Frailty Score, Morphologic Subtype May Indicate Surgical Outcomes in Ovarian Cancer

Katelyn Handley, MD

The treatment of ovarian cancer has seen major progress over the past decade, with advances in both identification and surgical intervention.

One major area of development is in the identification of high-grade serous ovarian cancers (HGSOC). According to a study presented at The Society of Gynecological Oncology (SGO) Annual Meeting on Women’s Cancer, there are distinct gross morphologic subtypes and clinical outcomes of HGSOC. ¹

The retrospective study looked at the video recordings of patients who underwent laparoscopic assessment of disease burden prior to primary debulking surgery or neoadjuvant chemotherapy. In total, 99 patients were evaluable, with 60 presenting uniform morphology (65% types 1 and 35% types 2) at all involved metastatic sites. Additionally, 81 exhibited a predominating morphology (58% types 1 and 42% type 2.

The analysis found that patients with uniform types 1 tumor morphology were more likely to exhibit an excellent response to neoadjuvant chemotherapy than those with type 2 (47% vs 18%, P =.13). A significantly higher estimated blood loss at the time of interval debulking surgery and a longer operative type was also seen in patients with a type 2 predominant tumor compared to those with a type 1 tumor.¹

Recent research on how those with different tumor morphologies react to surgery isn’t the only new study on that front. The study presented at the SGO Annual Meeting on Women’s Cancer, looks at how a frailty index can be used to determine the outcome of surgical intervention on frail patients with ovarian cancer.

The analysis looked at the surgical outcomes of 591 patients in relation to their modified frailty index score (mFI). Of the 591 patients, 57% had an mFI score of 0, 29% had a score of 1, and 14% had a score of 2 or higher. There were no differences in stage between the cohorts.²

The analysis found that patients with an mFI score of 2 or higher were offered laparoscopic surgery at a rate of 27.63%, compared to the rate of 42.77% and 48.58% for patients with an mFI score of 1 or 0, respectively. Additionally, patients with a higher score were less likely to undergo any tumor reductive surgery. Complications from surgery were also more common in these patients. A high mFI score was also associated with poorer progression-free survival (PFS).² 

In an interview with Targeted Oncology, Katelyn Handley, MD, discussed two studies on ovarian cancer subtypes and the use of a frailty index to determine patient outcomes before, during, and after ovarian cancer debulking surgery.

TARGETED ONCOLOGY: I was wondering if you could discuss your first abstract on morphologic subtypes of high-grade serous ovarian cancer and what were some of the key takeaways?

HANDLEY: This study was based on the clinical observation that advanced ovarian cancers don't all look the same. And so, we were excited to take that observation in a new direction to delve into why we're seeing these differences. And, of course, further studies are still needed to validate our findings. In terms of the study set up, this study was setup so that within the same patient population, we have various amounts of data. So, we have their videos from their initial surgery, we have their clinical data, and we have pretreatment tumor samples, all from the same patients. And so, this allowed us to look at those videos and analyze them from the standpoint of the appearance of the cancer or the tumors. And then take that information and compare it to the clinical outcomes. How did that individual patient do as well as compare it to the biology of the tumor itself? So, looking at the cellular level, the protein level, and even the RNA level.

TARGETED ONCOLOGY: What were the results and some of the key takeaways?

HANDLEY: We've determined that there are at least two different morphologic appearances to ovarian cancer and specifically high-grade serous ovarian cancer. We saw that with these 2 different types, they tended to have differences in the proteins and pathways that seemed to be driving them. One type tended to respond better to early chemotherapy and seem to be more immunologically active. Whereas the other type tended to appear resectable. And when we took those patients to the operating room, they tended to require a longer time in the operating room, more blood loss. And this type did not have as much immune response or immune activity.

TARGETED ONCOLOGY: How do you see this study impacting ovarian cancer care in the future?

HANDLEY: This is just the beginning of this new direction in studying ovarian cancer. So we are looking at multiple trajectories of where we're going to take this project in the future. But I think that ideally, if we really can get a better thorough understanding of why we see these differences, then, in this new era that we're living in of really targeted therapies, we may end up treating these 2 different types differently based on the appearance or based on those underlying differences that we're finding.

TARGETED ONCOLOGY: Onto your next abstract, can you discuss the frailty index and its impact on surgical intervention?

HANDLEY: Within our field, we see that a lot of our patients with ovarian cancer are elderly. And on top of that, they tend to have a lot of comorbid conditions or health problems outside of their cancer. And we are cognizant that these big surgeries and treatments that we put them through can really take a toll on their bodies. So, the intent behind this study was to try to find a more objective means of assessing a patient's risk at the onset prior to determining how to target their therapy.

TARGETED ONCOLOGY: What was the design of the study and the key takeaways and results from the study?

HANDLEY: This was a retrospective review based on prospectively collected data, in which we looked at each individual patient and determined their level of frailty, and then compared that to both their surgical outcomes and their overall cancer outcomes.

Frail patients tended to present with more advanced disease, and therefore they may require bigger or more aggressive surgeries. However, because we're seeing an increased risk in these patients for complications due to the surgery, and even death within that first 30 days after the surgery, it's important that frailty be taken into account when making these clinical and surgical decisions.

TARGETED ONCOLOGY: How do you see this impacting surgical intervention in the future?

HANDLEY: This study really highlighted and emphasized the importance, as well as the impact of frailty on the outcomes for these patients. I think that a lot of providers are going to look into the different methods of assessing frailty in those first clinic visits when they see these newer ovarian cancer patients to determine which direction treatment and therapies should take.

TARGETED ONCOLOGY: Are there any next steps for this research? Is another follow up study planned?

HANDLEY: It's a continuous process. You find one thing. And then that, of course, raises 10 more questions. And so, we are also looking at several directions with this. We are looking at implementing an mFI or frailty scale within our population to consider a prospective study on a similar topic. That's one potential move forward. Another way that we may look to analyze the data is to compare and add this data to what we already know, from other methods such as lab values, age, different factors that we know can impact the risk for these patients to determine if we can come up with a better overall scale or even better means than frailty alone to look at the risk in these patients.

TARGETED ONCOLOGY: What was your biggest overall takeaway from SGO this year?

HANDLEY: I think just that the future for this field is bright. I think that it's astonishing, just the progress that's been made over the past 6 years. If you look at the FDA approvals and ovarian cancer over the last 6 to 7 years, there are at least as many as there were the preceding 60 to 70 years. And that's just shocking. And so, it's just a blessing and a marvel to be involved in this field in some small way, during such a exciting time.

_REFERENCE:

_{1.Handley K, If looks could kill: Morphologic subtypes of high-grade serous ovarian cancer. Abstract Presented at: The Society of Gynecological Oncology Annual Meeting on Women’s Cancer; March 19-25. Accessed April 19, 2021. https://bit.ly/32sxpKm.}

_{2.Handley K, If looks could kill: Frailty repels the knife: The impact of frailty index on surgical intervention and outcomes. Abstract Presented at: The Society of Gynecological Oncology Annual Meeting on Women’s Cancer; March 19-25. Accessed April 19, 2021. https://bit.ly/32sxpKm.}