The Role of Surgery in Cancer

Transcription

1 The Role of Surgery in Cancer Farhat VN Din Senior Lecturer Chief Scientist Office Senior Clinical Fellow & Consultant Colorectal Surgeon

2 Disclosure Surgeon Scientist Optimist My own views

3 The next few minutes Incidence & mortality trends Contribution of surgery to cancer management Translational research in cancer surgery Aligning priorities to accelerate translation

4 Incidence and Mortality

5 Cancer in the UK CRUK

6 Cancer Scotland All cancers Number Rate (ASR) UK average Incidence Mortality NCIN e-cancer atlas

7 Cancer Scotland All cancers Number Rate (ASR) UK average Incidence Mortality NCIN e-cancer atlas

8 Trends in Cancer Incidence Scotland , age-adjusted

9 Most Common Cancers in Scotland 2015

10 Observed and Projected Incidence and Mortality Rates Age-standardised Incidence Age-standardised Mortlaity CRUK: cruk.org/cancerstats

11 Incidence Projections for Scotland Scottish Cancer Registry

12 Multimodality Cancer Treatment Radiotherapy Surgery Chemotherapy

13 Extent to which surgery airbrushed from media striking A widely cited analysis of cancer research stories published between 1998 and 2006 on the BBC website chosen by the researchers as an ideal surrogate for overall media impact found that stories about cancer drugs dominated, accounting for around 20% of all coverage. Br J Can 2008, 99:569 76

14 Media Influences Public Attitudes and Policy

15 Contribution of Surgery to Cancer Management

16 Cancer patient registrations Patients undergoing Surgery for Cancer Scotland Surgery status Yes Surgery status No Surgery status Not Known ISD, Scotland

17 Cancer patient registrations Surgery as First Treatment for Cancer Patients Year total surgery radiotherapy chemotherapy hormone other ISD, Scotland

18 Evolution of cancer surgery Hippocrates ( BC) early cancer descriptions- thought to be incurable Roman physician Celsus (28-50 BC) After excision, even when a scar has formed, none the less the disease has returned. Noted no cure once spread Galen ( AD) oncos Surgery cures breast cancer if completely removed at an early stage William Handley 1900 permeation theory Cancer surgery pioneers: remove the entire tumour & lymph nodes Theodor Billroth 1872 oesop. resection William Halstead 1880s radcical mastectomy Steven Paget 1889 seed and soil George Beatson 1896 oophorectomy in breast ca

19 Advances in Cancer Surgery * anaesthesia Bernard Fisher, Cancer Research 2008

20 Advances in Cancer Surgery Bernard Fisher, Cancer Research 2008

21 Its about the result.. Not the tools

22 Radical surgery William Halsted Johns Hopkins radical mastectomy Mastectomy through the ages, Neddy Merrill

23 Maximal to minimally invasive surgery Open surgery Laparoscopic surgery Robotic surgery technological advance vs oncological advance preserve oncological principles

24 Surgical remains central to cancer management Screening Diagnosis ( resection / biopsy) Staging Prophylactic surgery Reconstruction Primary treatment Palliation

25 Prophylactic Surgery-Cancer prevention

26 Relevance to surgeon Identification of inherited syndromes Stratify risk Screening Tailor surgery Post-operative surveillance Clinically relevant somatic mutations

27 Prophylactic surgery benefits of resection of normal organ from an asymptomatic individual > risk of surgery

28 Prophylactic cancer-risk reducing surgery

29 Criteria for prophylactic surgery High penetrance of the mutation or high lifetime risk Reliable test : genetic testing sensitive method for determining if disease-free operative morbidity low function of the removed organ restored You et al. World J Surgery, 2007

30 Prophylactic Mastectomy in Preventing Breast Cancer Time to Breast Cancer Diagnosis in Female BRCA1 Mutation Carriers Rebbeck et al; JCO 2004, 22,

31 Effect of Prophylactic Oophorectomy Ovarian and Breast Cancer Risk in BRCA1/2 Carriers Rebbeck TR et al. N Engl J Med 2002;346:

32 Cumulative Survival of Screened vs Symptomatic FAP patients E K L Mallinson et al. Gut 2010;59:

33 Extended Colectomy reduces risk by 4-fold in Lynch Syndrome Anele et al. Colorectal Disease, (6) pages

34 Surgery as Primary Treatment

35 What is the Evidence-Base Supporting the Assertion that Surgery Can Cure Established Cancer? No randomised trials ever conducted of surgery versus no treatment Evidence base that surgery is beneficial is only indirect - Observational studies - Descriptive studies of case series - Comparative studies of different techniques/approaches - Evidence from within randomised trials of chemotherapy/radiotherapy - Randomised trials of surgery alone against radiotherapy/chemotherapy

36 Estimated Contribution to Cancer Cure Cytotoxic Chemotherapy Morgan G et al. The contribution of cytotoxic chemotherapy to 5-year survival in adult malignancies. Clin Oncol 2004; 16:

37 Estimated Contribution to Cancer Cure Radiotherapy +/- ChemoRx for Rectal Cancer Preoperative chemoradiation versus radiation alone survival outcome Preoperative radiotherapy vs surgery alone absolute survival Gray R et al. Adjuvant radiotherapy for rectal cancer: a systematic overview of 8507 patients from 22 randomised trials. Lancet 2001;358(9290): De Caluwé L et al. Cochrane Database of Systematic Review. 28 FEB 2013 DOI: / CD pub3

