Lobectomy: no port at all?

Lobectomy: no port at all?

Yanping Ren1, Yuxin Jiao1, Xiangpeng Zheng1,2,3

1Department of Radiation Oncology, 2Zhang Guozhen Lung Cancer Center, Fudan University Huadong Hospital, Shanghai 200040, China; 3Department of Medical Physics, Kunshan Duke University, Kunshan 215316, China

Correspondence to: Xiangpeng Zheng, MD, PhD. Department of Radiation Oncology, Fudan University Huadong Hospital, Shanghai 200040, China. Email: Zhengxp@fudan.edu.cn.

Provenance: This is a Guest Editorial commissioned by Section Editor Maria Rodriguez, MD, FEBTS (Department of Thoracic Surgery, Brigham and Women’s Hospital, Boston, USA).

Comment on: Rosen JE, Salazar MC, Wang Z, et al. Lobectomy versus stereotactic body radiotherapy in healthy patients with stage I lung cancer. J Thorac Cardiovasc Surg 2016;152:44-54.e9.

Submitted Feb 12, 2017. Accepted for publication Feb 17, 2017.

doi: 10.21037/atm.2017.03.22

Over decades of development, surgical procedures in stage I non-small cell lung cancer (NSCLC) have been advanced from open thoracotomy to video-assisted minimally invasive thoracoscopic surgery (VATS). Lobectomy (with preference of VATS technique) remains the standard of care for stage I NSCLC (1). The unstopping advances in surgical devices and techniques have contributed to the VATS transition from the conventional multiportal approach to uniportal approach, which has demonstrated advantages in safety and preservation of patient’s quality of life over the former (2). Curiously, is that possible to perform lobectomy with no port at all, or to rephrase the question, is a noninvasive procedure reasonable and available for definitive treatment of this malignancy with outcomes same to or even better than surgery?

Radiotherapy, as a noninvasive procedure, has been used in treatment of lung cancer for almost a century. In its early days, it was once commented “worse than useless” due to poor efficacy but severe adverse effects (3). Thanks to the advancement in radiotherapy equipment, imaging and treatment planning system, radiotherapy has been leaped from the primitive dark time into the modern and bright era with characteristics of precision, accuracy and individualization. Among numerous emerging radiotherapy techniques, stereotactic body radiation therapy (SBRT) or stereotactic ablative radiotherapy (SABR) has attracted extensive attentions from the professionals and the public due to excellent therapeutic outcomes in certain localized solid tumors, especially lung cancer. By focusing high-energy radiation beams (X-ray mainly) to ablate tumors, SBRT can be considered as a procedure of tumor resection without any port. The noninvasiveness renders this treatment highly safe even in fragile and elderly patients. As a direct consequence, the introduction of SBRT has dramatically shifted the management strategy for elderly patients with stage I NSCLC with a 16% absolute increase in definitive treatment, a decline in the proportion of untreated elderly patients, and an improvement in OS (4).

The safety and efficacy of SBRT for stage I NSCLC have been investigated in various scenarios, including elderly patients, inoperable patients, patients with borderline comorbidities as well as operable patients. With sufficient supports from high-level evidences, the role of SBRT in elderly and inoperable patients is solid and steadfast. The NCCN guideline on NSCLC has recommended SBRT as an alternative treatment for those patients since the version V.2.2010 (5). Attracted by the excellent local control and acceptable overall survival in inoperable patients, oncologists, especially we radiation oncologists cannot help wondering how SBRT performs in otherwise healthy patients with operable early-stage NSCLC. Many retrospective studies with propensity matched analysis and meta analysis between SBRT and surgery showed encouraging results that SBRT might have comparable local control and overall survival to surgery (either lobectomy or sublobar resection), but some studies just reported opposite results (6). It is not surprising that the debate of SBRT and surgery in operable patients remains one of hot topics in multidisciplinary thoracic oncology. With the intent to solve the predicament, multiple randomized clinical trials, including ROSEL, STARS, JCOG 0403 and RTOG 0618 were funded. Due to poor accrual, the ROSEL and STARS were early terminated. The pooled analysis showed estimated overall survival at 3 years was 95% in the SBRT group compared with 79% in the surgery group, and recurrence-free survival at 3 years 86% vs. 80%, which did not quiet down the debate instead add more fuels. Certainly, this analysis suffered from small patient sample size and short follow-up (7), and received extensive critiques from thoracic surgical colleagues. Despite that, the endeavor in exploring answers is not abating with ongoing prospective studies, including SABRTooTH, RTOG3502, VALOR and STABLE-MATES (8).

