Transoral laser excision is the currently recommended treatment for carcinoma in situ, and RT is the alternative option. For T1-2N0 and selected T3N0, cases amenable for larynx preservation can be treated with radiotherapy (RT) or partial laryngectomy /endoscopic or open surgery as indicated. Persistent residue after RT should be salvaged by appropriate surgery. Patients with residual disease after surgery should undergo re-resection and/or RT/CRT (chemoradiotherapy) depending on the existence of additional adverse factors.

Patients with T3N0-1 disease requiring total laryngectomy should undergo CRT (or RT if not candidate for systemic chemotherapy) or induction chemotherapy (Category 2B) or laryngectomy with ipsilateral thyroidectomy in N0 and laryngectomy with ipsilateral thyroidectomy and ipsilateral/bilateral neck dissection (ND) in N1. Patients with complete response at primary site after RT/CRT should undergo salvage ND if residual neck disease persists. If residual disease persists at primary site, patients should undergo salvage laryngectomy and ND as indicated. In surgically treated patients with adverse features such as ECE (+) or positive margins, adjuvant CRT is indicated with category 1 evidence. RT or CRT should be considered for patients with other risk factors. Further treatment following induction chemotherapy is determined by the response at primary tumor site. Patients with complete response (CR) should receive definitive RT (Category 1). If residual neck disease persists, salvage ND should be performed as indicated. Patients with partial response (PR) at primary site should receive RT (Category 1) or CRT (Category 2B). If residue persists following RT/CRT, salvage surgery is indicated. If primary site response is < PR, surgery is indicated. In such patients, if pathologically ECE (+) or surgical margins (+), CRT is indicated (Category 1). For patients with other risk factors, RT or CRT should be considered.

Patients with T3N2-3 disease requiring total laryngectomy should be treated with either CRT, laryngectomy with ipsilateral thyroidectomy and ipsilateral/bilateral ND, or induction chemotherapy followed by adjuvant treatment determined by response. Additional treatment should be performed similar to T3N1 disease as described above.

Patients with T4aN0-3 should undergo laryngectomy with total thyroidectomy and unilateral/bilateral ND as indicated. Such patients should receive postoperative RT or CRT, observation being reserved only for highly selected patients. For selected T4a patients refusing surgery, CRT or induction chemotherapy followed by RT/CRT is recommended. Any residual neck disease should be salvaged by ND, and residual disease at primary site should further be discussed with the patient for salvage surgery and ND.

T1-2 N0 and selected T3N0 cases amenable for larynx preservation can either be treated with RT or open partial supraglottic laryngectomy /endoscopic resection with/without ND. Persistent residue after RT should be salvaged by appropriate surgery. Patients with residual disease after surgery should undergo re-resection or RT (Category 1) or CRT (Category 2B) depending on the existence of additional adverse features.

Patients with T3N0-1 disease requiring total laryngectomy should undergo CRT (or RT if not candidate for systemic chemotherapy) or induction chemotherapy (Category 2B) or laryngectomy with ipsilateral thyroidectomy and ipsilateral/bilateral ND. Patients with complete response at primary site after RT/CRT should undergo salvage ND if residual neck disease persists. If residual disease persists at primary site, patients should undergo salvage laryngectomy and ND as indicated. In surgically treated patients with pN0 or only single node involvement without other adverse factors, adjuvant RT should be considered. Patients with adverse features such as ECE (+) or positive margins should undergo CRT (Category 1). RT or CRT should be considered for patients with other risk factors. Following induction chemotherapy, further treatment is determined by the response at primary tumor site. Patients with complete response (CR) at primary site should receive definitive RT (Category 1). If residual neck disease persists, salvage ND should be performed. Patients with partial response (PR) at primary site should receive RT (Category 1) or CRT (Category 2B). If residue persists following RT/CRT, salvage surgery is indicated. If primary site response is < PR, surgery is indicated. In such patients, if pathologically ECE (+) or surgical margins (+), CRT is indicated (Category 1). For patients with other risk factors, RT or CRT should be considered.

Patients amenable for organ preserving surgery with T1-2 N1-3 and selected T3N1 disease should be treated with definitive RT or CRT or partial supraglottic laryngectomy and ND or induction chemotherapy. For patients treated with RT or CRT, any residual neck disease should be salvaged by ND, and if residue persists at primary disease site, salvage surgery and ND should be considered as indicated. For surgically treated patients with ECE (+) or margins (+), CRT (Category 1) and RT/CRT for other adverse factors should be considered. Salvage treatment after induction chemotherapy should be performed as described above.

T3N2-3 patients requiring total laryngectomy should be treated with CRT, laryngectomy with ipsilateral thyroidectomy and ND, or induction chemotherapy followed by adjuvant treatment determined by response type as detailed previously. Additional treatment should be performed for either modality similar with to their T3N1 disease as described above.

