Patients included 880 men and 578 women (median age, 64.0 years; age range: 16–86 years). There were 489 nonsmokers and 969 smokers; the median smoking index was 570. The extent of pulmonary resection comprised lobectomy, bilobectomy, and pneumonectomy in 1265, 111, and 82 cases, respectively.

The histological classification of the lung cancer was adenocarcinoma, squamous cell carcinoma, adenosquamous carcinoma, large cell carcinoma, carcinoid, and others in 70.4%, 18.5%, 3.2%, 5.3%, 0.9%, and 1.8% of the cases, respectively (Table 1).

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(To view a larger version of Table 1, click here.)

The median follow-up period for all cases was 10.1 years from initial resection. The overall survival was 69.5% at 5- years and 52.5% at 10 years.

Among 1458 cases, recurrence developed after complete curative resection in 476 (32.6%) cases. Of them, recurrence developed within the first 5 years in 436 (91.6%) cases, late recurrence developed at 5–10 years in 28 (5.9%) cases, and ultra-late recurrence developed after 10 years in 12 (2.5%) cases. The recurrence rate in cases with stage I, II, and III of the disease was 14.8%, 39.6%, and 64.7%, respectively, indicating that the recurrence rate increased with the progression of the disease (Table 1).

A comparison of ultra-late recurrence cases with non-recurrence cases showed that none of the examined factors significantly influenced ultra-late recurrence (Table 2); however, lymphatic invasion (P=0.057) was close to significantly influencing it.

(To view a larger version of Table 2, click here.)

Table 3 presents the characteristics of the 12 cases (5 men, and 7 women; median age, 60 years; range, 49–70 years) in whom ultra-late recurrence developed. Most of these cases had a never to light smoking history (mean smoking index, 178). All cases had undergone lobectomy with systematic lymph node dissection.

(To view a larger version of Table 3, click here.)

Ultra-late recurrences developed 10.1–19.8 years (median, 12.1 years) after the resection. Of the 12 cases, 8 were judged to have pathological recurrences, and EGFR and ALK rearrangements in the tumor were confirmed in them. Molecular diagnosis could not be confirmed in one case because of the small biopsy specimen of the recurrent lesion; therefore, the case was judged to be recurrent on the basis of pathology and clinical course. Furthermore, of the 12 cases with ultra-late recurrence, 6 were of local recurrence and 6 of distant recurrence.

The histological classification was adenocarcinoma in 11 cases and atypical carcinoid in 1 case. All cases of adenocarcinoma were of invasive adenocarcinoma according to the 8th edition of UICC for Cancer staging system. The pathological stage was described according to the 7th and 8th editions of UICC for cancer staging system. There were four cases of pathological N-0, pl0, Ly0, and V0 and three cases of pathological N-1. Furthermore, recurrence developed over 15 years after complete resection in two cases; both cases were of adenocarcinoma with ALK rearrangement.

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