In this context, Rosen et al. conducted a retrospective study based on the National Cancer Database to compare the efficacy of lobectomy versus stereotactic body radiotherapy in healthy patients with stage I lung cancer (9). The major strength of this study is the large patient sample size in both lobectomy and SBRT cohorts. Unlike a meta-analysis, database-based study could have more controls on research objects by imposing strict criteria for query. In the SBRT cohort, “healthy” patients were defined by “a Charlson-Deyo comorbidity index of zero”. Using time-stratified Cox proportional hazards models and propensity-matched analysis (PMA), lobectomy appeared superior to SBRT (5-year survival 59% vs. 29%, 58% vs. 40%, respectively), opposite to the ROSEL/STARS. However, numerically, the 5-year survival in this study is far from satisfactory for both surgery and SBRT in comparison to over 70% in surgery and 50% in SBRT previously reported. The 11% gap in survival between selected SBRT patients for PMA (40%) and the whole “healthy” SBRT cohort (29%) is astonishing, implying that the so called “healthy” SBRT patients may not be as healthy as operable patients. In addition, 16% of patients in surgery cohort received systemic therapy but only 2% in SBRT cohort, which could generate significant impact on survival considering that both surgery and SBRT have been reported to have the similar pattern of failure, i.e. distant metastasis (10). There is no doubt that overall survival is the ultimate study end-point for efficacy evaluation of any treatment approach, including SBRT and lobectomy in stage I NSCLC. Nonetheless, the local control and pattern of failure are important indexes for comparison. Regretfully, this study did not reported results related to both indexes.

Two limitations are not addressed in this study. Both are related to heterogeneity. Firstly, the impact of technical heterogeneity in SBRT protocol should not be underestimated. During the study period of 2008–2012, as an emerging technique with higher requirement than conventional radiotherapy, SBRT was in its fast growing phase and more radiation oncologists initiated their SBRT programs for lung cancer patients. According to a survey, cumulative adoption of SBRT for lung cancer had approximately 5 times of increment from less than 10% in 2004 to higher than 50% in 2010 with various dose fractionation (11). Despite that a stringent definition of SBRT were used based on coding and biologically effective dose (BED), the quality assurance may vary among institutions considering that multiple international authoritative organizations and societies started to publish recommendations to guide and standardize the clinical practice of SBRT from the year of 2009 (12-15). Secondly, heterogeneity in patient selection for both surgery and SBRT may have profound impact on the comparison results. Besides the potential heterogeneity in comorbidity status, the other factor that is worthwhile to be noted but tends to be neglected is the discrepancy in early-stage NSCLC between surgery and SBRT. To be specific, adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) with GGO-predominant lesions (formerly bronchioloalveolar adenocarcinoma, now Tis, T1mi, T1a and part of T1b according to the 8th TNM classification of lung cancer (16) are excluded from SBRT trials mainly due to difficulty in real-time image guidance during treatment delivery and the risk for underdosing the target volume due to a loss of electronic disequilibrium, which could be more than 20% less than the calculated dose (17,18). However, both AIS and MIA are included in the surgery cohort and the proportion is not minimal but consistently growing due to the adoption of low-dose CT screening in high-risk population. Both diseases have an excellent 5-year survival of approximately 100% (19). Therefore, the imbalance in disease composition of early-stage lung cancer apparently favors the results in surgery cohort and could partly explain the better OS in cT1 diseases in this study.

