Accurate Cancer Screenings

Accurate Cancer Screenings

More often it comes to precision medicine in the context of treatment, but researchers control and prevention of cancer are applying these concepts to the screening of cancer. Extensively, this means finding ways to point out who is most likely to benefit from regular screenings.

On September 29, NCI sponsored a conference that brought together leading cancer screening and screening researchers to address the state of the art of accurate screening for five cancers: prostate, breast, colorectal, cervical and lung.

The purpose of the meeting was to allow researchers “to come up with ideas on how best to proceed” with a research program to better understand and perform precision screening, said lead organizer Dr. Pam Marcus of the  Research Program Epidemiology and Genomics of NCI.

A surprising topic that emerged from the meeting, said Dr. Marcus, was that while there are some common problems and challenges in screening for these five cancers, in many cases the problems and challenges are “very specific to the organs”.

Accurate Cancer ScreeningsPrejudices and benefits

In recent years the risks of overdiagnosis and overtreatment associated with cancer screening-in particular, breast and prostate cancer screening-have received intense scrutiny. The need to reduce those risks was a hidden trend throughout the conference.

“All screening programs can be harmful, but some can do well,” said Dr. Nora Pashayan of University College London in her opening address. “What matters is the balance of possible benefits against possible harm.”

Dr. Michael Gould of Kaiser Permanente of Southern California highlighted the challenges that lung cancer screening may have. Dr. Gould noted the changes that have emerged as a result of the National Lung Examination  Survey ( NLST ), which showed that current heavy smokers and those who quit were 20% less likely to die from lung cancer if they were examined with computed tomography spiral of doses lower than if examined with x – rays regular chest.

But, he said, the study also had a very high percentage of false positive results, which resulted in approximately 2% of participants undergoing an invasive procedure-whether biopsy or surgery- for what turned out to be a nodule Benign lung disease.

According to NLST results, Medicare and many other insurance companies now cover the cost of CT screening in current or past heavy smokers. But that change did not go smoothly, Dr. Gould noted.

As it happened in the NLST, he said, many current and ex-smokers who now come for screening have false positive results and are undergoing further testing, including invasive procedures-which may have their own complications, sometimes severe.

Researchers are exploring ways to better stratify these people based on their cancer risk, and Dr. Gould described some of these works. But in the absence of more definitive information about the risk as well as a history of smoking, he acknowledged that, at his institution, “We are still struggling with how to conduct screening in real life.”

Progress towards risk-based screening

There has been a considerable study of precision screening for breast cancer, which is also called risk-adjusted screening, said Dr. Pashayan. But, echoing a proverb that is heard all day, she recognizes that in this field “there are more questions than answers”.

In breast cancer and other cancers, factors such as family history, age, and medical history are often used to predict future cancer risk, which can help guide screening decisions. Dr. Pashayan and other researchers have been studying whether additional information, such as panels of genetic alterations known as mononucleotide polymorphisms (SNPs) – identified by genome-wide association studies – may help improve risk stratification.

She cited a large study that indicated that a “polygenic risk score” – based on the many variants of a woman’s risk associated with breast cancer – can identify women at increased risk for breast cancer. In the study, women with the highest polygenic risk score, for example, had a risk of breast cancer three times higher than that of women with lower scores.

Although these results suggest there is some promise when using this type of genetic information to help identify those who could benefit most from screening, many of these types of studies – in breast cancer but also in other cancers – are still preliminary and they will need to be refined and validated, Dr. Pashayan noted.

Screening for cervical cancer in the United States has already moved to a risk-based approach, said Dr. Mark Schiffman of NCI’s Division of Epidemiology and Genetics of Cancer (DCEG).

The change, he explained, is based on studies that established persistent infection with high-risk types of human papillomavirus ( HPV ) are responsible for almost all cases of cervical cancer and revealed the process by which the lesions precancerous evolve invasive cancer .

“We know a lot about the causal pathway in cervical cancer,” Dr. Schiffman said.

Although Pap smears are still routinely used to screen women for cervical cancer, clinicians now include the patient’s HPV status in the decision-making process, Dr. Schiffman said. According to current recommendations from leading medical societies, the presence of high-risk HPV types, which are identified with DNA- based evidence, should help guide decisions about issues such as the most appropriate range of screening.

But the current approach is not engraved in stone, warns Dr. Schiffman. As HPV vaccination rates increase, he explains, that will affect how cervical cancer screenings are done.

Challenges continue

There was also vigorous discussion about the type of evidence needed to make changes to screening practices: data primarily from demographic observational studies or data from randomized controlled trials.

Depending on the type of cancer and the extent and strength of the available data, there is evidence to support both opinions, noted Dr. Marcus. Working through these kinds of questions will be a key challenge in moving toward a precision medicine approach to screening, she added.

Although there is still a long way to go before precision screening tests are common for these cancers, Dr. Gould stressed that it is important to keep moving in that direction.

“When we are doing screenings, we are dealing with people who are healthy, and we are becoming patients,” he said. “We need to do our best to [examine people] safely and minimize harm.”

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