Q&A With Andreas Obermair

CHICAGO — Clinical practice guidelines are sometimes based on shoddy data that too often go unchallenged. Further, guidelines in gynecological cancer surgery have not always included the patient’s perspective, leading to poor quality-of-life outcomes for them.

That’s according to Andreas Obermair, MD, a gynecological cancer surgeon renowned for conducting studies that put guideline wisdom to the test. Director of the Queensland Centre for Gynaecological Cancer Research in Brisbane, Australia, Obermair also runs his own research laboratory, where he investigates less invasive treatments. He says these treatments will not only result in health outcomes equal to current practice but also lead to better recoveries and a higher postoperative quality of life.

Although some guidelines in gynecological cancers are based on Obermair’s work, he is critical of what he calls the field’s “complacency” when it comes to interrogating current standards of practice.

Obermair was involved in the practice-changing LACC trial. The prospective, randomized study upended the accepted standard of care in early-stage cervical cancer by demonstrating that minimally invasive radical hysterectomy was associated with lower rates of disease-free survival and overall survival than open abdominal radical hysterectomy. This paper was one of NEJM’s Notable Papers of 2018.

Obermair is currently planning to conduct another study he anticipates will challenge the standard of care. The randomized ENDO-3 trial, (NCT04073706), was designed to offer another treatment pathway in endometrial cancer, beyond the prevailing standard of surgical staging. The study is currently recruiting at several sites globally, including at Houston Methodist Hospital in Houston.

Another trial for which Obermair is an investigator is the ANVU, which will soon begin recruiting. This phase 2, open-label, multisite, three-group, randomized clinical trial is aimed at discovering whether intensive groin ultrasound monitoring is safe and cost-effective as a replacement for invasive groin lymph node dissection in vulvar cancer and whether it decreases the morbidity associated with vulvar cancer surgery.

This news organization spoke with Obermair about how guidelines both help and harm patients in gynecological cancers and why patients benefit when clinicians fight the status quo. Here are excerpts of the interview, edited for length and clarity.

At this American Society of Clinical Oncology (ASCO) 2024, you moderated a panel about controversies in gynecological cancers. One of the themes you hammered was that the best patient care informs patients about all possible treatment pathways and the potential downsides of each. Can you please explain how this ties in with your desire to interrogate guidelines?

Some of these guidelines are dogmatic and paternalistic. They don’t consider the patient’s perspective, but that is hugely important. Also, it can be easy to just adhere to the guidelines and not use clinical judgment about what might be the best approach for a certain situation. But also, often the evidence for the guidelines is weak, and if they were examined, then we might have more discussions about other options. It is always better for our patients if we at least research and share what we know about what might be best for them. What I criticize is the lack of options.

Can you give an example of this?

In early-stage endometrial cancer, the guidelines say to use surgical staging and node dissection. But these recommendations are not based on level 1 randomized evidence on the effectiveness of the treatment. They use evidence from cohort studies, and that is level 2. If these guidelines had included the patient’s input, they would acknowledge this. That would make room for different treatments, or for us to ask different questions, at least for some patient groups.

Some patients do not want to have the tumor surgically removed because they wish to have uterus-preserving treatment. And this is something that is close to my heart because I’ve done a randomized controlled trial (the FeMMe trial) on using a levonorgestrel intrauterine device in endometrial cancer. So I know, some patients actually reasonably prefer that to a hysterectomy, and some patients prefer not to have lymph node sampling or the staging.

FeMMe examined whether 165 women with endometrial cancer could be treated less invasively to reduce the need for surgery and preserve fertility; 82% of those with endometrial hyperplasia with atypia and 42% of those with endometrial cancer responded to the novel approach, which was most successful when combined with weight loss (67% response rate). Side effects in the study arm were low.

In the ANVU trial, I have come upon resistance from other clinicians who say there is no problem to solve in vulvar cancer, but I think there is, even if we can just do a sentinel node biopsy these days. I think treatment could be made a lot better. The morbidity in vulvar cancer remains horrendous, and the main morbidity comes from the groin node dissection.

I do admit that the associated morbidity has decreased in the last decade with the introduction of sentinel node biopsy, but it is not zero. And only about 50% of patients are eligible for the sentinel node biopsy. The remainder of patients have to have the full groin dissection. Maybe there is a way that gives patients a better quality of life and less morbidity. That’s what is motivating me to conduct the ANVU study and to randomize it for the best level of evidence.

Regarding the quality of evidence many guidelines are based upon, can you flesh that out more?

Yes, many guidelines rely on weak evidence. Maybe there is a better way to do things so that patients will have a better quality of life, but we don’t know because there hasn’t been an effort to find out. Complacency is a big enemy in the medical field.

We need to be more proactive about gathering high-quality data because with low-quality data we are not actually answering questions that need answering. All our research questions must focus on our patients — what is important and relevant to them.

Aside from complacency, what other barriers exist to developing a stronger evidence base for guidelines?

I will tell you a story about that. I was running a meeting for a medical device manufacturer recently. It was multidisciplinary, and there were about four specialists present. It appeared to me that we were all struggling with getting the evidence we needed.

That is because funding for surgical clinical trials is just very difficult to get. Medical trials are just so much easier to fund because there are industry interests, but typically, surgical device manufacturers have absolutely no interest in doing clinical trials because they don’t need it for registration. So, it is difficult to find funding for studies that would result in better evidence.

It’s fairly well accepted that while guidelines are not laws, they should be consulted, for the sake of standardizing care. What are your thoughts on that?

Guidelines are basically simplifications. They are required because not all clinicians who treat gynecological cancers are experts in that. Not all people are up to date with the latest evidence, and not all people are capable of reviewing the literature and making sense of it and drawing independent conclusions. It’s not always possible. Guidelines do that intellectual work.

I am critical of guidelines, but many of them in my field are based on my work, so I do value them.

For example, I do fewer ovarian cancer surgeries than I do other kinds of gynecological cancers, so I am happy to have guidelines for that. But I still need to use my clinical judgment.

Also, there are many places in the world that are under-resourced for gynecological cancers. So, maybe it will be an obstetrician that is doing the work, and they are not experts in this. So, they will need the guidelines.

But I don’t think authors of the guidelines realize their responsibility at times. They have a responsibility to the community because a lot of people will follow their guidelines and not question them. If the level of evidence is weak, then the authors should be more forthcoming about that. In situations where evidence is lacking, people come up with opinions and beliefs. That’s why I put the question out there: Are our guidelines actually trustworthy?

Obermair received grants from GSK, Cherish Women’s Cancer Foundation, and RBWH Foundation and honoraria from Stryker, Baxter, and AstraZeneca. He holds stock in his own company, SurgicalPerformance.