Kaposi sarcoma (KS) was first described in 1872 by the Hungarian dermatologist, Moritz Kaposi. From that time until the HIV and AIDS epidemic, KS remained a rare tumor. Classic KS is most commonly seen in Europe and North America in older men of Italian or Eastern European Jewish ancestry,[1] and endemic KS is most commonly seen in sub-Saharan Africa. The disseminated, fulminant form of KS associated with HIV disease is referred to as AIDS-associated KS to distinguish it from classic and endemic KS. Transplant-related KS (also sometimes called iatrogenic KS) is seen in patients receiving chronic immunosuppression therapy, such as after organ transplant.[2,3]
Although the histopathology of the different types of KS is essentially identical, the clinical manifestations and course of the disease differ dramatically.[2] Human herpesvirus 8 (HHV8), also known as Kaposi sarcoma-associated herpesvirus, was identified in KS tissue biopsies from almost all patients with classic, endemic, AIDS-associated, and transplant-related KS but was absent from noninvolved tissue.[2]
Classic KS is considered a rare disease. It occurs more often in men, at a ratio of approximately 10 to 15 men to 1 woman. In North American and European populations, the usual age at onset is between 50 and 70 years. Classic KS tumors usually present with one or more asymptomatic red, purple, or brown patches, plaques, or nodular skin lesions. The disease is often limited to single or multiple lesions usually localized to one or both lower extremities, especially involving the ankles and soles.
Classic KS most commonly runs a relatively benign, indolent course for 10 to 15 years or more, with slow enlargement of the original tumors and the gradual development of additional lesions. Venous stasis and lymphedema of the involved lower extremity are frequent complications. In long-standing cases, systemic lesions can develop along the gastrointestinal tract, in lymph nodes, and in other organs. The visceral lesions are generally asymptomatic and are most often discovered only at autopsy, though clinically, gastrointestinal bleeding can occur. As many as 33% of patients with classic KS develop a second primary malignancy, which is most often non-Hodgkin lymphoma.[4]
Endemic KS refers to KS diagnosed in patients, typically children and younger adults, living in sub-Saharan Africa. This classification was based on several reports from the 1950s of KS in this younger HIV-negative cohort in human herpesvirus–endemic African countries. Prior to the AIDS epidemic, the estimated incidence for endemic KS was highest (>6 per 1,000 person-years) in Uganda, Tanzania, Cameroon, and Congo. The etiology behind endemic KS is unclear but may possibly be related to saliva-sharing practices, chronic infection, and malnutrition.[3]
The clinical presentation of endemic KS varies and differs between children and adults. Whereas adults present with disease that resembles classic KS, children can have more aggressive disease, including diffuse lymphadenopathy, significant lymphedema, and visceral dissemination.[3]
The use of antiretroviral therapy for patients with AIDS-associated KS has been associated with a sustained and substantial decline in KS incidence in multiple large cohorts.[5-7] Antiretroviral therapy has delayed or prevented the emergence of drug-resistant HIV strains, profoundly decreased viral load, led to increased survival, and lessened the risk of opportunistic infections.[8] KS can still appear during antiretroviral therapy with complete suppression of HIV; most cases in the United States occur in patients with high CD4 counts receiving ongoing antiretroviral therapy.[9]
The disease often progresses in an orderly fashion from a few localized or widespread mucocutaneous lesions that may involve the skin, oral mucosa, and lymph nodes to more numerous lesions and generalized skin disease that involves visceral organs, such as the gastrointestinal tract, lung, liver, and spleen. Most patients with HIV disease who present with mucocutaneous KS lesions feel healthy and are usually free of systemic symptoms, as compared with HIV patients who first develop an opportunistic infection. AIDS-associated KS presents at sites that are much more varied than those seen in other types of this neoplasm. While most patients present with skin disease, KS involvement of lymph nodes or the gastrointestinal tract may occasionally precede the appearance of the cutaneous lesions.
