated with confounding factors for biopsies and treatment procedures. The patient population comes from two Louisiana healthcare systems and the patient pathways from nodule identification to diagnosis may not be generalizable to other healthcare systems throughout the country. However, findings regarding the stage at diagnosis are consistent with those previously reported throughout the literature. In addition, the linking of data from REACHnet with the Louisiana Tumor Registry resulted in many patients being excluded from the final cohort per protocol. For example, almost half of the patients with a diagnosis of lung cancer in REACHnet were excluded from the final sample because they had no record in the LTR or no record in the Tulane or Ochsner healthcare system. The impact of these patients on the patient pathway results is unknown.