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.

Therapy is based on staging and patient condition and utilizes one or more of the following approaches.

Surgery is the mainstay of therapy if feasible involving total abdominal hysterectomy with bilateral salpingo-oophorectomy. Other approaches include radiation therapy, chemotherapy, and hormonal therapy.

Prognosis is relatively poor.

Surgery, with as wide a margin of removal as possible, has generally been the most effective and preferred way to attack LMS. If surgical margins are narrow or not clear of tumor, however, or in some situations where tumor cells were left behind, chemotherapy or radiation has been shown to give a clear survival benefit. While LMS tends to be resistant to radiation and chemotherapy, each case is different and results can vary widely.

LMS of uterine origin do frequently, but not always respond to hormonal treatments.

Chemotherapy and radiotherapy are not as successful in the case of RCC. RCC is resistant in most cases but there is about a 4–5% success rate, but this is often short lived with more tumours and growths developing later.

Unlike classical seminoma, spermatocytic seminomas rarely metastasise, so radical orchidectomy alone is sufficient treatment, and retroperitoneal lymph node dissection and adjuvant chemotherapy or radiotherapy are generally not required.

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.

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.

CUP is a term that refers to many different cancers. For that reason, treatment depends on where the cancer is found, the microscopic appearance of the cancer cells, the biochemical characterization of the cells, and the patient’s age and overall physical condition. In women, who present with axillary lymph node involvement, treatment is offered along the lines of breast cancer. In patients, who have neck lymph node involvement, then treatment is offered along the lines of head and neck cancer. If inguinal lymph nodes are involved, then treatment may be offered along the lines of genitourinary cancer.

If the site of origin is unknown or undiscovered, then the histology of the tumor (e.g., adenocarcinoma, squamous cell or mesenchymal) can usually be identified, and a probable origin may be assumed. When this is possible, then treatment is based on the type of cell and probable origin. Based on histological subtype, combination chemotherapy may be selected. A combination of carboplatin and paclitaxel is often used. Advances techniques such as FISH and tissue of origin testing may also be employed. Germ cell tumors often carry abnormality of chromosome 12, which if identified, directs treatment for metastatic germ cell tumors.

No method is standard for all forms of CUP, but chemotherapy, radiation therapy, hormone therapy, and surgery may be used alone or in combination to treat patients who have CUP. Even when the cancer is unlikely to be cured, treatment may help the patient live longer or improve the patient’s quality of life. Radiation may be used to shrink a variety of local tumors. However, the potential side effects of the treatment must be considered along with the potential benefits.

In CUP to secondary neck nodes, surgery followed by external beam radiotherapy is sufficient.

For CUP with an unfavorable prognosis, treatment with taxanes may provide a slight survival benefit. The uncertainties and ambiguity inherent in a CUP diagnosis may cause additional stress for the patient.

For malignant teratomas, usually, surgery is followed by chemotherapy.

Teratomas that are in surgically inaccessible locations, or are very complex, or are likely to be malignant (due to late discovery and/or treatment) sometimes are treated first with chemotherapy.

The initial approach to tubal cancer is generally surgical and similar to that of ovarian cancer. As the lesion will spread first to the adjacent uterus and ovary, a total abdominal hysterectomy is an essential part of this approach and removes the ovaries, the tubes, and the uterus with the cervix. Also, peritoneal washings are taken, the omentum is removed, and pelvic and paraaortic lymph nodes are sampled. Staging at the time of surgery and pathological findings will determine further steps. In advanced cases when the cancer has spread to other organs and cannot be completely removed cytoreductive surgery is used to lessen the tumor burden for subsequent treatments. Surgical treatments are typically followed by adjuvant usually platinum-based chemotherapy.

Also radiation therapy has been applied with some success to patients with tubal cancer for palliative or curative indications

Small myelolipomas generally do not produce symptoms, and do not require treatment. Ongoing surveillance of these lesions by a doctor is recommended. Surgical excision (removal) is recommended for large myelolipomas because of the risk of bleeding complications.

