Surgical Aspects of Thoracic Malignancies

Albert S.Y. Chang¹, Thomas A. D’Amico², and David C. White¹

¹Duke University Medical Center, Duke Raleigh Hospital, Raleigh, NC, USA

²Duke University Medical Center, Durham, NC, USA

Case study 108.1

A 65-year-old smoker presents with a spiculated, peripheral 2.5 cm right upper lobe mass. Positron emission tomography–computed tomography (PET–CT) scan reveals intense uptake in the lesion with mildly hypermetabolic hilar and paratracheal lymph nodes but no evidence of distant disease.

1. Which is the preferred treatment option?

Referral for induction chemotherapy and radiation due to the presence of hilar and paratracheal lymphadenopathy
Invasive mediastinal staging by endobronchial ultrasound (EBUS) or mediastinoscopy, followed by right upper lobe diagnostic wedge resection and possible lobectomy if the lymph nodes are benign by frozen section
Proceed directly to thoracoscopy for diagnostic wedge resection and lymph node sampling, followed by lobectomy if the lymph nodes are benign
Percutaneous needle biopsy of the right lung mass to confirm malignancy, followed by thoracotomy to ensure complete lymph node dissection

Invasive staging of the mediastinum is important to confirm suspected stage III disease, as PET–CT scan has a significant false-positive rate, particularly in areas of endemic fungal infection. Alternatively, a negative PET–CT does not rule out stage III disease, as there is a false-negative rate of up to 5–10%, particularly for larger and more central tumors. Both EBUS with fine-needle aspirate and mediastinoscopy allow access to both the left and right paratracheal lymph nodes as well as the subcarinal area. There is growing evidence that the accuracy of EBUS is comparable to mediastinoscopy, with a lower risk of significant complications. If pathologic lymph nodes are suspected or identified, mediastinoscopy may allow for larger amounts of tissue to be obtained for complete pathologic analysis, including histologic subtyping as well as mutation analysis, helping to direct treatment decisions. If the lymph nodes are benign by invasive staging, then one can proceed to diagnostic thoracoscopy for wedge resection or biopsy of the tumor if possible prior to lobectomy. Diagnostic thoracoscopy initially would allow for sampling of the paratracheal and subcarinal lymph nodes, but not the left paratracheal nodes, and is more invasive than EBUS or mediastinoscopy, which are generally outpatient procedures. Diagnostic thoracoscopy for lymph node sampling is useful in certain situations; for example, following induction therapy in a patient with previous mediastinoscopy, or in a patient with limited neck extension contraindicating mediastinoscopy. Finally, while percutaneous needle biopsy is often obtained to confirm malignancy, it is not mandatory if a high clinical suspicion exists. Hilar (N1) involvement is not a contraindication to resection provided an R0 resection can be achieved, but identification of N2 disease mandates referral for systemic therapy prior to consideration of resection. While many surgeons prefer thoracotomy for bulky lymph node disease, evidence suggests that thorough lymph node dissection can be achieved safely by experienced surgeons using a thoracoscopic approach, and that the identification of occult lymph node disease is similar whether an open or thoracoscopic approach is used.

Case study 108.2

A 77-year-old man with 80-pack-year smoking history is referred for resection of a biopsy-proven, 1.5 cm. peripheral lingular squamous cell carcinoma. PET–CT reveals moderate uptake in the lesion, but no enlarged or PET-avid hilar or mediastinal lymph nodes and no distant disease. The patient’s pulmonary function tests reveal an FEV1 of 30% predicted, with a diffusion capacity of 32% predicted, and he has a history of coronary artery bypass grafting with a patent left internal mammary artery (LIMA) graft to the left anterior descending coronary artery.

1. Appropriate treatment options include which of the following?

Referral for stereotactic body radiation therapy (SBRT)
Referral for radiofrequency ablation of the tumor
Referral for cardiopulmonary exercise testing and consideration of resection if his VO₂ max (maximal oxygen consumption) is acceptable with a plan for lingular segmentectomy
All of the above

This patient is certainly high risk and requires careful consideration for any type of treatment planning. While patients with predicted postop diffusing capacity <50% predicted and predicted postop FEV1 <50% predicted are at increased risk of mortality following lobectomy, these numbers are not absolute contraindications to surgery, particularly if sublobar resection is an option. For stage IA non-small-cell lung cancer patients with small (<2 cm) tumors, meta-analysis suggests equivalent survival with sublobar resection when compared to lobectomy. In addition, patients with upper-lobe predominant emphysema may tolerate even lobectomy relatively well. The patient’s functional capacity is certainly important, and the use of minimally invasive techniques (video-assisted thoracoscopic surgery (VATS) or robotic segmentectomy–lobectomy) may help to minimize pain, reduce complications, and expedite recovery, and has been shown to reduce complications as lung function worsens. The presence of an intact LIMA graft is not an absolute contraindication to surgery, but an important consideration in operative planning. This patient should also be made aware of alternatives to resection for early-stage lung cancer. These include SBRT, which appears to achieve local control comparable to surgery with follow-up of almost 3 years, low risk of serious complications, and 3-year survival in excess of 50%. Radiofrequency ablation, which causes tumor necrosis by heating the cells, can also achieve excellent local control, although it works best for smaller tumors (<3 cm) that are away from the hilum where larger blood vessels can act as a heat sink, reducing the efficacy of the technique. Additional options, including wedge resection with placement of radioactive mesh along the staple line, are under investigation and show promise as well.

