If the tumor is operable, the first line of therapy should be surgical resection. Then, after surgical resection, adjuvant chemotherapy should be given, even in stage I disease. In patients with inoperable disease, chemotherapy alone should be given. A multi-disciplinary approach to the treatment, including surgeons, oncologists, pathologists, radiologists, and radiation oncologists, is often the best approach to managing these patients.

a) Surgical resection is mainstay of treatment, whenever possible. If tumor is completely removed, post-operative radiation therapy is typically not needed since acinic cell is considered a low-grade histology. Post-operative radiation therapy for acinic cell carcinoma is used if: 1) margins are positive, 2) incomplete resection, 3) tumor invades beyond gland, 4) positive lymph nodes.

b) Neutron beam radiation

c) Conventional radiation

d) Chemotherapy

In general, treatment for PanNET encompasses the same array of options as other neuroendocrine tumors, as discussed in that main article. However, there are some specific differences, which are discussed here.

In functioning PanNETs, octreotide is usually recommended prior to biopsy or surgery but is generally avoided in insulinomas to avoid profound hypoglycemia.

PanNETs in MEN1 are often multiple, and thus require different treatment and surveillance strategies.

Some PanNETs are more responsive to chemotherapy than are gastroenteric carcinoid tumors. Several agents have shown activity. In well differentiated PanNETs, chemotherapy is generally reserved for when there are no other treatment options. Combinations of several medicines have been used, such as doxorubicin with streptozocin and fluorouracil (5-FU) and capecitabine with temozolomide. Although marginally effective in well-differentiated PETs, cisplatin with etoposide has some activity in poorly differentiated neuroendocrine cancers (PDNECs), particularly if the PDNEC has an extremely high Ki-67 score of over 50%.

Several targeted therapy agents have been approved in PanNETs by the FDA based on improved progression-free survival (PFS):

- everolimus (Afinitor) is labeled for treatment of progressive neuroendocrine tumors of pancreatic origin in patients with unresectable, locally advanced or metastatic disease. The safety and effectiveness of everolimus in carcinoid tumors have not been established.

- sunitinib (Sutent) is labeled for treatment of progressive, well-differentiated pancreatic neuroendocrine tumors in patients with unresectable locally advanced or metastatic disease. Sutent also has approval from the European Commission for the treatment of 'unresectable or metastatic, well-differentiated pancreatic neuroendocrine tumors with disease progression in adults'. A phase III study of sunitinib treatment in well differentiated pNET that had worsened within the past 12 months (either advanced or metastatic disease) showed that sunitinib treatment improved progression-free survival (11.4 months vs. 5.5 months), overall survival, and the objective response rate (9.3% vs. 0.0%) when compared with placebo.

Surgery, if feasible, is the only curative therapy. If the tumor has metastasized (most commonly, to the liver) and is considered incurable, there are some promising treatment modalities, such as radiolabeled octreotide (e.g. Lutetium (Lu) DOTA-octreotate) or the radiopharmaceutical 131I-mIBG (meta iodo benzyl guanidine) for arresting the growth of the tumors and prolonging survival in patients with liver metastases, though these are currently experimental.

Chemotherapy is of little benefit and is generally not indicated. Octreotide or Lanreotide (somatostatin analogues) may decrease the secretory activity of the carcinoid, and may also have an anti-proliferative effect. Interferon treatment is also effective, and usually combined with somatostatin analogues.

As the metastatic potential of a coincidental carcinoid is probably low, the current recommendation is for follow up in 3 months with CT or MRI, labs for tumor markers such as serotonin, and a history and physical, with annual physicals thereafter.

Even if the tumor has advanced and metastasized, making curative surgery infeasible, surgery often has a role in neuroendocrine cancers for palliation of symptoms and possibly increased lifespan.

Cholecystectomy is recommended if there is a consideration of long-term treatment with somatostatin analogs.

In secretory tumors, somatostatin analogs given subcutaneously or intramuscularly alleviate symptoms by blocking hormone release. A consensus review has reported on the use of somatostatin analogs for GEP-NETs.