Due to observation of inferiority of SBRT in local control of larger tumors (T2) (20,21) and the predominant pattern of failure being distant metastases in approximately 20% of cases (22), systemic therapy has been hypothesized with potential survival benefit in such patients (23). Multivariable analysis has been conducted with intention to build models to predict patients who may benefit from adjuvant chemotherapy after SBRT. Among variables investigated, higher pretreatment FDG-PET maximum standardized uptake value, large tumor size (T2), and contact with mediastinal pleura in imaging are of prognostic value for patients with highest risk for distant failure (24,25), justifying the necessity of providing systemic adjuvant therapy (chemotherapy or targeted therapy) to these patients. In Rosen et al. study, only 2% of SBRT patients received chemotherapy, much less than 16% in surgery cohort, suggesting that there may be some patients in need of chemotherapy but not receiving in practice due to underestimating the disease severity.

In the treatment of early-stage lung cancer, lobectomy and SBRT are not necessarily a “zero-sum” game. Recently, a phase II clinical trial has been funded to investigate the combination of SBRT and surgery for early-stage NSCLC (MISSILE-NSCLC) with primary outcome measurement of percentage of patients who exhibit a lack of viable tumor after surgical resection (26). The interim safety results reported that the rate of acute grade 3–4 toxicity was 10% and no post-operative mortality occurred at 90 days. More commonly, lobectomy is used as a salvage treatment of local recurrence after SBRT, and vice versa (27-29).

“Loud is its sound, but never word it said”, a quote from The Tao Te Ching, one of ancient Chinese philosophies, somewhat reflects the evolution of therapeutic procedures in stage I NSCLC from massively invasive to less invasive to possible noninvasive. In the era of precision medicine, technological advances and clinical research over the past few decades have given radiation oncologists the capability to personalize treatments for accurate delivery of radiation dose based on genomic information, clinical parameters and anatomical information to achieve eradication of gross and microscopic tumors with preservation of health-related quality of life (30,31). And it is anticipated that the efficacy of SBRT will be continuously improved and promising.

Again, is it time for SBRT to overtake surgery as the treatment of choice for stage I NSCLC (32)? The answer is yes and no, dependent on the individual patient. What we are trying to do is to work closely as a part of a multidisciplinary team to serve our patients with the best, the most appropriate and cost-effective approaches as available as possible. As Dr. Timmerman stated in a commentary (33), “Our job then, as thoracic oncologists, is neither to valiantly protect turf nor aggressively unseat the champion, but rather to carry out valid clinical scientific experiments (i.e., prospective clinical trials) to appropriately characterize the best role for each therapy.” So, no port is good, but patient’s survival and quality of life matter more.


Funding: This work has been financially supported by the National Natural Science Foundation of China (Grant No. 81472794, 11505029), Shanghai Municipal Commission of Health (20134360), Shanghai Municipal Commission of Science and Technology (24119a0400), and the Young Investigator Fund of Fudan University (grant No. EYF163006).


Conflicts of Interest: The authors have no conflicts of interest to declare.


