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Borderline Resectable Pancreatic Cancer

Borderline Resectable Pancreatic Cancer . Fung Man Him Matrix QMH Joint Hospital Surgical Grand Round. Content. Epidemiology Definitions Evaluation Surgical Considerations Neoadjuvant chemotherapy. Cancer of the Pancreas. Rank 6 th in cancer mortality in Hong Kong

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Borderline Resectable Pancreatic Cancer

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  1. Borderline Resectable Pancreatic Cancer Fung Man Him Matrix QMH Joint Hospital Surgical Grand Round

  2. Content Epidemiology Definitions Evaluation Surgical Considerations Neoadjuvant chemotherapy

  3. Cancer of the Pancreas • Rank 6th in cancer mortality in Hong Kong • Rank 4th in the US • Overall 5 year survival: 5% • 80% Unresectable • 50-55% metastatic • 20-25% locally advanced • 20% resectable at presentation • Post resection and adjuvant treatment 5 year survival: 20% Stathis A et al. Nat Rev Clin Oncol. 2010

  4. Unresectable • Metastatic • Locally Advanced • R2 resection: no improvement in survival • R1 resection: reduced survival J Gastrointest Surg. 2000 • Median survival < 1 year Loehrer et al. J Clin Oncol 2011

  5. Borderline resectable Surgery is the only cure for CA pancreas R0 resection is crucial to long term survival Historically, vascular involvement renders resection with negative margin problematic and increases morbidities Increasing evidence to show vascular resection inselected cases does not compromise margin and hence the term “Borderline resectable pancreatic cancer”

  6. Borderline resectable pancreatic cancer • Involvement by tumor that exceeds one-half circumference of the vessel is highly specific for unresectable tumor Lu et al. AJR Am J Roentgenol. 1997 • Abutment: • Contact ≤ 180 degrees of circumference of blood vessel • Encasement: • Contact >180 degree of circumference of blood vessel

  7. Borderline resectable pancreatic cancer CHA: Common hepatic artery; SMA: Superior mesenteric artery; SMV: Superior mesenteric vein; PV: Portal vein; NCCN: National Comprehensive Cancer Network; AHPBA/SSAT/SSO: Americas Hepato-Pancreato-Biliary Association/Society for Surgery of the Alimentary Tract/Society of Surgical Oncology

  8. MD Anderson Katz MH et al. J Am Coll Surg 2008 Type B borderline resectable tumors • Suspicion of metastatic disease • Radiologically indeterminate liver lesions • Suspicious distant lymph node • Biopsy proven regional lymph node • Ca 19-9 greater than 1000 u/mL with a normal bilirubin • High risk of early treatment failure with surgery alone Schwarz L et al. Br J Surg 2014 Schwarz L et al. Hematol Oncol Clin North Am 2015

  9. MD Anderson Type C borderline resectable tumors marginal performance status severe pre-existing comorbidity profile (including advanced age) that put patient at high risk for a major surgical procedure

  10. Schwarz et al. Hematology/Oncology Clinics of North America 2015

  11. Evaluation • CT scan • Good spatial resolution, most widely used, recommended • Less sensitive for small hepatic and peritoneal metastases Wong et al. Clin Gastroenterol Hepatol. 2008  • MRI • More sensitive for subcentimeter liver and peritoneal metastases • PET CT • Helps to detect metastases • More sensitive than CT scan for distant disease • Need more data to support routine use Farma et al. Ann Surg Oncol. 2008

  12. Evaluation • EUS • Able to detect focal lesions as small as 2-3mm in size • sensitivities and accuracy approaching 100% and specificity >95% even for lesions <2 cm • Complementary to CT scan for vascular staging • Glazer et al. Pancreatology 2017 • 62 patients with BRPC (NCCN) • 97% R0 resection • 34 patients required venous resection • 88% identified by EUS; 67% identified by CT • EUS detected 11 (29%) patients that are not detected by CT • CT detected 4 patients that are not detected by EUS • Operator dependent