Transplant-related KS (also called iatrogenic KS) is diagnosed in patients who are therapeutically immunosuppressed, such as after an organ transplant. In fact, solid-organ transplant recipients are 200-fold more likely to develop KS than the general population. Risk factors include male sex, older age, higher levels of immune suppression, and living in HHV8-endemic areas.[3]
Transplant-related KS typically yields cutaneous lesions, though mucosal and visceral disease can occur. The lesions commonly occur within the first several months of immunosuppression therapy and regress with changes or reductions in immunosuppression.[3]
The staging evaluation of patients with classic Kaposi sarcoma (KS) should be individualized. The advanced age of most patients, localized nature of the tumor, rarity of visceral involvement, and usually indolent course of the disease should temper the extent of the evaluation. A careful examination of the skin and lymph nodes is sufficient in most cases.
For the rare patient with a rapidly progressive tumor or signs or symptoms of visceral involvement, appropriate evaluation is indicated. No universally accepted classification is available for AIDS-associated KS. Staging schemes that incorporate laboratory parameters as well as clinical features have been proposed. Since most patients with AIDS-associated KS do not die of the disease, factors besides tumor burden are apparently involved in survival.
The conventions used to stage KS and the methods used to evaluate the benefits of KS treatment continue to evolve because of changes in the treatment of HIV and in recognition of deficiencies in standard tumor assessment. The clinical course of KS, the selection of treatment, and the response to treatment are heavily influenced by the degree of underlying immune dysfunction and opportunistic infections.
The AIDS Clinical Trials Group (ACTG) Oncology Committee has published criteria for the evaluation of AIDS-associated KS.[1] The staging system incorporates measures of extent of disease, severity of immunodeficiency, and presence of systemic symptoms. As shown in Table 1 below, the ACTG criteria categorize the extent of the tumor as localized or disseminated, the CD4 cell number as high or low, and systemic illness as absent or present.
A subsequent prospective analysis of 294 patients entered on ACTG trials for KS between 1989 and 1995 showed that each of the tumor (T), immune system (I), and systemic illness (S) variables was independently associated with survival.[2] Multivariate analysis showed that immune system impairment was the most important single predictor of survival. In patients with relatively high CD4 counts, tumor stage was predictive. A CD4 count of 150 cells/µL may be a better discriminator than the published cutoff of 200 cells/µL. A study is under way to determine if quantifying viral load adds predictive value. None of the previous studies were conducted at a time when antiretroviral therapy was readily available. The impact of antiretroviral therapy on survival in KS requires continued assessment.
| Variable | Good Risk (0) | Poor Risk (1) |
|---|---|---|
| KS = Kaposi sarcoma; OI = opportunistic infection. | ||
| aMinimal oral disease is non-nodular KS confined to the palate. | ||
| b"B” symptoms are unexplained fever, night sweats, >10% involuntary weight loss, or diarrhea persisting >2 weeks. | ||
| (Any of the following) | (Any of the following) | |
| Tumor (T) | Confined to skin and/or lymph nodes and/or minimal oral diseasea | Tumor-associated edema or ulceration |
| Extensive oral KS | ||
| Gastrointestinal KS | ||
| KS in other non-nodal viscera | ||
| Immune system (I) | CD4 cells ≥200/µL | CD4 cells <200/µL |
| Systemic illness (S) | No history of OIs or thrush | History of OIs and/or thrush |
| No “B” symptomsb | “B” symptoms present | |
| Performance status ≥70 (Karnofsky) | Performance status <70 | |
| Other HIV-related illness (e.g., neurological disease or lymphoma) | ||
The ACTG proposed a unified treatment response evaluation system for AIDS-related KS for clinical practice and research.[1] After appropriate clinical examination and relevant interval imaging or endoscopy, patients are characterized as having complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD), based on the following criteria:
Classic Kaposi sarcoma (KS), as well as endemic KS in adult patients, is usually limited to the skin and has an indolent course. Thus, management for both is typically similar. Patients are predisposed to develop a second primary malignancy, and the treating physician should consider this factor when arranging a schedule of follow-up treatment for the patient.
Treatment options for localized skin disease include the following (options are equivalent):
For solitary lesions or lesions of limited extent, modest doses of radiation applied with a limited margin provide excellent control of disease in the treated area. Usually, superficial radiation beams, such as electron beams, are used. Some authors believe disease recurrence in adjacent untreated skin is common if only involved-field radiation therapy is used and claim better cure rates when extended-field radiation therapy is used.[1]
For low-voltage (100 kv) photon radiation therapy, 8 Gy to 10 Gy is given as a single dose or 15 Gy to 20 Gy is given over 1 week because solitary lesions control nearly 100% of local disease, but recurrence in adjacent areas is common.