  1. Vannucci F, Gonzalez-Rivas D. Is VATS lobectomy standard of care for operable non-small cell lung cancer? Lung Cancer 2016;100:114-9. [Crossref] [PubMed]
  2. Harris CG, James RS, Tian DH, et al. Systematic review and meta-analysis of uniportal versus multiportal video-assisted thoracoscopic lobectomy for lung cancer. Ann Cardiothorac Surg 2016;5:76-84. [Crossref] [PubMed]
  3. Shorvon LM. Carcinoma of the bronchus with especial reference to its treatment by radiotherapy. Br J Radiol 1947;20:443-9. [Crossref] [PubMed]
  4. Palma D, Visser O, Lagerwaard FJ, et al. Impact of introducing stereotactic lung radiotherapy for elderly patients with stage I non-small-cell lung cancer: a population-based time-trend analysis. J Clin Oncol 2010;28:5153-9. [Crossref] [PubMed]
  5. NCCN clinical practice guidelines in oncology: Non-small cell lung cancer. Version 3.2017. Available online: https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf
  6. Zheng X, Schipper M, Kidwell K, et al. Survival outcome after stereotactic body radiation therapy and surgery for stage I non-small cell lung cancer: a meta-analysis. Int J Radiat Oncol Biol Phys 2014;90:603-11. [Crossref] [PubMed]
  7. Chang JY, Senan S, Paul MA, et al. Stereotactic ablative radiotherapy versus lobectomy for operable stage I non-small-cell lung cancer: a pooled analysis of two randomised trials. Lancet Oncol 2015;16:630-7. [Crossref] [PubMed]
  8. Moghanaki D, Chang JY. Is surgery still the optimal treatment for stage I non-small cell lung cancer? Transl Lung Cancer Res 2016;5:183-9. [Crossref] [PubMed]
  9. Rosen JE, Salazar MC, Wang Z, et al. Lobectomy versus stereotactic body radiotherapy in healthy patients with stage I lung cancer. J Thorac Cardiovasc Surg 2016;152:44-54.e9. [Crossref] [PubMed]
  10. Bradley JD, El Naqa I, Drzymala RE, et al. Stereotactic body radiation therapy for early-stage non-small-cell lung cancer: the pattern of failure is distant. Int J Radiat Oncol Biol Phys 2010;77:1146-50. [Crossref] [PubMed]
  11. Pan H, Simpson DR, Mell LK, et al. A survey of stereotactic body radiotherapy use in the United States. Cancer 2011;117:4566-72. [Crossref] [PubMed]
  12. De Ruysscher D, Faivre-Finn C, Nestle U, et al. European Organisation for Research and Treatment of Cancer recommendations for planning and delivery of high-dose, high-precision radiotherapy for lung cancer. J Clin Oncol 2010;28:5301-10. [Crossref] [PubMed]
  13. Benedict SH, Yenice KM, Followill D, et al. Stereotactic body radiation therapy: the report of AAPM Task Group 101. Med Phys 2010;37:4078-101. [Crossref] [PubMed]
  14. Buyyounouski MK, Balter P, Lewis B, et al. Stereotactic body radiotherapy for early-stage non-small-cell lung cancer: report of the ASTRO Emerging Technology Committee. Int J Radiat Oncol Biol Phys 2010;78:3-10. [Crossref] [PubMed]
  15. Nagata Y, Wulf J, Lax I, et al. Stereotactic radiotherapy of primary lung cancer and other targets: results of consultant meeting of the International Atomic Energy Agency. Int J Radiat Oncol Biol Phys 2011;79:660-9. [Crossref] [PubMed]
  16. Travis WD, Asamura H, Bankier AA, et al. The IASLC Lung Cancer Staging Project: Proposals for Coding T Categories for Subsolid Nodules and Assessment of Tumor Size in Part-Solid Tumors in the Forthcoming Eighth Edition of the TNM Classification of Lung Cancer. J Thorac Oncol 2016;11:1204-23.
  17. Badiyan SN, Bierhals AJ, Olsen JR, et al. Stereotactic body radiation therapy for the treatment of early-stage minimally invasive adenocarcinoma or adenocarcnioma in situ (formerly bronchioloalveolar carcinoma): a patterns of failure analysis. Radiat Oncol 2013;8:4. [Crossref] [PubMed]
