Almost all patients require multidrug chemotherapy (often including ifosfamide and etoposide), as well as local disease control with surgery and/or radiation. An aggressive approach is necessary because almost all patients with apparently localized disease at the time of diagnosis actually have asymptomatic metastatic disease.

Treatment often consists of neoadjuvant chemotherapy, which may include vincristine, doxorubicin, and cyclophosphamide with ifosfamide and etoposide. After about three months of chemotherapy, the remaining tumor is surgically resected, irradiated, or both. The surgical resection may involve limb salvage or amputation. Complete excision at the time of biopsy may be performed if malignancy is confirmed at the time it is examined.

Treatment lengths vary depending on location and stage of the disease at diagnosis. Radical chemotherapy may be as short as six treatments at 3-week cycles, but most patients undergo chemotherapy for 6–12 months and radiation therapy for 5–8 weeks.

Radiotherapy has been used for localized disease. The tumor has a unique property of being highly sensitive to radiation, sometimes acknowledged by the phrase "melting like snow", but the main drawback is that it recurs dramatically after some time. Antisense oligodeoxynucleotides have been proposed as possible treatment by down-regulating the expression of the oncogenic fusion protein associated with the development of Ewing's sarcoma resulting from the EWS-ETS gene translocation. In addition, the synthetic retinoid derivative fenretinide (4-hydroxy(phenyl)retinamide) has been reported to induce high levels of cell death in Ewing's sarcoma cell lines "in vitro" and to delay growth of xenografts in "in vivo" mouse models.

Treatment is usually multimodal, involving surgery, chemotherapy and radiotherapy:

- Surgery, to remove the tumor and a safety margin of healthy tissue. This is the mainstay of synovial sarcoma treatment and is curative in approximately 20–70% of patients, depending on the particular study being quoted.

- Conventional chemotherapy, (for example, doxorubicin hydrochloride and ifosfamide), to reduce the number of remaining microscopic metastases. The benefit of chemotherapy in synovial sarcoma to overall survival remains unclear, although a recent study has shown that survival of patients with advanced, poorly differentiated disease marginally improves with doxorubicin/ifosfamide treatment.

- Radiotherapy to reduce the chance of local recurrence. The benefit of radiotherapy in this disease is less clear than for chemotherapy.

Treatment consists of surgical excision (the extent of which ranges from tumor excision to limb amputation, depending on the tumor) and in almost all cases radiation. Radiation eliminates the need for limb amputation and there is level I evidence to show that it leads to equivalent rates of survival (Rosenberg et al. NCI Canada). Radiation may be delivered either pre-op or post-op depending on surgeon and multidisciplinary tumor board's recommendations. Radiation can be omitted for low grade, Stage I excised tumors with >1 cm margin (NCCN). Chemotherapy remains controversial in MFH.

The usual site of metastatic disease is the lungs, and metastases should be resected if possible. Unresectable or inoperable lung metastasis may be treated with stereotactic body radiation therapy (SBRT) with excellent local control. However, neither surgery nor SBRT will prevent emergence of additional metastasis elsewhere in the lung. Therefore, role of chemotherapy needs to be further explored to address systemic metastasis.

In general, treatment for soft-tissue sarcomas depends on the stage of the cancer. The stage of the sarcoma is based on the size and grade of the tumor, and whether the cancer has spread to the lymph nodes or other parts of the body (metastasized). Treatment options for soft-tissue sarcomas include surgery, radiation therapy, and chemotherapy.

- Surgery is the most common treatment for soft-tissue sarcomas. If possible, the doctor will remove the cancer and a safe margin of the healthy tissue around it. It is important to obtain a margin free of tumor to decrease the likelihood of local recurrence and give the best chance for eradication of the tumor. Depending on the size and location of the sarcoma, it may, rarely, be necessary to remove all or part of an arm or leg.

- Radiation therapy may be used either before surgery to shrink tumors or after surgery to kill any cancer cells that may have been left behind. In some cases, it can be used to treat tumours that cannot be surgically removed. In multiple studies, radiation therapy has been found to improve the rate of local control, but has not had any influence on overall survival.

- Chemotherapy may be used with radiation therapy either before or after surgery to try to shrink the tumor or kill any remaining cancer cells. The use of chemotherapy to prevent the spread of soft-tissue sarcomas has not been proven to be effective. If the cancer has spread to other areas of the body, chemotherapy may be used to shrink tumors and reduce the pain and discomfort they cause, but is unlikely to eradicate the disease.

Treatment depends upon the site and the extent of the disease. Clear cell sarcoma is usually treated with surgery in the first place in order to remove the tumor. The surgical procedure is then followed by radiation and sometimes chemotherapy. Few cases of clear cell sarcoma respond to chemotherapy. Several types of targeted therapy that may be of benefit to clear cell sarcoma patients are currently under investigation.

