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Three Part Question

In patients with [non-small cell carcinoma suitable for lobectomy] does [VATS lobectomy compared to open lobectomy] provide equal [cancer clearance]

Clinical Scenario

You are referred a fit 66-year old man with a 2cm lesion in the periphery of his right lower lobe on CT scanning. Bronchoscopy was normal, and a CT guided biopsy has confirmed non-small cell lung cancer. His lung function is satisfactory for lobectomy. You have just been on a Video-assisted Thoracoscopic (VATs) Lobectomy course and he seems an ideal candidate for this procedure. The patient seems quite keen but then asks you if it cures his cancer just as effectively as the usual way. You reassure him, but resolve to check this in the literature.

Search Strategy

Medline 1966-Oct 2006 using the OVID interface.
[Lobectomy.mp OR Lobectomies.mp] AND [exp Thoracic Surgery, Video-Assisted/ OR VATS.mp OR videoendoscopic.mp OR video-assisted.mp ]

Search Outcome

The search strategy found 409 abstracts from which 21 were deemed to represent the best evidence on the subject. Due to space constraints 15 were fully tabulated. These are summarized in the table.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Kirby et al, 1995, USA	61 pts with stage I NSCLC patients randomised to muscle-sparing thoracotomy or VATS approach. 6 excluded after randomisation (benign disease or converted from VATS to open), 55 analysed. All pts had mediastinoscopy , CT scan, bone scan.	PRCT (Level 1b)	Survival	3 deaths, one ruptured AAA , one gallbladder cancer and one metastatic lung cancer.	Exclusion of VATS conversions to open means not intention-to-treat analysis. Little reporting of long-term (average 13 month) follow-up.
			Operating room time	Open Lobectomy 175 +/- 93 mins VATS Lobectomy 161+/- 61 mins
			Hospital stay	Open Lobectomy 8.3 +/- 4.8 days VATS Lobectomy 7.1 +/- 5.5 days
			Prolonged air leak	Open Lobectomy 8 pts VATS Lobectomy 3 pts
McKenna et al, 2006, USA	1,015 VATS lung resections for NSCLC (within report of 1,100 patients listed for VATS lobectomy for all causes). 5cm mini-thoracotomy without rib spreader.	Cohort study (level 2b)	Perioperative mortality	Perioperative mortality 0.8%, respiratory failure (3), pulmonary embolus (3), myocardial infarct (2), and venous mesenteric infarct (1).	Not all cancer resections.
			Conversion rate	2.5% conversion to open thoracotomy. (28 patients)
			Mean hospital stay	Mean 4.8 days. 20% discharged within 48 hours of surgery.
			Incision recurrence	5 patients (0.57%)
			4 year survival in a 298 patient subset reported in 1998[McKenna]	Stage I 4 year survival 70% (mean follow up 28.9 months). One port-site recurrence (0.3%).
Walker et al, 2003, UK	Cohort study (level 2b)	159 consecutive VATS lobectomies performed All clinical stage I or II disease, tumour <5cm. Universal cervical mediastinoscopy and thoracic CT Mean follow-up 38 months. (1-107months)	Tumour recurrence during follow up	Tumour recurred in 36 patients presenting as local recurrence in the hilum or mediastinum in nine (25%), metastatic disease in 23 (63.9%) and unknown pattern in four (11.1%). No wound implantation	Long term outcomes study with 100% follow up. 20 VAT additional procedures converted to open procedure ( 11%) 30 day mortality – 2 patients (PE and adrenal infarction) Is organising a multicentre PRCT
			5 year survival:	Stage I- 77.9% Stage II- 51.4% Stage III- 28.6%
			Operating time,	Median operative time 130 min , interquartile range (IQR) 41mins
			Blood loss	median 60ml. (IQR 91mls)
			Hospital stay	Mean stay 6 days ( IQR 3 days)
Thomas et al, 2002, France	Stage I NSCLC resection, 110 VATS, 404 open. Mixture sublobar, lobar and pneumonectomy resections. Lymph node dissection was also performed in all cases VATs used with minithoracotomy and a rib spreader.		5-year survival	VATS 62.9% Open resection 62.8%	Significantly more pneumonectomies and T2 tumours (p< 0.0001) in open group, therefore direct comparisons confounded.
			10 -year survival	VATS 44.2% (36.9–51.5)
			Intra-operative mortality	VATS 2.7% Open resection 3%
			Operative time, hospital stay	Not reported
Solaini et al, 2001, Italy	125 consecutive patients listed for VATS resection for stage I NSCLC less than 4cm in size. 108 lobectomies, 3 bilobectomies, 1 pneumonectomy (13 conversions).	Cohort study (level 2b)	Survival	3 year survival 85% +/- 9% (mean follow up 36 months).	Large series with excellent mortality figures. Large number (8.6%) of NSCLCs inadequately staged because of tumour maceration during extraction.
			In hospital mortality	0%
			Hospital stay	Mean 6.2 days
			Conversion rate	10.4%
Ohtsuka et al, 2004, Japan	106 patients with clinical stage I NSCLC listed for VATS anatomical lung resection. 3 port incisions and a 5 cm mini-thoracotomy, initially with a rib retractor then with tissue retractor only Of 95 VATS cases, 93 underwent systematic nodal dissection. ( Mean 21 nodes removed)	Cohort study (level 2b)	3 year survival ( Follow up 25months mean, 6-48mths	79% at 3 years (89% in pathological stage1). 10 (10.5%) recurrences, 6 of these locoregional (6.3%).	Study of stage I disease only. 86% follow up lower than some other studies. 86 lobectomies, 8 segment-ectomies, 1 bilobectomy
