Surveillance may be ‘new normal’ for cancer survivors’ follow-up care

Routine CT scans have long been considered an essential component of follow-up care to help extend survival and improve quality of life for cancer survivors.

Several studies presented at the ASCO Annual Meeting in June, however, questioned the benefits of surveillance imaging, and the researchers who presented those findings said the scans may cause more harm than good.

“Not only are scans not catching most relapses, but there are also other potential downsides,” Carrie A. Thompson, MD, a hematologist at Mayo Clinic in Rochester, Minn., told HemOnc Today. “The issues of radiation exposure and the cost of care are often brought up. False positives can lead to further testing, and anxiety certainly can be a component.”

HemOnc Today spoke with several clinicians about the role CT scans do — and should — play in follow-up care. Although they stopped short of recommending against scans, they emphasized a need for additional education for physicians and patients regarding the benefits and potential risks associated with that type of follow-up approach.

“It’s a matter of using scans at the right time,” Thompson said. “Any time a patient has a concern of relapse, whether they have developed symptoms that are similar to disease presentation or they come into clinic and you note an abnormal physical exam, a scan is the next step. Paying attention to what patients say ... is the way to go.”

Universal approach in colorectal cancer

The use of scans during follow-up care became more common during the 1980s.

“Over the past 20 years, as we have become better at curing cancer, we have moved to the domain of saying, ‘Maybe we don’t have to hammer away aggressively from the outset if we don’t achieve initial cure,’” Derek Raghavan, MD, PhD, a medical oncologist, president of Levine Cancer Institute and a HemOnc Today Editorial Board member, said in an interview. “Perhaps we can just follow-up some patients – for example, the woman who has completed adjuvant chemotherapy and is in remission or the young man with stage I testis cancer after orchiectomy who declines retroperitoneal lymph node dissection – with scans or X-rays and use them to determine the need for further active treatment.”

One of the challenges associated with the use of scans during follow-up is patient preference.

“American patients have high expectations about aggressiveness of therapeutic and diagnostic interventions, even when there are not clear data supporting current practices,” David H. Ilson, MD, PhD, a medical oncologist with Memorial Sloan-Kettering Cancer Center’s Gastrointestinal Oncology Service, a professor at Weill Cornell Medical College and a HemOnc Today Editorial Board member, said in an interview.

However, “aggressive” does not always translate to “effective,” federal data show. Unnecessary tests, physician visits, hospital services and other services account for as much as 30% of health care delivered in the United States, according to the Congressional Budget Office.

Efforts to change patient expectations would require stricter adherence to follow-up guidelines, as well as clearly defined health insurance coverage guidelines for tests that may offer little clinical benefit, Ilson said.

Questions about which form of follow-up care is preferable are difficult to answer, and decisions vary by specialty.

Mant and colleagues presented a study at ASCO that evaluated how well three follow-up regimens detected colorectal cancer recurrence in patients treated for stage I to III disease. The regimens included minimum follow-up, with a single CT scan at 12 to 18 months; CT imaging every 6 to 12 months; and blood carcinoembryonic antigen (CEA) testing every 3 to 6 months. Mean follow-up was 3.7 years.

Regular CT scanning and CEA measurement resulted in significantly higher rates of diagnosis of operable recurrent colorectal cancer than minimal follow-up.

However, researchers determined there is no benefit to monitoring with both CEA monitoring and CT. They suggested CEA monitoring combined with a single CT scan at 12 to 18 months — which yielded the same detection of potentially curable recurrence as more intensive CT screening — likely is cost-effective.

“This study challenges our assumptions that more intensive follow-up is required, suggesting that perhaps CEA monitoring and a single CT scan 12 to 18 months after surgery may be appropriate,” Ilson said.

However, ASCO’s guideline on follow-up care for colorectal cancer recommends CT scans of the chest, abdomen and pelvis annually for at least 3 years if recommended by a physician, plus quarterly CEA testing for at least 3 years.

Consequently, physicians who treat colorectal cancer likely will not change their practice and perform fewer follow-up scans.

