Howard A. Reber, MDHoward A. Reber, MD Professor of SurgeryProfessor of Surgery UCLA School of MedicineUCLA School of MedicinePancreatic Cancer Pancreatic Cancer Surgical Approach in the Surgical Approach in the USA - 2014USA - 2014Agi Hirshberg Center for Pancreatic Diseases at UCLAPancreatic CancerPancreatic Cancer EpidemiologyEpidemiology 2014 - 46,420 new cases in USA2014 - 46,420 new cases in USA 2014 - 39,590 deaths2014 - 39,590 deaths 4 4thth most common cancer killermost common cancer killer 2 2ndnd most common GI cancer killer most common GI cancer killer (colon #1)(colon #1)Pancreatic CancerPancreatic Cancer EpidemiologyEpidemiologyNew Cancer Deaths , United States, 2014. New Cancer Deaths , United States, 2014.Pancreatic CancerPancreatic Cancer EpidemiologyEpidemiologyIncidence increasing 1% yearlyPancreatic CancerPancreatic Cancer EpidemiologyEpidemiology 85% of new cases are advanced85% of new cases are advanced Locally advanced: blood vessels Locally advanced: blood vessels (Stage III)(Stage III) Distant spread to liver, lungs Distant spread to liver, lungs (Stage IV)(Stage IV)Late Presentation - Poor SurvivalLate Presentation - Poor SurvivalHowlander et al, SEER Cancer Statistics Review 2012. American Cancer Society, Cancer Facts 146(7):836-843. Donahue TR, Reber HA et alWhen/Whether to Operate?When/Whether to Operate? CT ImagingCT ImagingPVPVSMASMASVSVSMVSMVIMVIMVLRVLRVLGALGASASAHAHAPancreasPancreasAdrenalAdrenalDownstaging Downstaging of PaCaof PaCaSurvivalSurvival 25+ survivors 5-17 years25+ survivors 5-17 years Observed five-year survival rate: 28%Observed five-year survival rate: 28% 13 more close to 5 yrs with no 13 more close to 5 yrs with no recurrence recurrence Possible five year survival rate: 53%Possible five year survival rate: 53%Adjuvant TherapyAdjuvant Therapy Treatment given Treatment given afterafter surgery surgery (Whipple/distal)(Whipple/distal) Effort to eradicate any Effort to eradicate any remaining microscopic tumorremaining microscopic tumor Standard approachStandard approachNeoadjuvant TherapyNeoadjuvant Therapy Treatment given Treatment given beforebefore surgery in surgery in pts with resectable disease pts with resectable disease (Stage I and II)(Stage I and II) Some in USA recommend this Some in USA recommend this instead of surgery firstinstead of surgery first Advantages and disadvantages Advantages and disadvantages Theoretical AdvantagesTheoretical Advantages Almost all pts have Almost all pts have micrometastatic disease at micrometastatic disease at diagnosis diagnosis 1 cm - 28% have metastases1 cm - 28% have metastases 2 cm - 73%2 cm - 73% 3 cm - 94%3 cm - 94%So almost all pts So almost all pts couldcould benefit benefitIacobuzio-Donahue et al 2011 CellTheoretical AdvantagesTheoretical Advantages If given after surgery, up to 25% If given after surgery, up to 25% may not be treated at allmay not be treated at all If given before, more likely to be If given before, more likely to be physically fit and able to tolerate physically fit and able to tolerate treatment treatment Or treatment may start late if there Or treatment may start late if there were complicationswere complicationsEffect of Adjuvant Treatment Delay on SurvivalEffect of Adjuvant Treatment Delay on SurvivalIacobuzio-Donahue et al 2011 CellAvoid Treatment Delay After SurgeryAvoid Treatment Delay After Surgery70%40%Theoretical Advantages of Theoretical Advantages of Neoadjuvant TherapyNeoadjuvant Therapy Identify pts unlikely to benefit Identify pts unlikely to benefit from surgeryfrom surgeryDuring 2-3 mo treatment, up to During 2-3 mo treatment, up to 20% pts show metastases or develop poor performance status Is This an Advantage?Is This an Advantage?Is this good or bad?Good They are spared surgery that would not have helped orBad They missed their chance for resection and possible cureNeoadjuvant Therapy Neoadjuvant Therapy So why has it not become the So why has it not become the standard approach?standard approach? Several reasons are givenSeveral reasons are given Chemotherapy today has little Chemotherapy today has little effect in most ptseffect in most ptsNeoadjuvant Therapy Neoadjuvant Therapy At most, 1/3 of pts respond to At most, 1/3 of pts respond to neoadjuvant treatmentneoadjuvant treatment So 2/3 would delay resection by 2-3 So 2/3 would delay resection by 2-3 months, without effective treatment months, without effective treatment during that timeduring that time Disease could progressDisease could progressNeoadjuvant Therapy Neoadjuvant Therapy Although today Chemotherapy has Although today Chemotherapy has little effect in most ptslittle effect in most pts This could change with more effective This could change with more effective neoadjuvant regimens neoadjuvant regimens Or with the ability to selectively choose a Or with the ability to selectively choose a regimen specific for the molecular regime