			Hospital stay	7.6 days (range, 4 to 15 days).
			In hospital mortality	One death
			Conversions	11 patients (10%)
Iwasaki et al, 2004, Japan	140 patients undergoing VATS resection for stage I NSCLC under 3cm in size. (100 lobectomy, 40 segmentectomy) 3 ports and a 7 cm utility incision. Lymphadenectomy also performed by VATS	Cohort study (level 2b)	5 year survival	Stage pIa 90.9% Overall 5 year survival 77.3%- 76.7% for lobectomies vs. 77.8% for segmentectomy. Histological subtype, gender and T stage predict survival in a multivariate model.	No control group. Relatively large utility incision. No operative or hospital stay data given
			In hospital mortality	None
			Conversion rate	2.1%
Roviaro et al, 2004, Italy	257 consecutive clinical stage I NSCLC patients with a tumour <3cms scheduled for VATS lobectomy.	Retrospective Cohort study (level 2b)	Intra-operative and 60-day mortality, conversion rate, 3 and 5 year survival.	3 year survival 77.7% a (95%CI +/-7.3%), 5 year survival 63.6% T1N0 83.5% 3 years, 70.2% 5 years T2N0 71.1% 3 years, 56.1% 5 years	No operative or hospital stay data given
			Intra-operative mortality	None
			Conversion rate	24 % (Intraoperative frozen section of N2 nodes, positive cases converted to thoracotomy.) 57 for oncological reasons 39 for technical reasons.
Kaseda et al, 2000, Japan	204 VATS lobectomies, segment-ectomies or pneumonectomies for stage I cancer performed from 1992-2000.		5 year survival ( 50 followed up 1-69 months, median 30mths)	VATS 97% Open resection from previous series 78.5%	No operative time or hospital stay data
			Lung function post operation	VATS FEV1 1,805+/-557mls Open thoracotomy FEV1 1,576 +/-472mls
Shiraishi et al , 2006, Japan	160 patients undergoing lobectomy either by VATS (n=81) or open thoracotomy (n=79) for T1N0M0 NSCLC. Minithoracotomy or total VATS lobectomies were performed with full mediastinal dissection.	Retrospective cohort study (level 2b)	Recurrence	Local recurrence 8 VATS 4 open thoracotomy 14 distant recurrences	2 lost to follow up. 2 died of unknown cause.
			5 year survival	89.1% VATS 77.7% open (p=0.149)
			Conversion	14/95 converted to open procedure
			Operation time	VATS 226.7+/- 48.9minsOpen 224 +/ 64mins
			Surgical bleeding	VATS 142+/- 143mls Open 204+/- 223mls
Buhr et al , 1995, USA	2 case reports of tumour dissemination after VATS resection for lung nodules		case 1	1992 Right upper lobe peripheral nodule removed by VATS – adenocarcinoma. 1994 a 3cm tumour nodule was detected on the chest wall where the previous nodule was removed
			Case 2	Jan 2003, VATS wedge resection of peripheral 2cm right upper lobe tumour.Histology showed close resection margin, and pleural thoracoscopic lavage was positive. He died of carcinomatosis 14 mths postoperatively.
Downey et al, 1996, USA	Survey of 55 surgical members of the Video-Assisted Thoracic Surgery Study Group. Asked whether they knew of any cases of dissemination of tumour to the port sites.	Survey (level 3b)	21 Cases identified of recurrence	14 pts Incision recurrence. 2 pts Pulmonary staple line. 2 pts Pleura. 1 pts Staple line and incision. 1 pt Pleura and incision. 1 pt Pleura and staple line	Only 17 actually had incision dissemination. 7 pts used bag to remove tumour.
			Types of tumour	6 adenocarcinoma 3 squamous cell carcinoma 5 mesothelioma 7 other (metastatic)
Yamashita et al, 2000, Japan	32 stage I NSCLC patients undergoing VATS lobectomy. Historical control group of 57 patients with stage 1 NSCLC undergoing open lobectomy.	Cohort study (level 2b)	Circulating CEA mRNA levels in peripheral blood before, during, immediately after, then 2-3 and 5-6 weeks after surgery.	VATS Group 62% of 29 tested were negative for CEA pre-operatively, but only 2 patients (6.9%) remained consistently negative throughout surgery Open Lobectomy 32% of 57 open lobectomies consistently CEA negative during surgery In a separate analysis, consistently positive CEA mRNA assays correlated with reduced survival in the 57 open patients.	No correlation with reduced clinical survival in the VATS group .
Ng et al, 2005, Hong Kong SAR, China.	11 VATS lobectomy (including 1 bilobectomy), 10 thoracotomy controls (9 lobectomy, 1 bilobectomy).	Cohort study (level 2b)	Levels of total leukocytes, B cells, NK cells,T4 and T8 levels preoperatively and at days 1, 3 and 7.	Day 7 NK cell levels were lower in open compared with VATS groups. Lymphocyte, total T and T4 levels fell significantly postoperatively following thoracotomy but not VATS No survival difference over mean 4.5 year follow up.	No clinical correlation to reduced cancer survival shown
Sugi et al, 2000, Japan	100 consecutive patients with clinical stage IA non-small cell lung carcinoma Open thoracotomy (n=52) VATS lobectomy (n=48). Lymph node dissection performed		Recurrence	VATS 5/48 (10%), Open Thoracotomy 10/52 (20%)
			5 year survival	VATS 90% Open Thoracotomy 85%

