Prognosis and recurrence patterns in patients with early stage lung cancer: a multi-state model approach

Abstract

Background: We aimed to assess whether recurrence patterns affect survival and to use a multi-state model to predict the prognosis of early stage non-small cell lung cancer in patients who underwent surgical resection.Methods: Patients with early stage non-small cell lung cancer who underwent surgical resection at two tertiary medical centers between 2010 and 2015 were retrospectively analyzed. A multi-state model was employed with one initial state (surgery), two intermediate states (locoregional recurrence, distant metastasis), and one absorbing state (death), comprising five transitions: surgery to locoregional recurrence, surgery to distant metastasis, surgery to death without recurrence, locoregional recurrence to death, and distant metastasis to death. Cox proportional hazards models stratified for these transitions were performed with the risk factors; transition probabilities for each patient were predicted.Results: A total of 949 patients were identified [median age: 67 years, male: 614 (64.6%)]. Recurrence occurred in 194 (20.4%) patients (locoregional recurrence: 7.3%, distant metastasis: 13.1%). Hazard ratios for distant metastasis after surgery were higher for older age (hazard ratio: 1.03, 95% confidence interval:1.01-1.06) and adenocarcinoma (hazard ratio: 1.67, 95% confidence interval: 1.06-2.61). Lower lobe location exhibited a higher hazard ratio for death after surgery without recurrence (hazard ratio: 1.59, 95% confidence interval: 1.00-2.53). Stage IIB lung cancer showed a higher probability of transition to distant metastasis after surgery than other stages. Cumulative transition hazards rapidly increased in both recurrence patterns until approximately two years after surgery (locoregional recurrence: 0.052; distant metastasis: 0.104).Patients with distant metastasis were more likely to die within 5 years of surgery than those with locoregional recurrence (6.8% and 2.6%, respectively).Conclusions: With the multi-state model, risk factors and post-relapse survival probabilities differed between locoregional recurrence and distant metastasis. These findings may enable clinicians to establish personalized follow-up strategies for patients undergoing curative resection for early stage non-small cell lung cancer.

The nomogram for the prediction of overall survival after surgery in patients in early‐stage NSCLC based on SEER database and external validation cohort

“…The mortality rate of Stage I patients is higher in older age, male patients. 24,25 The risk of white race is higher, followed by Black race, Asians and Indians, which is consistent with previous studies. 25,26 Chemotherapy is negatively related to prognostic outcome of Stage IA NSCLC patients, whereas positively correlated with that of Stage IB NSCLC patients, conforming to prior reports.…”

“…We conducted multivariate data suggesting that, as expected, tumor size was positively correlated with the risk of poor differentiation. The mortality rate of Stage I patients is higher in older age, male patients 24,25 . The risk of white race is higher, followed by Black race, Asians and Indians, which is consistent with previous studies 25,26 .…”

Preoperative predictors for recurrence sites associated with poor post-recurrence survival after surgery of non-small cell lung cancer: a multicenter study

“…Motono et al analyzed seven postoperative patients with pleural dissemination and reported that young age and poor differentiation are risk factors for pleural dissemination [ 30 ]. Previous studies have reported that older age [ 8 ], adenocarcinoma histology [ 8 , 31 ], and higher stage [ 8 , 32 ] are associated with distant recurrence. Wu et al scored the risk of distal recurrence as smoking history, additional primary malignancy, non-anatomic resections, adenocarcinoma histology, pleural invasion, and angiolymphatic invasion and reported that intermediate- or high-risk groups had a higher frequency of distal recurrence [ 33 ].…”

“…Male sex, older age, smoking history, low-performance status, short-term recurrence, histological presence of symptoms, and poor differentiation have been reported to be poor prognostic factors for PRS [ 3 – 6 , 8 ]. However, there is still no consensus regarding the relationship between PRS and the site of recurrence.…”

“…Previous studies have reported that extrathoracic or distant recurrence is associated with poor prognosis [ 9 , 10 ]. Other studies have reported that patients with local recurrence had a survival advantage over those with distant recurrence [ 7 , 8 , 11 ]; however, in some studies, distant recurrence did not affect PRS [ 6 , 12 , 13 ].…”