Is lobectomy superior to sublobar resection for early-stage small-cell lung cancer discovered intraoperatively? Free

Summary

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was: Is lobectomy superior to sublobar resection (SLR) for early-stage (cT1/2N0) small-cell lung cancer (SCLC) discovered intraoperatively? Altogether, more than 360 papers were found using the reported search, of which 10 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Surgical treatment was shown to be superior to non-surgical treatment for early-stage SCLC in 8 papers. Seven papers showed that among patients treated surgically, lobectomy is associated with improved survival compared to SLR. One paper demonstrated both improved survival and improved freedom from local recurrence. However, 1 paper showed no difference when lobectomy was compared to anatomical segmentectomy. Three papers demonstrated significant rates of upstaging in surgical patients. Although both lobectomy and SLR are associated with improved survival compared with non-surgical treatment in early-stage SCLC, lobectomy is superior. Lobectomy was associated with improved median and overall survival, better upstaging and decreased local recurrence compared to SLR, although there is potential for selection bias and stage migration. Lobectomy should be considered the optimal approach for patients with early-stage SCLC.

INTRODUCTION

A best evidence topic was constructed according to a structured protocol. This is fully described in the ICVTS [1].

THREE-PART QUESTION

In patients with a solitary pulmonary nodule found intraoperatively to have cT1/2N0 small-cell lung cancer (SCLC), does lobectomy provide superior outcomes to sublobar resection (SLR) in terms of survival and local recurrence?

CLINICAL SCENARIO

You perform wedge resection and node sampling for a solitary pulmonary nodule. Intraoperative pathology diagnoses SCLC. All mediastinal nodes are negative. The patient would tolerate lobectomy. Is wedge resection adequate, or would completion lobectomy provide better outcomes since disease appears to be limited to the lung?

SEARCH STRATEGY

A systematic search was performed in MEDLINE from 1950 to January 2018 using the PubMed interface [small-cell OR small cell lung cancer OR SCLC] AND [lung] AND [lobectomy OR wedge OR segmentectomy OR sublobar] NOT [non-small OR NSCLC].

SEARCH OUTCOME

Three hundred and sixty-four papers were found using the reported search. From these, 10 papers were identified that provided the best evidence to answer the question. These are presented in Table 1.

RESULTS

Varlotto et al. [2] reviewed the Survival, Epidemiology and End Results (SEER) database for Stage I or II SCLC, 1988–2005 (n = 2214, surgery in 607). The median survival for lobectomy was higher than SLR (50 vs 30 months, P = 0.006). Both lobectomy and SLR had longer survival than radiation ± chemotherapy (SEER does not include chemotherapy data) (20 months, P < 0.0001, P < 0.002, respectively).

Weksler et al. [3] reviewed the SEER database for Stage I or II SCLC in a partially overlapping period, 1998–2007 (n = 3566, surgery in 895). The median survival for lobectomy was superior to wedge resection (39 vs 28 months, P < 0.0001). Wedge was superior to radiation ± chemotherapy (16 months, P < 0.0001). Schreiber et al. [4] used SEER data from an overlapping period, 1988–2002, examining ‘localized’ disease (T1/2N0) and ‘regional’ disease (T3/4N0 or T1-4N1–2) (n = 14 179). Surgery was performed in 863 patients (387 localized, 476 regional). For all, (localized and regional) the median survival for lobectomy was higher than SLR, pneumonectomy or non-surgical treatment (radiation ± chemotherapy) (40 vs 23 vs 20 vs 13 months, P < 0.001). Lobectomy for localized disease had even higher survival (median 65 months, 52.6% 5-year overall survival). SLR with localized disease survival was not reported.

Ahmed et al. [5] reviewed the SEER database for Stage I SCLC, 2007–2013 (n = 1902, surgery in 543). The survival for lobectomy was superior to SLR (66 vs 24 months, P < 0.001). Patients for whom ≥4 lymph nodes were removed showed superior survival compared to patients with <4 nodes removed (60 vs 25 months). The removal of ≥4 nodes predicted survival in a multivariate analysis, and ≥4 nodes were more often removed via lobectomy (78.5% vs 21.5%). Lobectomy outcomes may be related, in part, to the improved node harvest.