Comment(s)

Kirby et al published the first RCT in this area. 55-patients were randomized to VATs or muscle sparing thoracotomy. There were no differences in length of day(around 7 days) operating time(mean 2½ hrs) and only 2-patients died after mean 13-months follow up. This study demonstrated operative equivalence with the open technique but was too small to make any conclusions regarding operative cancer clearance. The only other RCT in this area looked at acute phase response in 41 patients who either underwent VATS or open thoracotomy. There was a decrease in these markers although because there was no follow up data for these patients we did not tabulate this paper[Craig]. Robert McKenna Jnr presented the Sinai Medical centre series of 1,100 VATs lobectomies in 2006. They report a mean 4.7-day inpatient stay with 20% being discharged in less than 2-days. The perioperative mortality was 0.8% and the conversion rate was 2.5%. However no longer term survival was presented other than a 298 patient subset in a previous paper where a 4-year survival of 70% for Stage Ia was reported. Walker et al presented a cohort of 159 VATs lobectomies, showing a 78% 5-year survival for Stage I cancer (51% for stage II). There was an 11% conversion rate and a mean hospital stay of 6 days. Mention in this paper was given to having obtained ethical approval to perform a multi-centre randomised trial in this area. Thomas et al published a series of 110 VATS resections of stage I tumours, compared to open controls. The 5-year survival was 63% which was the same as the open group. Of note they used a mini-thoracotomy with a rib spreader in all cases. Solaini et al reported 112 VATS resections who achieved an 85% 3-year survival, with a mean 6 day hospital stay. Interestingly 7 resection samples were too macerated on extraction to accurately determine their 'T' status. Ohtsuka et al reported a 79% 3-year survival in 106 patients who had a VATS lung cancer resection. Interestingly all patients also had systematic lymph node dissection by VATS with an average 21 lymph nodes removed per patient. Iwasaki et al reported a 77% 5-year survival for stage I patients with tumours under 3cms having a VATS resection. Roviaro et al reported a 5-year survival of 64% for stage I cancer patients with a tumour <3m having a VATS resection. Kaseda et al reported their experience with 204 VATS resections. Post-operative lung spirometry was superior to open controls and in a subgroup of 50-patients followed up for a median 30 months, survival was 97% for the VATS patients compared to 79% for open controls. Shirashai et al compared 81 VATs resections to 79 open procedures. Operating time and blood loss were the same, as was 5-year survival with 89% in VATS patients and 78% in the open group. Other cohorts have also been reported with similar results which were not tabulated due to our own table space restraints[Gharagozloo, Okada, Lewis, Shigemura]. There has been some concern that a VATS procedure can cause seeding of the tumour to the chest wall. Buhr presented 2 cases, although only one of them sounded like true seeding. Downey published the results of a survey of 55 VATS surgeons who were asked if they had seen any cases of incision seeding. He reported 21 cases that included 5 patients with mesothelioma and 11 cases of NSCLC, and 17 cases directly recurring in the incision line. However there is no denominator to these findings and the incidence of recurrence in open incision lines is unknown. Yamashita et al measured blood carcinoembryonic antigen (CEA) mRNA in patients undergoing VATS resections. 16 of 18 patients had positive blood levels intraoperatively compared to a previous study in open lobectomy patients where only 18 of 35 patients were positive intraoperatively. They hypothesised that the lack of manual handling of the lung meant that firm lung retraction and tumour manipulation by instruments may cause an increased level of tumour disruption. Another study measured immunosuppresion levels during VATS or open surgery. Ng et al found a significantly reduced level of immunosuppression in the VATS group.