These medications may also anatomically stabilize or shrink tumors, as suggested by the PROMID study (Placebo-controlled prospective randomized study on the antiproliferative efficacy of Octreotide LAR in patients with metastatic neuroendocrine MIDgut tumors): at least in this subset of NETs, average tumor stabilization was 14.3 months compared to 6 months for placebo.

The CLARINET study (a randomized, double-blind, placebo-controlled study on the antiproliferative effects of lanreotide in patients with enteropancreatic neuroendocrine tumors) further demonstrated the antiproliferative potential of lanreotide, a somatostatin analog and recently approved FDA treatment for GEP-NETS. In this study, lanreotide showed a statistically significant improvement in progression-free survival, meeting its primary endpoint. The disease in sixty five percent of patients treated with lanreotide in the study had not progressed or caused death at 96 weeks, the same was true of 33% of patients on placebo. This represented a 53% reduction in risk of disease progression or death with lanreotide based on a hazard ratio of .47.

Lanreotide is the first and only FDA approved antitumor therapy demonstrating a statistically significant progression-free survival benefit in a combined population of patients with GEP-NETS.

Other medications that block particular secretory effects can sometimes relieve symptoms.

ACC can be treated with a Whipple procedure or (depending on the location within the pancreas) with left partial resection of pancreas.

These lesions rarely require surgery unless they are symptomatic or the diagnosis is in question. Since these lesions do not have malignant potential, long-term observation is unnecessary. Surgery can include the removal of the head of the pancreas (a pancreaticoduodenectomy), removal of the body and tail of the pancreas (a distal pancreatectomy), or rarely removal of the entire pancreas (a total pancreatectomy). In selected cases the surgery can be performed using minimally invasive techniques such as laparoscopy.

In ES-SCLC, combination chemotherapy is the standard of care, with radiotherapy added only to palliate symptoms such as dyspnea, pain from liver or bone metastases, or for treatment of brain metastases, which, in small-cell lung carcinoma, typically have a rapid, if temporary, response to whole brain radiotherapy.

Combination chemotherapy consists of a wide variety of agents, including cisplatin, cyclophosphamide, vincristine and carboplatin. Response rates are high even in extensive disease, with between 15% and 30% of subjects having a complete response to combination chemotherapy, and the vast majority having at least some objective response. Responses in ES-SCLC are often of short duration, however.

If complete response to chemotherapy occurs in a subject with SCLC, then prophylactic cranial irradiation (PCI) is often used in an attempt to prevent the emergence of brain metastases. Although this treatment is often effective, it can cause hair loss and fatigue. Prospective randomized trials with almost two years follow-up have not shown neurocognitive ill-effects. Meta-analyses of randomized trials confirm that PCI provides significant survival benefits.

Complete radical surgical resection is the treatment of choice for EMECL, and in most cases, results in long-term survival or cure.

Since Krukenberg tumors are secondary (metastatic), management might logically be driven by identifying and treating the primary cancer. The optimal treatment of Krukenberg tumors is unclear. The role of surgical resection has not been adequately addressed but if metastasis is limited to the ovaries, surgery may improve survival. The role of chemotherapy and/or radiotherapy is uncertain but may sometimes be beneficial.

For treatment purposes, MCACL has been traditionally considered a non-small cell lung carcinoma (NSCLC). Complete radical surgical resection is the treatment of choice.

There is virtually no data regarding new molecular targets or targeted therapy in the literature to date. Iwasaki and co-workers failed to find mutations of the epidermal growth factor receptor (EGFR) or the cellular Kirsten rat sarcoma virus oncogene "K-ras" in one reported case.

In cases of LS-SCLC, combination chemotherapy (often including cyclophosphamide, cisplatinum, doxorubicin, etoposide, vincristine and/or paclitaxel) is administered together with concurrent chest radiotherapy (RT).

Chest RT has been shown to improve survival in LS-SCLC.

Exceptionally high objective initial response rates (RR) of between 60% and 90% are seen in LS-SCLC using chemotherapy alone, with between 45% and 75% of individuals showing a "complete response" (CR), which is defined as the disappearance of all radiological and clinical signs of tumor. However, relapse rate remains high, and median survival is only 18 to 24 months.

