The great debate flashes: Surgery versus stereotactic ...

Cite this article as: Weder W, Moghanaki D, Stiles B, Siva S, Rocco G. The great debate flashes: Surgery versus stereotactic body radiotherapy as the primary treatment of early-stage lung cancer. Eur J Cardiothorac Surg 2018;53:295–305.

The great debate flashes: Surgery versus stereotactic body radiotherapy as the primary treatment of early-stage lung cancer Walter Wedera, Drew Moghanakib, Brendon Stilesc, Shankar Sivad and Gaetano Roccoe,* a b c d e

Department of Cardiothoracic Surgery, University Hospital Zurich, Zurich, Switzerland Department of Radiation Oncology, Hunter Holmes McGuire VA Medical Center, Virginia Commonwealth University, Richmond, VA, USA Department of Cardiothoracic Surgery, Weill Medicine, New York Presbyterian, New York, NY, USA Department of Radiation Oncology, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, Australia Department of Thoracic Diseases, Istituto Nazionale Tumori, IRCCS, Fondazione ‘G. Pascale’, Naples, Italy

* Corresponding author. Department of Thoracic Diseases, Istituto Nazionale Tumori, IRCCS, Fondazione ‘G. Pascale’, Via Semmola 81, 80131 Naples, Italy. Tel: +39-81-5903262; fax: +39-81-5903823; e-mail: [email protected] (G. Rocco). Received 31 August 2017; received in revised form 23 October 2017; accepted 28 October 2017

Abstract Stereotactic body radiotherapy is gaining favour as an alternative therapeutic modality to surgery for patients with early-stage lung cancer. An exponential increase of contributions in the literature has generated a bulk of discordant evidence supporting therapeutic choice for the treatment of fit and medically inoperable patients. This ‘Great Debate Flashes’ paper aims at producing an up-to-date, concise and user-friendly review of the arguments that surgeons and radiation oncologists bring forward in the discussions with patients and colleagues. Keywords: Lung cancer • Stereotactic body radiotherapy • Surgery • Thoracotomy • Thoracoscopy

SURGERY

LONG-TERM OUTCOME IS SUPERIOR

Walter Weder, Zurich, Switzerland; Brendon Stiles, New York, NY, USA; Gaetano Rocco, Naples, Italy

Cure or prolonged survival is the primary objective for most lung cancer patients. Surgical resection with or without adjuvant therapy provides the best long-term outcome for operable patients with lung cancer and is therefore recommended as the treatment of choice in the guidelines of medical societies throughout the world. The Lung Cancer Study Group reported an 80% recurrencefree survival at 5 years when treated with lobectomy compared to 60% with sublobar resection in the only randomized trial of lobectomy versus limited resection for patients with T1N0 NSCLC [1]. The survival curves are in parallel for 3 years, after which time separation begins. Importantly, most literature on SBRT reports only 3-year survival data for operable early-stage NSCLCs, which is a clearly too short of an observation period and generally does not allow firm conclusions. Furthermore, several comparative studies looking at late survival data show a clear benefit for surgically treated patients. In a recent meta-analysis of 12 cohort trials with 13 598 patients with T1 NSCLC, it was shown that lobectomy was superior to SBRT, despite most studies reporting only 3-year overall survival (OS) [2]. Even wedge resection—not the recommended treatment for operable lung cancer patients—showed a better 5-year OS than SBRT, 49.9% vs 31%, in an analysis of 6295 patients from the National Cancer Database (NCDB) [3]. Those studies, despite propensity matching, can be criticized for ‘sicker’ patients affecting survival in the radiotherapy group. However, examining

Introduction There are at least 5 reasons why surgical lobectomy in general or limited resection in selected situations remains the standard of care for operable patients with clinical Stage I lung cancer [non-small-cell lung cancer (NSCLC)]. Anatomical resection provides the best long-term outcome, is safe and associated with low morbidity, allows exact staging and provides enough tissue for detailed histological and molecular analysis, simplifies interpretation of follow-up imaging as the lesion is resected and, finally, is associated with relatively modest impairments in pulmonary function or even improvement in selected emphysema patients. Stereotactic body radiotherapy (SBRT) or stereotactic ablative radiotherapy (SABR), the oncological equivalent to wedge resection, represent a valuable treatment option for smaller tumours in inoperable patients and has a defined place there. However, to propose it for operable patients is not supported by data. The literature is full of comparative reports, which all have their limitations and should be interpreted with caution.

