Ovarian cancer screening (still) doesn't save lives

 - Jennifer Middleton, MD, MPH

Five years ago, I wrote about the pitfalls of advertising ovarian cancer screening (specifically, the ROCA test) to post-menopausal persons given the dearth of evidence supporting a mortality or morbidity benefit. The primary study that I cited, the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), released preliminary data in 2016. While they offered the tantalizing suggestion that ovarian and tubal cancer screening may offer a small benefit, they also acknowledged that the mortality of its participant groups did not appear markedly different. Now, after following these 200,000+ participants for a median of 16.3 years, the UKCTOCS researchers are definitively reporting no difference in mortality rates among those who were screened for ovarian and tubal cancer compared to those who were not. 

The UKCTOCS enrolled participants who were post-menopausal from across the United Kingdom and randomized them into three groups: annual multimodal screening (MMS) using ROCA, annual transvaginal ultrasound screening (USS), or no screening. The completed study, published earlier this month, found that:

Compared with no screening, there was a 47·2% (95% CI 19·7 to 81·1) increase in stage I and 24·5% (−41·8 to –2·0) decrease in stage IV disease incidence in the MMS group. Overall the incidence of stage I or II disease was 39·2% (95% CI 16·1 to 66·9) higher in the MMS group than in the no screening group, whereas the incidence of stage III or IV disease was 10·2% (−21·3 to 2·4) lower. 1206 women died of the disease: 296 (0·6%) of 50 625 in the MMS group, 291 (0·6%) of 50 623 in the USS group, and 619 (0·6%) of 101 314 in the no screening group. No significant reduction in ovarian and tubal cancer deaths was observed in the MMS (p=0·58) or USS (p=0·36) groups compared with the no screening group.

Although the MMS identified more cancers at an earlier stage, this early identification did not translate into a mortality benefit. In 2016, the UKCTOCS researchers responsibly advised caution regarding the risk of lead time bias in judging MMS' early detection ability; their assertion then that "follow-up is needed to assess the extent of the mortality reduction before firm conclusions can be reached on the long-term efficacy...of ovarian cancer screening" presciently predicted their final findings.

The United States Preventive Services Task Force (USPSTF) continues to recommend against ovarian cancer screening, and their rationale includes the important caveat that "screening for ovarian cancer can result in...many false-positive results, which can lead to unnecessary surgical interventions in women who do not have cancer." The Choosing Wisely campaign similarly advises against ovarian cancer screening in average risk, asymptomatic persons. As I wrote in 2016, we should continue to focus our preventive care on interventions that are proven to decrease mortality. This AFP article on "Diagnosis and Management of Ovarian Cancer" includes links to editorials that provide additional context regarding screening if you'd like to read more. 

Guest Post: Thinking about loss in medicine

 - Jason Kurland, MD

Seven years into my medical career and one year into COVID, I've been thinking a lot about loss. Thinking about the primary care patients I lost during COVID and those who died in years prior to the pandemic. I don't find myself missing every patient who has died months later, but I do think of the ones who saw me in clinic regularly every 3 months, then every 2, sometimes every 2 to 4 weeks when their health worsened. The ones I squeezed into an urgent care shift because they needed to be seen by someone familiar with their history. The ones I recognized immediately from my colleague's texts: "admitted your 67 y/o patient with CHF" or "recurrent GIB" or "decompensated cirrhosis." Since I practice full spectrum family medicine in a rural hospital, I may see some patients in clinic one week and in the Emergency Department (ED) or on the medical ward the next. On occasion, I might deliver their granddaughter’s child.

I recall the night over a year ago when we coded a 92 year-old woman, found down at home, only to hear a second ambulance arrive as I called the code. The new patient was her son, my primary care patient. I ended up diagnosing him with yet another myocardial infarction that night; he had five stents already. He survived another year and had many more clinic and virtual visits. Last spring, he was found pulseless on the bathroom floor at home. I walked past our single negative pressure ED room where my colleagues were struggling to restart his heart, unaware that it was him until a screener in the hall outside told me. I poked my masked and shielded head in the door to confirm his Do Not Resuscitate order, ending the code. I then broke the news by phone to his wife who was waiting outside the hospital, per our stringent pandemic visitor policies.

After all of those visits, the setbacks and the improbable upturns, my patient is gone. My role now is to comfort the family, help them process the loss. I feel a grim sense of pride in doing a good job of death care.

My patient no longer pops up reliably in my schedule. I have no reason to open the chart. The time I spent reading about one of their complications or discussing their care with a specialist who ultimately agrees "that's hard, there's no simple answer" no longer keeps me after clinic. I lose the pleasure of checking in with a patient whom I also happened to have liked as a person. I lose the moments when I tell a colleague who is taking care of my patient in our urgent care, "so, the history on that is...."

