Since the CAP’s cancer protocols were first developed in 1998 to help standardize pathology reports on cancer specimens, few have doubted the need for them or their usefulness to clinicians. It was in recognition of the protocols’ value that the American College of Surgeons’ Commission on Cancer mandated that pathologists use the protocols’ data elements in all surgical pathology reports on cancer specimens starting in 2004.
But the CAP’s Cancer Committee continually reviews and improves the protocols by updating the cancer case checklists themselves or by refining the background documentation each protocol includes. Revisions of the top five protocols (prostate, breast, lung, colon and rectal, and skin melanoma) will be published next month in the Archives of Pathology & Laboratory Medicine, while the other revised protocols will be made available online. They contain several substantive changes, and the format is more compact and user-friendly.
Some of the changes reflect an evolving international consensus on how pathology reports on cancer specimens can be most useful in helping clinicians make patient care decisions. The protocols’ authors are also working to synchronize the CAP’s protocols with the new American Joint Committee on Cancer, or AJCC, Cancer Staging Manual, 7th edition, and the most recent World Health Organization tumor classification system.
CAP Cancer Committee members say these efforts are all part of ensuring that the cancer protocols have an ever-wider impact on cancer care, while continuing to help pathologists in practice. And there is good evidence that the efforts are bearing fruit, for this year marked the first endorsement of the CAP’s cancer protocols by another country’s leading pathology organization.
The colon and rectal cancer protocol was updated extensively following user feedback and field trials, says lead author Mary K. Washington, MD, PhD, director of gastrointestinal and hepatic pathology at Vanderbilt University Medical Center, Nashville. “The protocol was published about a year ago in the Archives,” she explains. “The new version coming out in October basically incorporates some of the clarifications that arose from pathologists’ comments.”
One concern that had surfaced before the update was the subdivisions of T categories. “There had been some letters to the editor of the Archives on the T4 classification in particular, which was changed to foreshadow the coming changes in the AJCC 7th edition,” Dr. Washington says. “The updated colorectal cancer protocol will incorporate the new AJCC staging system.”
What’s different about the new checklists is the greater emphasis on ancillary testing and clarification about the margins, which for colon cancer are often complicated to assess, Dr. Washington says. This was one place where the committee decided to incorporate illustrations, drawn from the AJCC Cancer Staging Atlas, with AJCC permission. “These gave us an opportunity to clarify margin standards.”
Having trimmed redundant material in the old protocol, the committee has also now produced a leaner protocol. “The old protocol had separate sections for polyps, transanal excision of rectal tumor, and large resections, and the latter two were collapsed into one checklist. There was also a big section on cytopathology that just wasn’t that widely used or critical to the checklist items, so it was deleted.”
A wholesale reformatting has streamlined all the protocols, Dr. Washington says. “The original checklists, while they were very useful, were inclusive of a lot of clinical details, and they also had cytopathology sections. The idea behind the new protocols was to create a minimum data set for large-specimen cancer reporting, but also to create clinically relevant checklists for certain biopsies, such as prostate biopsy.”
“We have been working closely with the AJCC for some time,” says Peter Humphrey, MD, PhD, chief of the Division of Anatomic and Molecular Pathology at Washington University School of Medicine, St. Louis, and senior author of the prostate cancer checklist. “This allowed for pathologists to have input into the process of revising the new TNM schemes, which I think was vitally important. In addition, we could compare the new protocols with the new TNM changes to coordinate their release at nearly the same time.” While it’s taken a lot of time and effort, he emphasizes, “I think it’s going to be an extremely timely update.”
“The protocols don’t speak to treatment recommendations, but they are the foundation for treatment based on typing, grading, staging, and, for radical prostatectomies, margin status. Any approach to treatment obviously must start with those critical elements in the protocol.”
The protocols have historically been based on evidence-driven updating of reporting recommendations, and now the process draws on experts from around the world. “In addition to the international co-authors for the prostate protocol, we have clinician co-authors,” Dr. Humphrey says. “So many, many different experts, not only in pathology but also in clinical urology, have provided important comments.”
The illustrations are an important addition to all the protocols. “We’re a visually based specialty, after all,” Dr. Humphrey notes. “However, we did not have any illustrations in our last update of the protocols in 2006. This round, we had a medical illustrator draw one figure for us, while the other four figures are from the AJCC Cancer Staging Atlas, which is a companion to the AJCC Cancer Staging Manual. So that’s another link between the AJCC and the protocols.”
There was one big change in prostate cancer staging. “In staging of cancer invasion of the urinary bladder neck, it was previously felt it should be a pT4 category. But clearly a number of papers have been published demonstrating outcomes for patients with microscopic carcinoma invasion into the bladder neck are not like pT4 disease but rather lower stage pT3a. So this is a new staging change that’s actually quite important. After a lot of discussion, it was well accepted that this change needed to be made.”
The document also includes a comment that even though the AJCC decided to sub-stage pT2 cancers, “it was well agreed that this subdivision doesn’t have prognostic significance.” Pathologists, he explains, may spend a lot of time trying to define their case based upon three different subdivisions of pT2 disease, when in fact there is really no clinical difference.
The protocol updates changes in risk factors as well, Dr. Humphrey says. “We’ve cited new data on the change in risk for a subsequent diagnosis of prostate cancer on rebiopsy after a diagnosis of isolated high-grade PIN [prostatic intraepithelial neoplasia] in needle biopsy. This reflects how we’ve kept the references very, very current.”