Clinical Bottom Line

Repeated cohort studies have shown 5-year survival rates similar in the VATS groups to that achieved from Open thoracotomy. The majority of resections are in Stage I tumours less than 3-5cm in size and 5 year survival rates of 70% or better have consistently been reported. It is reasonable to assume that this cancer cure is similar to open resection although it must be remembered that significant selection bias occurs in all these non randomized studies. A few case reports have raised concerns about port site recurrence and seeding with VATS but the incidence of incision recurrence in open procedures is also unknown. Finally there is little data to support improved hospital stay, reduced costs or improved patient experience with VATS, and thus while equivalence has been well shown with the open technique , further randomized studies are required to demonstrate superiority.

References

1. Kirby TJ, Mack MJ, Landreneau RJ, Rice TW. Lobectomy--video-assisted thoracic surgery versus muscle-sparing thoracotomy. A randomized trial. J Thorac Cardiovasc Surg 1995;109(5):997-1001.
2. Craig SR, Leaver HA, Yap PL, Pugh GC, Walker WS. Acute phase responses following minimal access and conventional thoracic surgery. Eur J Cardiothorac Surg 2001;20(3):455-63.
3. McKenna RJ, Jr., Houck W, Fuller CB. Video-assisted thoracic surgery lobectomy: experience with 1,100 cases. Ann Thorac Surg 2006;81(2):421-5.
4. Walker WS, Codispoti M, Soon SY, Stamenkovic S, Carnochan F, Pugh G. Long-term outcomes following VATS lobectomy for non-small cell bronchogenic carcinoma. Eur J Cardiothorac Surg 2003;23(3):397-402.
5. Thomas P, Doddoli C, Yena S, Thirion X, Sebag F, Fuentes P, Giudicelli R. VATS is an adequate oncological operation for stage I non-small cell lung cancer. Eur J Cardiothorac Surg 2002;21(6):1094-9.
6. Solaini L, Prusciano F, Bagioni P, Di FF, Basilio PD. Video-assisted thoracic surgery major pulmonary resections. Present experience. Eur J Cardiothorac Surg 2001;20(3):437-42.
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14. Lewis RJ, Caccavale RJ, Bocage JP, Widmann MD. Video-assisted thoracic surgical non-rib spreading simultaneously stapled lobectomy: a more patient-friendly oncologic resection. Chest 1999;116(4):1119-24.
15. Shigemura N, Akashi A, Funaki S, Nakagiri T, Inoue M, Sawabata N, Shiono H, Minami M, Takeuchi Y, Okumura M, Sawa Y. Long-term outcomes after a variety of video-assisted thoracoscopic lobectomy approaches for clinical stage IA lung cancer: a multi-institutional study.[see comment]. J Thorac Cardiovasc Surg 2006;132(3):507-12.
16. Buhr J, Hurtgen M, Kelm C, Schwemmle K. Tumour dissemination after thoracoscopic resection for lung cancer. Journal of Thoracic and Cardiovascular Surgery 1995;110(3):855-6.
17. Downey RJ, McCormack P, LoCicero III J. Dissemination of malignant tumours after video-assisted thoracic surgery. A report of twenty-one cases. Ann Thorac Surg 1996;111:954-60.
18. Yamashita JI, Kurusu Y, Fujino N, Saisyoji T, Ogawa M. Detection of circulating tumor cells in patients with non-small cell lung cancer undergoing lobectomy by video-assisted thoracic surgery: a potential hazard for intraoperative hematogenous tumor cell J Thorac Cardiovasc Surg 2000;119(5):899-905.
19. Ng CS, Lee TW, Wan S, Wan IY, Sihoe AD, Arifi AA, Yim AP. Thoracotomy is associated with significantly more profound suppression in lymphocytes and natural killer cells than video-assisted thoracic surgery following major lung resections for cancer. J Invest Surg 2005;18(2):81-8.
20. Sugi K, Kaneda Y, Esato K. Video-assisted thoracoscopic lobectomy achieves a satisfactory long-term prognosis in patients with clinical stage IA lung cancer. World J Surg 2000;24(1):27-30.
21. McKenna RJ, Jr., Wolf RK, Brenner M, Fischel RJ, Wurnig P. Is lobectomy by video-assisted thoracic surgery an adequate cancer operation? Ann Thorac Surg 1998;66(6):1903-8.