C The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved. V

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GREAT DEBATE – THORACIC

GREAT DEBATE

European Journal of Cardio-Thoracic Surgery 0 (2018) 1–11 doi:10.1093/ejcts/ezx410

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W. Weder et al. / European Journal of Cardio-Thoracic Surgery

just healthy patients, Rosen et al. [4] reported a significantly better 5-year OS of 59% when treated with a lobectomy versus 29% with SBRT in a propensity-matched analysis of 1781 pairs of patients with T1/T2 NSCLC. Matched patients who were recommended surgery but who refused and opted for SBRT had an inferior 5-year OS compared to patients undergoing lobectomy (40% vs 58%; P = 0.010) [4]. Radiation oncologists may counter these real-world, large database studies with the pooled randomized data published by Chang et al. [5]. However, the fallacies of this post hoc analysis have been well described [6]. Together the STARS and ROSEL studies accrued less than 4% of the patients needed to adequately address the question of whether stereotactic radiation was equivalent to surgical resection. The worse-than-expected outcomes in the 16-patient STARS surgical cohort drove the analysis [5, 6].

MODERN LUNG CANCER SURGERY IS SAFE AND MINIMALLY INVASIVE Early-stage NSCLC is resected by a minimally invasive lobectomy or segmentectomy with mediastinal lymphadenectomy in 60– 80% of patients at specialized centres, by either multiportal or uniportal video-assisted thoracoscopic surgery or roboticassisted approaches, with strict quality control metrics [6, 7]. No such databases or quality control exist for SBRT. Following surgery, hospitalization time is typically 3–6 days, and most patients are back to normal life within 2–4 weeks. Thirty-day mortality, including high-risk patients, is 1.5–2.0% across national databases and is less than 1% at specialized centres [7–9]. Grade 3 morbidities occur in less than 10% of patients. Even in high-risk patients, morbidity and mortality with limited resection are not statistically different from morbidity with SBRT at 90 days in prospective clinical trials [10].

SURGERY PROVIDES EXACT TISSUE DIAGNOSIS AND STAGING Surgical resection allows for exact diagnosis and staging. Even among suspected lung cancer patients enrolled in clinical trials, up to 16% of patients will have benign nodules [11]. These patients are apparently not included in long-term survival data. In contrast, in large series of SBRTs, 26–67% of patients did not have tissue confirmation [12, 13]. In addition to the risk of overtreatment and overestimation of survival, there is a corresponding real risk of understaging and undertreating patients with clinical Stage I lung cancer who are only managed with SBRT. The inadequacy of clinical staging has been addressed in many studies, with occult nodal disease in 13–15% of clinical stage Ia patients and upstaging in 20–35% of patients [14–16]. SBRT will not identify Stage IB–III patients who would be eligible for adjuvant chemotherapy, which has been demonstrated to improve survival in this cohort. Similarly, surgical resection facilitates the use of genetic and molecular markers in NSCLC patients. Although early-stage patients are not typically eligible for targeted therapies, such information is increasingly obtained and may be prognostic or guide treatment of recurrences. Radiation or needle biopsy alone may preclude molecular testing in many patients. Furthermore, it has been increasingly recognized that

the histological subtypes of adenocarcinoma determined by pathological evaluation are important for prognosis of progression or recurrence after limited field treatment [17, 18]. This information is unavailable with SBRT.

