The following guide was designed to help organizations decide how to implement routine tumor screening for Lynch syndrome in order to maximize success.

Making the case for Lynch Syndrome Screening

Engaging Stakeholders

  • Engaging all stakeholders early on will help everyone feel ownership and ensure there is “buy in”. However, you may wish to create a tentative plan, using this guide, and then obtain feedback from other key stakeholders such as:
    • pathologists
    • genetic counselors
    • geneticists
    • administrators
    • gastroenterologists
    • GI oncologists
    • colorectal surgeons
    • gynecological oncologists
  • Find one or more champions: Champions include people who will make this a priority. Champions also include those in a leadership position or someone whose opinion other key stakeholders value.
  • Ways to educate and engage
    • Hold a conference on Lynch syndrome tumor screening (provide continuing education credits)
    • Devote time to Lynch syndrome during tumor board meetings
    • Use LSSN introductory information and PowerPoints
    • Include a persuasive story about the positive effect screening can have for patients and their family (preferably a true story from your own institution)
    • Elicit any barriers to implementing screening at your own institution and arm yourself with information for overcoming barriers.
    • Send out an initiation letter announcing implementation of screening

Planning which tumor screening procedures to use

Who to screen

UTS considerations CBS considerations
  • Fewer patients will be missed if all CRC patients are automatically screened
  • UTS is more expensive than CBS, but there are several studies reporting UTS is cost-effective
  • Pathologists or clinicians won’t have to remember the Bethesda or other criteria
  • CBS will identify more patients than if no routine screening were performed, but fewer than UTS [an estimated 25-75% of patients are missed depending on the screening criteria used].
  • Screening a subset of patients is less costly than UTS
  • The process is harder to automate because physicians or pathologists are left to determine which tumors to screen unless there is a way to automatically flag the samples in your electronic medical record
  • Pathologists do not typically know or have access to the family history in order to apply all of the Bethesda criteria

Which specimens to screen (biopsy vs. surgical resections)

Biopsy considerations Surgical resection considerations
  • Enables surgical decision-making (subtotal vs. segmental resection)
  • Rectal tumors have not been exposed to neoadjuvent chemo & RT yet so IHC is more reliable than after neoadjuvent chemo
  • Often not enough tumor or normal tissue to do MSI
  • Screening could be done twice (once on biopsy and once on surgical resection) thereby decreasing cost effectiveness
  • Patient may be lost to follow-up if they don’t have surgery or have surgery elsewhere
  • Cannot inform surgical decision-making
  • Rectal tumors with neoadjuvent chemo & RT could have false absence of MSH6
  • Can perform MSI and/or IHC
  • Ensures test is only done once
  • Patient is less likely to be lost to follow-up

Who orders the screen

  • Setting up a system so screening is automatically done on all tumors has been described by some pathologists as the easiest approach for them and it saves them time.
  • If the screening needs to be ordered, there is always the possibility that cases will be missed (less likely if there is some way to flag criteria in electronic medical records).

What method of screening (IHC vs. MSI)

  • There is insufficient evidence to conclude that one method is better than the other
  • May determine based on institutional resources available
  • Some studies suggest IHC is less expensive
  • IHC requires more skill to interpret accurately
  • The potential increase in patient identification that could result from using both MSI and IHC on all tumors may not justify the added cost from a public health screening standpoint

Automatic reflex testing using hypermethylation or BRAF testing

  • Approximately 15% of sporadic tumors demonstrate microsatellite instability (MSI), usually due to MLH1 promoter hypermethylation. These individuals will have a positive tumor screen even though they do NOT have Lynch syndrome.
  • Additional screening to identify hypermethylation can help distinguish those with sporadic cancer from those who likely have Lynch syndrome and should be done on all MSI-high tumors or those with absence of MLH1 and PMS2.
  • Additional screening reduces the number of individuals who need to be seen by genetics for counseling and subsequent germline genetic testing and therefore saves patients time and potential worry.

Hypermethylation vs. BRAF as additional screening

  • Only hypermethylation should be done on endometrial tumors, but either hypermethylation or BRAF testing can be done on CRC tumors.
  • BRAF testing only identifies ~2/3 of CRC tumors with hypermethylation.
  • HOWEVER, many institutions already have BRAF V600E mutation testing available at their institution making this more feasible.
  • Hypermethylation testing could erroneously eliminate patients with Lynch syndrome due to MLH1 germline mutations and hypermethylation as their second hit (but this is believed to be uncommon).
  • Unless patients have other risk factors for hereditary cancer, those who have hypermethylated tumors or the presence of a BRAF V600E mutation need no further testing because it is unlikely they have Lynch syndrome.
  • It is critical to follow-through with genetic counseling and offer germline testing for those cases with NO evidence of hypermethylation and those who do NOT have a BRAF V600E mutation.

Screening and consent

  • Institutions DO NOT require explicit informed consent for tumor screening. Click here for an ethics decision from one institution concluding consent is not necessary.
  • However, an unpublished study showed that patients would like some information about tumor screening at the time of diagnosis.
  • Consent is typically needed before doing germline genetic testing to confirm a diagnosis of Lynch syndrome.

Planning for “screen positive” results follow-up

Importance of documenting positive results

  • These patients tend to have a better prognosis than other colorectal cancer patients and may be treated differently so this information can be useful in their care.
  • Several centers reported results getting lost in medical records and never being reported to patients.
  • Screen positive results should be entered into the pathology report and flagged in the electronic medical record if possible
  • Sample reports can be found here.

