First-line chemotherapy regimens for advanced or metastatic TCC consists of gemcitabine and cisplatin) (GC) or a combination of methotrexate, vinblastine, adriamycin, and cisplatin (MVAC).

Taxanes or vinflunine have been used as second-line therapy (after progression on a platinum containing chemotherapy).

Immunotherapy such as pembrolizumab is often used as second-line therapy for metastatic urothelial carcinoma that has progressed despite treatment with GC or MVAC.

In May 2016 FDA granted accelerated approval to atezolizumab for locally advanced or metastatic urothelial carcinoma treatment after failure of cisplatin-based chemotherapy. The confirmatory trial (to convert the accelerated approval into a full approval) failed to achieve its primary endpoint of overall survival.

Transitional cell carcinoma (TCC) can be very difficult to treat. Treatment for localized stage TCC is surgical resection of the tumor, but recurrence is common. Some patients are given mitomycin into the bladder either as a one-off dose in the immediate post-operative period (within 24 hrs) or a few weeks after the surgery as a six dose regimen.

Localized/early TCC can also be treated with infusions of BCG into the bladder. These are given weekly for either 6 weeks (induction course) or 3 weeks (maintenance/booster dose). Side effects include a small chance of developing systemic tuberculosis or the patient becoming sensitized to the BCG causing severe intolerance and a possible reduction in bladder volume due to scarring.

In patients with evidence of early muscular invasion, radical curative surgery in the form of a cysto-prostatectomy usually with lymph node sampling can also be performed. In such patients, a bowel loop is often used to create either a "neo-bladder" or an "ileal conduit" which act as a place for the storage of urine before it is evacuated from the body either via the urethra or a urostomy respectively.

Surgical excision or laser therapy are possible treatments. Surgical excision alone was effective for controlling VC, but elective neck dissection was not necessary even in patients in the advanced stages.

LCIS may be treated with close clinical follow-up and mammographic screening, tamoxifen or related hormone controlling drugs to reduce the risk of developing cancer, or bilateral prophylactic mastectomy. Some surgeons consider bilateral prophylactic mastectomy to be overly aggressive treatment except for certain high-risk cases.

Because most bladder cancers are invasive into the bladder wall, surgical removal is usually not possible. The majority of transitional cell carcinomas are treated with either traditional chemotherapy or nonsteroidal anti-inflammatory drugs.

Early radio-sensitive tumors are treated by radiotherapy along with irradiation of cervical nodes. The radiation uses high-energy X-rays, electron beams, or radioactive isotopes to destroy cancer cells.

Induction chemotherapy is the treatment adapted for shrinking the tonsil tumor. It is given prior to other treatments, hence, the term induction. After the therapy is completed, the patient is asked to rest and is evaluated over a period of time. Then the patient is given chemo-radiation therapy (a combination of chemotherapy and radiation) to completely destroy the tumor cells.

Treatment of invasive carcinoma of no special type (NST) depends on the size of the mass (size of the tumor measured in its longest direction):

- <4 cm mass: surgery to remove the main tumor mass and to sample the lymph nodes in the axilla. The stage of the tumor is ascertained after this first surgery. Adjuvant therapy (i.e., treatment after surgery) may include a combination of chemotherapy, radiotherapy, hormonal therapy (e.g., tamoxifen) and/or targeted therapy (e.g., trastuzumab). More surgery is occasionally needed to complete the removal of the initial tumor or to remove recurrences.

- 4 cm or larger mass: modified (a less aggressive form of radical mastectomy) radical mastectomy (because any malignant mass in excess of 4 cm in size exceeds the criteria for a lumpectomy) along with sampling of the lymph nodes in the axilla.

The treatment options offered to an individual patient are determined by the form, stage and location of the cancer, and also by the age, history of prior disease and general health of the patient. Not all patients are treated the same way.

Most conjunctival squamous cell carcinomas are removed with surgery. A few selected cases are treated with topical medication. Surgical excision with a free margin of healthy tissue is a frequent treatment modality. Radiotherapy, given as external beam radiotherapy or as brachytherapy (internal radiotherapy), can also be used to treat squamous cell carcinomas.

Carcinoma "in situ" is, by definition, a localized phenomenon, with no potential for metastasis unless it progresses into cancer. Therefore, its removal eliminates the risk of subsequent progression into a life-threatening condition.