SURGICAL RESECTION SIMPLIFIES FOLLOW-UP IMAGING Another issue of potential confusion and harm to patients is the excessive use of radiological studies used to monitor patients following SBRT. An analysis of Surveillance, Epidemiology and End Results (SEER)-Medicare data recently demonstrated that SBRT patients received a median of 6 computed tomography (CT) scans and 2 positron emission tomography (PET) scans in their first 2 years post-treatment compared to just 4 CT scans and 0 PET scans for matched surgery patients [19]. The issue of ‘scanxiety’ is real, has been increasingly discussed by patients and is compounded by the cumulative radiation risks of excessive diagnostic radiology studies [20]. These issues and risks are particularly relevant to operable patients with a long life expectancy. Underlying the increased use of imaging with SBRT is the uncertainty of how to best follow these patients radiographically over the long term and the question of when to biopsy persistent nodules. Despite high rates of infield local control in the first 3 years after SBRT, lobar and regional failure is almost 40% by 5 years, making radiographic follow-up of critical importance [21, 22].

LOBECTOMY OR LIMITED RESECTION DO NOT SIGNIFICANTLY IMPAIR LUNG FUNCTION The reduction in lung function measured by forced expiratory volume in 1 s is 9–16% after a lobectomy and 3–11% after sublobar resection [23, 24], which is clinically not relevant for patients with an adequate pulmonary reserve prior to surgery. This is comparable to the 6.7% loss seen with SBRT [23, 24]. The maximum depression after surgery is observed after 2 months, which partially recovers by 6–9 months [24]. In patients with moderateto-severe emphysema and hyperinflation, lung function may even improve at 3 months due to the volume reduction effect and improved respiratory mechanics [24–27]. In prospective studies using well-established assessment tools, median qualityof-life scores actually improve following surgery, even in highrisk patients [28, 29].

Conclusions In conclusion, surgical resection remains the standard of care for patients with operable early-stage NSCLC. Surgery is safe and allows for optimal diagnosis, staging and treatment of patients with lung cancer. Although SBRT has a role in the treatment of high-risk patients with NSCLC, medical inoperability is best determined by the surgeon, ideally in a multidisciplinary setting. Even carefully selected high-risk patients can be expected to have low morbidity and excellent long-term results with surgical resection. Given the ongoing debate, the surgical community should support ongoing clinical trials such as SABRTooTH, RTOG 3502, STABLEMATES and VALOR [30–34] to help establish the proper role of stereotactic radiation in the treatment of lung cancer patients.


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Central message SABR

Core issue

Minimally invasive surgery

When a lung nodule has a predicted likelihood of cancer Need for preoperative histology Many SBRT outcomes include patients without preoperative >85%, it is often safer to treat with SBRT versus attempting biopsy. Up to 16% of patients with suspected lung cancer will a biopsy or wedge [27] have benign nodules [12] A majority of patients undergoing SBRT for Stage I NSCLC Clinical vs pathological staging have a pathological diagnosis, but not all [91]

Among cStage I patients, 13–15% have clinically occult nodal metastases and over 20% will be upstaged to >_pStage II [2, 3]

Likelihood of mortality after SBRT is very low in patients Functional inoperability with severe COPD. SBRT is available whenever it is unsafe to operate [92]

‘Inoperability’ can only be assessed by a surgeon. Patients with FEV1 and DLCO Grade 3 CTCAE cally _3 CTCAEs is similar between surgery and SBRT [17–20]

Minimal changes in health-related QOL occurs after SBRT. QOL In the ROSEL study, SBRT had significantly less impact on QOL than surgery [51]

Surgical resection does not adversely affect QOL. QOL scores increased to above baseline after surgery and remained unchanged at 1 year [13]

SBRT is cheaper than surgery; however, cost-efficacy varies Costs depending on what inputs are modelled. Prospective comparative data are required [61]

For operable patients with low expected mortality, surgery is a more cost-effective strategy than SBRT [21, 22]

COPD: chronic obstructive pulmonary disease; cStage: clinical stage; CT: computed tomography; CTCAE: common terminology criteria for adverse events DLCO: diffusing capacity of the lungs for carbon monoxide; FEV1: forced expiratory volume in 1 s; NCDB: National Cancer Database; NSCLC: non-small-cell lung cancer; OS: overall survival; pStage: pathological stage; PET: positron emission tomography; QOL: quality of life; RCT: randomized controlled trial; SABR: stereotactic ablative radiotherapy; SBRT: stereotactic body radiotherapy.