The treatment of choice is complete surgical removal ("i.e.," complete resection). Teratomas are normally well-encapsulated and non-invasive of surrounding tissues, hence they are relatively easy to resect from surrounding tissues. Exceptions include teratomas in the brain, and very large, complex teratomas that have pushed into and become interlaced with adjacent muscles and other structures.

Prevention of recurrence does not require "en bloc" resection of surrounding tissues.

International Federation of Gynecology and Obstetrics (FIGO) staging is done at the time of surgery:

Most people with cancer of unknown primary origin have widely disseminated and incurable disease, although a few can be cured through treatment. With treatment, typical survival with CUP ranges from 6 to 16 months. Survival rates are lower in cases with visceral metastatic disease, ranging from 6 to 9 months. Survival rates are higher when the cancer is more limited to lymph nodes, pleura, or peritoneal metastasis, which ranges from 14 to 16 months. Long-term prognosis is somewhat better if a particular source of cancer is strongly suggested by clinical evidence.

Intratesticular masses that appear suspicious on an ultrasound should be treated with an inguinal orchiectomy. The pathology of the removed testicle and spermatic cord indicate the presence of the seminoma and assist in the staging. Tumors with both seminoma and nonseminoma elements or that occur with the presence of AFP should be treated as nonseminomas. Abdominal CT or MRI scans as well as chest imaging are done to detect for metastasis. The analysis of tumor markers also helps in staging.

The preferred treatment for most forms of stage 1 seminoma is active surveillance. Stage 1 seminoma is characterized by the absence of clinical evidence of metastasis. Active surveillance consists of periodic history and physical examinations, tumor marker analysis, and radiographic imaging. Around 85-95% of these cases will require no further treatment. Modern radiotherapy techniques as well as one or two cycles of single-agent carboplatin have been shown to reduce the risk of relapse, but carry the potential of causing delayed side effects. Regardless of treatment strategy, stage 1 seminoma has nearly a 100% cure rate.

Stage 2 seminoma is indicated by the presence of retroperitoneal metastasis. Cases require radiotherapy or, in advanced cases, combination chemotherapy. Large residual masses found after chemotherapy may require surgical resection. Second-line treatment is the same as for nonseminomas.

Stage 3 seminoma is characterized by the presence of metastasis outside the retroperitoneum—the lungs in "good risk" cases or elsewhere in "intermediate risk" cases. This is treated with combination chemotherapy. Second-line treatment follows nonseminoma protocols.

Estrogen-containing medications can exacerbate LAM and are contraindicated. Agents that antagonize the effects of estrogen have not been proven to be effective for treatment, but no proper trials have been done. A trial of bronchodilators should be considered in LAM patients, because up to 17% to 25% have bronchodilator-responsive airflow obstruction. Oxygen should be administered to maintain oxyhemoglobin saturations of greater than 90% with rest, exercise and sleep. Bone densitometry should be considered in all patients who are immobilized and/or on antiestrogen therapies, and appropriate therapy instituted for osteoporotic patients. Proper attention should be paid to cardiovascular health following natural or induced menopause. Immunizations for pneumococcus and influenza should be kept up to date. Pulmonary rehabilitation seems to be particularly rewarding in young, motivated patients with obstructive lung disease, but studies to assess this intervention's effect on exercise tolerance, conditioning and quality of life have not been done.

Uterine fibroids can be treated with the same methods like sporadic uterine fibroids including antihormonal treatment, surgery or embolisation. Substantially elevated risk of progression to or independent development of uterine leiomyosarcoma has been reported which may influence treatment methods.

The predisposition to renal cell cancer calls for screening and, if necessary, urological management.

The skin lesions may be difficult to treat as they tend to recur after excision or destructive treatment. Drugs which affect smooth muscle contraction, such as doxazosin, nitroglycerine, nifedipine and phenoxybenzamine, may provide pain relief.

Topical lidocaine patches have been reported to decrease in severity and frequency of pain cutaneous leiomyomas.