Surgery is important in the treatment of most sarcomas. Limb sparing surgery, as opposed to amputation, can now be used to save the limbs of patients in at least 90% of extremity tumor cases. Additional treatments, including chemotherapy and radiation therapy, may be administered before and/or after surgery. Chemotherapy significantly improves the prognosis for many sarcoma patients, especially those with bone sarcomas. Treatment can be a long and arduous process, lasting about a year for many patients.

- Liposarcoma treatment consists of surgical resection, with chemotherapy not being used outside of the investigative setting. Adjuvant radiotherapy may also be used after surgical excision for liposarcoma.

- Rhabdomyosarcoma is treated with surgery, radiotherapy, and/or chemotherapy. The majority of rhabdomyosarcoma patients have a 50–85% survival rate.

- Osteosarcoma is treated with surgical resection of as much of the cancer as possible, often along with neoadjuvant chemotherapy. Radiotherapy is a second alternative although not as successful.

In women, chemotherapy may damage the ovaries and cause infertility. To avail future pregnancies, the woman may preserve oocytes or ovarian tissue by oocyte cryopreservation or ovarian tissue cryopreservation prior to starting chemotherapy. However, the latter may reseed the cancer upon reinsertion of the ovarian tissue. If it is performed, the ovarian tissue should be examined for traces of malignancy at both the pathological and molecular levels prior to the grafting of the cryopreserved tissue.

Kaposi sarcoma is not curable, but it can often be treatable for many years. In KS associated with immunodeficiency or immunosuppression, treating the cause of the immune system dysfunction can slow or stop the progression of KS. In 40% or more of peoples with AIDS-associated Kaposi sarcoma, the Kaposi lesions will shrink upon first starting highly active antiretroviral therapy (HAART). However, in a certain percentage of such people, Kaposi sarcoma may again grow after a number of years on HAART, especially if HIV is not completely suppressed.

People with a few local lesions can often be treated with local measures such as radiation therapy or cryosurgery. Weak evidence suggests that antiretroviral therapy in combination with chemotherapy is more effective than either of those two therapies individually. Limited basic and clinical evidence suggest that topical beta-blockers, such as timolol, may induce regression of localized lesions in classic as well as HIV-associated Kaposi sarcoma. In general, surgery is not recommended, as Kaposi sarcoma can appear in wound edges. In general, more widespread disease, or disease affecting internal organs, is treated with systemic therapy with interferon alpha, liposomal anthracyclines (such as Doxil) or paclitaxel.

Treatment is primarily surgical, with chemotherapy and radiation therapy sometimes used.

The NCCN guideline recommends CCPDMA or Mohs surgery for the best cure rate of DFSP. Mohs surgery can be extremely effective. It will remove the tumor and all related pathological cells without a wide-area excision that may overlook sarcoma cells that have penetrated muscle tissue.

The standard of care for patients with DFSP is surgery. Usually, complete surgical resection with margins of 2 to 4 cm (recommended) is performed. The addition of adjuvant radiotherapy (irradiation) improves local control in patients with close or positive margins during the surgery. A special surgical technique, the "Mohs micrographic surgery" (MMS), can be employed in patients with DFSP. MMS is technically possible if the DFSP is in an anatomically confined area. A high probability of cure of DFSP can be attained with MMS as long as the final margins are negative. Patients who have a recurrent DFSP can have further surgery, but the probability of adverse effects of surgery and/or metastasis is increased in these patients. The Mohs surgery is highly successful.

Imatinib is approved for treatment. As is true for all medicinal drugs that have a name that ends in "ib," imatinib is a small molecular pathway inhibitor; imatinib inhibits tyrosine kinase. It may be able to induce tumor regression in patients with recurrent DFSP, unresectable DFSP or metastatic DFSP. There is clinical evidence that imatinib, which inhibits PDGF-receptors, may be effective for tumors positive for the t(17;22) translocation.

Treatment of rhabdomyosarcoma is a multidisciplinary practice involving the use of surgery, chemotherapy, radiation, and possibly immunotherapy. Surgery is generally the first step in a combined therapeutic approach. Resectability varies depending on tumor site, and RMS often presents in sites that don't allow for full surgical resection without significant morbidity and loss of function. Less than 20% of RMS tumors are fully resected with negative margins. Fortunately, rhabdomyosarcomas are highly chemosensitive, with approximately 80% of cases responding to chemotherapy. In fact, multi-agent chemotherapy is indicated for all patients with rhabdomyosarcoma. Before the use of adjuvant and neoadjuvant therapy involving chemotherapeutic agents, treatment solely by surgical means had a survival rate of <20%. Modern survival rates with adjuvant therapy are approximately 60–70%.