STEREOTACTIC BODY RADIOTHERAPY OR STEREOTACTIC ABLATIVE RADIOTHERAPY Drew Moghanaki, Richmond, VA, USA; Shankar Siva, Melbourne, Australia

Introduction Stereotactic body radiotherapy or sterotactic ablative radiotherapy is increasingly being discussed as a potential treatment of choice

for surgically fit patients with early-stage NSCLC. The potential for this to be already occurring was recently illuminated by a report of more than 30 000 patients in the USA with Stage I NSCLC that demonstrated the use of SBRT increased 16% between 2004 and 2012, while the rates of surgery declined by 15% [35]. It is an outpatient treatment that is convenient, well tolerated and offers primary tumour control rates greater than 90% with 3-year survival probabilities similar to surgery (see Table 1). These outcomes have been widely reproducible and not limited to high-volume centres with extensive institutional expertise [36].




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Figure 1: Three- and 5-year overall and cancer-specific survival rates in the surgical literature. Reproduced with permission from Paul et al. [19], which has been published under a CC-BY-NC creative commons licence. SABR: stereotactic ablative radiotherapy; SLR: sublobar resection; VATS: video-assisted thoracoscopic surgery.

Figure 2: Overall survival of propensity-matched patients subjected to lobectomy or stereotactic ablative radiotherapy. Reproduced from Rosen et al. [4] (with permission from Elsevier). SBRT: stereotactic body radiotherapy; Tx: treatment type.


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Figure 3: Overall survival of propensity-matched patients subjected to lobectomy and stereotactic ablative radiotherapy who were recommended but refused surgery. Reproduced from Rosen et al. [4] (with permission from Elsevier). SBRT: stereotactic body radiotherapy.

Figure 4: Comparison of 1- and 3-year overall survival rates of SBRT versus surgery in the stereotactic ablative radiotherapy literature. Reproduced from Zhang B, Zhu F, Ma X, Tian Y, Cao D, Luo S et al. Matched-pair comparisons of stereotactic body radiotherapy (SBRT) versus surgery for the treatment of early stage non-small-cell lung cancer: a systematic review and meta-analysis. Radiother Oncol 2014;112:250–5 (with permission from Elsevier). CI: confidence interval; M-H: Mantel–Haenszel; OS: overall survival; SBRT: stereotactic body radiotherapy.

A SAFER TREATMENT The most likely reason SBRT has gained such popularity relates to patient and physician preferences for non-surgical options, particularly when there is hope for a treatment that can avoid the need for anaesthesia and hospitalization. Although low post-surgical mortality rates less than 1% are often reported at large academic medical

institutions, similarly reassuring outcomes have been difficult to reproduce in the broader medical community [37]. For example, a review of 12 surgical series published between 2007 and 2013 demonstrated that the 90-day surgical mortality was between 2.7% and 9.3%, a value that is approximately twice the 30-day mortality rates that are historically quoted [38].



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Figure 5: Comparison of 1- and 3-year CSS rates of SBRT versus surgery in the stereotactic ablative radiotherapy literature. Reproduced from Zhang B, Zhu F, Ma X, Tian Y, Cao D, Luo S et al. Matched-pair comparisons of stereotactic body radiotherapy (SBRT) versus surgery for the treatment of early stage non-small-cell lung cancer: a systematic review and meta-analysis. Radiother Oncol 2014;112:250–5 (with permission from Elsevier). CI: confidence interval; CSS: cancer-specific survival; SBRT: stereotactic body radiotherapy.