Ensuring patient is offered genetic counseling and germline testing

  • Patients with a positive screen will need information about germline testing in order to make an informed decision. Patients can either receive a full pre-test genetic counseling session or a shorter informed consent session with plans for a full genetic counseling session once results of germline testing are available.
  • When patients cannot be reached, it may be useful to send a letter. Sample letters for screen positive patients are included in the implementation section of this website and are tailored according to whether IHC or MSI is used.

Value of a single tracking person/system

  • To ensure screen positive patients are offered genetic counseling and testing to confirm a diagnosis of Lynch syndrome, several institutions reported the need for results to be sent to a designated person who takes responsibility for ensuring that the patients and/or treating physicians are aware and follow-up.
  • Several institutions have found higher patient follow-up rates when a single person (with a back-up person) is responsible for results tracking.

Value of having a genetic counselor or trained nurse disclose results

  • Having a genetic counselor (GC) or trained nurse in genetics disclose results has been helpful for some institutions because they already have the knowledge about Lynch syndrome and deal with this routinely. Plus, this takes the burden off physicians who have several other competing demands and may be unable to prioritize spending time discussing genetic implications.
  • A few institutions with successful patient follow-up  found that when GCs disclose screening results they indicate they are calling on behalf of Dr. _______ (the patient’s treating physician). In other successful cases GCs do not even call first, but rather they meet in-person with the patient immediately before or after the patient meets with the treating physician as part of routine follow-up appointment.
  • Some centers (though not quite as successful) have routine communication with genetic counselors who remind treating physicians which patients need follow-up and the physicians subsequently stress to the patient the importance of follow-up and this may require a high level of knowledge about Lynch syndrome among many different providers whose focus is not genetics.

Value of disclosure at a follow-up appointment

  • Several institutions report difficulty contacting patients and overcame this by meeting them at a follow-up post-op appointment for a brief pre-test counseling session to facilitate germline testing.
  • This is not always possible, but the experience at OSU and Cleveland Clinic provide data to support the value of this approach.


Other steps to facilitate patient follow-through with genetic counseling and confirmatory testing

  • Eliminate any need for the patient to be referred to genetics or automate the referral and scheduling process
  • Schedule GC follow-up to coincide with another follow-up visit
  • Have all healthcare providers involved in patient care stress the importance of follow-up
  • Make patients aware of available funds for germline testing of uninsured patients who meet certain qualifications, or any other funding that may be available to ensure patients can access germline testing
  • Follow-up again with patients if they have not followed through because they may have fewer competing demands or feel a bit less overwhelmed after treatment
  • Send a letter to the treating physician to remind them to follow-up with the patient and/or to send a referral (included in implementation section)
  • Communicate during tumor boards to remind treating physicians of which patients still need to follow-up
  • Put an electronic reminder system in place

Planning for “screen negative” results follow-up

  • Negative screening results should be documented in the chart. However, simply putting results in the chart means that the opportunity to catch patients at high risk for other hereditary cancer syndromes may be lost.
  • Having an active tracking mechanism or someone review basic information about patients with negative results can identify others for whom a genetics referral is appropriate. This improves quality of care and has resulted in the diagnosis of other hereditary cancer syndromes.
  • Some centers send a standardized result letter to all screen negative patients. (See implementation section). This is useful in case they are asked about this in the future and it also provides an opportunity to explain that there may be other causes of hereditary cancer and encourage the patient to talk with their physician and/or make an appointment if they have “red flags” that would suggest genetic counseling is indicated.
  • Rarely have institutions reported that physicians routinely mention negative results to the patient and review whether a genetics appointment is warranted for other reasons (e.g. polyposis, strong family history, multiple primaries, early age at diagnosis).

Executing the Plan

  • Regardless of how well you plan, it is unlikely that you can anticipate everything.
  • Most institutions we have talked to have altered their plans and this is to be expected.
  • Maintaining records on how the plan was executed including changes that are made (and on what dates) is critical when evaluating the outcomes.
  • It may also be useful to assess the timeliness of follow-up and results disclosure.

Reflecting and Evaluating to Ensure Quality

Importance of tracking

  • Several institutions are NOT routinely tracking what happens whether patients follow-up with germline genetic testing even though it is critical for ensuring or improving successful implementation.
  • Providing stakeholders with feedback (particularly when a patient is identified with Lynch syndrome) has helped others to promote ongoing support for the screening program and has helped to win over some individuals who were skeptical or hesitant to perform screening in the first place.
  • Although few negative outcomes have been reported thus far, tracking of any perceived negative outcomes is critical to making improvements or averting issues in the future.

Value of reflecting on the implementation process

  • By discussing what seems to work and what does not, several centers have developed ways to streamline or improve their process.
  • This should be done periodically, and whenever there are any changes in key personnel, challenges with patient follow-through, or any perceived negative outcomes.

Knowing if you are successful

  • In addition to patient follow-through with genetic counseling and germline testing, other implementation outcomes have been measured at several different institutions and this data is relatively easy to collect and compare with expected outcomes based on data from large centers that have been doing screening for years.
  • An excel spreadsheet has been created where you can track the number of screen positive patients you can expect, the number who will require counseling and germline testing (depending on your screening protocol), and the number of patients with Lynch syndrome who are expected to be identified. This can be used for quality control if the numbers are substantially different than expected. However, if volumes are low, numbers could differ from what is expected  simply due to chance. [NOTE: This excel spreadsheet can also be a useful tool to anticipate counseling volumes when preparing to start a screening program].

Dealing with challenges that may arise with tumor screening

A list of frequently asked questions for dealing with various challenges has been compiled.

Note: This guide was developed using the Consolidated Framework for Implementation Research (CFIR), review of the literature, and data from discussions with numerous stakeholders at organizations that have and have not implemented tumor screening.