Discussion

In the past few years, along with prolongation of life expectancy in the general population, the incidence of laryngeal SCC in the elderly population has been rising. In the past year, median age at diagnosis of laryngeal cancer was 65 years. More than 22 per cent of new cases of laryngeal SCC occurred in patients aged over 75 years, and 5.5 per cent were over the age of 84 years. The incidence of laryngeal cancer deaths among patients aged over 75 years and over 84 years was 32.2 per cent and 9.9 per cent, respectively.¹² With an ongoing ageing of the population, we will likely face increasing numbers of very elderly laryngeal cancer patients in the coming years.

The majority of patients with laryngeal SCC will present with advanced disease (stages III and IV) requiring multimodality therapy.^{Reference Argiris and Eng13} This often results in significant acute toxicity and long-term morbidity, which can be profound in older patients, along with their co-morbidities and impaired functional status. Subsequently, older patients are often less likely to receive optimal treatment than younger patients.^{Reference de Rijke, Schouten, Schouten, Jager, Kopperjan and van den Brandt14–Reference Jones19} As long as there is a paucity of clinical trial data available to determine standard management for elderly patients, many may continue to receive non-standard or suboptimal treatment.

At present, recommendations for the management of elderly patients with laryngeal SCC are based on retrospective studies or subset analyses of prospective trials. In primary non-metastatic tumours, surgery and radiotherapy have remained the cornerstones of care.^{Reference Barzan, Veronesi, Caruso, Serraino, Magri and Zagonel3}

The main dilemma in the treatment of this age group concerns the costs versus the benefits of treatment. Curative treatment can include either adequate surgery or radiation with dosage over 60 Gy. However, these treatments may cause temporary side effects, and the question is whether patients will benefit from this attempt or die as a result of it. Another issue is life expectancy at this age regardless of the treatment, and how the treatment or disease will affect this expectancy.

The controversy regarding age as an important factor for treatment selection already existed two decades ago, when Pignon et al.^{Reference Pignon, Horiot, Van den Bogaert, Van Glabbeke and Scalliet16} published a meta-analysis that pooled data from 1589 patients (26 per cent were over 65 years) enrolled in five European Organisation for Research and Treatment of Cancer (‘EORTC’) trials. Survival and toxicity were examined after splitting the database into seven age categories, three of which belonged to the elderly population (65–69 years, 70–75 years and over 75 years). No differences were observed in overall survival, locoregional control, acute objective mucosal reactions, weight loss or late effects. However, functional mucosal reactions, corresponding to symptoms experienced by the patients, were more common in older adults. Although this age dependency disappeared after adjustment for performance status, it was suggested that elderly people might tolerate acute toxicity less well than their younger counterparts.^{Reference Pignon, Horiot, Van den Bogaert, Van Glabbeke and Scalliet16} Several subsequent studies noted higher mortality rates among older patients, but concluded this was due to higher co-morbidity status rather than chronological age.^{Reference Mell, Dignam, Salama, Cohen, Polite and Dandekar20,Reference Ildstad, Tollerud, Bigelow and Remensnyder21}

Many studies have shown that older patients receive suboptimal, less aggressive treatment,^{Reference Olmi and Ausili-Cefaro22–Reference Syrigos, Karachalios, Karapanagiotou, Nutting, Manolopoulos and Harrington24} resulting in lower rates of survival,^{Reference Sesterhenn, Teymoortash, Folz and Werner23,Reference Syrigos, Karachalios, Karapanagiotou, Nutting, Manolopoulos and Harrington24} while others have noted that elderly patients may achieve comparable outcomes when treated with similar therapies as their younger counterparts.^{Reference Bernardi, Barzan, Franchin, Cinelli, Balestreri and Tirelli25–Reference Maggiore, Curran, Witt, Haraf, Vokes and Cohen31}

Derks et al.^{Reference Derks, de Leeuw, Hordijk and Winnubst6} divided elderly patients into two groups (aged 70–79 years, and 80 years or more). The proportions of patients receiving standard treatment in the 45–60 years, 70–79 years, and 80 years or more populations were 89 per cent, 75 per cent and 36 per cent, respectively, whereas no treatment was given to 4 per cent, 13 per cent and 18 per cent of cases from the respective groups.