Because SCLC usually metastasizes widely very early on in the natural history of the tumor, and because nearly all cases respond dramatically to chemotherapy and/or radiotherapy, there has been little role for surgery in this disease since the 1970s. However, recent work suggests that in cases of small, asymptomatic, node-negative SCLC's ("very limited stage"), surgical excision may improve survival when used prior to chemotherapy ("adjuvant chemotherapy").

Several drugs that target molecular pathways in lung cancer are available, especially for the treatment of advanced disease. Erlotinib, gefitinib and afatinib inhibit tyrosine kinase at the epidermal growth factor receptor. Denosumab is a monoclonal antibody directed against receptor activator of nuclear factor kappa-B ligand. It may be useful in the treatment of bone metastases.

After surgery, adjuvant chemotherapy with gemcitabine or 5-FU can be offered if the person is sufficiently fit, after a recovery period of one to two months. In people not suitable for curative surgery, chemotherapy may be used to extend life or improve its quality. Before surgery, neoadjuvant chemotherapy or chemoradiotherapy may be used in cases that are considered to be "borderline resectable" (see Staging) in order to reduce the cancer to a level where surgery could be beneficial. In other cases neoadjuvant therapy remains controversial, because it delays surgery.

Gemcitabine was approved by the United States Food and Drug Administration (FDA) in 1997, after a clinical trial reported improvements in quality of life and a 5-week improvement in median survival duration in people with advanced pancreatic cancer. This was the first chemotherapy drug approved by the FDA primarily for a nonsurvival clinical trial endpoint. Chemotherapy using gemcitabine alone was the standard for about a decade, as a number of trials testing it in combination with other drugs failed to demonstrate significantly better outcomes. However, the combination of gemcitabine with erlotinib was found to increase survival modestly, and erlotinib was licensed by the FDA for use in pancreatic cancer in 2005.

The FOLFIRINOX chemotherapy regimen using four drugs was found more effective than gemcitabine, but with substantial side effects, and is thus only suitable for people with good performance status. This is also true of protein-bound paclitaxel (nab-paclitaxel), which was licensed by the FDA in 2013 for use with gemcitabine in pancreas cancer. By the end of 2013, both FOLFIRINOX and nab-paclitaxel with gemcitabine were regarded as good choices for those able to tolerate the side-effects, and gemcitabine remained an effective option for those who were not. A head-to-head trial between the two new options is awaited, and trials investigating other variations continue. However, the changes of the last few years have only increased survival times by a few months. Clinical trials are often conducted for novel adjuvant therapies.

Chemotherapy has relatively poor curative efficacy in SRCC patients and overall survival rates are lower compared to patients with more typical cancer pathology. SRCC cancers are usually diagnosed during the late stages of the disease, so the tumors generally spread more aggressively than non-signet cancers, making treatment challenging. In the future, case studies indicate that bone marrow metastases will likely play a larger role in the diagnosis and management of signet ring cell gastric cancer.

In SRCC of the stomach, removal of the stomach cancer is the treatment of choice. There is no combination of chemotherapy which is clearly superior to others, but most active regimens include 5-Fluorouracil (5-FU), Cisplatin, and/or Etoposide. Some newer agents, including Taxol and Gemcitabine (Gemzar) are under investigation.

In a single case study of a patient with SRCC of the bladder with recurrent metastases, the patient exhibited a treatment response to palliative FOLFOX-6 chemotherapy.

Several treatments can be administered via bronchoscopy for the management of airway obstruction or bleeding. If an airway becomes obstructed by cancer growth, options include rigid bronchoscopy, balloon bronchoplasty, stenting, and microdebridement. Laser photosection involves the delivery of laser light inside the airway via a bronchoscope to remove the obstructing tumor.

The role of radiotherapy as an auxiliary (adjuvant) treatment after potentially curative surgery has been controversial since the 1980s. The European Society for Medical Oncology recommends that adjuvant radiotherapy should only be used for people enrolled in clinical trials. However, there is a continuing tendency for clinicians in the US to be more ready to use adjuvant radiotherapy than those in Europe. Many clinical trials have tested a variety of treatment combinations since the 1980s, but have failed to settle the matter conclusively.