38 Contribution of Surgery to Cancer Survival Radiotherapy/Neoadjuvant ChemoRadiotherapy Breast Cancer Rectal Cancer Breast-Conserving Surgery With or Without Radiotherapy J Natl Cancer Inst. 2004;96(2): Rahbari et al. Neoadjuvant Radiotherapy for Rectal Cancer: Meta-analysis of Randomized Controlled Trials. Ann Surg Oncol (2013) 20:

39 Surgical Debulking in Ovarian Cancer Overall Survival Progression-free Survival Dubois et al. Cancer 2009; 115,

40 Hepatic Resection for Colorectal Cancer Liver Metastases Radiofrequency ablation (RFA) vs Resection Van Amerongen et al. HPB 2017

41 Negative Surgical Resection Margin Key determinant of overall survival RO Resection: complete resection with no microscopic residual tumour R1 Resection: complete resection with no grossly visible tumour, microscopic cancer may be left behind (margins positive) R2 Resection: partial resection, with grossly visible tumour left behind

42 Hepatic Resection for Colorectal Cancer Liver Metastases Importance of clear resection margin N=557 CRC patients with liver mets Poultsides GA et al. HPB ; 43-9

43 Evidence Base that Surgery can Cure Cancer I IIA IIB III IV Evidence obtained from a single randomized controlled trial or from a systematic review or meta-analysis of randomized controlled trials Evidence obtained from at least one well-designed controlled study without randomisation Evidence obtained from at least one other well designed quasi-experimental study Evidence obtained from well-designed nonexperimental descriptive studies, correlation studies and case studies Evidence obtained from expert committee reports or opinions and/or clinical experiences of respected authorities, or case reports

44 Surgery & Cancer Research

45 Changes to surgical training Changes due to reduced NHS funding Increased research red tape Reduced industry funding to surgery Reduced funding for clinical academic posts Challenges unique to surgical research

46 Multidisciplinary management of cancer patients Complex decision making Radiologist Pathologist Surgeon Oncologist Primary disease Is there a curative option (surgery)? Is patient fit for surgery? Is neo adjuvant treatment indicated? Post operation is adjuvant Rx indicated? What will predict response? Surgery Remove primary cancer (R0) Remove lymph nodes Minimise morbidity and mortality Restore anatomy Reconstruct

47 Surgical Research in Complex Decision Making Patient selection surgery neo/adjuvant treatment metastatic disease Biomarkers personalised / precision response to Rx Developing new technologies

48 Personalised Rx vs Intra-tumoural Heterogeneity

49 Technology: perception vs evidence

50 Living with Symptoms after Surgery Increasing group of survivors Patient-reported outcome measures Quality of life Function post-surgery

51 Surgical research in Cancer Prevention Understand basic science and biology Translational relevance Personalised / precision Population level Translational science Tissue banking Clinical trials Window trials Technical innovation

52 Population risk of cancer General population High Average Familial settings Sporadic Familial High penetrance Risk Environmental risk factors Diet & obesity Lifestyle Physical activity Smoking

53 Heritable Colorectal Cancer Risk Malcolm Dunlop, Edinburgh

54 Environment, energy imbalance & mutations in CRC obesity exercise diet Metabolism and energy signalling in cells energy imbalance within cells

55 Translational Research Opportunities

56 Dysregulated Wnt alters organoid budding phenotype in intestine wild-type Apc flox/flox small intestine

57 % budding Aspirin promotes budding phenotype in human FAP organoids control aspirin 29 d Percentage of budding organoids * normal colonic mucosa CTRL ASP CTRL ASP Normal mucosa Adenoma colonic adenoma *

58 Pretty good

59 Could do better

60 Future of cancer research and surgery Discovery Invention Innovation Cancer biology Genomics Risk stratification Routine data collection and integration NHS Technology

61 number cannot treat our way out of cancer Chris Wild, IARC PubMed Year cancer chemotherapy prevention chemoprevention

62 Why certain cancers increasing? prevalence in risk factors diet and lifestyle obesity fertility and age at first child screening/ incidental findings

63 If you could do one thing Reduce risk overall through behaviour change Detect cancer early with accurate diagnostic blood test Identify those at higher risk and prevent disease Intervention to prevent / decrease risk of disease Limit overtreatment of established cancer Routine NHS- integrated biobanking Biomarkers: normal pre-cursor lesion cancer recurrence

64 Aligning priorities Government Cancer Charities Public Healthcare professional

65 Scottish Cancer Foundation 1997 Facilitate research aimed at addressing the high incidence of cancer in Scotland, and the poor outcomes in patients who develop the disease Support collaborative cancer research Inform public on cancer prevention Provide advice to policy makers Promote cancer prevention

66 Scottish Cancer Prevention Network Move evidence on cancer risk reduction into everyday life, practice and policy Awareness about cancer prevention Advocacy for action on prevention Health inequalities in cancer prevention widening perspectives

67 Current architecture cancer research Spaces Methods/ technologies People

68 Aerial views.. Spaces Methods/ technologies People

69 Thank you IGMM