Some forms of CIS (e.g., colon polyps and polypoid tumours of the bladder) can be removed using an endoscope, without conventional surgical resection. Dysplasia of the uterine cervix is removed by excision (cutting it out) or by burning with a laser. Bowen's disease of the skin is removed by excision. Other forms require major surgery, the best known being intraductal carcinoma of the breast (also treated with radiotherapy). One of the most dangerous forms of CIS is the "pneumonic form" of BAC of the lung, which can require extensive surgical removal of large parts of the lung. When too large, it often cannot be completely removed, with eventual disease progression and death of the patient.

Immunotherapy research suggests that treatment using "Euphorbia peplus", a common garden weed, may be effective. Australian biopharmaceutical company Peplin is developing this as topical treatment for BCC. Imiquimod is an immunotherapy but is listed here under chemotherapy.

Cervical cancers can recur with symptoms of vaginal bleeding and/or discharge, pelvic pain, pain in the back and legs, leg swelling (edema), chronic cough and weight loss. It can recur in the vagina, pelvis, lymph nodes, lung, or liver. “If radiation was not given previously, recurrences that are confined to the pelvis may be treated with external beam radiation with chemotherapy and intracavitary or interstitial radiation therapy. If radiation therapy was already given, the only option is the removal of the vagina, uterus, and the bladder and/or rectum with the creation of an artificial bladder-a pelvic exenteration. The five-year survival rate after a pelvic exenteration is about 50 percent.” (womenscancercenter.com) Chemotherapy is useful in women with recurrent tumors which cannot be removed surgically or in women with metastatic diseases. Chances of survival of chemotherapy, if diagnosed in early stage, is grater than 50%.

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.

Wide, radical, complete surgical excision is the treatment of choice, with free surgical margins to achieve the best outcome and lowest chance of recurrence. Radiation is only used for palliation. In general, there is a good prognosis, although approximately 50% of patients die from disease within 3–10 years of presentation.

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

This type of carcinoma is commonly managed by local resection, cryotherapy, topical chemotherapy, and radiotherapy. Multimodal therapy has been shown to improve both visual prognosis and survival.

Mohs micrographic surgery has become the treatment of choice for this form of cancer. When used as the primary treatment modality for sebaceous carcinoma of the eyelid, Mohs surgery is associated with significantly lower local and distant recurrence rates.

Radiotherapy is commonly used to treat Merkel-cell cancers. The radiotherapy fields used are usually very large so as to cover sufficient areas of skin. This is necessary because of MCC's aggressive local and regional metastatic behavior.

Adjuvant radiotherapy has been shown to be effective in reducing the rates of recurrence and in increasing the survival of patients with MCC. Patients who present with no distant metastases and a negative sentinel lymph node biopsy have a very good prognosis when treated with both surgery and radiotherapy (approximately 90% survival rate at five years).

Metastatic MCC may respond to treatment with chemotherapy and/or radiation, but current multimodal therapies are usually not curative. Intensive treatment can be effective in shrinking the tumor and improving operability when tumors are too large to be removed or located in a place where removal would be difficult or dangerous, or in palliation of signs and symptoms caused by metastatic tumors.

NUT midline carcinoma is very resistant to standard chemotherapy treatments. The tumor may initially respond to therapy, and then rapid recurrence is experienced, followed by death. A multimodality approach to treatment is advocated, especially since most patients present with advanced disease. Treatment must be tailored to the individual patient, with several promising new targeted molecular therapies in clinical trials. Specific molecular targeted therapies (BET inhibitors and histone deacetylase inhibitors (HDACi)) may help to yield growth arrest of the neoplastic cells. Overall, there is a mean survival of 6–9 months.

Surgery is usually the first treatment that a patient undergoes for Merkel-cell cancer. Lesions usually appear purple-red in color, and there is little else to distinguish this variant of skin cancer from other types. Its identity usually comes as a surprise after surgery and pathologic examination.

As with surgery for most other forms of cancer, it is normal for the surgeon to remove a border of healthy tissue surrounding the tumor. While it has been thought that leaving this margin may not be as critical as it is in the surgical resection of melanoma, studies also reveal that local recurrences are fairly common in MCC near the site of the surgery.