For electron-beam radiation therapy (EBRT), 4 Gy is given once weekly for 6 to 8 consecutive weeks with a 4-MeV to 6-MeV electron beam. Ports should include the entire skin surface 15 cm above the lesion.
Surgical excision may benefit patients with small superficial lesions, but local recurrence is likely to occur. However, multiple small excisions can continue to be performed for good disease control.
Based on extent and accessibility of lesions, alternate modalities such as cryo-, laser, intralesional, and topical therapy can be used. Use of these modalities is based on evidence extrapolated from treatment of AIDS-associated KS.[2,3]
Treatment options for advanced skin disease include the following:
Modest doses can be effective in controlling widespread skin disease. The type of radiation (i.e., photon vs. electron) and fields used must be tailored to suit the distribution of disease in the individual patient.[1] Radiation therapy options include the following:
EBRT used in this manner gave long-term results that were superior to those obtained with radiation therapy administered to successive individual lesions as they appeared.[4]
Because classic KS is such a rare disease in the United States, and is usually treated initially with radiation therapy, few patients have been treated with chemotherapy. Its use in classic KS is based on data extrapolated from treatment of AIDS-associated KS, and no randomized prospective trials have compared one agent with another in classic KS. The agents listed below have potential benefit.
PLD has shown activity in several case series and single-institution analyses.[5-8]
Evidence (PLD):
Paclitaxel has shown activity in both AIDS-associated and classic KS in small case series.[9-12]
Evidence (taxanes):
Single-agent vinblastine [13-16], oral etoposide [17-19], and gemcitabine [20-22] have all shown good activity in classic and AIDS-associated KS.
Evidence (other chemotherapy agents):
Agents that modulate the immune system, such as imide drugs and interferon alfa-2b, have shown efficacy in both classic and AIDS-associated KS.
Pomalidomide has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of KS in patients with and without HIV.
Evidence (pomalidomide):
Pomalidomide is teratogenic, prescribed through a Risk Evaluation and Mitigation Strategy (REMS) program, and it should be given with aspirin to mitigate venous thromboembolism risk.
Interferon alfa-2b is approved by the FDA for treatment of AIDS-associated KS. It is sometimes used off-label for classic KS.
Evidence (interferon alfa-2b):
Immune checkpoint inhibitor therapy has been tested in classic KS and yielded promising results.
Evidence (pembrolizumab monotherapy):
Evidence (ipilimumab and nivolumab):
Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
Treatment of AIDS-associated Kaposi sarcoma (KS) may result in the following:
No data are available, however, to show that treatment improves survival.[1] In addition to antitumor treatment, essential components of an optimal KS treatment strategy in this population include antiretroviral treatment, prophylaxis for opportunistic infections, and rapid recognition and treatment of intercurrent infections. Therefore, close collaboration between oncologists and HIV specialists is vital.
