Most lumps or masses that develop on the thigh or leg are from trauma or benign causes. In rare cases, however, a leg lump can be the presenting sign of an aggressive cancer called a soft tissue sarcoma (STS). Although uncommon, STS can be lethal. My wife and I lost a close friend this week to metastatic STS. In addition to her devoted husband, she is survived by her three teenage children. Another good friend’s girlfriend was diagnosed recently with a high grade (aggressive) STS of the leg that had already metastasized (spread) to multiple sites in her lungs, making the disease essentially incurable. Given these recent events affecting my friends’ lives, I’m taking the opportunity to revisit the topic of STS (first posted with “Sean’s Story” in January 2011).
Historically, patients who developed soft tissue sarcomas were at risk of losing “life and limb,” quite literally. This type of cancer is much less common than many carcinomas. The most common site in the body to develop STS is the thigh. Because of the local aggressiveness of these tumors, as recently as the 1970s the local treatment of STS was amputation of the affected limb. Fortunately, that type of drastic surgery is rarely needed today. In the U.S., it’s estimated that over 10,000 patients will be diagnosed and 4,000 patients will die of STS each year. Although the median age at diagnosis is 65, these tumors may occur in children, young adults (our friends), and the elderly. The lifetime risk of developing STS is about 0.3%, or 1 in 300 people. According to the most recent NCI’s SEER Cancer Statistics Review, the relative 5-year survival following a diagnosis of STS for all stages combined is 67%. If the disease is localized, then the 5-year survival is 84%. Patients with regional spread to lymph nodes have a 5-year survival rate of 62%. Those with distant, metastatic disease (most commonly to the lungs) have a 17% survival rate at 5 years following diagnosis.
Risks & Causes
Most who are diagnosed with STS don’t have specific risk factors. Some patients will relate a history of recent trauma to the area prior to diagnosis. However, it’s thought that the trauma merely makes the patient aware of the mass, rather than serving as a cause of the cancer. (“Doc, I fell on my leg a couple of weeks ago and it’s still swollen and hard.”) Uncommon genetic abnormalities such as neurofibromatosis, Li Fraumeni, and Gardners syndromes place patients at a high risk of developing STS relative to the general population. Regular exposure to certain chemicals including arsenic, certain herbicides, and vinyl chloride may also increase risk. Lastly, radiation exposure, including RT for cancer treatment, places patients at a low (much less than 1%) risk for radiation-induced STS.
Signs & Symptoms
The classic presentation of a patient with STS is a painless mass in the thigh, or any other muscular or soft tissue area of the body. The patient may describe the mass as appearing suddenly and/or enlarging rapidly. Occasionally the mass will cause discomfort or pain due to pressure on nearby structures and nerves. Soft tissue sarcoma may also arise in an area call the retroperitoneum, the back of the abdomen. A mass occasionally may be seen or felt in these cases.
When a suspicious mass is seen or felt by the patient or his/her primary doctor, a referral should be made to an orthopedic or other surgical oncologist who has significant experience with these types of tumors. Ideally, if STS is suspected, the biopsy should remove a piece of the tumor and the incision should be placed over the central portion of the mass. This type of biopsy is termed an incisional biopsy. Common subtypes of STS include malignant fibrous histiocytoma (MFH), liposarcoma, and fibrosarcoma, though there are many others.
The American Joint Commission on Cancer (AJCC) Tumor Node Metastasis (TNM) system is utilized for staging STS. In addition to standard laboratory evaluation, patients should undergo CT or MRI of the affected area. MRI is preferred to provide detailed anatomical information if the primary STS arises within an extremity or joint. Patients with masses in the retroperitoneum will generally be served well with CT imaging. Pathologists play a very important part in not only diagnosis but also staging of STS, since tumor grade (how aggressive the cells appear under the microscope) is a critical component of the staging of STS.
Patients with high grade (grade 3 or 4; very aggressive) STS have a very high risk of cancer spreading to distant sites, most commonly the lungs. In fact, roughly 50% of patients with grade 3 STS will develop lung metastasis. For all but the earliest, low-grade tumors, CT of the chest should be obtained to ensure no evidence of lung metastases at the time of diagnosis. Unlike many carcinomas and lymphomas, most types of STS don’t commonly spread to lymph nodes. The few subtypes that are known to do so include clear cell, rhabdomyosarcoma (the most common type of STS to occur in children), embryonal, alveolar and synovial cell types. In addition to tumor grade, size, and depth of invasion (all of which are part of the AJCC staging system), patient age and overall condition are important factors for the patient’s outcome. The overall survival 5 years following diagnosis by AJCC stage is: 90% for stage I, 80% for stage II, 55% for stage III, and 20% for stage IV.
For small superficial, low-grade STS, surgical removal with a wide margin of normal tissue around the tumor is generally adequate. These tumors have low risk of returning locally and/or spreading to distant sites, so cure rates are excellent. Unfortunately, STS are commonly intermediate to high grade, often large, and deep. They present two problems: local and distant. As mentioned earlier, historically patients with STS of the extremities underwent amputations to control the local tumor, since it had been shown that removing only the tumor itself resulted in an unacceptably high rate of the cancer returning and patients dying. Thanks to work by investigators at the National Cancer Institute (NCI), it was determined in major RCTs that wide local excision of the tumor followed by postoperative radiation therapy (RT) to the region resulted in a recurrence rate of <10% and spared patients’ limbs. Amputation was no longer required for the majority of patients. A major trial that tested the role of preoperative versus postoperative RT revealed that overall survival was sightly better in the preoperative group. Preoperative RT resulted in a higher risk of wound complications. The current standard of care at many major cancer centers incorporates preoperative RT followed by surgery. The RT dose is delivered daily, 5 days per week over 5-5.5 weeks preoperatively. Patients who are treated postoperatively require a longer, 6.5-7 week course, usually encompassing a much larger area.
Systemic treatment for patients with high grade STS that hasn’t metastasized (spread to distant sites such as the lungs) has shown a small but real benefit in terms of improving patients’ survival without disease returning. Unfortunately, the active chemotherapy drugs for STS are strong IV medications including adriamycin and ifosfamide. Side effects include hair loss and nausea, significant fatigue, weakness, and a very low risk of permanent heart damage.
Those patients who develop spread to the lungs or other distant sites are generally incurable. Chemotherapy for this group of patients may extend their survival and improve long-term quality of life, albeit with the risk of side effects as noted above. For patients who have limited metastatic disease, such as one or two nodules in the lungs, there’s a potential survival benefit if they’re able to have these metastases surgically removed. While the majority of these patients will still have their cancer return later, a small subset will be cured.
– Patrick Maguire MD