Modest survival benefits have been reported in patients with advanced laryngeal cancer treated with surgery rather than chemotherapy or radiation therapy, according to new research, but a number of factors may limit any broad change in recommendations, and patients need to be fully informed based on multidisciplinary input.
That is the conclusion of a new study, now online ahead of print in JAMA Otolaryngology Head and Neck Surgery (doi:10.1001/jamaoto.2014.1671), which investigated treatment and outcomes data on 5,394 patients with stages III or IV laryngeal squamous cell carcinoma between 1992 and 2009, using the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database.
After adjusting for year of diagnosis, age, cancer stage, gender, race, marital status, and laryngeal subsite, the researchers found a 30 percent higher risk of mortality among patients treated with chemotherapy or radiation therapy alone, compared with their counterparts who underwent surgical excision.
Among subgroups, stage III cancer, glottic subsite, female gender, and married status appeared to have a positive impact on disease-specific and overall survival, whereas age and African origin had a negative impact.
Patients who had surgery had better two-year and five-year disease-specific survival rates (70 vs. 64 percent and 55 vs. 51 percent, respectively) and overall survival (64 vs. 57 percent and 44 vs. 39 percent, respectively) than patients who did not undergo surgery. Nonsurgical treatment increased over time: 32 percent in the 1992-to-1997 patient group, 45 percent in the 1998-to-2003 group, and 62 percent in the 2004-to-2009 group.
The gap in survival between the two groups consistently narrowed in recent years: Patients who were diagnosed between 2004 and 2009 had longer survival than those diagnosed earlier—likely due to improvements in radiation and chemotherapy strategies, the researchers speculated. The rate of chemo/radiation therapy increased steadily to about 60 percent.
Possible Reasons for the Differences
The lead author of the report, Uchechukwu C. Megwalu, MD, Assistant Professor of Otolaryngology, Head and Neck Surgery at Icahn School of Medicine at Mount Sinai Hospital, Queens Hospital Center in Jamaica, NY, noted that although the database does not include many details about patient treatment, possible reasons for the findings include poor patient selection for surgical versus non-surgical treatment, inadequate patient follow-up and/or incomplete treatment, and interrupted treatment sessions.
“There are several potential reasons for the differences between patients in clinical trials and those treated in ‘real world’ settings,” he said. “The most significant is that patients in clinical trials tend to have better survival, so we have to be careful in interpreting such findings with patients in general.”
Such patients are more likely to receive more consistent treatment and follow-up than others, and clinical trials have strict inclusion criteria for performance status and other medical conditions, so patients in trials are, on average, healthier from the outset, he said.
“This means that results from randomized clinical trials may not directly translate to patients treated in the community setting. In the real world, these risk factors cannot be tightly controlled. Also, survival outcomes of cancer patients may depend on the expertise of those treating them. Trials are usually conducted by experts, but the average provider may not have the necessary expertise. This also includes follow-up of patients treated with chemo/radiation therapy.”
He also noted that the one clinical trial comparing surgical therapy to organ preservation included patients treated at Veterans Administration facilities. While those authors did not specify how many women were included, it is likely that the majority of the patients were men.
The psychosocial aspects of surgery also need to be better addressed, Megwalu continued, noting that many cancer patients have trouble navigating the health care system: “It takes a long time to complete chemo/radiation, and these patients often delay or do not complete their treatment. I believe this is a recipe for disaster as well as a good area for future research. I also think that we really need to be more selective when referring patients for chemo/radiation.”
In addition to survival, the decision to undergo surgical versus non-surgical treatment also needs to take into account quality-of-life considerations, he said. “About 64 percent of patients who underwent chemo/radiation in the VA study were able to preserve their voice box, which is attractive, although with surgical removal they can still talk using a vocal prosthesis. However, patients need to know that there is a slightly lower rate of survival. Right now many are being told that surgery and chemo/radiation are equivalent, but in the real world this may not be the case.”
He noted that although patients in the analysis were not randomized, “we feel the data does present a good estimate of what is going on in the U.S. population. I think that it is a fair representation.”
A population-based study available online ahead of print in The Laryngoscope (doi:10.1002/lary.24658), examined trends in the use of laryngectomy versus chemoradiation, also using the SEER database. The researchers, led by Caitriona B. O'Neill, MBA, PhD, of the Center for Health Policy and Outcomes at Memorial Sloan Kettering Cancer Center, discovered that the proportion of patients who received total laryngectomy fell from 74 percent in 1999 to 26 percent by 2007.
In addition, nearly 20 percent of chemoradiation patients underwent tracheostomy after treatment and 57 percent required a feeding tube. Moreover, total laryngectomy was associated with an 18 percent lower risk of death after adjustment for patient and disease characteristics.
Asked for her perspective for this article, Hong Zhang, MD, PhD, Chief of Radiation Oncology at Highland Hospital and Associate Professor at the University of Rochester Medical Center, said that she doubts the findings will change treatment decision-making. The SEER database, she pointed out, does not provide information on patients' performance status or other medical conditions, or why individuals received surgical or non-surgical treatment or had concurrent chemotherapy with radiation.
“We do not know the radiation treatment fields and doses and whether there were any interruptions during radiation treatment,” she said. “The database also does not provide information about how closely these patients were followed after completing treatment. Although there is a very small survival difference observed in this study between individuals having surgery and conservation treatment, the finding should not change the current practice.”
Zhang said that several factors need to be considered in opting for chemoradiation therapy. For example, at her center, a multidisciplinary team looks at the tumor's location and extent, and patient characteristics such as age, performance status, medical comorbidities, and social support before recommending surgery or an organ-preservation approach.
“Quality of life is always a consideration,” she continued. “This is extremely important. Patients who plan to undergo non-organ-preserving surgery must be told that there will be alteration of breathing and speech. Physicians need to take all of this into consideration when recommending treatment options.”
The take-home message, she said, is that laryngeal cancer is a very challenging disease to treat and the survival difference between surgery and an organ-preservation approach is quite minimal, if any, in the modern era, with careful patient selection and a skilled comprehensive care team.
“The investigators have done a very interesting study and the findings underscore the challenge of treating patients with laryngeal cancer, but ultimately the choice of treatment should be made by the patient, with the support of multidisciplinary care team,” she concluded.
“One size does not fit all when it comes to options, and every patient is different.”