Local or regional lymph nodes are usually removed if the lesion is more than 1 cm in diameter, due to a high risk that they will contain cancer cells (micrometastasis) that could develop into a new tumor or spread further. Sometimes, however, the doctor will first perform a sentinel lymph node biopsy. In this procedure, the doctor injects a dye or radioactive substance near the tumor. This material flows into adjacent lymph nodes, which are identified, removed, and checked for cancer cells, indicating the sites where cancer is most likely to spread (the "sentinel" nodes). This procedure has been demonstrated to be an important prognostic indicator. Results help dictate the use of appropriate adjuvant therapies. Usually, however, surgery alone is insufficient to control Merkel-cell carcinoma.

Most squamous cell carcinomas are removed with surgery. A few selected cases are treated with topical medication. Surgical excision with a free margin of healthy tissue is a frequent treatment modality. Radiotherapy, given as external beam radiotherapy or as brachytherapy (internal radiotherapy), can also be used to treat squamous cell carcinomas.

Mohs surgery is frequently utilized; considered the treatment of choice for squamous cell carcinoma of the skin, physicians have also utilized the method for the treatment of squamous cell carcinoma of the mouth, throat, and neck. An equivalent method of the CCPDMA standards can be utilized by a pathologist in the absence of a Mohs-trained physician. Radiation therapy is often used afterward in high risk cancer or patient types.

Electrodessication and curettage or EDC can be done on selected squamous cell carcinoma of the skin. In areas where SCC's are known to be non-aggressive, and where the patient is not immunosuppressed, EDC can be performed with good to adequate cure rate.

High-risk squamous cell carcinoma, as defined by those occurring around the eye, ear, or nose, is of large size, is poorly differentiated, and grows rapidly, requires more aggressive, multidisciplinary management.

Nodal spread:

1. Surgical block dissection if palpable nodes or in cases of Marjolin's ulcers but the benefit of prophylactic block lymph node dissection with Marjolin's ulcers is not proven.

2. Radiotherapy

3. Adjuvant therapy may be considered in those with high-risk SCC even in the absence of evidence for local mestastasis. Imiquimod (Aldara) has been used with success for squamous cell carcinoma "in situ" of the skin and the penis, but the morbidity and discomfort of the treatment is severe. An advantage is the cosmetic result: after treatment, the skin resembles normal skin without the usual scarring and morbidity associated with standard excision. Imiquimod is not FDA-approved for any squamous cell carcinoma.

In general, squamous cell carcinomas have a high risk of local recurrence, and up to 50% do recur. Frequent skin exams with a dermatologist is recommended after treatment.

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

Appropriate sun-protective clothing, use of broad-spectrum (UVA/UVB) sunscreen with at least SPF 50, and avoidance of intense sun exposure may prevent skin cancer.

Nasopharyngeal carcinoma can be treated by surgery, by chemotherapy, or by radiotherapy. The expression of EBV latent proteins within undifferentiated nasopharyngeal carcinoma can be potentially exploited for immune-based therapies.

Treatment may include the following:

- Surgery with or without radiation

- Radiotherapy

Fast neutron therapy has been used successfully to treat salivary gland tumors, and has shown to be significantly more effective than photons in studies treating unresectable salivary gland tumors.

- Chemotherapy

Cancers often grow in an unbridled fashion because they are able to evade the immune system. Immunotherapy is a method that activates the person's immune system and uses it to their own advantage. It was developed after observing that in some cases there was spontaneous regression. Immunotherapy capitalises on this phenomenon and aims to build up a person's immune response to cancer cells.

Other targeted therapy medications inhibit growth factors that have been shown to promote the growth and spread of tumours. Most of these medications were approved within the past 10 years. These treatments are:

- Nivolumab

- Axitinib

- Sunitinib

- Cabozantinib

- Everolimus

- Lenvatinib

- Pazopanib

- Bevacizumab

- Sorafenib

- Temsirolimus

- Interleukin-2 (IL-2) has produced "durable remissions" in a small number of patients, but with substantial toxicity.

- Interferon-α

Activity has also been reported for ipilimumab but it is not an approved medication for renal cancer.

More medications are expected to become available in the near future as several clinical trials are currently being conducted for new targeted treatments, including: atezolizumab, varlilumab, durvalumab, avelumab, LAG525, MBG453, TRC105, and savolitinib.