Cumulative events remain at risk Follow
Cumulative events (remain at risk)
Follow-up interval (mo)
Relapse per follow-up interval
Relapse Event LR
(P ¼ .54) between the imaging and symptomatic groups (Figure 2A). However, patients with a symptomatic LR experienced relapse more quickly than those identified by surveillance imaging (7.2 vs. 16.4 months; P ¼ .04) (Figure 2B). Patients who continued to smoke during CRT had more frequent symptomatic LR events than those who did not smoke (P ¼ .003). In addition, patients with symptomatic relapses had a worse median OS compared to those with relapse identified by surveillance imaging (23 vs. 36 months; P ¼ .013) (Figure 2C).
The appropriate follow-up of NSCLC patients after curative-intent treatment has long been debated. Currently available data address this question inadequately because of the spectrum of disease stages, treatment approaches, and frequency and type of surveillance imaging used. To our knowledge, this study represents the largest analysis to date evaluating surveillance in stage III NSCLC patients treated with curative-intent modern-day delivery of CRT at a high-volume cancer center.
In this study, we found that approximately 75% of relapse events occurred within 1 year after CRT, and this risk gradually declined to < 5% at 3 years (Table 3). Additionally, we found that identifi-cation of relapse based on symptomatic presentation versus surveil-lance imaging portended a worse OS (23 vs. 36 months, respectively).
Presently the ACCP guidelines for NSCLC recommend at least biannual surveillance CT chest imaging along with history and clinical examination for the first 2 years, and annual follow-up thereafter. The ESMO guidelines have been recently updated to recommend CT chest imaging every 6 months for those patients who are suitable for salvage therapy; otherwise, annual imaging is the minimum recommendation.11 Although the NCCN guidelines previously had similar recommendations, suggestions for surveil-lance after definitive treatment were recently updated to include a CT chest with or without Thapsigargin every 3 to 6 months for the first 3 years.12 Although these have been proposed, to our knowledge, there are no data to support the current recommendations, espe-cially in the setting of definitive CRT.
Many of the surgical series that guide the current posttreatment surveillance recommendations combined early and locally advanced stage patients in their time-to-event analyses, which may skew the representation of the optimal follow-up interval in unresectable locally advanced disease. In contrast to these studies, we evaluated time-based relapse events in a relatively homogenous cohort of stage
III NSCLC patients treated with CRT, which would remove bias
created by grouping relapse patterns across different disease stages. Similar to previous retrospective surgical series, 7,8 we found the majority of relapse events in stage III patients occurred within 1 year of completing treatment. Of note, approximately half of these re-lapses occurred within 6 months of completing CRT, which is the minimum surveillance interval recommended by the ACCP and ESMO. These results suggest that patients are at the highest risk of relapse within the first 6 months of completing CRT.
Prior studies suggest symptomatic relapses may occur in 40% to 76% of NSCLC patients.8,15,16 In our study, 56% of patients with relapse sought medical attention as a result of relapse-related symptoms before scheduled surveillance imaging. We observed no differences in the median onset of any relapse, RR, or DR when
G. Daniel Grass et al
Figure 1 Cumulative Relapse Incidence Per Follow-up Interval in Patients With Disease Relapse After Definitive Chemoradiotherapy.
(A) Relapse Events Are Binned Into Defined Follow-up Intervals. Incidence Is Represented as Percentage of Total Relapse Events. (B) Cumulative Relapse Incidence Stratified by Disease Stage
CUMULATIVE RELAPSE INCIDENCE (%)
FOLLOW-UP INTERVAL (MONTHS)
CUMULATIVE RELAPSE INCIDENCE (%)
Overall IIIA IIIB
FOLLOW - UP INTERVAL (MONTHS)
Figure 2 Time to Relapse and Overall Survival Stratified by Symptomatic Presentation or Asymptomatic Detection by Surveillance Imaging. (A) Freedom From Any Relapse. (B) Freedom From Local Relapse. (C) Overall Survival
Relapse Events After Chemoradiotherapy
comparing the two methods of relapse detection. In contrast, pa-tients with symptomatic LR had a substantially more rapid median onset compared to those identified by surveillance imaging (7.2 vs. 16.4 months; P ¼ .04) (Figure 2B). It can be inferred that patients with LR symptoms presented earlier because of lung cancereassociated symptoms, such as airway compression, he-moptysis, and increased shortness of breath. There was likely no difference in symptomatic presentation versus surveillance imaging in the onset of DR because the majority of these patients equally presented with pain or neurologic symptoms from osseous and brain metastases, respectively.