Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

glottic or supraglottic

1st line – laryngeal-sparing surgery (± neck dissection) or radiation therapy

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ACUTE
|
glottic or supraglottic
|
T1 or T2: N0 M0
1st line – 

laryngeal-sparing surgery (± neck dissection) or radiation therapy

Treatment in T1 and T2 N0 M0 tumors involves single-modality treatment with surgery or radiation therapy.[1]​ Larynx-sparing surgery (e.g., endoscopic laser resection, transoral robotic surgery, laryngofissure, cordectomy, vertical partial laryngectomy) or radiation therapy are equally effective in terms of tumor control and survival.[39]

Neck dissection is usually performed in addition to surgery in T1-T2 N0 M0 supraglottic tumors, although some patients may elect not to do a neck dissection for T1 N0 M0 tumors. Neck dissection may also be needed in addition to surgery in certain T1-T2 N0 M0 glottic tumors.[1]

In glottic tumors, larynx-sparing surgery is reported to have local cancer control rates ranging from 86% to 98% and a 5-year disease-specific survival rate of 92% to 97%.[40] Although the data vary, larynx-sparing surgery and radiation therapy for treatment of T1 and T2 laryngeal cancers show similar survival rates.​[42][43]​​ In experienced hands, endoscopic resection of T1 lesions has been shown to yield better outcomes than definitive radiation therapy.[43] However, one systematic review showed similar voice outcomes between surgery and radiation therapy.[39]​ Single-mode treatment of T1 laryngeal cancer with radiation therapy has a similar survival rate to surgery.

For carcinoma in situ, endoscopic resection is preferred if possible.[1]​ For patients with adverse features on final pathology (i.e., close or positive margins, extranodal extension, etc.), adjuvant therapy is also recommended.

In supraglottic tumors, open or endoscopic surgery is comparable to radiation therapy alone, although some report that there is a higher local control rate with surgery.[43] For patients with T1 and T2 cancers, transoral microlaser surgery or transoral robotic surgery should be offered where possible as a treatment option in addition to open surgery, other larynx-sparing surgeries, and radiation therapy.[63] There is insufficient evidence to determine whether the endoscopic surgical techniques are superior to radiation therapy but the vocal and quality of life outcomes for radiation therapy and transoral laser surgery appear to be equivalent.[44][45][46]​  

Plus – post-treatment speech rehabilitation

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ACUTE
|
glottic or supraglottic
|
T1 or T2: N0 M0
Plus – 

post-treatment speech rehabilitation

Treatment recommended for ALL patients in selected patient group

Speech therapy is appropriate after surgery, radiation therapy, chemoradiotherapy, or any combination of these modalities. All patients should be screened for dysphagia during intake, treatment course, and survivorship. There are validated dysphagia tools for assessment.[38]

1st line – partial or total laryngectomy (+ neck dissection) or radiation therapy or chemoradiotherapy

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ACUTE
|
glottic or supraglottic
|
T1 or T2: N1-N2c M0
1st line – 

partial or total laryngectomy (+ neck dissection) or radiation therapy or chemoradiotherapy

Patients with N1-N2c M0 staging (N1 M0, N2a M0, N2b M0, or N2c M0) have more deeply invasive lesions with regional lymph node metastases ≤6 cm in size but no distant metastases.

Laryngeal surgery (with partial or total laryngectomy) or radiation therapy or concurrent chemotherapy and radiation therapy is recommended.[1]

Cisplatin or carboplatin may be given with or without fluorouracil.[1]​ In cases of excessive toxicity, patients may be treated with the monoclonal antibody cetuximab. Adjuvant chemotherapy may be used postoperatively for certain unfavorable tumor characteristics (e.g., angiolymphatic or perineural invasion, extracapsular spread).[47] 

Neck dissection is recommended for patients undergoing laryngectomy prior to adjuvant radiation therapy or chemoradiotherapy.[48]

See local specialist protocol for chemotherapy dosing guidelines.

Primary options

cisplatin

OR

carboplatin

OR

cisplatin

or

carboplatin

-- AND --

fluorouracil

OR

cetuximab

Plus – post-treatment speech rehabilitation

Back
ACUTE
|
glottic or supraglottic
|
T1 or T2: N1-N2c M0
Plus – 

post-treatment speech rehabilitation

Treatment recommended for ALL patients in selected patient group

Speech therapy is appropriate after surgery, radiation therapy, chemoradiotherapy, or any combination of these modalities. All patients should be screened for dysphagia during intake, treatment course, and survivorship. There are validated dysphagia tools for assessment.[38]

1st line – partial or total laryngectomy (+ neck dissection) or chemoradiotherapy

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ACUTE
|
glottic or supraglottic
|
T3: N0-N2c M0
1st line – 

partial or total laryngectomy (+ neck dissection) or chemoradiotherapy

Patients with N0-N2c M0 staging have either no regional or distant lymph node metastases (N0 M0) or regional lymph node metastases ≤6 cm in size but no distant metastases (N1 M0, N2a M0, N2b M0, or N2c M0).

