Indeterminate Pulmonary Nodules in Patients with Colorectal Cancer

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1 Indeterminate Pulmonary Nodules in Patients with Colorectal Cancer Jai Sule 1, Kah Wai Cheong 2, Stella Bee 2, Bettina Lieske 2,3 1 Dept of Cardiothoracic and Vascular Surgery, University Surgical Cluster, National University Health System 2 Yong Loo Lin School of Medicine, National University of Singapore 3 Div of Colorectal Surgery, Dept of Surgery, University Surgical Cluster, National University Health System Indeterminate Pulmonary Nodules in Patients with Colorectal Cancer 1

2 Background Chest computed tomography (CT) is now accepted standard for screening for pulmonary metastases in patients diagnosed with colorectal cancer (CRC) Staging chest CT scans in patients with CRC yield a significant number of sub-centimeter nodules too small to characterize Indeterminate pulmonary nodules (IPNs) pose a significant challenge in terms of management and follow up of these patients NICE clinical guideline 131 (2011) guidance.nice.org.uk/cg131 The Association of Coloproctology of Great Britain and Ireland. Guidelines for the Management of Colorectal Cancer Indeterminate Pulmonary Nodules in Patients with Colorectal Cancer 2

3 Aims Identify incidence of IPNs in patients diagnosed with CRC Identify the incidence of pulmonary metastases in CRC patients found to have IPNs Identify factors predicting the development of pulmonary metastases in these patients Determine an optimal timeline to screen for the development of pulmonary metastases Indeterminate Pulmonary Nodules in Patients with Colorectal Cancer 3

4 METHODOLOGY Indeterminate Pulmonary Nodules in Patients with Colorectal Cancer Indeterminate Pulmonary Nodules in Patients with Colorectal Cancer 4

5 Methodology Database review of patients diagnosed with CRC between Included all patients with Staging CT thorax within 3 months of diagnosis of CRC Excluded patients with pulmonary metastases on staging CT or concomitant malignancy / pulmonary disease Followed up patients with IPNs up to 1cm diameter historically for development of pulmonary metastases Analyzed IPN positive patients with resected primary CRC for factors predicting development of pulmonary metastases Chi square and Mann Whitney U test where appropriate Indeterminate Pulmonary Nodules in Patients with Colorectal Cancer 5

6 RESULTS Indeterminate Pulmonary Nodules in Patients with Colorectal Cancer Indeterminate Pulmonary Nodules in Patients with Colorectal Cancer 6

7 Results Patients diagnosed with CRC from n=1536 Patients who underwent staging CT thorax n=300 Patients who met inclusion criteria n=277 Patients with IPNs n=58 (20.9%) Patients without IPNs n=219 (79.1%) Underwent CRC resection n=55 Pulmonary metastases (PM+) n=14 (25.5%) PM+ n=14 (24.1%) PM+ n=20 (9.1%) Fisher s 1-tailed [p-0.003] Indeterminate Pulmonary Nodules in Patients with Colorectal Cancer 7

8 Demographics (IPN positive patients) Variable Group N (%) Gender Male 33 (60) Age 65 Median 69 (range 30-88) years 32 (58.2) Smoking status Smoker 12 (22.6) Cancer Site AJCC Stage Colon Rectosigmoid Rectum T1 T2 T3 T4 N0 N1 N2 M0 M1 (liver) 41 (74.6) 6 (10.9) 8 (14.6) 0 (0) 2 (3.7) 34 (63) 18 (33.3) 20 (37) 18 (33.3) 16 (29.6) 46 (83.6) 9 (16.4) Indeterminate Pulmonary Nodules in Patients with Colorectal Cancer 8

9 Demographics (IPN positive patients) Variable Group N (%) Number of IPNs 3 32 (58.2) Size of IPNs 5mm 21 (38.2) CEA level >5 18 (33.3) Histological grade Neo-adjuvant Therapy Adjuvant Therapy Moderate Poorly differentiated Chemotherapy Radiotherapy Chemotherapy Radiotherapy 44 (84.6) 8 (15.4) 7 (12.7) 4 (7.3) 26 (48.2) 5 (9.3) Median follow up period 2.3 ( ) years Indeterminate Pulmonary Nodules in Patients with Colorectal Cancer 9

10 Kaplan-Meier Log Rank p=0.002 Indeterminate Pulmonary Nodules in Patients with Colorectal Cancer 10

11 Analysis Univariate analysis of the development of pulmonary metastases Variables PR+ RR 95% CI No. of IPNS 3 < 3 Size in mm 5 < 5 CEA > 5 5 Grade Adjuvant chemo Adjuvant RT Poor Mod No Yes No Yes Indeterminate Pulmonary Nodules in Patients with Colorectal Cancer 11

12 Analysis Analysis of development of pulmonary metastases (Mann-Whitney U test) Variables p-value T Stage 0.46 N Stage 0.04 Indeterminate Pulmonary Nodules in Patients with Colorectal Cancer 12

13 DISCUSSION Indeterminate Pulmonary Nodules in Patients with Colorectal Cancer Indeterminate Pulmonary Nodules in Patients with Colorectal Cancer 13

14 Discussion Current spiral CT scans have increased sensitivity and may reveal increasingly smaller lesions Our study revealed a higher proportion of patients with IPNs on staging CT 20.9% vs 9% in pooled study Also revealed a higher proportion of patients with IPNs developing pulmonary metastases 24.1% vs 10.8% Our study did not show a significant difference for IPN number and size as seen with other studies Andreas Nordholm-Carstensen et al. Indeterminate Pulmonary Nodules at Colorectal Cancer Staging: A Systematic Review of Predictive Parameters for Malignancy. Ann Surg Oncol (2013) 20: SN Griffiths et al. Characterisation of indeterminate pulmonary nodules in colorectal cancer. International Journal of Surgery 10 (2012) 575e577 Indeterminate Pulmonary Nodules in Patients with Colorectal Cancer 14

15 CONCLUSION Indeterminate Pulmonary Nodules in Patients with Colorectal Cancer Indeterminate Pulmonary Nodules in Patients with Colorectal Cancer 15

16 Conclusion Staging CT thorax yields a substantial proportion of IPNs, the majority of which do not develop into pulmonary metastases. IPNs confer >2x the risk of developing pulmonary metastases. Lymph node status at diagnosis of CRC was the only significant predictive factor for the development of pulmonary metastases. A routine follow-up CT scan should be done approximately 9 months after the diagnosis of CRC to screen for pulmonary metastases. Indeterminate Pulmonary Nodules in Patients with Colorectal Cancer 16

17 Thank you Indeterminate Pulmonary Nodules in Patients with Colorectal Cancer 17

18 Indeterminate Pulmonary Nodules in Patients with Colorectal Cancer 18

19 Limitations Retrospective review of patients with IPNs Individual IPNs not followed up for development of pulmonary metastases histologically Majority of patients diagnosed with CRC prior to 2011 did not have CT thorax scans Overall sparse population with IPNs and presence of missing data in earlier patients precluded use of multivariate analysis Indeterminate Pulmonary Nodules in Patients with Colorectal Cancer 19