Ovarian Cancer Screening and Symptom Awareness Consensus Statement
Finding a method of early detection for ovarian cancer has been a primary focus of research for years, and was believed to be a promising approach to stopping women, or anyone born with ovaries, from dying of the disease. Some other cancers have demonstrated that earlier stage diagnoses can lead to better prognoses, and an oft-cited statistic has been that when caught in stage I the survival rate for ovarian cancer is over 95% five years later. However, this stage-related survival statistic can be misleading, and research has revealed that the reality for ovarian cancer is not as straightforward.
Ovarian cancer is a highly heterogeneous disease; many different distinct types of cancers are called “ovarian.” Within the most common type — e.g., epithelial ovarian cancers — there are distinct subtypes (high-grade serous, low-grade serous, clear cell, etc.), and even when someone is diagnosed with the same subtype, that person’s cancer is still unique. This helps explain how some patients diagnosed at stage III never recur and are cured, while others diagnosed at an earlier stage may recur and ultimately die from the disease.
Scientists are still trying to determine why, but regardless of the stage at diagnosis, some ovarian cancers are deadlier than others. In many cases, the stage at diagnosis may not significantly impact whether a patient dies from the disease. Detecting ovarian cancer earlier in the course of its disease progression — which could be at an earlier stage — may not prevent a woman from dying.
Results from a large clinical trial (UKCTOCS) that investigated the effectiveness of currently available ovarian cancer screening methods (screening is defined as checking for a disease when there are no symptoms) clearly revealed this complexity. In addition to finding that screening average-risk women with CA-125 and ultrasound does not reduce ovarian cancer mortality, the trial revealed that in many women identifying their cancer at Stage I or Stage II did not impact their mortality. And importantly, these women were estimated to have been diagnosed an average 18 months prior to the onset of symptoms. These women seem to have had a cancer that was just inherently more aggressive; detecting it at an earlier stage was not enough to prevent them from dying from the disease and did not prolong their lives.
Equally paradoxically, the same study showed that some women (albeit a minority of women) diagnosed in late stage did very well. Their late-stage diagnosis did not condemn them to a poor prognosis, because there was something about their cancer that was less aggressive, and their positive outcome would have occurred whether diagnosed earlier or later.
While these results were not what anyone wanted them to be, they are incredibly important and do provide key insights to guide ovarian cancer research going forward. It is clear that for early detection to dramatically improve outcomes, new yet undiscovered methods will need to be developed so the cancer can be discovered much earlier for those with the more aggressive ovarian cancer. How much earlier is unknown, though researchers have hypothesized it could be as much as five years or more to increase life expectancy. The technology for this does not currently exist (or hasn’t been recognized as such) and once it does it will need to be evaluated in a large, randomized trial which will take many years. The need for a randomized controlled trial is in many ways frustrating but UKCTOCS illustrates just how important it is not to take short cuts and rely on evidence of stage shift or early detection without mortality data. Unfortunately, this means that a viable screening/early detection approach for average risk patients is probably 10-20 years away.
Importantly, not only do current screening methods not save lives in the general population, but they can also actually cause harm. Screening can lead to false positive tests, resulting in a cascade of anxiety-provoking investigations and sometimes unnecessary surgeries that can pose emotional and physical risks to patients, not to mention financial hardship.
The study also indicated that promoting symptom awareness will not save lives. The screening found cancers in women before they developed symptoms and on average 18 months before symptoms would have led to clinical diagnosis. Given that this early intervention before symptoms developed did not save lives it is regrettably hard to argue that prompt attention to symptoms when they eventually occur will save lives.
This is incredibly hard information to accept and runs contrary to almost all messaging related to ovarian cancer awareness to date. However, the UKCTOCS trial was large, rigorous, and definitive and to ignore learnings gained from it is detrimental to the wellbeing of women and the future of ovarian cancer research.
It is possible that symptom recognition leading to a timelier diagnosis could allow: more time to get appropriate referrals to specialists; an easier course of treatment if surgery and chemo occur before the patient is very sick; less complicated surgery; and easing of psychological distress from delayed diagnosis. However, we must reluctantly accept and be honest with the women we are trying to help, that there is no evidence that recognizing the symptoms earlier will change the course or outcome of the illness for the patient.
For these reasons, a singular focus on educating the general public about the symptoms of ovarian cancer is not the best use of valuable resources. Additionally, people diagnosed with ovarian cancer and their families should be freed from the burden of believing that if only they had recognized and acted on the symptoms earlier, they would have a vastly different outcome, as we know this is not the case.
As an organization, OCRA will continue to include symptom awareness as part of our messaging to both the medical community and public, so that patients obtain timely, high quality and optimal care. But we will focus our larger efforts on messaging that has been proven to improve outcomes for patients with ovarian cancer.
Given that we know that screening the general public for ovarian cancer using CA-125 and ultrasound does not save lives in the general population, and that population screening, which can reduce mortality is likely decades away, what does this mean for the ovarian cancer community? It means we have an important opportunity to focus on what CAN improve outcomes. We have more clarity than ever before on how to best direct valuable resources to have the most impact to benefit the most people, both now and in the future.
Let us instead focus on amplifying powerful messages proven to improve outcomes in ovarian cancer:
- Encouraging women, or anyone born with ovaries, to know their risk;
- Promoting genetic testing to at-risk populations, engaging in the consideration of population based genetic testing, and taking action when necessary is more beneficial — a sure way to decrease incidence and mortality;
- Encouraging those who are undergoing pelvic surgeries for benign conditions (hysterectomy, tubal ligations, cysts, endometriosis) to consider having their fallopian tubes removed. As the fallopian tube is the origin of most high-grade serous cancers, fallopian tube removal has been shown to dramatically reduce risk for a later ovarian cancer diagnosis. This has been referred to as “opportunistic salpingectomy”);
- Educating about the symptoms of ovarian cancer, so that patients may receive a prompt diagnosis, which may ease psychological distress and facilitate treatment;
- Educating to ensure every person diagnosed with ovarian cancer is seen by a gynecologic oncologist and has access to the best standard of care;
- Educating patients to utilize genomic testing for more personalized treatment;
- Encouraging cascade testing for patients’ family members when a mutation that increases ovarian risk is discovered;
- Promote consideration of participation in clinical trials.
[Special consideration: It is important to note that the UKCTOCS trial did not include women at high risk of ovarian cancer because of a strong family history of breast or ovarian cancer or a genetic predisposition. Therefore, the UKCTOCS results do not exclude a role for screening among the high-risk group. Other large studies in the USA and UK, using CA-125 interpreted by the Risk of Ovarian Cancer Algorithm (ROCA) and ultrasound have been conducted in the high-risk group of women. They were not randomized controlled trials so there is no mortality data for this population but evidence from the UK and US trials shows a stage shift and less complex surgery in screen-detected cases. While the gold standard of care for women at high risk of ovarian cancer is preventative surgery, screening can be a reasonable option for those who have had thorough counselling and have made an informed decision to delay surgery or are unwilling to undergo surgery.]