sublobar resection updates

1. Extent of surgical resection in early stage NSCLC
Journal club 11th August 2022
Lim / Zhu

3. One of the earliest reports in 1973 – 15-year experience with 129 segmentectomies

4. Pros and cons of limited resection
Pros Cons
• Worsened local recurrence
• Preserve lung function
– Improve QoL?
– Permit another surgery
patients develop a second
primary lung cancer?
Is this true? By how much? By how much?
What are the risk factors?
• Margins
• Tumour characteristics?

5. Lobectomy vs Sublobar resection
• Ginsberg and Rubinstein
• Lung Cancer Study Group published in Chest 1994
• "Randomized Trial of Lobectomy Versus Limited
Resection for T1N0 Non-Small Cell Lung Cancer"
• 247 patients with cT1N0 <3cm NSCLC randomized to
lobectomy versus sublobar resection

6. • 1/3 wedge, 2/3
segmentectomy in limited
resection group
• Minimum FU: 4.5 years
• Key findings:
– Tripling of locoregional
recurrence with sublobar
resection
– Increase in overall and
cancer-related mortality

7. • Caveat: Occult intralobar metastatic disease likely present
at time of surgery
• Dogma: Lobectomy is the oncologically "complete"
operation
• Of note, 495 of 771 were not randomized for variety of
reasons, 1/4 of those patients were understaged
preoperatively

9. Surgical margin
Lung segments are fan-shaped, with
the apex at the hilum and base on the
pleural surface
Tumours which are larger and/or
centrally located inevitably will be
excised with smaller margins

12. Consolidation / tumour ratio
• Fleischner Society:
bidimensional average of the
long and short dimensions
• cTNM: max diameter
• pTNM: max diameter from 3D
• Assumption: Ground-glass vs
solid differentiates lepidic vs
invasive components of
tumours well

14. Radiological-pathological correlation
• Son et al. studied 191 resected pure GGNs that had been
diagnosed as AIS, MIA, or invasive adenocarcinoma, and
on pathologic examination, they found that only 38 (20%)
were AIS whereas 61 (32%) were MIA and 92 (48%) were
invasive adenocarcinoma.
– 75th percentile attenuation value >= 470 HU and entropy
correlates with invasive adenoCA.

15. • On pathologic examination of 46 pure GGNs larger than
1.0 cm by thin-section CT scan, MIA was found in 20% of
cases and invasive adenocarcinoma in 39%; however,
no patient, including those who underwent sublobar
resection, had a recurrence.
– Size correlates with invasive adenoCA.

16. GGNs with total diameter >3.0cm
• 3735 Japanese patients with GGO >3.0cm

17. • GGO-dominant lung cancer exceeding
3.0 cm can be considered to be in a
group of patients with nodal-negative
disease and excellent prognosis

18. JCOG 0201
• What is a non-invasive adenoCA?
– No nodal involvement
– No vascular invasion
– No lymphatic invasion
• 545 adenoCA lobectomy with mediastinal dissection
• Radiological-pathological correlate

19. • CTR 0.25 <= 2.0cm defines a radiologically non-invasive
CA lung

22. JCOG 0804
• 1-arm study with sublobar resection for radiologic
noninvasive lung cancer based on the criteria of
JCOG0201
• 5-year RFS was 99.7%
• The macroscopic surgical margin should be 5 mm or
more, which is confirmed by evaluating the distance
between the tumor and the parenchyma staple or cut line.
(Median 15mm achieved)

23. • “The resected specimen should be sent to the pathologist
intraoperatively for evaluation of the surgical margin and
histology of the primary tumor by frozen-section
diagnosis, either pathology or cytology.”

24. JCOG 1906 EVERGREEN

26. JCOG 0802
• 1106 patients cT1a/bN0 CTR 0.5-1.0 recruited from 40
institutions from 2009 to 2014
• Randomized to lobectomy and segmenctomy
• 50% had solid tumours
• Primary outcome: OS
• Secondary outcome: Lung function

27. • Improvement in OS

28. • No difference in recurrence free survival

29. • Significantly more locoregional relapses occurred in
patients who had segmentectomy (n = 58, 11%) than in
those who had lobectomy (n = 30, 5%; p= 0.0018)
– Total relapse pattern, including patients who had distant relapse
plus those who had both distant and logoregional relapse, was
similar in the segmentectomy and lobectomy

30. • Lobectomy group had more deaths from other cancer
including second lung primary cancer (5.6% vs 2.2%)
• Additional intensive resections and therapies for treating
relapse or second primary lung cancer were performed
more frequently in patients after segmentectomy
compared with lobectomy

31. • Difference in reduction in median FEV1 at 1 year was
3.5%, which while statistically significant, did not reach
the predefined 10% difference to reach clinical
significance

32. • Survival, RFS, CSS better
with lobectomy overall
• For tumours <2.0cm, no
difference between the groups

34. JCOG 1211
• 390 patients segmentectomy for CTR <0.5, tumour size
<3cm
• Confirmatory trial
• Primary outcome: Relapse-free survival
• Recruitment completed in 11/2015

35. CALGB 140503
• cT1aN0 no requirement for CTR
• Pure GGOs excluded
• 697 patients randomized
• No difference in early perioperative morbidity and
mortality between sublobar resection and lobectomy
• Primary outcome: disease-free survival
• Secondary end points: overall survival, disease-free
survival and the secondary end points are overall survival
• Long-term results T/F

36. Conclusion (1)
For pure ground glass cT1a/bN0 CTR 0 – 0.25 NSCLC,
wedge resection with adequate margins alone
with rapid on-site pathological evaluation of surgical
margins,
achieving margins >1.5cm
leads to excellent disease-free survival.

37. Conclusion (2)
For well-staged predominantly solid cT1a/bN0 NSCLC,
segmentectomy, when compared with lobectomy,
performed in high-volume centres by experienced surgeons
with rapid on-site pathological evaluation of surgical
margins,
achieving margins >2.0cm or margin-tumour ratio >1.0
leads to similar overall and disease-free survival, despite a
higher rate of local recurrence.
Segmentectomy appears to better preserve lung function,
but the difference is not significant clinically.
This fits with a strategy of lung preservation surgery anticipating multiple
ground glass/lepidic nodules in a lifetime.
CALGB 140503 will provide more insights.

38. Conclusion (3)
• For ground glass nodules <2cm with CTR 0.25-0.50,
question remains as to whether wide wedge resection
suffices or segmentectomy is superior?
• For ground glass nodules 2-3cm with CTR 0.25-0.50,
question remains whether segmentectomy is enough or
lobectomy remains the gold standard
• These questions will be answered in JCOG 1211