Table 1: Survival rates when operable patients prefer SABR instead of surgery: medically operable patients treated with SABR Study

Year reported

Design

RTOG 0618 Multi-institutional, USA Timmerman et al. [72]

2013

Phase II

National Defense Med College Japan Uematsu et al. [64]

2001

STARS-ROSEL International, USA Chang et al. [5]

Patients

Median F/U (months)

2-year OS (%)

3-year OS (%)

26

25

84

77

Retrospective

29

36

86

2015

Phase III (incomplete)

31

40

95

VU University Netherlands Lagerwaad et al. [13]

2011

Retrospective

177

31

85

51

JCOG 0403 Multi-institutional, Japan Nagata et al. [21]

2015

Phase II

64

67

77

54

Multi-institutional Japan Onishi et al. [67]

2011

Retrospective

87

55

80

69

Multi-institutional Japan Shibamoto et al. [66]

2015

Retrospective

60

52

66

Multi-institutional Japan Komiyama et al. [14]

2015

Retrospective

661

35

74

Ofuna Chuo Hospital Japan Eriguchi et al. [65]

2017

Retrospective

88

40

74–90

5-year OS (%)

67–74

F/U: follow-up; OS: overall survival; SABR: stereotactic ablative radiotherapy.

In stark contradistinction, one of the greatest advantages of SBRT is its favourable side-effect profile. This assertion is supported by excellent treatment outcomes in frail and elderly patients who were determined to be unfit for surgery, many of whom had pre-existing cardiopulmonary comorbidities. Even

among this population, deaths from SBRT have been uncommon [38]. By comparison in an analysis of population-level data from the UK, the 90-day surgical mortality rate for those aged 70–74 years was 7.3%, 75–79 years was 8.2%, 80–85 years was 9.5% and 85 years and older was 16.4% [39].


With regard to treatment-related morbidity, the rates of SBRTrelated radiation pneumonitis Grade >_3 have been in the range of 4–8%, with a 2–3% rate of rib fractures and 3 years are not well-established’ [55]. It deserves mention that discussions about a non-surgical option are particularly helpful for patients when they learn that the home-to-home time is often longer than just the hospital stay, given the postoperative discharges are frequently to skilled nursing facilities [56].

THE OPTION TO AVOID A BIOPSY With low rates of associated toxicity, SBRT without biopsy is now increasingly advocated when the clinical probability of malignancy is high (>85%) [57]. In populations with a low likelihood of infectious pulmonary nodules, validated algorithms that utilize medical history, CT and 18F-fludeoxyglucose-PET characteristics help predict this probability [58]. The appropriateness of SBRT without biopsy is supported by the European Society of Medical Oncology guidelines and provides a clinical advantage for patients who are frail [59]. It helps avoid the risks of surgery for benign disease in

A growing body of literature now suggests that OS and cancerspecific survival rates for patients with Stage I NSCLC may actually be higher after SBRT. These data, though limited to premature interrogations of incomplete randomized data [63], and a reliance on primarily non-randomized series, have focused on reporting the outcomes of surgically fit patients. Yet the results are remarkable, and as listed in Table 1, the 3- and 5-year OS rates with SBRT range between 77% and 95% [5, 13, 21, 64, 65] and 51% and 74% [13, 21, 65–67], respectively, with 5-year cause-specific survival rates between 82% and 90% [65]. Comparison of these values to historical surgical series is intriguing and offers hope that SBRT offers a superior treatment but would be fundamentally and statistically invalid without a truly randomized comparison. Both radiation oncologists and thoracic surgeons may wonder how SBRT could lead to superior OS when the primary tumour may regrow in approximately 10% of cases and a commonly accepted 10–15% risk of occult N1/N2 metastasis in patients who are clinically staged. The premise draws upon precedence in oncology from randomized clinical trials of organ preservation for malignancies of the larynx, breast, anus, bladder and extremities that faced similar challenges and ultimately established a standard of care with upfront radiotherapy with reservation of a salvage oncologic resection for the minority of patients who develop local or loco-regional progression [68]. It also considers the avoidance of perioperative complications that can be fatal in poorly selected patients. The approach of upfront SBRT for lung cancer has now been found to be safe with reports of salvage resections that include minimally invasive salvage techniques that are associated with minimal to no adhesions in the thorax [69–73]. The largest series of salvage surgery after SBRT recently reported on the outcomes of 37 patients who underwent salvage surgery after SBRT [70]. The median interval time between SBRT and salvage surgery




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was 16 months (range 7–71), and the median size of relapse at the time of surgery was 1.6 cm (range 0.7–4.0). A single patient died in this series during the first 90 days after salvage surgery due to a complication unrelated to previous SBRT. Median OS after salvage surgery was 46.9 months, and 3-year survival was 71.8%.

