Surgical Advances Improve QoL in Gynecologic Cancers

Partner | Cancer Centers | <b>John Theurer Cancer Center</b>

Mira Hellmann, MD, discusses surgical and systemic advancements in the field of gynecologic oncology.

Mira Hellmann, MD

Surgical advances across gynecologic cancers have significantly improved quality of life (QoL) for patients, explained Mira Hellmann, MD, adding that, beyond surgery, more systemic therapies are also gaining traction in the space.

“The field is very exciting and is changing its paradigm a lot. It used to be a heavily weighted surgical field—which it still is—but the incorporation of targeted therapies and immunotherapies is changing the face of the field significantly,” said Hellmann. “I'm excited to see where this is all going to land because it's going to significantly improve patient outcomes, both in terms of quality of life as well as oncologic outcomes.”

Optimal surgical approaches vary depending on the gynecologic malignancy. For example, minimally invasive surgery has demonstrated efficacy with regard to survival outcomes and QoL in endometrial cancer. In cervical cancer, however, research has shown it is better to proceed with an open surgical approach to prevent disease recurrence and improve survival. Robotic surgical methods have also been a welcome addition, she added.

With regard to systemic approaches, PARP inhibitors and immunotherapies continue to be evaluated across settings, and CAR T-cell therapy is under investigation, Hellmann said.

In an interview with OncLive, Hellmann, a gynecologic oncologist at John Theurer Cancer Center, Hackensack University Medical Center, discussed some of these surgical and systemic advancements in the field of gynecologic oncology.

OncLive: What progress has been made regarding surgery in gynecologic oncology?

Hellmann: The evolution of surgical techniques in gynecologic malignancies has been quite significant over the past decade. Previously, we were doing very large incisions for all of our surgeries, including hysterectomies.

That has evolved over the years. We have gone from large incisions to doing laparoscopy for a lot of our surgeries. One of the big studies that looked at that was the Gynecologic Oncology Group LAP2 study, which compared minimally invasive surgery to open surgery for endometrial cancer. The results show no difference in outcomes regarding the oncologic process, but there was a significant improvement in QoL in the immediate postoperative period of about 6 months [for patients who received minimally invasive surgery]. That became the standard— when possible, to do minimally invasive surgery for endometrial cancer.

Since then, the field has even progressed more with the introduction of robotic surgery, which allowed for more extensive surgical procedures to be done laparoscopically. It also allowed for us to offer laparoscopy to a wider patient population, such as a morbidly obese population, which oftentimes was difficult.

It has also been used in cervical cancer for treatments up until November 2018, when a large study came out in the New England Journal of Medicine comparing minimally invasive surgery with radical hysterectomy and staging for cervical cancer. Unfortunately, the results showed that patients who had minimally invasive surgery did not fare as well as those who had open hysterectomies and staging for cervical cancer, including an increase in recurrence, decrease in progression-free survival (PFS), and decrease in overall survival. The minimally invasive approach to cervical cancer has gone to the side, and now we are reverted back to performing open radical hysterectomy since staging because of those data.

How are minimally invasive surgery and other advanced techniques being used in the field?

In terms of endometrial cancer, the minimally invasive surgery keeps on progressing. We actually recently had some data looking at sentinel lymph node mapping in endometrial cancer. Most of the time, that is done laparoscopically or robotically, where dye is injected in order to allow us to map the sentinel lymph nodes in lieu of performing a complete lymph node dissection. The benefit is that we avoid the complications related to lymph node dissection such as lymphedema, pain, lymphocyst, and increased risk of infection and bleeding during the surgery.

With robotic surgery, we are able to identify sentinel lymph nodes. There was a study that came out, called the FIRES trial, which looked at the efficacy and safety of sentinel lymph node mapping in endometrial cancer. We determined that sentinel lymph node mapping has a 99% negative predictive value, meaning it is very safe and effective in terms of detecting metastatic disease to the lymph nodes in endometrial cancer. The only caveat is that, to date, there is no published data from a randomized, controlled trial showing equal oncologic outcomes in patients who had sentinel lymph node mapping and those who didn't.

What systemic treatments have led to advances in the gynecologic oncology space?

PARP inhibitors have created a whole world of treatments and management. Initially, we thought it was limited to BRCA1/2-mutated patients, but there has been more and more studies that demonstrate efficacy [with PARP inhibitors] in patients who don't have a BRCA1/2 mutation. Research shows that PARP inhibitors have efficacy in patients who are homologous recombination deficiency (HRD)-positive. Some studies show that patients who have non-BRCA1/2 mutations or are not HRD-positive also have benefit from PARP inhibitors.

Sentinel lymph node mapping was a significant improvement because patients did suffer significantly from lymph node dissection in the pelvis, including significant impairment to quality of life.

That goes along with the other advancement of minimally invasive surgery in the management of gynecologic malignancies. Other targeted therapies are making headway in gynecologic oncology. Checkpoint inhibitors are definitely gaining foothold in the world of gynecologic oncology, but it has yet to be determined where [this class of agents] stands. There were some data looking at pembrolizumab (Keytruda) in recurrent endometrial cancer, [in which the PD-1 inhibitor] showed a significant improvement in progression-free survival (PFS). Another study looked at pembrolizumab with lenvatinib (Lenvima), [which showed an improvement in PFS] as well. Pembrolizumab has also been approved for treatment in advanced cervical cancer, and is under investigation in the upfront setting for cervical cancer, as well.

CAR T-cell therapy is in its baby steps, but hopefully it will show promise in the world of gynecologic oncology. Right now, it's being used a lot more routinely in liquid tumors. Slowly, it's gaining a foothold in solid tumors, as well. There are a couple of trials open in cervical cancer in CAR T-cell therapy, so I'm hoping that will yield significant results.

Ramirez PT, Frumovitz M, Pareja R, et al. Minimally invasive versus abdominal radical hysterectomy for cervical cancer. N Engl J Med. 2018;379(20):1895-1904. doi: 10.1056/NEJMoa1806395.