Treatment in T3 tumors involves either concurrent chemotherapy and radiation therapy or surgery.

Partial or total laryngectomy can be used depending on location and size of the tumor; partial laryngectomy allows for preservation of speech and swallowing function in highly selected cases. The choice between surgery and concurrent chemoradiotherapy for patients with primary T3 tumors is a matter of debate.[49][50]​ Chemoradiotherapy has the advantage of allowing better preservation of speech and swallowing function if the alternative option requires total laryngectomy. However, a retrospective observational cohort study of over 7000 patients from the National Cancer Database found that, in patients with T3 laryngeal cancer, those treated with chemoradiotherapy had a significantly increased risk for death compared with those treated with total laryngectomy (hazard ratio=1.18; P=0.03).[49] Radiation alone, however, has been shown to be inferior to the above-mentioned therapies for T3 and T4 tumors.​[49][51][52]​ 

Cisplatin (preferred) or carboplatin may be given with or without fluorouracil.[1]​ In cases of excessive toxicity, patients may be treated with the monoclonal antibody cetuximab. However, the addition of cetuximab to cisplatin in combination with radiation does not improve outcome compared with radiation plus cisplatin only.[53] Similarly, altered fractionated radiation plus cisplatin does not confer any advantage over standard cisplatin chemoradiation.[54]

Other chemotherapy options for T3 tumors to be given concurrently with radiation therapy include: fluorouracil/hydroxyurea, carboplatin/paclitaxel, cisplatin/paclitaxel, docetaxel, or docetaxel/cetuximab.[1][55]​​

Neck dissection is recommended for persistent neck disease after chemoradiotherapy and in patients undergoing laryngectomy with clinically positive neck disease.[48] The role of neck dissection following chemoradiotherapy, however, remains controversial.[56]

Adjuvant chemotherapy may be used postoperatively for certain unfavorable tumor characteristics (e.g., positive margins, >4 lymph nodes, extracapsular spread).[47] 

Locoregional control and larynx preservation were found to be significantly improved with concomitant chemoradiation compared with induction chemotherapy followed by radiation therapy or compared with radiation therapy alone.[57]

However, induction chemotherapy, with management based on response, remains an option for all but T1-T2 N0 glottic and supraglottic cancer.[1]

See local specialist protocol for chemotherapy dosing guidelines.

Primary options

cisplatin

OR

carboplatin

OR

cisplatin

or

carboplatin

-- AND --

fluorouracil

OR

fluorouracil

and

hydroxyurea

OR

cisplatin

or

carboplatin

-- AND --

paclitaxel

OR

docetaxel

OR

docetaxel

and

cetuximab

OR

cetuximab

Plus – post-treatment speech rehabilitation

Back
ACUTE
|
glottic or supraglottic
|
T3: N0-N2c M0
Plus – 

post-treatment speech rehabilitation

Treatment recommended for ALL patients in selected patient group

Speech therapy is appropriate after surgery, radiation therapy, chemoradiotherapy, or any combination of these modalities. All patients should be screened for dysphagia during intake, treatment course, and survivorship. There are validated dysphagia tools for assessment.[38]

1st line – total laryngectomy (± neck dissection) or chemoradiotherapy or radiation therapy

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ACUTE
|
glottic or supraglottic
|
T4 or N3 or M1: suitable for definitive treatment
1st line – 

total laryngectomy (± neck dissection) or chemoradiotherapy or radiation therapy

Patients with N3 staging have regional lymph node metastases >6 cm. Patients with M1 staging have distant metastases. Treatment involves either concurrent chemotherapy and radiation therapy or surgery. Neck dissection and adjuvant (postoperative) radiation therapy may also be required. For M1 disease, surgery is not usually first-line treatment.