Wakeam et al. [6] performed a propensity-matched review of Stages I–IIIA SCLC in the National Cancer Database (NCDB), 2004–2013, comparing surgery plus chemotherapy vs chemoradiation (n = 29 994). Surgery had longer survival in pN0 (35.1–42.7 vs 22.1 months, P < 0.001), pN1 (24.2 vs 18.3 months, P = 0.03) and pN2 (17.6–22.3 vs 14.6 months, P = 0.007). In 2619 resected patients, lobectomy had higher survival compared with any other procedures, for Stages I, II and IIIA [hazard ratio (HR) = 0.52, 0.81, 0.63, respectively]. Wakeam et al. [7] published a separate study of T1/2N0 SCLC in NCDB, 2004–2013, that found that patients treated with lobectomy, compared to SLR, tended to be younger, better educated, higher income, less likely on Medicaid, more often T1 than T2 and more likely treated in an academic or high-volume centre. These factors may contribute to improved outcomes seen with lobectomy.

Combs et al. [8] also reviewed Stages I–IIIA SCLC in NCDB, 1998–2011. Of 28 621 ‘potentially resectable’ patients, 2476 underwent resection. Five-year survival was higher for lobectomy compared to SLR (nearly all wedge resections) for Stage I (49% vs 30%, P = not stated) and for Stages I–IIIA combined (40% vs 21%, P < 0.0001).

Thomas et al. [9] published a review of the NCDB T1/2N0 SCLC treated with surgery and adjuvant chemotherapy, 2004–2013 (n = 477). Of these, 75.6% had a lobectomy or greater and 25% of patients were upstaged by surgery, 81% because of nodes resected, potentially a benefit of lobectomy over SLR.

In 2014, Takei et al. [10] published a review of resected SCLC in the Japanese Joint Committee of Lung Cancer Registry, 2004 (n = 243). Five-year survival was higher for lobectomy or bilobectomy than wedge (58.3% vs 30.6%, P = 0.002). Segmentectomy was associated with the highest survival 63.6%, though not significant compared to lobectomy (P = 0.78).

Stish et al. [11] reviewed resected SCLC at the Mayo Clinic, 1985–2012 (n = 54). Diagnosis was made intraoperatively in 63%. Five-year survival for the 31 patients undergoing lobectomy or greater resection was superior to the 21 patients undergoing SLR (16 wedge and 5 segmentectomy) (48% vs 15%, P = 0.03). Local recurrence was more likely after SLR (HR 3.5, P = 0.01), and type of surgery was the only independent risk factor for local recurrence. Of 24 patients with recurrence, 8 were isolated intrathoracic recurrences, isolated to the lung in 5, indicating a potential benefit of more aggressive surgery.

The reviewed studies were heterogeneous with respect to stage, preoperative staging and adjuvant therapy. Many were small series drawn from extended periods of time. As retrospective studies, each is subject to selection bias and stage migration. Two (Wakeam et al. [6] and Thomas et al. [9]) used the NCDB data from the same time period, and a third (Combs et al. [7]) used an overlapping time period but different stages and end points. Varlotto et al. [2], Weksler et al. [3] and Schreiber et al. [4] analysed partially overlapping data from SEER. Weksler et al. included only SEER codes for SCLC (Stage I or II), whereas Varlotto et al. also included fusiform-cell carcinoma (Stage I or II) and Schrieber et al. included fusiform, oat and intermediate cell (‘non-metastatic’). One study was excluded because it examined the same data in an overlapping time period as Varlotto et al., with similar results [12]. Several other studies were excluded that had very small number of patients.

The American College of Chest Physicians [13], American Society of Clinical Oncology [14] and European Society of Medical Oncology [15] recommend surgery for cT1/2N0 SCLC but do not distinguish between types of resection. Findings summarized here support the National Comprehensive Cancer Network [16] recommendation of lobectomy over SLR.

CLINICAL BOTTOM LINE

Although both lobectomy and SLR are associated with improved survival compared with non-surgical treatment in early-stage SCLC, lobectomy is superior. Lobectomy was associated with improved median and overall survival, better upstaging and decreased local recurrence compared to SLR, although there is potential for selection bias and stage migration. Lobectomy should be considered the optimal approach for patients with early-stage SCLC.

Conflict of interest: none declared.

REFERENCES