Sirolimus is an mTOR inhibitor that stabilizes lung function and improves some measures of life in LAM patients. It is approved by the FDA for use in LAM, based on the results of the Multicenter International LAM Efficacy and Safety of Sirolimus (MILES) Trial. MILES data supports the use of sirolimus in patients who have abnormal lung function (i.e. FEV1<70% predicted). Whether the benefits of treatment outweigh the risks for asymptomatic LAM patients with normal lung function is not clear, but some physicians consider treatment for declining patients who are approaching the abnormal range for FEV1. Sirolimus also appears to be effective for the treatment chylous effusions and lymphangioleiomyomatosis. The benefits of sirolimus only persist while treatment continues. The safety of long term therapy has not been studied.

Potential side effects from mTOR inhibitors include swelling in the ankles, acne, oral ulcers, dyspepsia, diarrhea, elevation of cholesterol and triglycerides, hypertension and headache. Sirolimus pneumonitis and latent malignancy are more serious concerns, but occur infrequently. Sirolimus inhibits wound healing. It is important to stop therapy with the drug for 1–2 weeks before and after elective procedures that require optimal wound healing. Precautions must be taken to avoid prolonged sun exposure due to increased skin cancer risk.

Treatment with another mTOR inhibitor, everolimus, was reported in a small, open-label trial to be associated with improvement in FEV1 and six-minute walk distance. Serum levels of VEGF-D and collagen IV were reduced by treatment. Adverse events were generally consistent with those known to be associated with mTOR inhibitors, although some were serious and included peripheral edema, pneumonia, cardiac failure and "Pneumocystis jirovecii" infection. Escalating doses of everolimus were used, up to 10 mg per day; higher than what is typically used clinically for LAM.

Serum VEGF-D concentration is useful, predictive and prognostic biomarker. Higher baseline VEGF-D levels predicts more rapid disease progression and a more robust treatment response.

Hormonal approaches to treatment have never been tested in proper trials. In the absence of proven benefit, therapy with progesterone, GnRh agonists (e.g., Lupron, goserelin) and tamoxifen are not routinely recommended. Doxycycline had no effect on the rate of lung function decline in a double blind trial.

Sirolimus is often effective as first-line management for chylothorax. If chylous leakage or accumulations persist despite treatment, imaging with heavy T2 weighted MRI, MRI lymphangiography or thoracic duct lymphangiography can be considered. Pleural fusion procedures can be considered in refractory cases.

Spermatocytic seminomas are not considered a subtype of seminoma and unlike other germ cell tumours do not arise from intratubular germ cell neoplasia.

Usually, treatment of a lipoma is not necessary, unless the tumor becomes painful or restricts movement. They are usually removed for cosmetic reasons, if they grow very large, or for histopathology to check that they are not a more dangerous type of tumor such as a liposarcoma. This last point can be important as the characteristics of a "bump" are not known until after it is removed and medically examined.

Lipomas are normally removed by simple excision. The removal can often be done under local anaesthetic, and takes less than 30 minutes. This cures the great majority of cases, with about 1–2% of lipomas recurring after excision. Liposuction is another option if the lipoma is soft and has a small connective tissue component. Liposuction typically results in less scarring; however, with large lipomas it may fail to remove the entire tumor, which can lead to regrowth.

New methods under development are supposed to remove the lipomas without scarring. One is removal by injecting compounds that trigger lipolysis, such as steroids or phosphatidylcholine.

Current treatment options include:

- Surgical debulking

- High-dose Corticosteroid therapy

- Cyclosporin

- Interferon-α

- Chemotherapy

- Vemurafenib. It would appear that approximately half these patients harbor point mutations of the BRAF gene at codon 600 substituting the amino acid glutamine for valine. Vemurafenib, an oral FDA approved targeted agent to the BRAF protein for melanoma, shows dramatic activity in patients Erdheim–Chester disease whose tumor contains the same mutation. In 2017 the US FDA approved vemurafenib for this indication.