Chemoradiotherapy or surgery are equally effective if cartilage is not involved. Total laryngectomy is recommended over concurrent chemotherapy and radiation therapy if cartilage is involved.​[58] In cases of cartilage invasion, positive or close margins, multiple positive cervical lymph nodes, or extracapsular extension of disease, adjuvant (postoperative) chemoradiotherapy is recommended. Neck dissection after chemoradiotherapy is recommended for persistent neck disease and in patients undergoing laryngectomy with clinically positive neck disease.[48] The role of neck dissection following chemoradiotherapy in an N0 neck, however, remains controversial.[56] Good local control has been demonstrated after open partial laryngectomy in patients with radiorecurrent laryngeal cancer, although the technique is not widely practiced in this setting.[59]

The choice of chemotherapy agents for patients receiving definitive treatment is the same as for T3 tumors.[1] Adjuvant chemoradiotherapy may be used postoperatively for certain unfavorable tumor characteristics (e.g., angiolymphatic or perineural invasion, extracapsular spread).[47]

The preferred regimen is high-dose cisplatin, or a combination of carboplatin plus fluorouracil. Other recommended regimens include weekly cisplatin, or carboplatin plus paclitaxel. In addition, the following regimens may be potentially useful: a combination of fluorouracil plus hydroxyurea; cetuximab; a combination of cisplatin plus fluorouracil or paclitaxel; or docetaxel (if cisplatin ineligible).[1]

​​​ Immunotherapy with pembrolizumab or nivolumab may also be recommended for unresectable tumors.[1] ​Subcutaneous nivolumab/hyaluronidase may be substituted for intravenous nivolumab.[1]

Locoregional control and larynx preservation were found to be significantly improved with concomitant chemoradiation compared with induction chemotherapy followed by radiation therapy or compared with radiation therapy alone.[57]

Some patients with limited metastases at initial presentation may be candidates for surgery, concurrent chemotherapy and radiation therapy, or radiation therapy alone.[1]

Some patients with T4 tumors that are unresectable, but with no metastases, may be candidates for concurrent chemotherapy and radiation therapy, or induction chemotherapy followed by radiation therapy, or radiation therapy alone.[1] If a patient’s performance status is poor, then they may be offered palliative radiation therapy, single-agent systemic therapy, or best supportive care.[1]

See local specialist protocol for chemotherapy dosing guidelines.

Primary options

cisplatin

OR

carboplatin

and

fluorouracil

Secondary options

carboplatin

and

paclitaxel

OR

fluorouracil

and

hydroxyurea

OR

cetuximab

OR

cisplatin

-- AND --

fluorouracil

or

paclitaxel

OR

docetaxel

Tertiary options

nivolumab

OR

nivolumab/hyaluronidase

OR

pembrolizumab

Plus – post-treatment speech rehabilitation

Back
ACUTE
|
glottic or supraglottic
|
T4 or N3 or M1: suitable for definitive treatment
Plus – 

post-treatment speech rehabilitation

Treatment recommended for ALL patients in selected patient group

Speech therapy is appropriate after surgery, radiation therapy, chemoradiotherapy, or any combination of these modalities. All patients should be screened for dysphagia during intake, treatment course, and survivorship. There are validated dysphagia tools for assessment.[38]

Consider – postoperative chemoradiotherapy

Back
ACUTE
|
glottic or supraglottic
|
T4 or N3 or M1: suitable for definitive treatment
Consider – 

postoperative chemoradiotherapy

Treatment recommended for SOME patients in selected patient group

In cases of cartilage invasion, positive or close margins, multiple positive cervical lymph nodes, or extracapsular extension of disease, adjuvant (postoperative) chemoradiotherapy is recommended. See local specialist protocol for dosing guidelines.

1st line – systemic therapy

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ACUTE
|
glottic or supraglottic
|
T4 or N3 or M1: not suitable for definitive treatment but candidate for systemic therapy
1st line – 

systemic therapy

Patients who have unresectable or metastatic disease and no options for surgery or radiation therapy may nonetheless be candidates for systemic therapy. A patient’s performance status may limit the systemic options available to them. Those with a higher Eastern Cooperative Oncology Group (ECOG) score (i.e., >2) will have to weigh the risks and benefits of treatment toxicity. First-line regimens recommended by US guidelines include: pembrolizumab with a platinum compound (cisplatin or carboplatin) and fluorouracil; or pembrolizumab monotherapy (for tumors that express programmed death-ligand 1 [PD-L1] with a combined positive score [CPS] ≥1).[1]

Subsequent line (if not previously used): nivolumab (if disease progression on or after platinum therapy); pembrolizumab (if disease progression on or after platinum therapy).[1] Subcutaneous nivolumab/hyaluronidase may be substituted for intravenous nivolumab.[1]

