ASCO 2014
Overdiagnosis and Overtreatment: The Cancer Paradigm
Some experts argue that overdiagnosis (OD) and overtreatment (OT) of cancer is common and increasingly costly. Others argue that current cure rates are high because of the screening processes currently in place. Both viewpoints were debated during the session “Overdiagnosis and Overtreatment in Cancer: Point/Counterpoint.”

“Cancer Overdiagnosis and Overtreatment, or Appropriate Attention to Early Disease?” was the question posed by Barbara L. Smith, MD, PhD, Massachusetts General Hospital. The goals of cancer care have been to minimize mortality, prolong life, reduce morbidity of treatment, prevent primary cancers, and to provide access to quality care for all. Of late, the discussion has led to including cost-effectiveness and avoiding excess treatment.

For several years now, death rates from cancer have seen a dip and cancer incidence rates have plateauedan indicator that the strategy is working. The cornerstones of success of modern care include earlier detection, improved treatments (multimodality care option), a combination of early detection and better treatment, and also improvement in overall population health. Healthier patients can work through the toughest treatments.

Dr Smith wonders whether diminishing returns may be resulting in overkill. “Are cancer patients being administered more treatment than needed?” More importantly, can a similar success be obtained with lighter treatment?

She provided an example of the increasing use of bilateral mastectomy for early-stage breast cancer. The numbers were at 3% back in 1998 but are up to 18% in 2007. The question to ask: Is it necessary? Patients want the procedure for peace of mind, to reduce their chances of recurrence. But how about the oncologist?

This is a challenge being discussed across a spectrum of disease states such as hypertension and cholesterol. Some of the questions that oncologists need to ask include:
  • What is the optimal way to screen (sensitivity/specificity goals, cost, limitations of diagnostic technologies)?
  • What should be the threshold for treatment?
  • What are the morbidity and mortality goals?
An ideal example is that of the recent debate about using Papanicolaou (Pap) test cytology versus human papillomavirus (HPV) DNA testing. Pap has proven successful in reducing cervical mortality, but the role of HPV in disease has been recognized, and recently the cobas test was approved as a primary HPV screen.

The sensitivity of the screening is idealthe problem lies in the fact that 10% of patients who are Pap-positive have pre-cancer, but some cancers are HPV-negative. Additionally, there may be cancer-independent transient HPV infections that could result in false positive results. Only 10% of women with high-risk HPV develop persistent infection. The result: unnecessary colposcopies and biopsies following HPV testing.

However, a recent study showed that patients are the ones who want screening and would even overrule their physician in wanting to get screened.

Can improved treatment reduce the need for screening? Not yet, said Dr Smith. We still cannot reliably distinguish between patients with indolent and aggressive cancer. “Cost is the elephant in the rooman unsustainable and sensitive topic that comes up with 'death panels,' 'rationing,' etcetera,” she said.

The other elephant in the room is malpractice liability. Delays in diagnosis are common claims in malpractice suits, and variations in guidelines (eg, annual vs biennial screening for breast cancer) can increase a physician’s exposure to such suits.

What will it take to change practice? A change in physician perspective and a change in patient expectations may be the answer. Additionally, cost constraints need to be modified, guidelines need to be standardized, and medico-legal issues need to be addressed.

Dr Smith concluded by saying that implementing small changes can lead to the bigger goals of:
  • Stretching screening intervals.
  • Tweaking thresholds for intervention.
  • Reducing cost of treatment.
Rinaa S. Punglia, MD, MPH, Dana-Farber Cancer Institute, presented “The Case Against Overdiagnosis and Overtreatment of Cancer.”

OD/OT are inherent in breast cancer screening, and OD is central to the mammography debate in breast cancer. “OD usually leads to OT. A treatment does not necessarily alter outcomes,” said Dr Punglia.

The solution to this problem, she believes, lies in informed decision making (IDM) by opening a dialogue. Decision to screen can lead to false positives, but also to early diagnosis and improved outcomes. IDM can be used to reduce OT.

For example, ductal carcinoma in situ (DCIS) has historically been treated with mastectomy, but that approach may be too drastic. Today, patients undergo breast preservation surgery, which can leave patients at risk for a second breast event in the preserved breast, but can be followed with radiation therapy (RT). Meaningful outcomes for a patient after RT include: recurrence, treatment of recurrence, and breast preservation. On the contrary, RT can be costly.

So how does one decide if a patient receives RT? It is an expensive treatment. DCIS overestimates a patient’s risk of recurrence, and decision making is difficult for patients. Therefore, individual decision making is keylay the options down and help patients make the right choice. Dr Punglia shared knowledge on a decision-making tool actively being used at Dana-Farber (www.onlineDeCISion.org) which helps both patients and providers alike.

The final viewpoint in this debate, “The Case for Overdiagnosis and Overtreatment of Cancer,” was presented by Laura Esserman, MD, MBA, University of California, San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center.

In March 2012, the National Cancer Institute (NCI) convened a workshop to generate ideas for a research agenda around OD. According to Dr Esserman, a critical shift in philosophy is needed to explain that the previous approach of OD saves lives.

The old paradigm of cancer was of inexorable progression―or that every patient has the same rate of disease progression. That has changed, and we know today that is far from true. Oncologists recognize that there is variable progression in patients and that there are IDLE lesions (indolent lesions of epithelial origin) that may not affect mortality. Therefore, understanding the biology of the cancer is extremely important.

Although the spectrum of disease has been realized and understood, the definition of cancer has not evolved. If a patient thinks 'cancer,' they think they will die if they are not treated.
Said Dr Esserman, “A very important question is: what do you know, when do you know, and how do you act on what you know?”

The need of time is a new approach to cancer treatment rather than arguments on 30-year-old guidelines. However, it is extremely important to understand outcomes before changing guidelines. 'Increased detection saves lives' is too simple: the concept is much more complex.

We have to recognize and gain a better understanding of IDLE disease―for example, does a tumor with little potential for metastasis and with little chance of progression/death require aggressive treatment?

IDLE tumor gene signatures could help define ultra-lowrisk tumors. This could be validated in various cohorts and used to stratify patients with high- and low-risk tumors.

Dr Esserman ended her argument by recommending that a better-tailored definition should replace the word ‘cancer,’ companion diagnostics should be coupled with treatment, and observational registries should be created to identify IDLE disease.
 
More on AJMC.COM