There are two main methods of chemotherapy treatment for RMS. There is the VAC regimen, consisting of vincristin, actinomyocin D, and cyclophosphamide, and the IVA regimen, consisting of ifosfamide, vincristin, and actinomyocin D. These drugs are administered in 9–15 cycles depending on the staging of the disease and other therapies used. Other drug and therapy combinations may also show additional benefit. Addition of doxorubicin and cisplatin to the VAC regimen was shown to increase survival rates of patients with alveolar-type, early-stage RMS in IRS study III, and this same addition improved survival rates and doubled bladder salvage rates in patients with stage III RMS of the bladder.

Radiation therapy, which kill cancer cells with focused doses of radiation, is often indicated in the treatment of rhabdomyosarcoma, and the exclusion of this treatment from disease management has been shown to increase recurrence rates. Radiation therapy is used when resecting the entirety of the tumor would involve disfigurement or loss of important organs (eye, bladder, etc.). Generally, in any case where a lack of complete resection is suspected, radiation therapy is indicated. Administration is usually following 6–12 weeks of chemotherapy if tumor cells are still present. The exception to this schedule is the presence of parameningeal tumors that have invaded the brain, spinal cord, or skull. In these cases radiation treatment is started immediately. In some cases, special radiation treatment may be required. Brachytherapy, or the placement of small, radioactive “seeds” directly inside the tumor or cancer site, is often indicated in children with tumors of sensitive areas such as the testicles, bladder, or vagina. This reduces scattering and the degree of late toxicity following dosing. Radiation therapy is more often indicated in higher stage classifications.

Immunotherapy is a more recent treatment modality that is still in development. This method involves recruiting and training the patient's immune system to target the cancer cells. This can be accomplished through administering small molecules designed to pull immune cells towards the tumors, taking immune cells pulled from the patient and training to attack tumors through presentation with tumor antigen, or other experimental methods. A specific example here would be presenting some of the patient's dendritic cells, which direct the immune system to foreign cells, with the PAX3-FKHR fusion protein in order to focus the patient's immune system to the malignant RMS cells. All cancers, including rhabdomyosarcoma, could potentially benefit from this new, immune-based approach.

The Stehlin Foundation currently offers DSRCT patients the opportunity to send samples of their tumors free of charge for testing. Research scientists are growing the samples on nude mice and testing various chemical agents to find which are most effective against the individual's tumor.

Patients with advanced DSRCT may qualify to participate in clinical trials that are researching new drugs to treat the disease.

Treatment of VAS is through aggressive surgery. As soon as the tumor is recognized, it should be removed with very wide margins to ensure complete removal. Treatment may also include chemotherapy or radiation therapy. The most significant prognostic factor is initial surgical treatment. One study showed that cats with radical (extensive) initial surgery had a median time to recurrence of 325 days versus 79 days for cats with marginal initial excision. The expression of a mutated form of p53, a tumor suppressor gene, is found commonly in VAS and indicates a poorer prognosis.

Prognosis depends on the primary tumor grade (appearance under the microscope as judged by a pathologist), size, resectability (whether it can be completely removed surgically), and presence of metastases. The five-year survival is 80%.

The prognosis for DSRCT remains poor. Prognosis depends upon the stage of the cancer. Because the disease can be misdiagnosed or remain undetected, tumors frequently grow large within the abdomen and metastasize or seed to other parts of the body.

There is no known organ or area of origin. DSRCT can metastasize through lymph nodes or the blood stream. Sites of metastasis include the spleen, diaphragm, liver, large and small intestine, lungs, central nervous system, bones, uterus, bladder, genitals, abdominal cavity, and the brain.

A multi-modality approach of high-dose chemotherapy, aggressive surgical resection, radiation, and stem cell rescue improves survival for some patients. Reports have indicated that patients will initially respond to first line chemotherapy and treatment but that relapse is common.

Some patients in remission or with inoperable tumor seem to benefit from long term low dose chemotherapy, turning DSRCT into a chronic disease.

Based on a survey of >800, surgical removal of the entire involved kidney plus the peri-renal fat appeared curative for the majority of all types of mesoblastic nephroma; the patient overall survival rate was 94%. Of the 4% of non-survivors, half were due to surgical or chemotherapeutic treatments. Another 4% of these patients suffered relapses, primarily in the local area of surgery rare cases of relapse due to lung or bone metastasis.. About 60% of these recurrent cases had a complete remission following further treatment. Recurrent disease was treated with a second surgery, radiation, and/or chemotherapy that often vincristine and actinomycin treatment. Removal of the entire afflicted kidney plus the peri-renal fat appears critical to avoiding local recurrences. In general, patients who were older than 3 months of age at diagnosis or had the cellular form of the disease, stage III disease, or involvement of renal lymph nodes had a higher recurrence rate. Among patients with these risk factors, only those with lymph node involvement are recommended for further therapy.

