The treatment of choice in stage I lung cancer has traditionally been lobectomy with 5 years OS rates ranging between 60 and 70% and 12 years OS rates between 69% (T: 5–15 mm) and 43% (T > 45 mm).Citation2 However, in the real world practice most patients are medically or functionally non amendable to surgery especially elderly patients.
It must be noted that radiation therapy has indeed been revolutionized since the 1970's up till now, where surgery was considered the only treatment option. Therefore, the role of radiation therapy in the curative management of early stage lung cancer has evolved dramatically. Where once medically inoperable patients had no treatment or unsatisfactory treatment options, such as conventional radiation therapy or limited surgery, nowadays the standard of care for this specific group of patients is Stereotactic Body Radiation Therapy (SBRT).Citation3 SBRT has been shown to have local control survival (LC) rates in 2–3 years ranging between 84 and 98% and OS at 2–3 years between 43 and 75%.Citation4
Actually, only three studies mentioned in the meta-analysis, have been conducted comparing surgery and SBRT, giving SBRT a head start on all endpoints studied overall survival (OS), disease-free survival (DFS), local control survival (LC), regional control survival (RC), loco-regional control survival (LRC), and distant control survival (DC). Mindful of these outcomes Quality of Life (QOL) after SBRT for early stage lung cancer seems self-evident to be higher in the SBRT group.Citation5 This further indicates the appropriateness of SBRT in medically inoperable patients.
Therefore, the main question is the role of SBRT in operable patients. The argument has been that following up on patients after SBRT that OS seems to decline after 3 years compared to surgical series. However, this has been noted in a group of patients that most likely succumb to comorbidities than their lung primary. Looking at the SEER results on studies comparing SBRT in Stage I NSCLC in operable patients, results at 1 year are comparable 95% vs. 94% and at 3 years seem to decline for the SBRT group.Citation6 But looking closer at this analysis the Grills IS et al. trial 2010Citation7 had older patients with severe comorbities supporting this difference, however the Verstegen NE et al. trial 2013Citation8 compared VATS to SBRT in patients matched for gender, PS, stage, tumor location, histology, comorbidity index and FEV1, as did the Crabtree T et al. trial 2013Citation9 with 257 patients, and these trials at 3 years showed comparable OS (77 vs. 80%). When propensity score matched analysis was performed, in total survival outcomes were similar with a lower toxicity profile in the SBRT treatments.
Furthermore, about a decade ago Japan suggested that SBRT may be appropriate for medically operable patients as well. A study conducted by Onishi et al. showed similar OS in patients groups with 3 years OS >80% and 5 years OS >70%.Citation10 So far, three phase 3 random trials have been initiated to compare SBRT with surgery in patients with early-stage NSCLC (the STARS trial [NCT00840749], the ROSEL trial [NCT00687986], and the ACOSOGZ4099 trial [NCT01336894]), but all were closed early because of slow accrual. Taking into account that randomized trials are currently ongoing comparing surgical resection to SBRT with OS being the main endpoint, one must conclude that in terms of QOL and toxicity SBRT is definitely favored.
One may argue how an oncologist can disregard nodal staging in a primary lung tumor. In fact, SBRT does not allow for lymph node dissection; however >40% of patients in the US has no nodes removed during the time of surgery. In addition, the purported benefit of nodal dissection in Stage I NSCLC has not been supported in randomized trials and in light of the negative predictive value of PET in this stage of 99%, one must argue that this is not the downside of SBRT.Citation11 And if comparing nodal recurrence after SBRT staged with CT and PET the rate is approximately 10%Citation12 and the rate of false negative nodes in surgical series again staged by both examinations, is approximately 12%.Citation13 This is further supported by the randomized trial ACOSOC Z0030 which showed no benefit in surgical series of lymphadenectomy during pulmonary resection in patients with negative lymph node sampling.Citation14
In conclusion, SBRT and lobectomy seem to be equivalent with perhaps better outcomes in terms of survival for SBRT as suggested by the randomized trials conducted and further supported by the current meta-analysis. Inevitably, the main and difficult question is the role of SBRT in the operable patient. Several intrinsic limitations in interpreting data do exist in the available literature to date, such as patient cohorts. However, undoubtedly SBRT is safe, efficient and better tolerated than surgery. In clinical practice one must use a multidisciplinary approach to determine the best treatment based on an individual basis. This metanalysis may facilitate decision making as well as the results of the ongoing trials.
Conflict-of-interest statement
No potential conflicts of interest. No financial support.
AUTHOR CONTRIBUTIONS
All authors equally contributed to this paper with conception and design of the study, literature review and analysis, drafting and critical revision and editing, and final approval of the final version.
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