  18. Louie AV, Senan S, Dahele M, et al. Stereotactic ablative radiation therapy for subcentimeter lung tumors: clinical, dosimetric, and image guidance considerations. Int J Radiat Oncol Biol Phys 2014;90:843-9. [Crossref] [PubMed]
  19. Travis WD, Brambilla E, Noguchi M, et al. International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol 2011;6:244-85. [Crossref] [PubMed]
  20. Dunlap NE, Larner JM, Read PW, et al. Size matters: a comparison of T1 and T2 peripheral non-small-cell lung cancers treated with stereotactic body radiation therapy (SBRT). J Thorac Cardiovasc Surg 2010;140:583-9. [Crossref] [PubMed]
  21. Paul S, Lee PC, Mao J, et al. Long term survival with stereotactic ablative radiotherapy (SABR) versus thoracoscopic sublobar lung resection in elderly people: national population based study with propensity matched comparative analysis. BMJ 2016;354:i3570. [Crossref] [PubMed]
  22. Senthi S, Lagerwaard FJ, Haasbeek CJ, et al. Patterns of disease recurrence after stereotactic ablative radiotherapy for early stage non-small-cell lung cancer: a retrospective analysis. Lancet Oncol 2012;13:802-9. [Crossref] [PubMed]
  23. Jumeau R, Bahig H, Filion E, et al. Assessing the Need for Adjuvant Chemotherapy After Stereotactic Body Radiation Therapy in Early-stage Non-small Cell Lung Carcinoma. Cureus 2016;8:e901. [PubMed]
  24. Shultz DB, Trakul N, Abelson JA, et al. Imaging features associated with disease progression after stereotactic ablative radiotherapy for stage I non-small-cell lung cancer. Clin Lung Cancer 2014;15:294-301.e3. [Crossref] [PubMed]
  25. Allibhai Z, Taremi M, Bezjak A, et al. The impact of tumor size on outcomes after stereotactic body radiation therapy for medically inoperable early-stage non-small cell lung cancer. Int J Radiat Oncol Biol Phys 2013;87:1064-70. [Crossref] [PubMed]
  26. Palma DA, Nguyen TK, Kwan K, et al. Short report: interim safety results for a phase II trial measuring the integration of stereotactic ablative radiotherapy (SABR) plus surgery for early stage non-small cell lung cancer (MISSILE-NSCLC). Radiat Oncol 2017;12:30. [Crossref] [PubMed]
  27. Nguyen TK, Palma DA. Pros: After stereotactic ablative radiotherapy for a peripheral early-stage non-small cell lung cancer, radiological suspicion of a local recurrence can be sufficient indication to proceed to salvage therapy. Transl Lung Cancer Res 2016;5:647-50. [Crossref] [PubMed]
  28. Chen F, Matsuo Y, Yoshizawa A, et al. Salvage lung resection for non-small cell lung cancer after stereotactic body radiotherapy in initially operable patients. J Thorac Oncol 2010;5:1999-2002. [Crossref] [PubMed]
  29. Neri S, Takahashi Y, Terashi T, et al. Surgical treatment of local recurrence after stereotactic body radiotherapy for primary and metastatic lung cancers. J Thorac Oncol 2010;5:2003-7. [Crossref] [PubMed]
  30. Scott JG, Berglund A, Schell MJ, et al. A genome-based model for adjusting radiotherapy dose (GARD): a retrospective, cohort-based study. Lancet Oncol 2017;18:202-11. [Crossref] [PubMed]
  31. Baumann M, Krause M, Overgaard J, et al. Radiation oncology in the era of precision medicine. Nat Rev Cancer 2016;16:234-49. [Crossref] [PubMed]
  32. Love SM, Hardman G, Mashar R, et al. Is it time for SABR to overtake surgery as the treatment of choice for stage I non-small cell lung cancer? Ann Transl Med 2016;4:535. [Crossref] [PubMed]
  33. Timmerman RD. Surgery versus stereotactic body radiation therapy for early-stage lung cancer: who's down for the count? J Clin Oncol 2010;28:907-9. [Crossref] [PubMed]
Cite this article as: Ren Y, Jiao Y, Zheng X. Lobectomy: no port at all? Ann Transl Med 2017;5(Suppl 1):S9. doi: 10.21037/atm.2017.03.22