Of course it makes sense that patients who have an outsized presence in my professional life can, sometimes, have an outsized presence in my emotional life. On good days, it feels like what I do really matters. Even when I have nothing medical to offer, I sense my longtime patients appreciate a familiar voice. But my patients and I inevitably share an asymmetric intimacy. I learn secrets about them, and I am present at their moments of extreme vulnerability. I might share a fact about me or show them a picture of my daughter being goofy. I can drop a detail into our visit that humanizes me or connects with something in their life. But ultimately, I am there for them.

My profession doesn't have a custom or a process for my grieving. Twice in the last year, I had to stifle the impulse to ask a terminally ill patient I’ve known for years for a selfie with them. I recognized, even as the thought occurred, that the request was inappropriate, that it blurred a line. Reflecting since, I realize I just wanted something by which to remember them, to recall our connection, shared jokes and disappointments, our relationship.

**

Dr. Kurland is Director of the Emergency Department at Zuni Comprehensive Community Health Center in New Mexico.

AAFP updates recommendations on lung cancer screening

- Sarah Coles, MD and Alexis Vosooney, MD

Recently the U.S. Preventive Services Task Force (USPSTF) updated its recommendation statement on lung cancer screening, lowering the age to start screening and pack year eligibility. The USPSTF now recommends annual screening for lung cancer with low-dose computed tomography (LDCT) in adults aged 50 to 80 years who have at least a 20 pack-year smoking history and currently smoke or have quit within the past 15 years. Screening should stop once a person has not smoked for 15 years or has health issues that limit life expectancy or the ability and desire to have curative lung surgery.

The American Academy of Family Physicians (AAFP) disagreed with the previous (2013) USPSTF recommendation, which was based predominantly on a single trial, the National Lung Screening Trial (NLST). At that time, the AAFP concluded there was insufficient evidence to recommend for or against LDCT lung cancer screening. The AAFP had concerns about the generalizability of the trial (conducted in a large, academic medical center with a population that was younger and more likely to be current smokers than in the general population), the uncertain magnitude of benefit and the potential for harm, overdiagnosis, and uncertainty about optimal screening intervals. Championing the science, the AAFP highlighted concerns about this recommendation and called for additional research, and that challenge was met.

The new evidence review commissioned by the USPSTF includes seven randomized clinical trials (RCTs) of lung cancer screening with LDCT. NLST and the NELSON trial were the largest and the only trials powered to detect lung cancer mortality benefits to screening. Screening resulted in a difference in lung cancer specific mortality of 0.46%. The relative risk reduction for lung cancer mortality is 16-20%. The NELSON trial demonstrated a number needed to screen (NNS) to prevent one lung cancer death of 130 over 10 years of follow up. These improvements in cancer specific mortality are comparable or greater than other recommended screening tests such as breast cancer screening. A modeling study was also performed comparing screening strategies with different starting and stopping ages, frequency, and eligibility criteria. This analysis suggested that the 2021 USPSTF recommendation would result in more benefit than the 2013 recommendation.

Among studies conducted in the US, rates of overdiagnosis and false positives varied widely, with false positives generally declining with each screening round. In NLST, false positives led to invasive procedures and complications were rare. Use of current nodule management strategies such as Lung-RADS can reduce false positive rates and decrease unnecessary invasive procedures and improve the balance of benefit and harms.

After a robust discussion that included the strength of evidence, the risk of harm, the likelihood and magnitude of benefit, and the impact on health equity, the AAFP’s Commission on Health of the Public and Science agreed that there was sufficient data from clinical trials and observational studies to recommend screening and supported the USPSTF recommendation.

Further research is needed into harms of screening, particularly rates and consequences of overdiagnosis, unnecessary procedures, and barriers to implementation in community settings. None of the included studies in the USPSTF systematic review provided estimates for the lifetime risk of radiation-induced cancers or fatal cancers from continuing annual screening up to age 80. The general population is less likely to benefit than the study participants in NSLT and NELSON trials because of higher risks of other causes of death, such as heart disease. These trials were mainly conducted at large, academic medical centers with access to case management, specialized radiologists, and surgical expertise. Community based practices may not have the same resources to navigate positive results and follow up needs. The studies had poor racial and gender diversity, and the impact of screening on health equity for communities of color is unknown.

As with all screening recommendations, family physicians should discuss the potential benefits and risks of harm with each patient when considering lung cancer screening. The National Cancer Institute has developed resources to help clinicians with these discussions. While lung cancer screening does appear to help, smoking cessation remains key to reducing lung cancer deaths.

Introducing the 2021-2022 AFP Jay Siwek Medical Editing Fellow: Dr. Jorge Finke

 - Jennifer Middleton, MD, MPH

It's my pleasure to introduce our 2021-2022 Jay Siwek Medical Editing Fellow, Dr. Jorge Finke, whose fellowship year will begin June 1. Here are some highlights from a recent interview:

1. Tell us a little about yourself. 

I was born in the Dominican Republic and moved to the U.S. at the age of four. I grew up in a small working-class city north of Boston, which inspired me to focus my medical career on community medicine. I graduated from college and medical school in Massachusetts and decided to stay for family medicine residency at UMass. As a new attending, I’ve been working at a community health center in Boston which provides care to underserved patients. I love teaching and mentoring students at all stages of their education, so I hope I can continue integrating those opportunities in my career. 