“Recent studies have established the utility of CEA screening, and this is accepted as standard practice for follow-up after curative treatment of colorectal cancer,” Ilson said. “Although use of CT scans during follow-up for colorectal cancer is controversial, it is fairly universally performed.”

A shift in DLBCL

Thompson and colleagues presented data at ASCO from a prospective, multi-institutional study that suggested scheduled follow-up scans did little to help detect relapse in patients with diffuse large B-cell lymphoma (DLBCL).

The researchers assessed the use of surveillance scans in 644 patients with newly diagnosed DLBCL treated with anthracycline-based immunochemotherapy. All patients were monitored for cancer relapse and the need for additional treatment.

Only eight patients — equating to 8% of those who relapsed and 1.5% of all patients who entered post-treatment follow-up — had relapse detected solely by planned surveillance scans before the appearance of any clinical signs or symptoms.

About two-thirds of the patients who relapsed developed symptoms and presented to their physician earlier than their planned follow-up visit, whereas about one-third had relapse detected during a planned follow-up visit. Among those who relapsed, 68% were symptomatic, 55% had abnormalities in blood tests and 42% had an abnormal finding on a physical exam, according to researchers.

“These findings are important to help guide physicians in making decisions about how frequently to order scans in patients with DLBCL following treatment,” Thompson told HemOnc Today.

Those decisions should be tailored to each individual, Thompson said.

“For any type of cancer, whether it’s a diagnosis or treatment and follow-up, we all strive to be very patient-centered,” she said. “I hope that others can use this data to optimize and individualize patient care.”

Reasonable alternative in Hodgkin’s lymphoma

Another study presented at ASCO explored the ability of routine surveillance imaging to detect asymptomatic relapse in classical Hodgkin’s lymphoma.

The analysis by Pingali and colleagues included 207 patients who experienced complete remission after first-line therapy at three tertiary hospitals between 2001 and 2010. Patients were categorized into two groups — 131 underwent routine surveillance imaging and 76 underwent clinical surveillance.

Patients in the routine surveillance group received a mean of 4.77 scans vs. 1.11 for patients in the clinical surveillance group.

At 4 years, researchers observed similar OS rates between arms (P=.74). They reported five deaths (3.8%) in the routine surveillance imaging group and four deaths (5.3%) in the clinical surveillance group. The relapse rates were 4.6% in the routine surveillance group and 6.6% in the clinical surveillance group (P=.64 for relapse at 5 years).

The researchers, therefore, concluded there was no survival benefit for routine surveillance imaging in this patient population.

“The evidence supporting routine scans as follow-up for all lymphoma patients is rather small, or even non-existent,” Raghavan said. “One could make a case that patients could get a psychological benefit from knowing that another set of scans is clear, but that information doesn’t really translate into saying they are cured forever. You could argue that taking a careful history and performing a meticulous physical exam, perhaps supported by blood work, is as reasonable a way to follow-up many patients with lymphoma as doing a bunch of MRI and PET scans. To my knowledge, there is no evidence that finding a recurrence of Hodgkin’s disease at day 10 will provide any survival benefit compared with making the diagnosis when a peripheral node presents itself or the patient starts to develop B symptoms.”

Cost, radiation concerns

The concerns that surround the use of routine imaging scans extend beyond their survival benefit.

Cost is a significant factor, said Bruce D. Cheson, MD, professor of medicine in the department of hematology and oncology at Georgetown/Lombardi Comprehensive Cancer Center.

The study by Pingali and colleagues suggested it required about $590,000 worth of scans to identify one relapse among patients with Hodgkin’s lymphoma.

“Yet we are radiating a lot of patients and increasing the cost of medical care considerably,” Cheson said. “Of the relapses identified in [the Pingali study], patients were able to be salvaged and there was no impact on overall outcome. In the setting of constricted health care dollars, we have to be prudent in how we use tests — particularly those that are unnecessary, and surveillance scans fall into this category.”

Increased radiation exposure also must be considered.

An estimated 68 million CT scans are performed each year in the United States, according to the American College of Radiology.