LETTING GO OF MISLEADING RETROSPECTIVE DATA Comparative effectiveness studies are often employed when there is insufficient evidence to clearly dismiss one treatment approach as inferior to another. However, methodologies to account for imbalances in patient populations, such as propensity matching, are imperfect and often misleading [74]. For example, in a systematic review of 45 publications of Stage I NSCLC from 2006 to 2013, there was no difference in survival at 2 years (70% vs 68%) for 3201 SABR patients and 2038 surgery patients [75]. In an analysis of data from 2000 to 2012, 40 studies of SABR with 4850 patients and 23 studies of surgery with 7071 patients were included. After adjustment for age and proportion of operable patients, SBRT and surgery had similar estimated overall and disease-free survival [76]. A separate summary of 12 published comparative effectiveness studies concluded similar outcomes when comparing SABR and surgery when accounting for competing risks for death from age and comorbidities at 3 and 5 years [77]. Yet, at the same time, there are contradictory reports that are predominantly found in the surgical literature—a recent analysis of the NCDB showed lower 5-year survival for SBRT compared with wedge resection even after adjustment for covariates (31.0% vs 49.9%, P < 0.001) [3].

SUPPORTING PHASE III TRIALS THAT MATTER It deserves acknowledgement that the premature analysis of the STARS and ROSEL pooled analysis was inherently flawed and unreliable for extrapolation [5, 60]. However, discounting the surgical outcomes of 79% survival at 3 years, it is intriguing that survival in the SBRT group was 95% at 3 years when surgically fit patients were enrolled. This report was notable for its sensationalized coverage by the lay media [78], as the results showed a 16% improvement in survival versus surgery [hazard ratio (HR) 0.14; log-rank P = 0.037]. However, while the main criticism related to a small sample size of only 58 patients, it is instructive to recall that this is the identical sample size as the original randomized trial of surgery versus radiation at Hammersmith Hospital that was published in 1963 and established the primacy of surgery ever since [79]. As it may no longer be known whether surgery or SBRT is the optimal treatment for Stage I NSCLC [80], there is greater equipoise than ever before to randomize patients between these 2 treatments. This is evidenced by a total of 8 randomized trials to date that have been funded and approved for activation by the institutional review boards (Open: NCT02984761, NCT02468024 and NCT01753414; Closed: NCT01622621, NCT00687986, NCT008 40749, NCT02629458, and NCT01336894—details available at www.clinical trials.gov). It will ultimately be the data from these trials that will allow for the most meaningful analyses to determine in which subsets of patients surgery or SBRT may be superlative [81]. But, until then, it appears that enthusiasm for SBRT may likely continue to cause a shift in referrals and patient preferences.

THE IMPORTANCE OF TEMPERAMENT It may be tempting for some to consider SBRT has arrived and is the preferred option whenever a patient wants to avoid surgery. However, there is a need for caution and awareness that the vast majority of surgical patients fare well after modern surgery in high-volume centres with experienced hands. It is likely that on the heels of completed randomized Phase III trials, we will become aware of the subsets of patients for whom surgery will make the difference between cure and uncontrolled metastatic disease. We may also learn about the scenarios that SBRT offers a higher probability for cure than resection. So, for those who may be currently indiscriminately offering SBRT to surgically fit patients, without Level I evidence to know in whom this may be appropriate or not, we share 4 important caveats that all enthusiasts should consider:

1. Limited follow-up. The available data for surgically fit patients treated with SBRT remains mired by short follow-up that is frequently less than 5 years. Surgically fit patients frequently have a greater than 10-year life expectancy and should be aware that their survival beyond 3–5 years following SBRT is largely unknown. 2. Delayed treatment of N1/N2 disease. It is inevitable that 10–15% of clinical Stage I NSCLC patients treated with SBRT will harbour occult N2 disease. It is possible that earlier identification of N1/N2 disease with surgical staging can improve patient outcomes with earlier initiation of earlier secondary therapies. However, models have shown that while the 5-year OS of patient upstaged at surgery can be improved by 5% with adjuvant chemotherapy, this benefit applies to only 1 in 200 patients who undergo surgery, given a 15% rate of upstaging and two-third rate of patients fit enough to receive postoperative chemotherapy [82]. Even an operative mortality rate of 0.5% counteracts this potential benefit. Next, it is unclear whether early salvage therapies that are initiated once N1/N2 relapse is identified during post-SBRT surveillance compromises survival or not. In one of the largest series to date (n = 772), salvage approaches are applicable to 92.7% of patients with isolated regional recurrence, with a 5-year OS (42.9%) similar to those of patients without recurrence after SBRT (53.5%) [83]. 3. Challenge of post-SABR radiographic scars: SBRT-induced peritumoural fibrosis frequently emerges on post-SBRT CT scans, requires advanced training to distinguish from tumour relapse and is thus often overestimated as a treatment failure even though rigorously conducted prospective studies report failure rates less than 10% [36, 72, 84–86]. A deleterious consequence of this uncertainty can lead to unnecessary salvage lobectomies when no tumour was present [87]. Evidencebased guidelines have only recently emerged to guide interpretation of evolving scars and should be referenced by clinicians who follow these patients after SBRT [88]. Ideally, any concern on CT is best corroborated with a follow-up 18F-fludeoxyglucose -PET/CT evaluation, as well as biopsy confirmation, when considering a salvage resection [59, 70]. 4. An indispensable need for multidisciplinary collaboration. Surgically fit patients who are interested in SABR have a


critical need for comanagement with a thoracic surgeon. First and foremost, it is to ensure that the informed consent process for SBRT is completed, as patients need to be fully aware of their option for surgery and that it remains the preferred option in all evidence-based guidelines when they have a less than 1.5% risk of operative mortality [55]. Next, it is to ensure timely access to surgical management whenever concern arises regarding local relapse. A hurried consultation to a thoracic surgeon, who has not yet met the patient, to consider for salvage resection of a potential relapse is not good practice and should be avoided whenever possible.

[6]

[7]

[8]

[9]

Conclusions SBRT is a highly effective treatment for Stage I NSCLC that is rapidly gaining popularity while the rates of surgery for this disease continue to decline. SBRT is convenient, cost-effective and associated with fewer serious side effects than surgery. Data that suggest QOL is favourable after SBRT are leading many to believe surgery may no longer be the preferred treatment for Stage I NSCLC. Yet, long-term survival beyond 3–5 years is not well established, and surgically fit patients deserve the completion of randomized trials to better understand the ramifications of treatment decisions. Until that occurs, radiation oncologists and thoracic surgeons are strongly advised to comanage surgically fit patients who prefer SABR, whether driven by enthusiasm or other motives.

[10]

[11]

[12]

[13]

[14]

ACKNOWLEDGEMENTS The authors thank Suresh Senan for his thoughtful comments and reviews throughout the preparation of this editorial. Conflict of interest: Drew Moghanaki is the co-chair of the Veterans Affairs Lung Cancer Surgery or Stereotactic Radiotherapy Trial, has received research funding from the Veterans Affairs Cooperative Studies Program and has received honoraria and travel expenses from Varian Medical Systems. Shankar Siva does not have any conflicts of interested relevant to this work. He has received research funding from Varian Medical Systems and Merck-Sharp-Dohme pharmaceuticals and travel expenses from Bristol-Meyer-Squibb and Astellas pharmaceuticals.

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