Robotic Surgery vs Radiation in Oropharyngeal Cancer

Roxanne Nelson, RN, BSN

June 12, 2019

CHICAGO — For patients with oropharyngeal squamous cell cancer (OPSCC), opting for radiation therapy rather than surgery may result in better swallowing outcomes, which in turn may mean a better quality of life, according to new findings.

The findings come from the first, and so far only, randomized trial to compare the two modalities in the first-line setting for this cancer.

After transoral robotic surgery (TORS), a mild decline in swallowing function was observed in 40% of patients, as compared with 26% of patients in the radiation therapy group.

"All things taken together, survival was similar between the arms," said lead author Anthony Nichols, MD, associate professor in the Department of Otolaryngology – Head and Neck Surgery at the University of Western Ontario in Canada. "However, there were significant differences in the spectrum of toxicity and quality of life between the two arms."

He noted that patients in the surgical group of the study experienced less tinnitus and hearing loss, less neutropenia, and less constipation. However, there were two different swallowing metrics, and each of these favored the radiotherapy group, and were either statistically significantly better or bordered on statistical significance, said Nichols.

While the clinical meaning of this is debatable, there was less pain and pain medication used in the radiation therapy group at 1 year, he said. "There were no bleeding episodes, there was less trismus, and there was a trend toward less shoulder impairment in these patients," he added.

Nichols presented the findings here at the annual meeting of the American Society of Clinical Oncology.

"Swinging Pendulum" Between Surgery and Radiotherapy 

Radiation therapy has historically been the standard treatment for OPSCC, but TORS has surpassed radiation therapy in the US as the most common approach, Nichols commented. The switch in modalities was largely based on assumptions that TORS would reduce toxicity and improve quality of life.

"The management of oropharyngeal cancer has truly been a swinging pendulum," said Nichols. "Historically, many cases were managed with open resection, which was largely replaced by radiation and chemoradiation protocols in the 1990s and 2000s, but there's always been a subset of centers that have carried out transoral resections of oropharyngeal cancer."

After the US Food and Drug Administration approved TORS in 2009, these numbers "skyrocketed," he said.

In 2013, 82% of patients with T1 and T2 oropharyngeal cancers underwent primary surgery, and Nichols pointed out that this "huge shift in management was carried out in the absence of Level 1 evidence."

"To our knowledge, there are no randomized trials comparing primary surgery to primary radiation for oropharyngeal cancer for any endpoint," he said.

MDADI Score Superior with Radiation

The goal of the current study was to compare swallowing quality of life at 1 year for patients undergoing a primary radiation approach as compared with TORS and neck dissection for oropharyngeal cancer.

The study involved 68 patients with T1 and T2 oropharyngeal cancers after stratification for P16 status, who were randomized to receive either primary radiation with or without chemotherapy (n = 34), or to undergo TORS with neck dissection (n = 34), with adjuvant therapy given based on pathological findings.

The median age of patients was 59 years, and primary tumor sites were palatine tonsil (74%) or base of tongue (26%). Groups were well-balanced for baseline factors, including p16 status (88% in each group). In group one, patients receive radiation alone at a dose of 70 Gy for T1 and T2, N0 disease. Those who were node positive received chemoradiation with a dose of 70 Gy plus high dose cisplatin.

In the surgery group, patients underwent TORS of the primary site with neck dissection at levels 2 through 4, with ipsilateral external carotid artery ligation. Tracheostomies were carried out for area protection at the discretion of the treating surgeon.

The primary endpoint was a definitive comparison of swallowing quality at 1-year using the MD Anderson Dysphagia Inventory (MDADI), powered to detect a 10-point improvement (a clinically-meaningful change [CMC]) in the TORS group.

At a median follow-up of 27 months, MDADI scores at 1-year were statistically superior in the radiation therapy group (86.9 vs. 80.1 in the TORS arm; P = .042), but not meeting the definition of a CMC.