A study by de Gonzalez and colleagues, published in Archives of Internal Medicine, estimated that about 29,000 future cancers could be attributable to the CT scans performed in the United States in 2007 alone.

Recent research has suggested 1.5% to 2% of cancers in the United States may be attributable to CT scans, said Anne Blaes, MD, assistant professor in the department of hematology, oncology and transplantation at The University of Minnesota and a HemOnc Today Editorial Board member.

Clinicians also must take patients’ emotional well-being into account, Blaes said.

Although most patients are screened with CT and PET scans at regular intervals, most relapses are identified through symptoms, physical exams or laboratory abnormalities.

“Studies have suggested quality of life was impaired by conducting routine surveillance,” she said. “Patients’ lives were actually worse due to anxiety and false-positive findings.”

False-positive findings also lead to risky procedures and additional costs, Blaes said.

A study by Drotman and colleagues, published in the American Journal of Roentgenology, evaluated whether nearly 2,400 pelvic CT scans in patient with breast cancer improved detection of metastatic disease. The data suggested that pelvic CT scans led to 204 additional tests and, of these, 84.6% were normal, benign or indeterminate.

“We are putting patients through all of the unnecessary procedures that don’t really seem to help,” Blaes said.

Evolution of guidelines

Guidelines, such as recommendations by ASCO and the National Comprehensive Cancer Network against any type of routine surveillance for metastatic disease in breast cancer due to costs and radiation risk, continue to evolve as researchers evaluate various follow-up strategies.

In 2010, ASCO’s Cost of Care Task Force undertook an initiative to identify five diagnostic tests or treatment interventions in oncology that are frequently ordered and often expensive, yet are not supported by evidence as having clinical value.

ASCO contributed its “Top Five” to the Choosing Wisely campaign, an initiative of the ABIM Foundation designed to encourage physicians and patients to evaluate the need for medical procedures and tests that may be unnecessary or cause harm.

ASCO’s list included:

“The Top Five list contributed by ASCO to the Choosing Wisely campaign provides not only a set of specific practices that should be questioned, but also — and perhaps more importantly — an opportunity to emphasize the importance of evidence-based medicine in arriving at clinical decisions,” Lowell E. Schnipper, MD, clinical director of Beth Israel Deaconess Medical Center Cancer Center, and colleagues wrote in the Journal of Clinical Oncology.

Standards will continue to evolve as new evidence emerges, Thompson said.

“The current way of thinking — and practice — will likely change,” she said. “The guidelines for follow-up have changed within the past 10 years, and I suspect that they will be updated again moving forward.”

Patient, physician education

Study results suggest some patients underestimate the risks associated with routine imaging scans, highlighting a need for additional patient education.

In a 2010 study published in the Annals of Emergency Medicine, Baumann and colleagues concluded patients tend to feel more confident when CT scans are part of the medical evaluation, yet they have a poor understanding of the associated radiation exposure risk and underestimate their previous imaging experience.

In their study, the researchers questioned more than 1,100 patients admitted to their institution who presented with stomach pain to rate their agreement to factual statements such as: “Will getting two or three CT scans of the abdomen expose you to the same amount of radiation as people who lived near the atomic blast that ravaged Hiroshima in 1945 but survived?”

Results indicated that half of those surveyed said they had very little faith in the comparison between Hiroshima survivors and patients who had CT scans — rating their agreement at 13 on a scale from 0 to 100.

In addition, patients reported that CT scans and blood work increase their confidence on their medical evaluation.

“There is a push from patients for scans,” Blaes said. “I recently had a patient in clinic who had just completed her adjuvant chemotherapy, and she asked, ‘What kind of surveillance will we be doing?’ In other words, ‘How do I know that I am going to be OK?’ Patients have a hard time understanding that scans may not really be helpful. Surveillance and follow-up, however, are important.”

Some clinicians may feel they do not have the time to explain the risk–benefit ratio to patients, Blaes said.

“When you are in a busy clinical practice, in some ways it’s easier to just order the test and move along,” she said. “In turn, this appeases the patient.”

