Expert Insight Into: Sublobar Resection for Patients with Peripheral Small Adenocarcinomas of the Lung: Surgical Outcome is Associated with Features on Computed Tomographic Imaging

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Clinical Insights

Tumor shadow disappearance rate (TDR) on high-resolution computed tomography of <2 cm tumors appears to provide a simple and reliable means of identifying noninvasive adenocarcinomas of the lung.
Relapse-free and overall survival rates at 5 years achieved with sublobar resection in patients with <2 cm tumors that have a TDR >50% suggest that limited pulmonary resection may be an acceptable means of treating these very early non–small-cell lung cancers.
This is a small, retrospective study that suffers from many of the potential flaws of such studies. Its reliability, however, is suggested by very similar findings in several other small, phase 2 studies. The findings do, however, require confirmation in a large, prospective trial before it would be appropriately applied to clinical practice.
The important clinical points are: tumors that are largely ground glass on computed tomography often represent pure bronchioloalveolar carcinomas, tumors that are pure bronchioloalveolar carcinomas very rarely metastasize to lymph nodes, and these tumors may therefore be the ideal candidate tumors for which to consider sublobar resection.

Past randomized trial results comparing segmental or wedge sublobar resection versus lobectomy in patients with T1N0M0 non–small-cell lung cancer (NSCLC) showed a greater risk of locoregional recurrence, and ultimately reduced survival, with limited pulmonary resection. Thus, lobectomy has been considered the procedure of choice for even these early lung cancers. However, recent advances in imaging techniques and the pathologic description of bronchioloalveolar carcinoma and other less invasive variants of adenocarinoma of the lung have led to reconsideration of sublobar resection. For example, use of tumor shadow disappearance rate (TDR) on high-resolution computed tomography (CT) may make it possible to identify tumors that are suitable for limited resection. TDR represents the ratio of the tumor area seen on high-resolution CT on mediastinal windows versus the tumor area seen on lung windows. Since tumors with a TDR >50% have been shown not to be associated with lymph node involvement and only rarely with microscopic invasion, sublobar resection may be a viable approach for treating this subgroup of early tumors.

To investigate this possibility, Nakayama and colleagues conducted a retrospective study of 123 patients who underwent sublobar resection of T1N0M0 tumors measuring 2 cm or less in diameter on high-resolution CT. Sixty of these patients were excluded from the study because they had multiple lung cancers, a history of previously treated lung cancer or other malignancies, or second lung cancers detected during follow-up after resection of their primary tumors. The remaining 63 patients were classified on the basis of TDR as having either "air-containing type" (TDR >50%) or "solid-density type" (TDR <50%) tumors.

Intentional sublobar resection, defined as segmentectomy or wedge resection in patients considered suitable for lobectomy, was performed in 39 (85%) of 46 patients with air-containing type tumors. The remaining seven patients with air-containing type cancers were unsuitable for lobectomy due to limited pulmonary function or other comorbidities and thus were considered to have undergone "compromised resections." In contrast, compromised resections were performed in 15 (88%) of the 17 patients with solid-density type tumors (see Table 1). Wedge resections were the preferred approach for both types of tumors, with 38 (83%) patients with air-containing type tumors and 11 (65%) patients with solid-density type tumors having this surgical procedure.

The two types of tumors differed significantly. Solid-density tumors were larger than air-containing tumors (mean: 15.6 vs 10.5 mm, respectively; P <.0001) and more commonly advanced (three patients had stage T2 disease compared with none of those with air-containing tumors; all remaining patients in both groups were T1; P = .0243). In addition, solid-density tumors were more likely than air-containing tumors to be associated with blood vessel invasion (present in 7 versus 0, respectively; P <.0001) or lymphatic invasion (present in 4 versus 0, respectively; P = .0048).

Sublobar resection resulted in significantly better overall survival and relapse-free survival rates in patients with air-containing type tumors than in those with solid-density type (both overall and relapse-free survival: P <.0001). Compared with a 5-year overall survival rate of 95% in patients with air-containing tumors, the overall survival rate at 5 years in those with solid-density tumors was only 69%. Similarly, no patient with an air-containing type tumor had relapsed at 5 years, whereas 57% of those with solid-density type tumors had suffered a recurrence (see Table 1). Both deaths in patients with air-containing tumors were due to other diseases, and neither had signs of recurrence. By comparison, 7 of the 17 patients with solid-density tumors died of recurrent lung cancer (see Table 1). Five of these seven patients had locoregional recurrences: two had pleural dissemination, two had pulmonary metastases, and one had mediastinal lymph node involvement. The remaining two patients had liver metastases.

