What is Kaposi's Sarcoma? 

A soft tissue tumour which can occur in a number of distinct areas of the body, it is caused by human herpesvirus-8 (HHV-8).² The condition can have varying presentations and prognosis.¹ Kaposi sarcoma (KS), while rare worldwide, is mostly diagnosed in patients with an immunocompromised immune system, including those with acquired immunodeficiency syndrome (AIDS) or those who have undergone organ transplantation.¹ Globally, the highest rates of KS have been noted in sub-Saharan Africa, owing to its prevalence to transmission via saliva in early years during the ongoing AIDS epidemic.² For those with AIDS related KS, targeted antiretroviral treatment of the HIV usually sees a regression of the KS.² There is a 20% mortality rate associated with KS, and in many cases, the patient may develop secondary malignancy, which can lead to a poor prognosis. Overall, the underlying condition associated with KS can be responsible for the varying prognosis.¹

Epidemiology of Kaposi’s Sarcoma

• Classic: male: female ratio 17:1 and occurs primarily in patients over 50 years old of Eastern European and Mediterranean descent¹
• Endemic: most commonly diagnosed in the paediatric population in Africa, the rates coincide with HHV-8 positivity, although rates vary throughout the country, male: female ratio 2:11. The high rate of KS in African women contrasts sharply with the extremely low KS incidence among women in resource-rich countries⁶ and immunosuppressed patients: male: female ratio of 3:11
• AIDS-related KS: It is an AID’s AIDS-defining illness and is seen in HIV patients with CD4 counts less than 200 cells/mm3 1. Male homosexual HIV positive patients are 10 times more likely to be at increased risk of developing KS. The prevalence of AIDS-related KS was drastically reduced following the widespread introduction of antiretrovirals, which restored immunocompetence amongst patients, keeping the HIV status under control²
• Overall, there is a significant epidemiological disparity relating to KS between regions and population groups. In 2020, 73% of cases of Kaposi Sarcoma were documented in Africa, along with 86.6% of the deaths from KS worldwide³

What is the clinical presentation and staging of Kaposi Sarcoma?

The presentation of KS can be obvious in most scenarios. Most commonly, the condition is identified via the appearance of skin lesions. 

Skin lesions: Red, purple, or brown in colour lesions or nodules; often on lower limbs, face or in the oral cavity. During the height of the AIDS epidemic, the visibility of these skin lesions was a highly stigmatising sign of HIV infection.² 

• Visceral involvement: internal organs involving the gastrointestinal tract, lungs, and liver, with symptoms such as bleeding, breathlessness, or total organ dysfunction²
• Swelling
• Systemic symptoms: fever, weight loss

The terminology ‘staging’ is used when talking about cancer. It is related to the amount of cancer detected in the body (both tumour size and location). It can assist in determining if the cancer has spread, and it aids in patient prognosis.⁵ AIDS related KS is the only subtype of the condition to have a tumour staging system- the AIDS Clinical Trials Group (ACTG) for classification of KS. It categorises a patient's prognosis into either good risk or poor risk. See section ‘What is the scoring system for prognostic staging of Kaposi’s Sarcoma?’ for more information on ACTG.

What factors can affect the prognosis of patients with Kaposi’s Sarcoma?

The factors listed below jointly play a role in patient survival, disease progression and determine treatment protocols. 

A. Type of KS

• AIDS-related: more aggressive, poorer prognosis without therapy
• Classic/endemic/ organ transplant: slower progression

B. Immune status

• CD4 count (especially <200 cells/µL in HIV patients) is linked to worse outcomes
• HIV viral load and ART adherence are critical for a good prognosis

C. Tumour burden

• Extent and location of lesions (cutaneous vs. visceral)
• • The presence of swelling or ulceration worsens the prognosis

D. Systemic symptoms

Presence of opportunistic infections -fever, weight loss, night sweats.

F. Response to therapy

• Antiretroviral therapy (ART) responsiveness - dramatic outcome improvements
• Effectiveness of chemotherapy, radiation, or immunotherapy

E. Co-morbidities

Secondary malignancies or conditions can lead to a poor prognosis.

What is the scoring system for prognostic staging of Kaposi’s Sarcoma?

Unlike most cancers, an official scoring system for KS does not exist. The ACTG criteria and staging system were designed for AIDS- related KS only. It provides direction for patient prognosis and guides treatment in HIV positive KS patients.⁶ It classifies 3 variables: tumour extent (T), immune status (I) and systemic symptoms (S) into 2 categories: good risk (0) and poor risk (1).⁶ See the table below for parameters and outcomes. Good risk T0, I0, S0 would equate to a good prognosis, whereas a patient with T (1), I (1), S (1) would have a much poorer prognosis.²

There are several limitations to the ATCG model, including: unavailability of medical records, in Sub-Saharan Africa, no access to resources such as laboratory testing for CD4+ levels, HIV viral load or organ function tests and adherence to or availability of ART for patients. The variability in the parameters demonstrates the need to identify additional biomarkers in KS staging for newer, improved prognostic models.⁶

In many cases, prognosis has been determined by KS subtype following historical trends for the same. Modified prognostic models exist for non- AIDS related KS patients which also take additional variables into account, including response to ART, haemoglobin levels, HIV viral load and internal organ functions. In areas like SSA, where laboratory or imaging is unavailable, a staging model involves focus on symptoms, lesion coverage and daily functional impact. 