Case study 108.3

A 66-year-old woman who has never smoked and has normal lung function presents for her annual physical exam. She complains of nonspecific respiratory symptoms, and a chest X-ray is obtained, revealing a subtle right-sided lung nodule. CT scan confirms a subpleural right upper lobe ground-glass lesion (1 cm), a 1.5 cm peripheral right lower lobe nodule with both solid and ground-glass components, and a left upper lobe ground-glass lesion (8 mm), again relatively peripheral. A PET scan demonstrates very low-grade uptake in the right lower lobe nodule with a background level in the upper lobe lesion and no uptake in the left-sided lesion.

1. Which is the best treatment option?

Percutaneous needle biopsy of at least two lesions to confirm advanced-stage disease, with subsequent referral for cytotoxic chemotherapy
Wedge resection of the most peripheral lesion to confirm malignancy, followed by referral for cytotoxic chemotherapy for multifocal disease
Invasive mediastinal staging with plan for right lower lobectomy, right upper lobe wedge resection, and left upper lobectomy
Right thoracoscopy for wedge resection and/or segmentectomy to remove both right-sided lesions to ensure complete resection, while minimizing the amount of lung resected, followed by pathologic analysis including screening for epidermal growth factor receptor (EGFR) and ALK mutations, and close follow-up or resection of the left-sided lesion

This patient likely has multifocal adenocarcinoma in situ (formerly termed “bronchioloalveolar carcinoma”) or minimally invasive adenocarcinoma. She has a high likelihood of having the EGFR receptor mutation, potentially making her a candidate for targeted therapy with erlotinib. Surgical resection may still be curative, however, and should be pursued with the goal of removal of gross disease with negative margins, while making an effort to preserve as much lung as possible. Complete resection of adenocarcinoma in situ or minimally invasive adenocarcinoma, even with non-anatomic resection, is associated with excellent long-term survival. Therefore, options such as wedge resection and segmentectomy should be utilized where possible. Mediastinoscopy is not likely to be helpful, as even if there is an invasive component in one or more of the lesions, the chance of mediastinal lymph node metastases is very low (<5%) given the small size and peripheral nature of the lesions. Similarly, PET scan is often not useful, as adenocarcinoma in situ and minimally invasive adenocarcinoma tend not to have significant activity on PET scan. Percutaneous needle biopsy is often difficult for these small lesions, and often does not yield adequate tissue for diagnosis, or for analysis of EGFR mutations.

Case study 108.4

A 72-year-old smoker is referred with a large, right infrahilar mass. Bronchoscopy with brushings is diagnostic of squamous cell carcinoma of the right lower lobe. PET scan reveals significant uptake in the lesion, with low-grade uptake in right hilar lymph nodes, but no evidence of distant disease. The patient undergoes cervical mediastinoscopy with biopsies of 2R, 4R, 4L, and level 7 lymph nodes, all of which are benign. Right lower lobectomy and mediastinal lymph node sampling is performed using a thoracoscopic approach. At the time of surgery, the mass is adherent to the parietal pleura, but there is no evidence of invasion. Final pathology reveals a 4.5 cm. squamous cell carcinoma invading the visceral pleura but not extending into the parietal pleura, with negative margins, and with surrounding pneumonia and reactive lymph nodes (pT2pN0pMx).

1. How should the patient be counseled?

Thoracotomy would have been preferable due to the size of the mass and the ability to achieve more complete lymph node dissection
No further treatment is necessary as an R0 resection was achieved, and there is no evidence of lymph node involvement
Adjuvant chemotherapy should be strongly considered given the large size of the tumor and the significant incidence of distant recurrence
Chest wall resection should have been performed given the adherence of the tumor to the parietal pleura, and, in the absence of this, radiation therapy to the chest wall should be considered

While, early on, VATS lobectomy was thought to be most suited for small (<3 cm), peripheral tumors, there is growing evidence of its efficacy for larger, more central lesions. Documented advantages of thoracoscopic lobectomy include reduced postoperative pain, shorter hospital stay and chest tube duration, and better tolerance of adjuvant chemotherapy when compared to patients undergoing thoracotomy. In addition, while early opponents of VATS lobectomy questioned the adequacy of lymph node sampling, multiple studies have supported the ability to perform equivalent lymph node sampling–dissection to that achieved by thoracotomy. In addition, survival after VATS lobectomy appears to be similar to that achieved following thoracotomy. Despite the absence of lymph node involvement, this patient is at high risk for recurrent disease due to the large size of the tumor. Adjuvant chemotherapy has been associated with significant survival benefit in resected non-small-cell lung cancer, including stage IB and stage II disease. While the chest wall margin may be close, there is no indication for adjuvant radiation therapy, which currently is generally reserved for N2 disease or positive margins.

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