- Radiation therapy

All current treatments have had varying degrees of success.

The vinca alkaloids and anthracyclines have been used most commonly in ECD treatment.

Radiation may be used to treat stage II seminoma cancers, or as adjuvant (preventative) therapy in the case of stage I seminomas, to minimize the likelihood that tiny, non-detectable tumors exist and will spread (in the inguinal and para-aortic lymph nodes). Radiation is ineffective against and is therefore never used as a primary therapy for nonseminoma.

Chemotherapy is the standard treatment for non-seminoma when the cancer has spread to other parts of the body (that is, stage 2B or 3). The standard chemotherapy protocol is three, or sometimes four, rounds of Bleomycin-Etoposide-Cisplatin (BEP). BEP as a first-line treatment was first reported by Professor Michael Peckham in 1983. The landmark trial published in 1987 which established BEP as the optimum treatment was conducted by Dr. Lawrence Einhorn at Indiana University. An alternative, equally effective treatment involves the use of four cycles of Etoposide-Cisplatin (EP).

Lymph node surgery may also be performed after chemotherapy to remove masses left behind (stage 2B or more advanced), particularly in the cases of large nonseminomas.

Removing the tumor by either surgical resection or liver transplant can be used in the treatment of hepatoblastoma. In some cases surgery can offer a cure. Chemotherapy may be used before and after surgery and transplant.

Chemotherapy, including cisplatin, vincristine, cyclophosphamide, and doxorubicin are used for the systemic treatment of hepatoblastoma. Out of these drugs, cisplatin seems to be the most effective.

Everolimus is FDA approved for the treatment of angiomyolipomas. Treatment should be considered for asymptomatic, growing AML measuring larger than 3 cm in diameter.

Angiomyolipoma do not normally require surgery unless there is life-threatening bleeding. Some centres may perform preventative selective embolisation of the angiomyolipoma if it is more than 4 cm in diameter, due to the risk of haemorrhage.

People with tuberous sclerosis are advised to have yearly renal scans, though it is possible that patients with very stable lesions could be monitored less frequently. The research in this area is lacking. Even if no angiomyolipoma is found, one can develop at any life stage. The angiomyolipoma can grow rapidly.

In tuberous sclerosis, typically many angiomyolipomas affecting each kidney. It is not uncommon for more than one intervention to be required during lifetime. Since kidney function may already be impaired (up to half the kidney may be lost before function loss is detectable), it is vital to preserve as much kidney as possible when removing any lesion. Large angiomyolipomas are treated by embolisation which reduces the risk of haemorrhage and can also shrink the lesion. A side effect of this treatment is postembolisation syndrome: severe pain and fever however this is easily managed and lasts only a few days.

A ruptured aneurysm in an angiomyolipoma leads to blood loss that must be stopped (though embolisation) and compensated for (through intravenous fluid replacement). Therefore, removal of the affected kidney (nephrectomy) is strongly discouraged though may occur if the emergency department is not knowledgeable about tuberous sclerosis.

Embolisation involves inserting a catheter along the blood vessels to the tumour. The blood vessels are then blocked, typically by injecting ethanol or inert particles. The procedure can be very painful, so analgesics are used. The destroyed kidney tissue often causes post-embolisation syndrome, which manifests as nausea, vomiting, fever and abdominal pain, and lasts a few days. Embolisation (in general) has an 8% rate of morbidity and a 2.5% rate of mortality, so is not considered lightly.

Patients with kidney loss should be monitored for hypertension (and treated for it if discovered) and avoid nephrotoxic drugs such as certain pain relievers and IV contrast agents. Such patients who are unable to communicate effectively (due to age or intellectual disability) are at risk of dehydration. Where multiple or large angiomyolipomas have caused chronic kidney disease, dialysis is required.

Robotic assisted partial nephrectomy has been proposed as a surgical treatment of a ruptured angiomyolipoma combining the advantages both of a kidney preservation procedure and the benefits of a minimal invasive procedure without compromising the safety of the patient.