The last important change is the new stage groupings for prostate cancer. “For the first time, these incorporate serum PSA level and also Gleason score,” he says, “and that’s a big change. The uniform use of Gleason grading is a change from past AJCC publications and previous protocols. We now emphasize that the worldwide standard is that Gleason staging should be performed.”
There has been a substantial effort to develop consensus on prostate cancer grading and staging approaches among the international community of urologic pathologists, Dr. Humphrey says. At the meeting last March of the International Society of Urological Pathology, “urologic pathologists from around the world attended, and an entire day was devoted to issues pertaining to handling, sampling, and diagnosis of radical prostatectomy tissues.” Dr. Humphrey worked closely with John Srigley, MD, first author of the protocol, and the other authors of the prostate protocol to incorporate this consensus into the new protocol.
The formal endorsement of all CAP cancer protocols by the Canadian Association of Pathologists, which was announced July 14, is a significant development and will help the protocols have a wider influence even beyond North America, Dr. Humphrey says. It is the first time another country has endorsed the cancer protocols, and it reflects a unique partnership between the CAP in the U.S. and the Canadian association. CAP president Jared N. Schwartz, MD, PhD, said in a statement: “It is a huge step for our colleagues to the North. They want to continue to have our help.”
The breast cancer protocol has also incorporated significant changes, says Susan C. Lester, MD, PhD, chief of the Breast Pathology Service at Brigham & Women’s Hospital in Boston and lead author of the breast protocol. “There is an invasive cancer protocol and a separate one for in situ carcinoma. The revised invasive protocol is more comprehensive. We were very sensitive to the issue of which elements are absolutely required and which are recommended.” This round, “only those we felt are absolutely required and must be reported by pathologists are listed as required.”
One of the main problems with the prior protocol, she explains, was that it required pathologists to locate cancer within the breast, and often that information was not available to the pathologists. Many pathologists had sent queries to the CAP about this part of the old protocol, she says. “For pathologists who were trying to comply with the protocol, this element created the most problems. So we’ve included an option for cases in which this information is not available.”
They also increased the information within the notes to help pathologists provide standard information. To provide a specific grade for cancer, the pathologist has to count the number of mitoses for a high-powered field, and that can vary from microscope to microscope. “So we’ve provided a table to help determine the size of the field and how that translates into how many mitoses to count,” Dr. Lester says.
The protocol greatly expands information on cancer, with illustrations enhancing the descriptions. “Now we have several illustrations to help pathologists distinguish different types of skin involvement, different types of multiple cancers, cases with or without an extensive intraductal component, and different types of metastatic patterns in lymph nodes. A whole section of the protocols provides supporting information to help people systematically and accurately report these features of breast cancers.”
Perhaps the most controversial part of the protocol for invasive breast cancer was the reporting of estrogen receptor and progesterone receptor, she says. “It’s obviously a complicated issue, and there are many different opinions within the pathology community on reporting.” The American Society of Clinical Oncology and the CAP are working on guidelines for reporting and the protocol addresses this concisely. “But we’ve tried to make it flexible enough to allow different methods of reporting,” Dr. Lester says.
Perhaps another sign of the increasing relevance of the cancer protocols is the addition of two protocol-related questions to the Laboratory Accreditation Program anatomic pathology checklist. There was only one phase II question until recently; it was to check whether all scientifically validated data elements needed for grading, staging, and prognostication are included in the pathology report.
Now a new phase 1 question asks: “For specimens with malignant diagnoses from definitive cancer resections and specific biopsies as outlined in the CAP Cancer Protocols, are pathology reports audited at least annually to ensure that all scientifically validated data elements are included?” This checklist item requires that the laboratory evaluate, at least once per year, 30 consecutive reports from cancer resections and specific biopsies as outlined in the cancer protocols. If the three-month total is less than 30, it must evaluate all of the reports. At least 90 percent of the reports must contain all of the scientifically validated elements from the cancer protocols and checklists, or else the laboratory must implement appropriate corrective action.
A new phase 0 question asks: “For specimens from definitive cancer resections, are all scientifically validated data elements, as outlined in the CAP Cancer Protocols, reported in a synoptic format?”
Looking ahead, the Cancer Committee is planning to include in the notes to the protocols some discussion of the relevant molecular testing for cancers, and it is working with the CAP Molecular Oncology Committee to that end. Says Dr. Washington, “We want to give people in the community information on what tests they should know about, when they’re usually ordered, and so on—not necessarily to make them experts in interpreting the tests but to give them guidance on common types of molecular tests for various types of cancer.”
There is increasing consistency of world standards for reporting of cancer pathology, she notes, and the CAP’s efforts are helping with that. The British Royal College of Pathologists has similar standards, and the CAP is working with Australian pathologists to collaborate on checklists and protocols. “I think the College’s protocols will become more global as we move forward, because CAP’s lists are already developed, and I think more countries will be adopting them in some form rather than developing new ones from scratch,” Dr. Washington says.
As the protocols continue to be refined, Dr. Lester stresses that continuing collaboration among all sectors of pathology and cancer clinicians will be crucial. “It was very helpful to me as head of a panel to have a large number of pathologists providing their opinions as well as having medical oncologists and a surgeon,” she says. “This isn’t supposed to be one group of people dictating to everyone else. These are protocols everyone can agree on.”
Anne Paxton is a writer in Seattle. CAP cancer checklists and background documentation are now available free of charge and can be downloaded from the CAP Website. Printed versions can be purchased by calling CAP customer service at 800-323-4040, option 1#.