F. Christopher Holsinger, MD, FACS, is Assistant Professor and Attending Surgeon in the Department of Head and Neck Surgery at The University of Texas M.D. Anderson Cancer Center in Houston.
For years, radical surgery was the only treatment for head and neck cancer (HNSCC). For intermediate and even early-stage disease, there were few surgical options that could achieve reproducible oncologic and functional results, especially for patients with laryngopharyngeal cancer. For instance, the indications for time-honored approaches in conservation surgery were limited: the supraglottic horizontal laryngectomy (SGL) and vertical partial laryngectomy (VPL) were excellent operations, but narrow selection criteria confined these procedures to infrequent use. As a result, radically ablative surgical approaches were more commonly used when optimal local and regional control was the goal.
Yet, in the 1980s, management of the neck was evolving, and the modified radical dissection, followed later by the selective cervical lymphadenectomy, became accepted oncologic yet function-sparing procedures. But there were no coincident evolution and few innovations for the management of the primary tumor. Bigger was still better when it came to managing the primary tumor. Microvascular reconstruction permitted larger and more generous resections. But despite large resections and their mutilating sequelae, postoperative radiation therapy was still needed for optimal local and regional control. This endgame in surgery may have perhaps led to a search for better options for patients with head and neck cancer.
In 1991, the Department of Veterans Affairs Laryngeal Cancer Study demonstrated equivalence in overall survival between patients treated with total laryngectomy with postoperative radiation therapy compared with patients treated with induction chemotherapy and radiation.1 Since this landmark study, primary nonsurgical treament has assumed a greater role in the treatment of patients with head and neck cancer. With the advent of improvements in radiotherapy (RT) such as intensity-modulated RT and the advent of concurrent chemotherapy with radiation, more treatment options are available to patients. In 2003, with the publication of the RTOG 91-11 study,2 the standard treatment for intermediate to advanced stage laryngeal cancer became concurrent chemotherapy with radiation therapy (cRT). By then, the paradigm had changed and the cRT approach was routinely used for all subsites within the head and neck. With a few exceptions, the head and neck surgeon became predominantly a salvage surgeon, managing cancer in the oral cavity and the neck. Applications to training programs in head and neck surgical oncology plummeted to an all-time low.
As otolaryngologists-head and neck surgeons, we manage the long-term sequelae of patients with HNSCC, whether treated with surgery, radiation alone, or concurrent chemoradiation. With aggressive cRT approaches, some patients perform remarkably well, with excellent oncological results and functional sequelae limited to xerostomia and mild dysphagia. Inexplicably, others do much worse. While avoiding the mutilating sequelae of radical surgical approaches, these combined cRT approaches for organ preservation can be associated with extensive morbidity, leading to adverse functional speech and swallowing outcomes. At least an important minority of patients treated with cRT end up with a preserved anatomic organ, but with significant functional compromise, necessitating tracheotomy and/or gastrostomy. Worse still, for those patients treated with cRT who later require salvage total laryngectomy, postoperative complications are increased but survival is significantly diminished.3
Despite these risks inherent in treatment selection, there are no criteria to predict favorable outcomes, oncologically or functionally. Yet with little knowledge of the underlying biology of the HNSCC and virtually no understanding about which patients respond to this cRT approach, we forge on with this nonsurgical paradigm.
Striking a Balance
Are we starting to see a swing of the pendulum? Are we beginning to move away from a reflexive radical nonsurgical approach, perhaps not back to surgery only as the predominant treatment modality, but to a healthy and mature happy medium?
Many have questioned whether the goal for therapy should be striking a balance between the expectation of oncological control and function preservation, rather than simply preserving the organ. In all three disciplines-medical oncology, radiation oncology, and head and neck surgery-risk-based stratification is an important emerging concept in treatment selection.
With intensity-modulated radiation therapy (IMRT), the toxicity of external-beam therapy may be limited to the target tissues, sparing salivary function and collateral damage. But is in-field morbidity higher? How much does IMRT reduce xerostomia? In medical oncology, with the publication of the Bonner trial, cetuximab has emerged an alternative to platin-based chemotherapy. But is this approach on par with concurrent platin-based therapy?
At the same time, conservation surgery of the head and neck has enjoyed a quiet renaissance. Transoral laser microsurgery and supracricoid partial laryngectomies (SCPLs) have been established as viable approaches to treat laryngeal carcinoma. Both European and American schools have developed in the practice of transoral laser microsurgery. Radical or mutilating ablative procedures are no longer the only surgical options. Function-preserving surgery is now a real option for our patients. But are there enough surgeons properly trained to do it? The fiberoptic carbon dioxide laser4 and transoral robotic surgery (TORS)5 are important new tools in the hands of a new generation of head and neck surgeons. However, despite numerous single-institution studies, no Phase III RCT multi-institutional studies have been published examining the efficacy of these new open and endoscopic approaches. Surgical technique and expertise vary from center to center. Can surgeons even perform a randomized trial? The ACOSOG trial in SLN mapping (Z0360) suggests that prospective clinical trials can be done in otolaryngology-head and neck surgery.
How to Reach the Center
Regardless of the discipline, new techniques and technologies are available for patients with head and neck cancer. And so the pendulum is swinging back.
But to where? Hopefully to a balanced center, where treatment decisions are made using evidence-based data and scientific inquiry, focusing foremost on oncologic efficacy but also considering functional outcome.
To avoid the unpredictable consequences of either surgical or nonsurgical radicalism and to embrace a new risk-based approach, we must learn more about the disease we treat.
Surprisingly, little is known about which HNSCC patients respond to chemotherapy and radiation. Whereas systemic therapy for breast cancer is given based on a panel of well-known biomarkers, including estrogen, progesterone, and HER2/neu expression, there are no such biomarkers are currently used in the treatment of head and neck cancer. The role of epidermal growth factor receptor has been explored, but at present molecular targeted therapies are just now being introduced.
As a solid tumor, the molecular heterogeneity of HNSCC has confounded the identification of clinically useful prognostic biomarkers. Since survival is equivocal regardless of a primary surgical or nonsurgical approach, treatment is often based on the desire to avoid morbidity. Patients and their physicians are essentially wagering for organ preservation, rather than basing choices on data-although, in some cases, the numbers are good.
Do all patients respond the same to radiation therapy? Do certain patients tend to develop fibrosis and others not? Which patients respond to platin-based chemotherapy? Which to taxanes? Such questions are being studied actively in several laboratories around the country but a larger and focused effort will be necessary to identify a robust panel of these biomarkers.
To achieve these goals, a multidisciplinary team is crucial. As leaders of that team, head and neck surgeons must establish the criteria for treatment selection and provide tissue for study. Most important, we must lead the clinical trials to establish this new standard of care.
- Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. The Department of Veterans Affairs Laryngeal Cancer Study Group. N Engl J Med 1991;324;1685-90.
- Forastiere AA et al. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med 2003;349:2091-8.
- Weber RS et al. Outcome of salvage total laryngectomy following organ preservation therapy: the Radiation Therapy Oncology Group trial 91-11. Arch Otolaryngol Head Neck Surg 2003;129:44-9.
- Temelkuran B et al. Wavelength-scalable hollow optical fibres with large photonic bandgaps for CO2 laser transmission. Nature 2002;420:650-3.
- Hockstein NG, O’Malley BW Jr, Weinstein GS. Assessment of intraoperative safety in transoral robotic surgery. Laryngoscope 2006:116:165-8.
©2006 The Triological Society