 2. What got you interested in medical writing and editing? 

My residency program placed a strong emphasis on the practice of evidence-based medicine. I had the realization that much of what we we learn and are trained to do in medical school is not always founded in evidence, and that evidence is always changing. This inspired me to continually ask questions about the “why” and think more critically about how we practice. It led me to read more journal articles and have active conversations with my colleagues around practice-changing information I would find. A faculty member offered me the opportunity to write a “Cochrane for Clinicians” article for American Family Physician, which gave me a taste of medical writing, and I’ve been looking for more ways to get involved ever since. 

 3. What are you hoping to get out of the fellowship? 

I’m excited to be a part of the editorial team. Working with experienced editors will help me learn to better evaluate and appraise manuscripts, which will hopefully, in turn, make me a better editor and writer. I’ll be constantly exposed to new advances in clinical practice that will help me both in my day-to-day care of patients but also allow me to share these insights with my colleagues. Through this fellowship, I hope to learn and grow as both a clinician and teacher, which will give me greater career range and help me become a more well-rounded physician. 

 4. Is there anything else you'd like AFP readers to know about you? 

Outside of work, I’m always looking to try new things and pick up new hobbies. I enjoy the creativity of trying new recipes and cooking for my wife who is my personal taste-tester. I enjoy sailing in Boston during the summers. I visit my family in the Dominican Republic when I can and enjoy relaxing at the beaches there. Within my work, I am passionate about caring for underserved populations, addiction medicine, and medical education.

Understanding and managing long COVID

 - Kenny Lin, MD, MPH

Although 90% of non-hospitalized patents with acute COVID-19 have complete symptom resolution by 21 days, the rest suffer from a wide range of nonspecific symptoms for weeks to months, collectively known as post-acute sequelae of SARS-CoV-2 (PASC) or long COVID. An AFP editorial on long COVID published last December advised that family physicians perform limited testing in these patients guided by the clinical assessment; for those with normal results, "recommended management ... consists of emotional support, ongoing monitoring, symptomatic treatment (e.g., acetaminophen for fever), and attention to comorbidities." A virtual workshop convened that month by the National Institutes of Health (NIH) noted that long COVID symptoms "have been reported among persons of all ages," including children, and that this syndrome potentially represents an enormous chronic health burden; since at least 32 million people have had COVID-19 in the U.S. alone, 3 million or more could be affected. 

Evidence gaps highlighted by workshop speakers included the epidemiology, clinical spectrum, and natural history, and pathophysiology of long COVID. In January, Dr. Francis Collins announced that the NIH would use a Congressional appropriation of $1.15 billion over four years to fund a PASC Initiative to support "a combination of ongoing and new research studies and the creation of core resources ... to help us understand the long-term effects of SARS-CoV-2 infection, and how we may be able to prevent and treat these effects moving forward." 

Two recent electronic health record studies have advanced our understanding of long COVID in the U.S. A cohort study of more than 73,000 non-hospitalized COVID-19 survivors in the Veterans Health Administration (VHA) found that compared to non-hospitalized VHA users who did not have COVID-19, the former group had an increased risk of death beyond the first 30 days of illness (HR 1.59, 95% CI 1.46-1.73) and were more likely to seek outpatient care and have more frequent visits. In addition, the study found an excess burden of respiratory conditions, nervous system conditions, mental health disorders, metabolic disorders, cardiovascular conditions, and gastrointestinal disorders in the COVID-19 cohort at 6 months of follow-up. Similarly, a Centers for Disease Control and Prevention (CDC) study of 3,171 non-hospitalized adults at Kaiser Permanente Georgia who had a positive SARS-CoV-2 polymerase chain reaction result from April to September 2020 found that 69% attended one or more outpatient visits 28 to 180 days after their COVID-19 diagnosis. 68% of these patients had visits for a new primary diagnosis; although most visits were with primary care clinicians, 38% visited with a new specialist. The volume of visits for symptoms potentially related to COVID-19 (throat or chest pain, shortness of breath, malaise and fatigue) declined after 60 days, but some continued through 120 to 180 days.

In a perspective paper in The Milbank Quarterly, Dr. Zackary Berger and colleagues observed that primary care clinicians will play important roles in providing and coordinating care for vulnerable patients with long COVID. The racial health disparities seen in acute COVID-19 will likely translate into similar disparities in long COVID, exacerbated by structural barriers to health and care access (economic, geographical, housing and segregation, and occupational) that could impede recovery. The authors recommended boosting health system resources devoted to primary care and addressing the root causes of inequity though actions to mitigate the social determinants of health. Whether the upcoming CDC guidelines on long COVID heed these sensible recommendations remains to be seen.