T4aN0-3 patients should undergo laryngectomy with total thyroidectomy and unilateral/bilateral ND as indicated. Such patients should receive postoperative RT or CRT, observation being reserved only for highly selected patients. For selected T4a patients refusing surgery, CRT or induction chemotherapy followed by RT/CRT is recommended. Any residual neck disease should be salvaged by ND, and residual disease at primary site should further be discussed with the patient for salvage surgery and ND.

Subglottic tumors are exceedingly rare, accounting for only 2 % of all laryngeal cancers. Most patients present with advanced disease (T3-4 N+). Definitive RT, CRT, and surgery are treatment options for such patients. If surgery is chosen, total laryngectomy should be performed regarding the tumor location and invasion of thyroid and/or cricoid cartilages. Postoperative RT/CRT should be considered to increase locoregional control rates. Salvage surgery is indicated in any patient with residual primary or neck disease.

Stage of disease is the strongest prognostic factor for laryngeal carcinoma (Table 9.1). Among staging parameters, M-stage determines the survival, while T- and N-stage are strong predictors of local control and distant metastasis, respectively. Female patients, in general, do better than male counterparts.

Functional larynx preservation without any decrease in local control and survival rates is the ultimate goal of any treatment directed to any stage of laryngeal carcinoma.

Although stripping and RT are options for carcinoma in situ, early RT should be preferred because recurrence is frequent and hoarsening of the voice may become evident due to cord thickening after repeated stripping. Additionally, many patients with carcinoma in situ have obvious lesions that probably contain invasive carcinoma, and early RT will spare many patients from repeat biopsy and many others from unavoidable RT.

Transoral laser excision and RT are options for T1 and T2 glottic tumors. As the voice quality is inversely related with the quantity of tissue removed, RT is the first choice of treatment in many centers, surgery being reserved for RT failures. Five years local control rates following RT are in the range of 85–95 % for T1 and 60–89 % for T2 tumors [1].

There is a direct association between the overall treatment time and local control rates for laryngeal carcinoma patients treated with definitive RT. Longer treatment duration related with lower dose per fraction in the range of 1.8–1.9 Gy results in poorer local control rates compared to same total doses with >2 Gy per fraction. In a prospective randomized study reported by Yamazaki et al., authors compared 2 Gy/fr (n = 89) and 2.25 Gy/fr (n = 91) and reported significantly higher local control rates with 2.25 Gy/fr (94 % vs. 77 %; p = 0.004) [2].

As respective 5-year isolated neck recurrence rates are 0, 3, and 8 % for T1, T2A, and T2B patients, neck treatment is not indicated [3]. Achievement of local control is of extreme importance as neck recurrences increase up to 20–25 % in primary disease site recurrences, which may be a sign of distant metastasis and poor survival [4].

Similar with glottic cancers, early supraglottic cancers can be treated with either of transoral laser excision, open surgery, or RT. As local control and voice quality outcomes are similar many centers prefer RT as the initial management option. In a series of 274 T1-2 supraglottic larynx cancer patients treated with RT demonstrated excellent 5-year local control (T1 = 100 % vs. T2 = 86 %) and cause specific survival (T1 = 100 % vs. T2 = 93 %) rates [5].

For locally advanced laryngeal carcinoma, total laryngectomy, induction chemotherapy followed by surgery or RT/CRT, and concurrent CRT are options for treatment.

The era of larynx preservation with CRT emerged with the publication of Veterans Affairs Laryngeal Cancer Study in 1991 [6]. In this study, 332 stage III or IV laryngeal cancer patients were randomized into induction chemotherapy with cisplatin and fluorouracil followed by RT or surgery followed by RT groups. Although overall 2-year survival rates were 68 % for both groups, larynx was preserved in 64 % of patients in the induction chemotherapy arm. Significant differences between the two groups were seen with fewer local failures in the surgery group (p = 0.0005) and fewer distant metastases in the chemotherapy group (p = 0.016). These results led to a shift in advanced-stage laryngeal cancer treatment toward a primary nonsurgical approach, reserving total laryngectomy for salvage.

The RTOG 91–11 study randomly compared three nonoperative approaches in the treatment of 547 patients with stage III or IV laryngeal cancer: induction chemotherapy (cisplatin and fluorouracil) followed by RT, RT given concurrently with cisplatin, and RT alone [7]. Primary aim was to determine proper timing of chemotherapy (induction vs. concurrent). At 2 years, proportion of patients maintaining an intact larynx was greatest in the concurrent CRT group (88 %), compared to the induction chemotherapy (75 %; p = 0.005) and the RT alone groups (70 %; p < 0.001). Locoregional control was also significantly better in the concurrent CRT group than the induction chemotherapy and RT alone group (78 % vs. 61 % vs. 56 %, respectively). Both chemotherapy arms had longer disease-free survival compared to RT alone. Other randomized studies of larynx preservation are as summarized in Table 9.2.