Most patients with good-risk disease, defined by the AIDS Clinical Trials Group as T0, show tumor regression with antiretroviral therapy alone.[2-4] Patients with poor-risk disease, defined as T1, usually require a combination of antiretroviral therapy and chemotherapy with discontinuation of the chemotherapy after disappearance of the skin lesion.[2-4]
Treatment options for AIDS-associated KS include the following:
Small localized lesions of KS may be treated by electrodesiccation and curettage, cryotherapy, or by surgical excision. KS tumors are also generally very responsive to local radiation therapy, and excellent palliation has been obtained with doses at 20 Gy or slightly higher.[5,6] Radiation therapy is generally reserved to treat localized areas of the skin and oral cavity. It is used less often to control pulmonary, gastrointestinal tract, or other sites of KS lesions. Localized KS lesions have also been effectively treated with intralesional injections of vinblastine.[7] Alitretinoin 0.1% gel provided local control in a randomized, prospective, multicenter trial.[8][Level of evidence B3]
In AIDS-associated KS, the already profoundly depressed immunologic status of the patient limits the therapeutic usefulness of systemic chemotherapy. Systemic chemotherapy studies in patients with AIDS-associated KS have used doxorubicin, bleomycin, vinblastine, vincristine, etoposide, paclitaxel, and docetaxel alone or in combination.[9-13][Level of evidence C3] The combination of antiretroviral therapy and liposomal doxorubicin resulted in a 5-year overall survival rate of 85% in 140 patients with T1 disease.[3][Level of evidence C3]
Randomized multicenter trials showed an improvement in response rate (45%–60% vs. 20%–25%) and a more favorable toxic effects profile for pegylated liposomal doxorubicin (PLD) or liposomal daunorubicin, compared with the combination of doxorubicin, bleomycin, and vincristine or bleomycin and vincristine.[14-16][Level of evidence B3] During antiretroviral therapy, both PLD and paclitaxel are active single agents with response rates close to 50%.[17][Level of evidence B3]
The interferon alfas have also been widely studied and show a 40% objective response rate in patients with AIDS-associated KS.[18,19] In these reports, the responses differed significantly according to the following prognostic factors:
Several treatment studies have combined interferon alfa with other chemotherapeutic agents. Overall, these trials have shown no benefit with the interferon-chemotherapy combinations as compared with the single-agent activities.
Recombinant interferon alfa-2a and recombinant interferon alfa-2b were the first agents approved for the treatment of KS. Approval was based on single-agent studies performed in the 1980s before the advent of antiretroviral therapy. The early studies demonstrated improved efficacy at relatively high doses.
High-dose monotherapy is rarely used today, and instead, interferon is given in combination with other anti-HIV drugs in doses of 4 to 18 million units. Neutropenia is dose limiting, and trials of doses of 1 to 10 million units combined with less myelosuppressive antiretroviral agents are in progress. Response to interferon is slow, and the maximum effect is seen after 6 or more months. Interferon should probably not be used to treat patients with rapidly progressive, symptomatic KS.
Imatinib is a c-kit/platelet-derived growth factor receptor inhibitor.
Evidence (imatinib):
Bevacizumab is a humanized, anti–vascular endothelial growth factor monoclonal antibody.
Evidence (bevacizumab):
Evidence (interleukin-12):
Pomalidomide has been approved by the U.S. Food and Drug Administration for use in AIDS-associated KS.
Evidence (pomalidomide):
Pomalidomide is teratogenic, prescribed through a Risk Evaluation and Mitigation Strategy (REMS) program, and it should be given with aspirin to mitigate venous thromboembolism risk.
Evidence (bortezomib):
Immune reconstitution inflammatory syndrome (IRIS) is a hyperimmune response in patients with HIV/AIDS within the first 6 months of starting antiretroviral therapy. Kaposi sarcoma (KS)-associated IRIS (KS-IRIS) is not well-defined, but is considered to be the sudden clinical worsening of previous KS ("paradoxical") or the new presentation of KS (“unmasked”) in close proximity to starting or modifying antiretroviral therapy.[26]
Estimates for KS-IRIS incidence vary from 2% to 39%, with the highest risk in patients with any of the following characteristics:[26,27]
KS-IRIS typically presents with increased swelling/tenderness of lesions, new or worsening edema, and visceral or pulmonary involvement.
Management of KS-IRIS typically includes continuing antiretroviral therapy and initiating systemic treatment, such as liposomal doxorubicin or paclitaxel, for KS. The evidence for use of chemotherapy to prevent KS-IRIS is mixed, but can be considered on an individual basis.[26] Glucocorticoids are avoided due to the risk of dramatic worsening of KS.[27,28] Thalidomide has also been used for steroid-refractory IRIS.[29]
Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
In general, transplant-related Kaposi sarcoma is effectively managed by reduction in immunosuppression and does not require systemic treatment. Transitioning immunosuppression therapy to an mTOR inhibitor, such as sirolimus, has demonstrated efficacy in small studies and can be considered.[1]
Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
This summary was comprehensively reviewed and extensively revised.
This summary is written and maintained by the PDQ Adult Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® Cancer Information for Health Professionals pages.
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of Kaposi sarcoma. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.
This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
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PDQ® Adult Treatment Editorial Board. PDQ Kaposi Sarcoma Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/soft-tissue-sarcoma/hp/kaposi-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389335]
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