Challenges in Improving Preanalytic Specimen Handling of Routine Cancer Biospecimens

The American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) HER2 testing guideline for breast cancer published in 2007¹  was the first evidence-based guideline that directly addressed the critical importance of controlling preanalytic variables for biospecimens to improve the accuracy of cancer biomarker testing. This publication marked a significant change for surgical pathologists by introducing internationally recognized standards for tissue handling that applied to all breast biopsy and resection specimens.

In this issue of the Archives, Compton et al²  propose a new set of recommendations that are meant to apply to blood and tissue specimens from all other cancer patients. The authors and the CAP's Personalized Health Care Committee should be commended for this comprehensive review and for attempting to set standards for specimens other than breast. The goal of this work is laudable and full implementation of the recommendations should lead to improvements in test accuracy, but there will be significant barriers to their adoption that need to be addressed.

Some of the specimen-handling requirements in the original ASCO/CAP HER2 guideline, such as time to fixation (cold ischemia time) and time in fixative, were not universally accepted by pathologists upon publication. This was partly because of concerns that the recommendations were not evidence based and partly because of the need to develop policies and procedures for other departments and personnel outside the laboratory. Ensuring that all breast specimens were processed into paraffin within the original fixation interval of 6 to 48 hours was a challenge, as pathologists were not used to asking surgeons to adjust their schedules so that biomarker testing would comply with guideline recommendations. Nonetheless, follow-up surveys showed that compliance with the guideline did improve over time.^3–5 

These new recommendations include a maximum fixation time of 36 hours for all cancer specimens. Given the difficulty pathologists had with the original fixation interval for breast tissues, compliance with this even shorter interval for all specimens from cancer patients (and those who have not yet been diagnosed with cancer) will be much harder to achieve. Adjusting staffing to ensure that a specimen obtained late in the week or on weekends is processed within 36 hours will be extremely difficult for resource-constrained facilities and those that send specimens elsewhere for processing. Other challenges that can be expected include the need to document in the pathology record preanalytic variables for every cancer specimen. We can all agree on the importance of ensuring accurate biomarker testing for every cancer patient, but these realities represent unfortunate impediments to full implementation.

Translating recommendations into routine laboratory practices is often difficult but not impossible. Compton et al²  clearly describe the molecular degradation caused by prolonged formalin fixation at room temperature and suggest refrigeration as a possible path forward to solve this problem. After the ASCO/CAP HER2 guideline was published in 2007, subsequent research^6–8  showed that formalin fixation for up to 72 hours had no detrimental impact on test results and the guideline was revised accordingly.⁹  This new article may similarly trigger research into the effects of refrigeration or other cost-effective approaches to preserving molecular integrity, and solutions to some of these problems may be found.

Studies on acceptance and implementation of laboratory practice guidelines have shown that their adoption can be facilitated by various tools such as algorithms, templates, and teaching materials.¹⁰  To assist pathologists in implementing the HER2 guideline, the CAP developed various educational programs including Webinars, seminars at annual meetings and online, and faculty-led programs. Similar efforts will be needed to help laboratories reach the goals spelled out in these new recommendations.

It is unrealistic to think that a single mandated approach will work for every recommendation, and pathologists and organizations such as CAP and the American College of Surgeons will need to work together to find solutions appropriate for the many different practice settings. The CAP Personalized Health Care Committee may be in a position to coordinate this activity by exploring barriers to implementation and helping find practical answers.

Recognizing these challenges, the authors note that addressing even some of the factors will improve the baseline quality of specimens and that an effort over time is needed. These recommendations may be viewed as a first step, with the hope that they will ultimately be applied to any specimen for which biomarker testing is needed.