  13. Evaluation • CA 19-9 • preoperative CA 19-9 correlate with pancreatic cancer staging Karachristos A et al. J Gastrointest Surg. 2005 • post-resection CA 19-9 levels prior to initiation of adjuvant chemotherapy have independent prognostic value, can be followed to indicate response to therapy Hess V Lancet Oncol. 2008 • Should be checked • Before surgery • After surgery before adjuvant • During surveillance

  14. Surgical considerations Mesenterico-portal venous resection Arterial resection

  15. Comparable survival Yekebas et al. Ann Surg 2008 482 pancreatic resections for ductal adenocarcinoma in Germany 100 vascular resections vs 382 no vascular resection 77 true histological vascular invasion; 23 no histological vascular invasion No neoadjuvant No difference in T, N staging and margin negative rate (90% vs 82%) No difference in hospital morbidity (39.7 % vs 40.3%) No difference in hospital mortality (4% vs 3.7%) No difference in median survival: 15 months vs 16 months, p=0.9 Nodal staging and histological grading were the only factors to predict survival

  16. Comparable survival • Cheung TT et al. World J Gastroenterol. 2014  • 78 patients with pancreaticoduodenectomy for cancer of pancreas from 2001 to 2012 • 32 vascular resections vs 46 standard PD; No neoadjuvant • No difference in overall survival or disease free survival • one-year, three-year and five-year overall survival rates – • 70.6%, 33.3% and 22.2% (vascular resection) vs • 71.1%, 23.6% and 13.5%, (standard) P = 0.815 • No difference in pancreatic fistula rates (15.6% vs 21.7%) • No difference in hospital mortality (3.1% vs 4.3%)

  17. Mesenterico-portal venous resection Kelly et al. Journal of Gastrointestinal Surgery July 2013 492 patients from 6 tertiary centres from 2000 to 2007 70 had vein resections (14%), 422 did not (86%) No difference in R0 resection (66 vs 75%) No difference in median disease-free survival (8.6 months vs 13.9 months) No difference in median overall survival (12.4 months vs 19.3 months) Higher perioperative morbidity (51 vs. 33 %; p < 0.01) More blood loss (1,032 ± 956 vs. 602 ± 507 mL; p < 0.01)

  18. Arterial resections Limited data Mollberg et al. Annals of Surgery 2011 Meta-analyses of 26 retrospective studies of resection of pancreatic cancer from 1973 to 2010 366 arterial resections vs 2243 no arterial resections Significantly greater perioperative morbidity (median 53.6%) Significantly greater perioperative mortality (median 11.8%)

  19. Morbidity and mortality Worni et al JAMA Surg. 2013 10206 patients with pancreatic resection for malignant disease from 2000 to 2009 in the US 412 patients (4%) with VR, increasing from 0.7%(2000) to 6% (2009) VR is associated with higher risk for intraoperative (8.7% vs 5.8%, p=0.001) and postoperative (49% vs 43.4%, p=0.008) complications Also higher mortality (6% vs 1.9%, p<0.001) Bleeding / vascular complications / liver ischemia / venous congestion

  20. Guideline and Consensus Clear evidence supporting straightforward operative exploration and resection of mesenterico-portal axis No good evidence that arterial resections during right-sided pancreatic resections are of benefit. Such resections may be harmful with increased morbidity and mortality and should not be recommended on a routine basis International Study Group of Pancreatic Surgery (ISGPS) Surgery, 2014

  21. Neoadjuvant chemo-radiotherapy Theoretical benefits Early treatment of micrometastases Select patients with more favourable tumour biology for surgery Achieve downstaging and/or increase the likelihood of R0 resection Ensures the use of chemotherapy Evans DB et al. Ann Surg oncol 2010 Katz MH et al. Arch Surg 2012 FOLFIRINOX / mFOLFIRNOX / Gemcitabine / combinations Emerging evidence Debatable especially for isolated, resectable venous involvement ISGPS. Surgery 2014

  22. Summary Definitions of borderline resectable cancer of pancreas Venous resection should be considered if R0 resection and reconstruction is possible in selected patients, noting possibly higher morbidity Complementary role of EUS in the evaluation of vascular involvement to CT Evidence on neoadjuvant chemo/chemo-irradiation emerging

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