;"This was statistically significant," said Nichols. "We note that the difference between these two arms, of 6.8, did not meet our prespecified criteria for a clinically meaningful change. However, when we looked at the subdomains of the MDADI, including the global and emotional scores, these were also statistically significant."

"We also note that the composite score was statistically significant with a P value of .049, and some people think that is the most clinically relevant score," Nichols added.

When looking at functional oral intake scores, at 1 year, 100% of patients in the radiation and chemoradiation group were eating a total oral diet with no restrictions, while 16% of the surgical patients required special food preparation. This bordered on statistical significance (P = .055).

At 1 year, one patient in the radiation group had a gastrostomy feeding tube, but Nichols noted that he had a normal voice score and his tube was subsequently removed 3 months later. None of the patients in the TORS group required a gastrostomy tube.

There was no difference in overall or progression free survival between the two groups, but Nichols emphasized that these were secondary endpoints and the study was not powered to detect a difference.

Nichols said that these patients will now be followed long-term, and noted that a comparison of long-term outcomes "may indeed lead to different conclusions, as we've seen in other head and neck cancer trials."

In addition, the team intends to analyze the outcomes of other trials, such as ECOG 33-11, which will provide definitive functional and quality of life outcomes that can be compared with this trial.

"We've already opened Order 2, which is a Phase 2 de-intensification trial for P16 positive oropharyngeal cancer, that compares de-intensified chemoradiation to primary surgery followed by adjuvant therapy," he said. "It opened in January 2018 and is already accruing well."

Surgery Is Still Needed

In a discussion of the study, Maie St. John, MD, PhD, professor and chair of the Department of Head and Neck Surgery at UCLA Health in Los Angeles, noted that at the time when TORS was "kind of becoming a new thing, we knew that this kind of endoscopic head and neck surgery was going to lead to poor functional outcomes in the immediate postop period, but that would then return within a few weeks of surgery."

"We have a very highly magnified view of the tumor on all the surrounding blood vessels," continued St. John, who was not involved with the current study. "We no longer had to split people's lips and mandibles to get back to these tumors, and we could have a very fast, functional recovery compared with open surgery."

However, she noted that the clinical evidence at the time had shown that radiation or chemoradiation was the way to treat oropharyngeal carcinoma, evidence based on a substantial amount of data generated from prospective clinical trials. "There had been no prospective data supporting the use of new surgical approaches such as TORS or TLM [transoral laser microsurgery] for oropharyngeal squamous cell carcinoma," she said.

In the current study, the initial trial endpoint was quality of life at 1 year. "And so, if you want to look at what favors radiotherapy in their conclusion at 1 year, look at swallowing functions using the MDADI and other instruments in terms of pain, bleeding, and trismus, but, if you want to favor surgery, you want to think about the side effects of chemotherapy," St. John pointed out.

The study had a modest sample size, and even though it was sufficiently powered, it still only had 68 patients. In terms of surgical expertise, she continued, many of the trials including this one, "have made an important point of really ensuring that the surgeons are all presenting you with data that is valid and that they have experience because all of this could lead to some variation in the data that we gather on the patients."

So the question is, where to go from here, and what does this mean? "I think it's always important to think about what the toxicities are," St. John said. "And what is the risk of leaving something on the table if we de-intensify?"

We still need the knife, but the knife need not be lonely anymore. Dr Maie St. John

"So what I'd like to leave you with is, 'We still need the knife, but the knife need not be lonely anymore,' " St. John concluded. "It's a multidisciplinary approach."

Nichols disclosed research funding from Novartis. St. John has disclosed no relevant financial relationships.

American Society of Clinical Oncology (ASCO) 2019 Annual Meeting: Abstract 6006. Presented May 31, 2019.

For more from Medscape Oncology, join us on Twitter and Facebook

Comments

3090D553-9492-4563-8681-AD288FA52ACE
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as:

processing....