If they cannot invest the time to have this conversation themselves, physicians should engage patients in psychosocial services to help patients cope with uncertainties and the challenges of adjusting to what is now called the “new normal of survivorship,” Blaes said.

Physicians also may need additional education, study results show.

In a 2011 study, Potosky and colleagues asked primary care physicians and oncologists to determine the type of surveillance a 4-year asymptomatic breast cancer survivor should receive. Results showed the clinicians recommended unnecessary tumor marker and imaging studies.

Researchers found 51% of PCPs and 31% of oncologists recommended tumor markers; 42% of PCPs and 22% of oncologists recommended chest X-rays; and 23% of PCPs and 3% of oncologists recommended bone scans.

“This is a huge problem among primary care physicians — they are afraid they are going to miss something,” Blaes said.

A better understanding

The studies presented at ASCO add to evidence from many other previously published studies questioning the use of follow-up scans, Cheson said.

“In some individual cases, an occasional scan may provide reassurance that the disease isn’t progressing,” Cheson said. “But for the patient who doesn’t have any disease following therapy — given the financial, psychosocial and safety reasons — it’s hard to justify doing surveillance scans.”

Other clinicians pointed to steps physicians and patients can take to better understand the potential benefits and risks of such procedures before finalizing a follow-up care plan.

Mayo Clinic has developed a survivorship clinic for lymphoma patients. This allows physicians to meet with patients directly after they complete therapy.

“One of the things we do when coordinating survivors’ care is provide written instructions of when to be concerned,” Thompson said. “There is just so much happening during treatment and when treatment ends, it can be an overwhelming time, so having patient education regarding survivorship care is crucial.”

Blaes emphasized the importance of additional education for PCPs, as well as the role detailed treatment plans and electronic health records can play in follow-up care.

“A cancer survivorship treatment plan is helpful from this perspective if part of that plan outlines recommendations that you don’t need regular PET or bone scans as part of surveillance,” she said. “Cancer survivorship plans help communication between the oncologists, patients and PCPs.”

The University of Minnesota uses the EPIC electronic health record system, which helps ensure all providers understand follow-up plans and ultimately may help with the development of those plans, Blaes said.

“It doesn’t tell a physician you cannot do a scan,” Blaes said, “but it reinforces that scans are not always indicated or that it’s not part of everybody’s surveillance follow-up.” – by Jennifer R. Southall

References:

Baumann BM. Ann Emerg Med. 2011;58:1-7.

Berrington de Gonzalez A. Arch Intern Med. 2009;169:2071-2077.

Congressional Budget Office. Increasing the value of federal spending on health care, testimony before the Committee on the Budget, US House of Representatives, July 16, 2008. Available at: www.cbo.gov/publication/41717. Accessed on Aug. 23, 2013.

Drotman MB. AJR Am J Roentgenol. 2001;176:1433-1436.

Potosky AL. J Gen Intern Med. 2011;26:1403-1410.

Schnipper LE. J Clin Oncol. 2012;30:1715-1724.

The following were presented at the ASCO Annual Meeting; May 31-June 4, 2013; Chicago:

Mant D. Abstract #3500.

Pingali SR. Abstract #8505.

Thompson CA. Abstract #8504.

For more information:

Anne Blaes, MD, can be reached at The University of Minnesota, Medicine-Hematology, Oncology and Transplantation, Mayo Mail Code 480, 420 Delaware St. SE, Minneapolis, MN 55455; email: blaes004@umn.edu.

Bruce D. Cheson, MD, can be reached at The Georgetown/Lombardi Medical Center, 3800 Reservoir Road., Washington, DC 20057; email: bdc4@georgetown.edu.

David H. Ilson, MD, PhD, can be reached at Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY, 10065; email: ilsond@mskcc.org.

Derek Raghavan, MD, PhD, FACP, FRACP, can be reached at Levine Cancer Institute, 1025 Morehead Medical Drive, Charlotte, NC 28204; email: derek.raghavan@carolinashealthcare.org.