Radiotherapy may form part of treatment to attempt to shrink a tumor to a resectable state, but its use on unresectable tumors remains controversial as there are conflicting results from clinical trials. The preliminary results of one trial, presented in 2013, "markedly reduced enthusiasm" for its use on locally advanced tumors.

Surgery and radiation therapy have been the major treatments for medullary thyroid carcinoma.

Clinical trials of protein kinase inhibitors, which block the abnormal kinase proteins involved in the development and growth of medullary cancer cells, showed clear evidence of response in 10-30% of patients. In the majority of responders there has been less than a 30% decrease in tumor mass, yet the responses have been durable; responses have been stable for periods exceeding 3 years. The major side effects of this class of drug include hypertension, nausea, diarrhea, some cardiac electrical abnormalities, and thrombotic or bleeding episodes.

Vandetanib, trade name Caprelsa, was the first drug (April 2011) to be approved by US Food and Drug Administration (FDA) for treatment of late-stage (metastatic) medullary thyroid cancer in adult patients who are ineligible for surgery.

Cabozantinib, trade name Cometriq, was granted marketing approval (November 2012) by the U.S. FDA for this indication. Cabozantinib which is a potent inhibitor of RET, MET and VEGF was evaluated in a double-blind placebo controlled trial. It was shown to improve overall survival by 5 months for the treated cohort vs. placebo, which was not statistically significant. However, cabozantinib was particularly effective in patients with the RET M918T mutation, extending overall survival by roughly 2 years, doubling survival vs. untreated patient (4 years vs. 2 year). Treatment with cabozantinib did require many dose reduction to mitigate side effects. It has been suggested that the trial dose of 140 mg was excessive, particularly in lower body mass patients. Ongoing trials have been scheduled to identify more optimal dosing regimes. Activity has been observed, in practice at doeses of 1.2 mg/kg.

Photodynamic therapy (PDT) is a new modality for treatment of basal-cell carcinoma, which is administrated by application of photosensitizers to the target area. When these molecules are activated by light, they become toxic, therefore destroy the target cells. Methyl aminolevulinate is approved by EU as a photosensitizer since 2001. This therapy is also used in other skin cancer types. The 2008 study reported that PDT was a good treatment option for primary superficial BCCs, reasonable for primary low-risk nodular BCCs, but a 'relatively poor' option for high-risk lesions.

Radiation therapy can be delivered either as external beam radiotherapy or as brachytherapy (internal radiotherapy). Although radiotherapy is generally used in older patients who are not candidates for surgery, it is also used in cases where surgical excision will be disfiguring or difficult to reconstruct (especially on the tip of the nose, and the nostril rims). Radiation treatment often takes as few as 5 visits to as many as 25 visits. Usually, the more visits scheduled for therapy, the less complication or damage is done to the normal tissue supporting the tumor. Radiotherapy can also be useful if surgical excision has been done incompletely or if the pathology report following surgery suggests a high risk of recurrence, for example if nerve involvement has been demonstrated. Cure rate can be as high as 95% for small tumor, or as low as 80% for large tumors. Usually, recurrent tumors after radiation are treated with surgery, and not with radiation. Further radiation treatment will further damage normal tissue, and the tumor might be resistant to further radiation. Radiation therapy may be contraindicated for treatment of nevoid basal-cell carcinoma syndrome. The 2008 study reported that radiation therapy is a good treatment for primary BCCs and recurrent BCCs, but not for BCCs that have recurred following previous radiation treatment.

Based on overall cancer staging into stages I to IV, papillary thyroid cancer has a 5-year survival rate of 100 percent for stages I and II, 93 percent for stage III and 51 percent for stage IV.

Because of its rarity, there have been no randomized clinical trials of treatment of GCCL, and all information available derives from small retrospective institutional series or multicenter metadata.

Surgery remains the mainstay of treatment for papillary thyroid cancer. The Revised 2009 American Thyroid Association guidelines for papillary thyroid cancer state that the initial procedure should be near-total or total thyroidectomy. Thyroid lobectomy alone may be sufficient treatment for small (<1 cm), low-risk, unifocal, intrathyroidal papillary carcinomas in the absence of prior head and neck irradiation or radiologically or clinically involved cervical nodal metastasis.