This manuscript suffers from several of the flaws that can occur in retrospective analyses. Most prominent among these is the fact that the type of surgical treatment given to the patients with the two types of tumors was unbalanced. The fact that a greater percentage of those with solid-density tumors underwent a compromised resection than those with air-containing tumors may in part account for the lower survival rates in the solid-density tumor group. Additionally, after exclusion of patients who had at presentation or subsequently developed other lung tumors, the study group represents a highly selected group of small, solitary tumors. However, the value of the paper lies not so much in suggesting that survival is better after sublobar resection of air-containing tumors when compared with solid tumors, but in showing that survival after sublobar resection approaches 100% in patients with single, small, air-containing tumors. The authors might also have noted that positron emission tomography (PET) may also be useful in identifying early, noninvasive tumors potentially suitable for sublobar resection, as these tumors do not demonstrate FDG-avidity in a high percentage of cases.

Although lobectomy continues in most surgeons' hands to be the standard-of-care operation for all subgroups of small NSCLCs, the results reported here demonstrate the potential of intentional sublobar resection as an approach to the treatment of very early, noninvasive NSCLC. The authors suggest that T1N0M0 tumors <2 cm in diameter, in the outer third of the lung, that have a TDR greater than 50% may be appropriate for limited pulmonary resection. This and a number of other similar phase 2 studies suggest that evaluation by TDR, as described here, or setting a cut-off value for percent ground glass opacity (GGO), as suggested by others, are reasonably accurate means of identifying very early, noninvasive adenocarcinomas of the lung. Although only a prospective, randomized trial will settle the issue definitively, the accumulating data is highly suggestive that these may be tumors for which sublobar resection is reasonable therapy.

Table 1. Sublobar Resection in Patients with Small Lung Cancers

	Tumor Type
	Air-Containing (n = 46)	Solid-Density (n = 17)
Resection
Intentional sublobar resection^a	39	0
Compromised sublobar resection^b	7	15^c
Histopathology
BAC	38	0
Non-BAC	8	17
Outcome
Overall survival (5 years)	95%	69%
Relapse-free survival (5 years)	100%	57%
Deaths
Recurrent lung cancer	0	7
Other causes/no evidence of recurrence	2	1
^aWedge resection/segmentectomy in patients who were considered candidates for lobectomy. Intentional sublobar resections were performed for patients with air-containing type tumors on CT images, provided these tumors were in the outer third of the lung parenchyma. ^bUnsuitable for lobectomy because of limited pulmonary function or other comorbidities. ^cLow-grade malignant tumor discovered during the operation in remaining 2 patients. BAC = bronchioloalveolar lung cancer.

Table 2. Possible Indications for Intentional Sublobar Resection

Clinically diagnosed early lung cancers (T1N0M0 tumors <2 cm in diameter, TDR>50%) that are located in the periphery of the lung

Pathologically confirmed noninvasive adenocarcinoma of the lung

Reference

Nakayama H, Yamada K, Saito H, et al. Sublobar resection for patients with peripheral small adenocarcinomas of the lung: surgical outcome is associated with features on computed tomographic imaging. Ann Thorac Surg. 2007;84:1675-1679.

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Expert Insight Into:
Sublobar Resection for Patients with Peripheral Small Adenocarcinomas of the Lung: Surgical Outcome is Associated with Features on Computed Tomographic Imaging

Medical Writer: Karen Gravelle, PhD
Expert Faculty: Dr. Joseph B. Shrager, MD

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Expert Insight Into: Sublobar Resection for Patients with Peripheral Small Adenocarcinomas of the Lung: Surgical Outcome is Associated with Features on Computed Tomographic Imaging

Medical Writer: Karen Gravelle, PhD Expert Faculty: Dr. Joseph B. Shrager, MD

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Expert Insight Into:
Sublobar Resection for Patients with Peripheral Small Adenocarcinomas of the Lung: Surgical Outcome is Associated with Features on Computed Tomographic Imaging

Medical Writer: Karen Gravelle, PhD
Expert Faculty: Dr. Joseph B. Shrager, MD