Carrie A. Thompson, MD, can be reached at Mayo Clinic, 200 First St. SW, Rochester, MN 55905; email: thompson.carrie@mayo.edu.

Disclosure: Blaes, Cheson, Ilson, Raghavan and Thompson report no relevant financial disclosures.

Is surveillance an effective alternative to follow-up scans for children?

It depends largely on the type of cancer.

Surveillance in pediatric, adolescent and young adult oncology is a complex issue. Surveillance generally involves a combination of routine follow-up clinical visits with detailed interval history and physical exam with anticipatory guidance of what signs and symptomatology to look out for, combined with laboratory evaluations and imaging.

The addition of surveillance radiologic imaging really depends on the type of cancer with which the patient has been diagnosed.

For example, a child with a history of acute lymphoblastic leukemia would not be getting imaging as a part of surveillance, whereas a patient with osteosarcoma — the most common primary bone tumor in children and adolescents — routinely has a chest CT every 3 to 4 months as part of their surveillance for development of pulmonary metastases.

The surveillance of pediatric malignancies, particularly solid malignancies, with serial imaging can be controversial. On one hand, there is increasing evidence that radiation exposure from routine imaging like CT scans can increase the risk of secondary malignancy. Also, there is always the question whether detecting recurrence sooner improves overall outcome. On the other hand, the development of recurrence in places where there may not be signs or symptoms of recurrence until the cancer has grown large enough to potentially no longer be removable is a problem. Furthermore, many pediatric malignancies cannot be followed with serum and/or urine markers, such as alpha fetoprotein (AFP) in childhood hepatoblastoma, or urine and serum catecholamines in neuroblastoma.

With the advent of newer imaging modalities, such as combined whole body PET/CT, there is the question whether this may be more effective for surveillance. However, there is no question that the cumulative radiation exposure for serial PET/CT is greater than for conventional low-dose CT imaging.

All in all, the imaging surveillance for pediatric malignancies largely depends on the type of cancer, the stage at diagnosis and the patterns of recurrence. For example, for bone and soft tissue sarcomas, we generally recommend a CT scan of the chest every 3 months for 2 to 3 years, followed by every 6 months for up to 5 years, followed by yearly plain films and/or CT. We will generally do MRI of the primary disease area for a soft tissue cancer and plain films for a bone cancer.

I generally do not recommend whole body PET/CT for long-term surveillance of solid tumors in children because there is increased radiation exposure, and it is unclear to me what benefit there is to OS and disease management.

The principles of imaging for pediatric malignancies need to adhere to the ALARA (as low as reasonably achievable) principle of radiation exposure. That is to say, give the least amount of radiation to evaluate the sites of concern, using MRI and ultrasound on select sites, while using low dose CT evaluating the chest.

Noah Federman, MD, is director of the pediatric bone and soft tissue sarcoma program at UCLA. He can be reached at nfederman@mednet.ucla.edu. Disclosure: Federman reports no relevant financial disclosures.

The benefits of imaging must outweigh any short or long-term risks associated with the exam.

The question of whether PET/CT can replace or supplement other surveillance imaging modalities has not been answered, but the radiation doses involved — particularly when compared with current lower-dose CT scans with iterative reconstruction — would be an important part of the equation. 

The type and frequency of surveillance would need to be based on the type of tumor and its behavior. Moreover, the risks and benefits of any test need to be weighed in the design of a surveillance algorithm, and these include the information to be gathered, the clinical need for that information and radiation exposure to the patient.

In other words, according to the American College of Radiology, for any imaging exam to be performed, the benefit to the patient must outweigh any short- or long-term risks associated with the exam. The amount of radiation used in that exam would factor into the risk assessment, and it would have to be evaluated against the benefit to the patient of the information provided by the scan.

Marta Hernanz-Schulman, MD, FAAP, FACR, is chair of the American College of Radiology Pediatric Imaging Commission. She also is a professor of radiology and pediatrics at Monroe Carrell Jr. Children’s Hospital at Vanderbilt. She can be reached at marta.schulman@vanderbilt.edu. Disclosure: Hernanz-Schulman reports no relevant financial disclosures.