According to Ortholan et al.,^{Reference Ortholan, Lusinchi, Italiano, Bensadoun, Auperin and Poissonnet32} 59 per cent of 200 patients aged 80 years or more and treated with curative intent including surgery and/or radiation therapy received age-adapted treatment. Other studies have shown that standard treatment with curative intent can be performed safely in elderly patients with a good performance status and without severe co-morbidities.^{Reference Metges, Eschwege, de Crevoisier, Lusinchi, Bourhis and Wibault33,Reference Schofield, Sykes, Slevin and Rashid34}

Other retrospective studies found radiotherapy to be feasible for patients aged 85 years and above, although only some of them (approximately 40 per cent) were able to receive standard treatment according to institution policy, being age-adapted in most patients.^{Reference Zachariah, Balducci, Venkattaramanabalaji, Casey, Greenberg and DelRegato35–Reference Wasil, Lichtman, Gupta and Rush38}

Several studies have shown that radiotherapy is effective and well tolerated in the elderly patient population, and advanced age alone should not be considered a contraindicator for radiation therapy.^{Reference Zachariah, Balducci, Venkattaramanabalaji, Casey, Greenberg and DelRegato35,Reference Yamakawa, Shiojima, Takahashi, Saito, Matsumoto and Mitsuhashi39,Reference Hishikawa, Kurisu, Taniguchi, Kamikonya and Miura40}

Geinitz et al.^{Reference Geinitz, Zimmermann and Molls41} demonstrated a benefit in definitive treatment, even in patients aged over 85 years, with expected survival of more than 4 years, with cure and disease-specific survival rates comparable to those observed in younger patients. The authors highlight the biological and molecular data, which could indicate an increase of ionising radiation sensitivity in the elderly due to a decreased ability to repair DNA damage. They conclude that age itself does not constitute a contraindication for radiotherapy, nor is it an indication for dose reduction.

Another matter of importance concerns fractionation schedules and radiation fields. A large meta-analysis of 15 trials enrolling 6515 SCC head and neck patients, showed that altered radiotherapy, especially hyper-fractionation, improved locoregional control and survival. However, the beneficial effect decreased with advancing age and poor performance status. This was explained by an increased proportion of non-cancer-related deaths in the elderly.^{Reference Geinitz, Zimmermann and Molls41} Therefore, conventional fractionation (1.8–2 Gy per fraction for five to seven weeks) remains the standard of care for these patients.

Transoral laser microsurgery is another treatment strategy for early laryngeal cancer, although, to our knowledge, randomised, prospective trials comparing transoral laser microsurgery with standard external beam radiotherapy are scarce. Feng et al. ^{Reference Feng, Wang and Wen42} conducted a large meta-analysis comparing outcomes associated with the treatment of T₁–T₂ glottic cancer. Their analysis demonstrated no significant difference in cure rates between transoral laser microsurgery and external beam radiotherapy. In the setting of recurrent laryngeal cancer, transoral laser microsurgery provides a useful means of surgical salvage.

The present study describes the patient and tumour characteristics, treatment, and outcome of patients aged over 84 years who received radiotherapy for laryngeal SCC. Most patients received a standard and full radiotherapy regimen. Only three patients had disease recurrence 1–3 years following the end of radiotherapy; two of these patients had survival of 3 years and 7 years, and the median overall survival was 3.55 years, suggesting that fit elderly patients may benefit from standard radiotherapy.

Comparison of the results with those from a younger cohort of patients demonstrates lower rates of tobacco use among elderly patients, as previously reported in literature.^{Reference Koch, Patel, Brennan, Boyle and Sidransky18,Reference Gugić and Strojan43} The very elderly patients with laryngeal cancer in our study tended to be diagnosed with early-stage disease, which differs from findings in other studies.^{Reference Pignon, Horiot, Van den Bogaert, Van Glabbeke and Scalliet16,Reference Mountzios44} Our patients were treated with less chemotherapy, but had similar rates of radiotherapy, implicating less aggressive treatment. The lower rates of recurrence and median overall survival noted in our study may be explained by the older age of our population.

There are several possible strategies for outcome improvement associated with decreasing treatment toxicity in elderly patients, including omitting chemotherapy, and reducing the radiotherapy dose or field. Whether the neck should be prophylactically treated as in younger patients remains unclear. We treated all but two patients without prophylactic radiation to the neck, while all recurrences occurred within the initial gross tumour volume field, suggesting that a better outcome and less toxicity may be achieved by minimising the radiation field in these patients.

The role of chemotherapy given concomitantly to radiation in the elderly population is controversial in the literature.^{Reference Tsukuda, Ishitoya, Mikami, Matsuda, Horiuchi and Taguchi45–Reference Merlano, Monteverde, Colantonio, Denaro, Lo Nigro and Natoli48} In our study, only 3 of 19 patients received chemotherapy, with no significant toxicity. These findings for this small number of patients may be hypothesis-generating, but could not be used to draw a general conclusion.

The present study has certain limitations. Firstly, the small cohort makes it difficult to reach statistical significance. However, to our knowledge, no large-scale randomised clinical trials have examined the outcome of radiotherapy in patients aged over 84 years, and the experience with this population is lacking. Secondly, the long follow-up period of the study may lead to certain ambiguities. Nevertheless, treatment modality, age at diagnosis and mortality should not be affected by this.

In conclusion, fit very elderly patients with laryngeal cancer, who have few co-morbidities and good geriatric performance status scores, may derive a similar survival advantage as their younger counterparts and should be treated irrespective of their age. Radiotherapy with standard regimens in smaller fields should be strongly considered in this patient population. Nevertheless, more large-scale prospective studies are needed.