Other recommended first and subsequent-line regimens include combination therapy or single agents. Options for combination therapy include: cetuximab with platinum compound (cisplatin or carboplatin) and fluorouracil; cisplatin with cetuximab; a platinum compound (cisplatin or carboplatin) with docetaxel or paclitaxel; cisplatin with fluorouracil; a platinum compound (cisplatin or carboplatin) with docetaxel and cetuximab; a platinum compound (cisplatin or carboplatin) with paclitaxel and cetuximab; pembrolizumab with a platinum compound (cisplatin or carboplatin) and docetaxel; or pembrolizumab with a platinum compound (cisplatin or carboplatin) and paclitaxel.[1]

Single-agent options include cisplatin, carboplatin, paclitaxel, docetaxel, fluorouracil, methotrexate, cetuximab, capecitabine, or afatinib.[1]

Patients for whom no treatment options have been effective or who are not candidates for therapy should be offered supportive care (e.g., pain control, counseling).

See local specialist protocol for chemotherapy dosing guidelines.

Primary options

pembrolizumab

-- AND --

cisplatin

or

carboplatin

-- AND --

fluorouracil

OR

pembrolizumab

OR

cetuximab

-- AND --

cisplatin

or

carboplatin

-- AND --

fluorouracil

OR

cisplatin

and

cetuximab

OR

cisplatin

or

carboplatin

-- AND --

paclitaxel

or

docetaxel

OR

cisplatin

and

fluorouracil

OR

cisplatin

or

carboplatin

-- AND --

docetaxel

or

paclitaxel

-- AND --

cetuximab

OR

pembrolizumab

-- AND --

cisplatin

or

carboplatin

-- AND --

docetaxel

or

paclitaxel

OR

cisplatin

OR

carboplatin

OR

docetaxel

OR

paclitaxel

OR

fluorouracil

OR

methotrexate

OR

cetuximab

OR

capecitabine

OR

afatinib

Secondary options

nivolumab

OR

nivolumab/hyaluronidase

OR

pembrolizumab

Plus – post-treatment speech rehabilitation

Back
ACUTE
|
glottic or supraglottic
|
T4 or N3 or M1: not suitable for definitive treatment but candidate for systemic therapy
Plus – 

post-treatment speech rehabilitation

Treatment recommended for ALL patients in selected patient group

Speech therapy is appropriate after surgery, radiation therapy, chemoradiotherapy, or any combination of these modalities. All patients should be screened for dysphagia during intake, treatment course, and survivorship. There are validated dysphagia tools for assessment.[38]

subglottic

1st line – chemoradiation or total laryngectomy plus adjuvant radiation therapy with or without chemotherapy

Back
ACUTE
|
subglottic
1st line – 

chemoradiation or total laryngectomy plus adjuvant radiation therapy with or without chemotherapy

Treatment of these subglottic tumors should be discussed at a multidisciplinary tumor board and may be treated with chemoradiation or by total laryngectomy and neck dissection surgery (including thyroidectomy) followed by radiation therapy, with or without chemotherapy.

Plus – post-treatment speech rehabilitation

Back
ACUTE
|
subglottic
Plus – 

post-treatment speech rehabilitation

Treatment recommended for ALL patients in selected patient group

Speech therapy is appropriate after surgery, radiation therapy, chemoradiotherapy, or any combination of these modalities. All patients should be screened for dysphagia during intake, treatment course, and survivorship. There are validated dysphagia tools for assessment.[38]

ONGOING

treatment not effective/appropriate

1st line – palliative care

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ONGOING
|
treatment not effective/appropriate
1st line – 

palliative care

Patients for whom no treatment options have been effective or who are not candidates for therapy should be offered supportive care.

Consider – chemotherapy or immunotherapy or molecular targeted therapies

Back
ONGOING
|
treatment not effective/appropriate
Consider – 

chemotherapy or immunotherapy or molecular targeted therapies

Treatment recommended for SOME patients in selected patient group

Chemotherapy can be used in combination therapy or as single agents in palliative circumstances. In addition, patients with advanced cancer who are not candidates for systemic chemotherapy may nonetheless benefit from immunotherapy or molecular targeted therapies, which may relieve symptoms and/or improve quality of life with fewer adverse effects than cytotoxic chemotherapy.

1st line – surgical salvage ± postoperative re-irradiation ± chemotherapy

Back
ONGOING
|
treatment not effective/appropriate
1st line – 

surgical salvage ± postoperative re-irradiation ± chemotherapy

Surgical salvage is the standard of care in patients with recurrent disease that is considered resectable and who are surgical candidates.[62]

Postoperative re-irradiation may be considered. In patients re-irradiated with curative intent, the addition of chemotherapy is typically used.[62]

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Choose a patient group to see our recommendations

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

Use of this content is subject to our disclaimer