Background: LS is among the most common cancer (CA) syndromes affecting 1:280 individuals and portends high lifetime CA risk. Clinical trials are currently evaluating whether FSPVAX could reduce LS CA risk. FSPVAX enhance immune response to diverse FSP neoantigens in MSI-H tumors and have shown promising results in an MSH2-mutant mouse model and metastatic MSI-H CRC. However, negative public attitudes towards vaccination could undermine this novel therapy. Here, we benchmark attitudes towards FSPVAX for CA prevention against intensive colonoscopy, for which uptake is high in LS, and aspirin chemoprevention, where uptake is generally lower. Methods: The PREVENTLynch survey was distributed electronically to participants in the Fox Chase Cancer Center (FCCC) Risk Registry. LS patients were invited to complete the one-time survey after providing informed consent, and received a gift card incentive upon completion. The study was approved by the FCCC IRB (20-8014). Demographic/personal/familial CA history were collected. Attitudes were measured on 9-point scales indicating low vs high agreement with belief statements: e.g.“Colonoscopy is a convenient way to lower my risk of LS-related CA.”Results: Overall 116 out of 220 invited LS patients completed the survey (response rate 53%). 76% were female, and mean age was 52.7 yrs. 72% had personal history of CA. COLO uptake was high (96%), while ASA uptake for prevention was modest (22%). Side effect concerns were higher for FSPVAX compared to both COLO and ASA (both p<0.001). FSPVAX offered patients significantly less reassurance than COLO (p<0.001) and was significantly less likely to be endorsed/pursued as a treatment (p<0.001). Convenience of FSPVAX was similar to COLO but less than ASA (p<0.001). LS patients with (vs w/o) a personal history of CA(p<0.05) and those >50 yrs old (vs<50)(p<0.05) were more likely to participate in a FSPVAX trial. Conclusions: LS patients’ attitudes towards FSPVAX are mixed. Concerns about side effects and efficacy may limit future uptake similar to ASA.

#p<0.001 FSPVAX compared to COLO.

&p<0.001 FSPVAX compared to ASA.