It has been suggested that mesoblastic nephroma patients with lymph node involvement or recurrent disease might benefit by adding the ALK inhibitor, crizotinib, or a tyrosine kinase inhibitor, either larotrectinib or entrectinib, to surgical, radiation, and/or chemotherapy treatment regimens. These drugs inhibit NTRK3's tyrosine kinase activity. Crizotinib has proven useful in treating certain cases of acute lymphoblastic leukemia that are associated with the "ETV6-NTRK3" fusion gene while larotrectinib and entrectinib have been useful in treating various cancers (e.g. a metastatic sarcoma, papillary thyroid cancer, non-small-cell lung carcinoma, gastrointestinal stromal tumor, mammary analog secretory carcinoma, and colorectal cancer) that are driven by mutated, overly active tyrosine kinases. Relevant to this issue, a 16-month-old girl with infantile fibrosarcoma harboring the "ETV6–NTRK3" fusion gene was successfully trated with larotrectinib. The success of these drugs, howwever, will likely depend on the relative malignancy-promoting roles of ETV6-NTRK3 protein's tyrosine kinase activity, the lose of ETV6-related transcription activity accompanying formation of ETV6-NTRK3 protein, and the various trisomy chromosomes that populate mesoblastic nephroma.

Epithelioid sarcoma (especially advanced stage, recurrent, or metastasized disease) has been shown to be resistant to traditional cancer therapies, necessitating further exploration of novel treatment methods and techniques. Because of the relatively poor response of epithelioid sarcoma to traditional cancer treatments (surgery, chemotherapy, and radiation), new treatment strategies are being looked to.

2004 research showed that CCSK patients exhibit an improved relapse-free survival from a longer course of therapy when using vincristine, doxorubicin, and dactinomycin, but their long-term survival is unchanged compared with patients receiving 6 months of therapy.

Depending on the grade of the sarcoma, it is treated with surgery, chemotherapy and/or radiotherapy.

The disease used to be uniformly fatal, with a 5-year survival rate between 10 and 35%. As a result, treatment was radical surgery. New multidrug chemotherapy regimens with or without radiation therapy are now used in combination with less radical surgery with good results, although outcome data are not yet available.

Blood tests to detect antibodies against KSHV have been developed and can be used to determine whether a person is at risk for transmitting infection to their sexual partner, or whether an organ is infected prior to transplantation. However, these tests are not available except as research tools, and, thus, there is little screening for persons at risk for becoming infected with KSHV, such as people following a transplant.

Radiotherapy is the most effective treatment for local disease either as the sole treatment for low-grade lymphoma or in combination with chemotherapy for intermediate- and high-grade lymphoma. Radiotherapy dose in range of 30-45 Gy administered in fractions are advised in treating the local orbital lymphomas.

Treatment with chemotherapy has been used with some success, particularly using lomustine, prednisone, doxorubicin, and cyclophosphamide. Because of the rapid progression of this aggressive disease, the prognosis is very poor.

Ocular oncology is the branch of medicine dealing with tumors relating to the eye and its adnexa.

Ocular oncology takes into consideration that the primary requirement for patients is preservation of life by removal of the tumor, along with best efforts directed at preservation of useful vision, followed by cosmetic appearance. The treatment of ocular tumors is generally a multi-specialty effort, requiring coordination between the ophthalmologist, medical oncologist, radiation specialist, head & neck surgeon/ENT surgeon, pediatrician/internal medicine/hospitalist and a multidisciplinary team of support staff and nurses.

Work out of Huntsman Cancer Institute (HCI) in Utah has demonstrated that ASPS might be driven in part by lactate both being used as a fuel and driving angiogenesis.

As described above, chloromas should always be considered manifestations of systemic disease, rather than isolated local phenomena, and treated as such. In the patient with newly diagnosed leukemia and an associated chloroma, systemic chemotherapy against the leukemia is typically used as the first-line treatment, unless an indication for local treatment of the chloroma (e.g. compromise of the spinal cord) emerges. Chloromas are typically quite sensitive to standard antileukemic chemotherapy. Allogeneic hematopoietic stem cell transplantation should be considered in fit patients with suitable available donor, as long term remissions have been reported.

If the chloroma is persistent after completion of induction chemotherapy, local treatment, such as surgery or radiation therapy, may be considered, although neither has an effect on survival.

Patients presenting with a primary chloroma typically receive systemic chemotherapy, as development of acute leukemia is nearly universal in the short term after detection of the chloroma.

Patients treated for acute leukemia who relapse with an isolated chloroma are typically treated with systemic therapy for relapsed leukemia. However, as with any relapsed leukemia, outcomes are unfortunately poor.

Patients with "preleukemic" conditions, such as myelodysplastic syndromes or myeloproliferative syndromes, who develop a chloroma are often treated as if they have transformed to acute leukemia.