- Minimal disease (diameter up to 1.0 centimeters) - hemithyroidectomy (or unilateral lobectomy) and isthmectomy may be sufficient. There is some discussion whether this is still preferable over total thyroidectomy for this group of patients.

- Gross disease (diameter over 1.0 centimeters) - total thyroidectomy, and central compartment lymph node removal is the therapy of choice. Additional lateral neck nodes can be removed at the same time if an ultrasound guided FNA and thyroglobulin TG cancer washing was positive on the pre-operative neck node ultrasound evaluation.

Arguments for total thyroidectomy are:

- Reduced risk of recurrence, if central compartment nodes are removed at the original surgery.

- 30-85% of papillary carcinoma is multifocal disease. Hemithyroidectomy may leave disease in the other lobe. However, multifocal disease in the remnant lobe may not necessarily become clinically significant or serve as a detriment to patient survival.

- Ease of monitoring with thyroglobulin (sensitivity for picking up recurrence is increased in presence of total thyroidectomy, and ablation of the remnant normal thyroid by low dose radioiodine 131 after following a low iodine diet (LID).

- Ease of detection of metastatic disease by thyroid and neck node ultrasound.

- Post-operative complications at high-volume thyroid surgery centers with experienced surgeons are comparable to that of hemithyroidectomy.

Arguments for hemithyroidectomy:

- Most patients have low-risk cancer with an excellent prognosis, with similar survival outcomes in low-risk patients who undergo total thyroidectomy versus hemithyroidectomy.

- Less likelihood of patient requiring lifelong thyroid hormone replacement after surgery.

Thyroid total body scans are less reliable at finding recurrence than TG and ultrasound.

Papillary tumors tend to be more aggressive in patients over age 45. In such cases, it might be required to perform a more extensive resection including portions of the trachea. Also, the sternocleidomastoid muscle, jugular vein, and accessory nerve are to be removed if such procedure allows apparently complete tumor resection. If a significant amount of residual tumor is left in the neck, external radiotherapy has been indicated and has proven useful especially in those cases when the residual tumor does not take up radioiodine.

After surgical thyroid removal, the patient waits around 4–6 weeks to then have radioiodine therapy. This therapy is intended to both detect and destroy any metastasis and residual tissue in the thyroid. The treatment may be repeated 6–12 months after initial treatment of metastatic disease where disease recurs or has not fully responded.

Patients are administered hormone replacement levothyroxine for life after surgery, especially after total thyroidectomy. Chemotherapy with cisplatin or doxorubicin has proven limited efficacy, however, it could be helpful for patients with bone metastases to improve their quality of life. Patients are also prescribed levothyroxine and radioiodine after surgery. Levothyroxine influences growth and maturation of tissues and it is involved in normal growth, metabolism, and development. In case of metastases, patients are prescribed antineoplastic agents which inhibit cell growth and proliferation and help in palliating symptoms in progressive disease.

After successful treatment, 35 percent of the patients may experience a recurrence within a 40-year span. Also, patients may experience a high incidence of nodule metastasis, with 35 percent cases of cervical node metastases. Approximately 20 percent of patients will develop multiple tumors within the thyroid gland.

There is ongoing discussion regarding the best management regarding the optimal surgical procedure for papillary thyroid cancer. Prognosis of patients with papillary thyroid cancer is found to be dependent on the patient's age, the size of the tumor, presence of metastatic disease, and the presence of tumor invasion into adjacent tissues near the thyroid gland. Recent studies have examined a more conservative approach to surgery and have demonstrated that hemithyroidectomy may be acceptable for patients with low-risk papillary thyroid cancer with tumor size 1 cm to 4 cm with no presence of invasion to tissues surrounding the thyroid or metastasis. Studies examining large databases of patients with papillary thyroid cancer have concluded that there is no survival advantage for patients with stage I papillary thyroid cancer size 1–4 cm receiving total thyroidectomy versus hemithyroidectomy. In light of this data, choosing the optimal course of surgical and medical management of papillary thyroid cancer should involve shared decision making from patient, endocrinologists, and surgeons.