Treatment implications based on prognosis

Treatment of KS is dependent on the classification and stage of the disease and should be tailored on an individual basis. Standard KS treatment has not changed in almost 30 years. AIDS related KS responds best by directly treating the HIV with antiretroviral therapy to suppress the virus and restore the patients’ immune system.⁴ Through obtaining a healthy immune system, ART grants those patients with HIV the ability to live long and healthy lives. In many circumstances and settings, however, many sufferers of HIV remain undiagnosed, untreated, or non-adherent to treatment, and, as a result, their HIV disease progresses.⁹

Treatment based on the different prognosis of KS:

• Good prognosis where the disease is localised – standard ART alone, localised therapy like cryotherapy or radiation can be used in addition if required. The aim is to control the disease, restore the immune system and cause lesion regression
• Intermediate prognosis where the staging is difficult to determine due to a mixture of presentations – ART plus a systemic therapy like chemotherapy or immunotherapy. The aim is to improve and monitor the immune system, to control the progression of lesions and to see patient improvement without causing toxicity
• Poor prognosis, the patient presenting with visceral inclusions and systemic illness- aggressive management is required combination of ART and chemotherapy, along with supportive care to treat infections, organ dysfunction or other complications. The aim is to improve the quality of life while managing complications. Palliative care is advised⁴
• Early diagnosis of KS is extremely important for the patient to receive a good prognosis and a treatment strategy which works effectively, initiating ART therapy as soon as possible. As of January 2025, the WHO are developing updated guidance on the management of advanced HIV disease, including models for KS, as the current guidelines date back to 2014⁷

What are the survival outcomes for patients with Kaposi’s Sarcoma?

Survival rates of patients are dependent on the KS subtype and whether the patient has access to treatment. KS is typically more aggressive in Africa, as patients often present late with advanced HIV. The disease is usually widely spread throughout the body and progresses rapidly, which impacts survival drastically. 6 In this scenario, patients frequently present with other comorbidities (Tuberculosis commonly), which also impact survival rates.

Survival rates based on KS subtype

• Classic: Usually ~ 5-year survival rate, as it is a condition seen most in elderly men, patients typically die with the condition and not from the condition
• Endemic: Varying survival rates, dependent on ART and chemotherapy access. Poor survival outcome in children and aggressive cases
• Organ-transplant recipients: The Survival rate is high if immunosuppressive therapy is reduced, ~ 5-year survival
• Aids- related: Varying survival rates, with ART treatment access and adherence, ~ 5-year survival rate
• Without ART treatment access, the average survival in aggressive cases⁸
• Overall, it is evident that ART plays a large role in improving long-term outcomes

What does the future look like for Kaposi’s Sarcoma?

In the context of medical advancements of novel therapies and biomarkers, the future of Kaposi Sarcoma detection and management is encouraging. Biomarkers are in development for HHV-8 viral load and cytokine profiles, along with patient genomic profiling. Global health efforts are creating accessibility to laboratory testing, early detection technologies and widespread access to ART treatment to those who need it, especially in resource-limited endemic countries like SSA. Access to ART will continue to reduce the incidence and improve the outcomes of AIDS related KS.

The systemic chemotherapy drugs used and effective recently are known as Liposomal chemotherapy (liposomal anthracyclines), which is showing promise during trials in the treatment of advanced KS.¹⁰ Another promising tool currently in research development is Immune checkpoint inhibitors (e.g., PD-1 inhibitors), which work as they allow the body’s T cells to better recognise and attack cancer cells.¹¹ Targeted therapies (e.g., anti-angiogenic agents) which slow down/ prevent tumour growth show promise also in the treatment of advanced KS.¹²

There is ongoing research into the use of HHV-8-directed therapy to treat KS, but it is in early stages of study.¹³ The development of a vaccine for HHV-8 could also become available as a preventative measure in the future.

Summary

The prognosis of Kaposi Sarcoma varies widely depending on subtype, immune function and access to treatment. AIDS-related KS outcomes have significantly improved with earlier diagnosis, along with timely access to ART and chemotherapy being key to improving patient survival rates through restoring the immune system function. The future of KS is closely tied to continued advancements and progress in HIV care, cancer treatment, and global access to care. With continued research and development of novel intervention options, KS may become increasingly rare and more manageable.