First described by Hungarian dermatologist Kaposi in 1872 [
Kaposi’s sarcoma typically presents as cutaneous purplish, reddish-blue, or dark brown/black macules, plaques, and nodules on the lower legs and feet with or without associated extremity lymphedema. Kaposi’s sarcoma lesions are heterogeneous with respect to both size and aggressiveness. Although most cases follow a chronic indolent course [
The demographics, epidemiology, diagnosis, and treatment for Kaposi’s sarcoma have changed significantly over the past 30 years with the spread of the HIV/AIDS epidemic in the early 1980s, the widespread introduction of combination highly active antiretroviral treatment (HAART) in the mid-1990s, and the advancing age of the United States population in the 2000s. The Miami Beach community had a unique position during this time span; it served a large group of elderly patients while also serving a population that was one of the epicenters for the HIV/AIDS epidemic in the United States [
In order to further understand this rare disease and its corresponding staging, treatment, and prognosis, we analyzed a large case series at our institution. With the knowledge gained from this study, we hoped to improve the quality of care at our institution.
This retrospective study was conducted with prior approval of the Mount Sinai Medical Center Institutional Review Board. We reviewed the tumor registry of Mount Sinai Medical Center in Miami Beach, FL, USA to identify all cases of Kaposi’s sarcoma diagnosed between January 1, 1987 and December 31, 2007. There were 143 cases identified according to the International Classification of Diseases-Oncology, 1st, 2nd, and 3rd Editions (ICD-O-1: 1976–1989, ICD-O-2: 1990–2000, ICD-O-3: 2001–2007 [
Epidemiological, staging, and treatment descriptive frequencies in a population of Kaposi’s sarcoma patients diagnosed at Mount Sinai Medical Center in Miami Beach, FL, USA.
Category | Median | Standard deviation |
---|---|---|
Age at diagnosis (years) | 41 | 19.9 |
| ||
Category | Number ( |
Percentage (%) |
| ||
Sex | ||
Female | 14 | 9.8 |
Male | 129 | 90.2 |
Race and ethnicity | ||
White, non-Hispanic | 86 | 60.1 |
White Hispanic | 40 | 28.0 |
Black | 17 | 11.9 |
Smoking status | ||
Nonsmoker | 61 | 42.7 |
Ex-smoker | 37 | 25.9 |
Current smoker | 21 | 14.7 |
Unknown | 24 | 16.8 |
Age range at diagnosis | ||
21–40 | 65 | 45.5 |
41–60 | 42 | 29.4 |
61–80 | 16 | 11.2 |
>80 | 20 | 14.0 |
Year of Kaposi’s diagnosis | ||
1987–1996 | 82 | 57.3 |
1997–2007 | 61 | 42.7 |
Site of initial presentation | ||
Nonskin | 18 | 12.6 |
Skin | 125 | 87.4 |
Stage at diagnosis | ||
Local | 61 | 40.6 |
Regional | 24 | 16.8 |
Distant | 58 | 40.6 |
Chemotherapy | ||
None | 115 | 80.4 |
Chemotherapy, single agent | 19 | 13.3 |
Chemotherapy, multiple agents | 9 | 6.3 |
Radiation therapy | ||
No radiation | 93 | 65.0 |
Radiation | 50 | 35.0 |
HIV status | ||
HIV-positive | 75 | 52.4 |
HIV-negative | 68 | 47.6 |
Descriptive statistics were used for analysis of clinical variables. The chi-square test of independence was used to assess associations between categories. A time-to-event analysis was constructed to evaluate overall survival (OS) in relation to clinical category. Survival time was defined as the period from date of diagnosis until date of death or date of last visit. Patients were classified into two categories based on their survival status: censored or death. The Kaplan-Meier [
Of the 143 KS patients identified, the majority were males (90.2%), non-Hispanic whites (60.1%) nonsmokers (42.7%) who were diagnosed between 1987 and 1996 (57.3%, Table
The Kaplan-Meier analysis demonstrated an overall survival of 27% at 5 years (Figure
Median, two- and five-year survival rates for demographic and clinical variables in a population of Kaposi’s sarcoma patients diagnosed at Mount Sinai Medical Center in Miami Beach, FL, USA.
Variable | Median survival (months) (95% CI) |
|
2-year survival (%) | 5-year survival (%) |
---|---|---|---|---|
Sex | 0.84 | |||
Female | 28 (3, 106) | 57.1 | 21.4 | |
Male | 23 (14, 26) | 45.0 | 20.9 | |
Race and ethnicity | 0.01 | |||
Non-Hispanic, white | 20 (12, 25) | 39.5 | 18.6 | |
Hispanic white | 56 (26, 128) | 70.0 | 32.5 | |
Black | 8 (2, 23) | 23.5 | 5.9 | |
Smoking status | 0.32 | |||
Nonsmoker | 23 (13, 31) | 47.5 | 19.7 | |
Ex-smoker | 17 (8, 28) | 43.2 | 21.6 | |
Current smoker | 36 (13, 134) | 61.9 | 28.6 | |
Unknown | 15 (4, 26) | 33.3 | 16.7 | |
Age at diagnosis, years (range) | 0.34 | |||
21–40 | 22 (10, 26) | 43.0 | 28.0 | |
41–60 | 18 (9, 26) | 39.0 | 22.0 | |
61–80 | 38 (4, 128) | 61.0 | 46.0 | |
>80 | 32 (12, 88) | 65.0 | 31.0 | |
Year of Kaposi’s diagnosis | 0.004 | |||
1987–1996 | 14 (9, 23) | 35.0 | 12.0 | |
1997–2007 | 87 (38, —) | 65.0 | 56.0 | |
Site of initial presentation | 0.04 | |||
Skin | 23 (20, 28) | 48.0 | 29.0 | |
Nonskin | 9 (3, 26) | 30.0 | 29.0 | |
Stage at Diagnosis | 0.17 | |||
Local | 32 (14, 76) | 54.1 | 27.9 | |
Regional | 22 (7, 123) | 50.0 | 16.7 | |
Distant | 17 (9, 24) | 36.2 | 15.5 | |
Chemotherapy | 0.26 | |||
None | 23 (18, 29) | 47.8 | 23.5 | |
Chemotherapy, single agent | 14 (5, 52) | 47.4 | 10.5 | |
Chemotherapy, multiple agents | 9 (3, 24) | 22.2 | 11.1 | |
Radiation therapy | 0.98 | |||
No radiation | 23 (12, 31) | 46.2 | 22.6 | |
Radiation | 22 (12, 28) | 46.0 | 18.0 | |
HIV status | 0.91 | |||
HIV-positive | 19 (9, 26) | 41.3 | 22.7 | |
HIV-negative | 25 (21, 32) | 51.5 | 19.1 |
*Log-rank and Wilcoxon tests.
Kaplan-Meier curve demonstrating the overall survival (27% at 5 years) in a population of Kaposi’s sarcoma patients diagnosed at Mount Sinai Medical Center in Miami Beach, FL, USA.
Kaplan-Meier curve demonstrating a significantly improved survival based on ethnicity (non-Hispanic white versus Hispanic white,
Kaplan-Meier curve demonstrating a significantly improved survival based on date of diagnosis (1997–2007 versus 1987–1996,
Kaplan Meier curve demonstrating a significantly improved survival based on site of initial presentation (skin versus non-skin;
Multivariate analysis revealed Hispanic whites were 45% less likely to die than non-Hispanic whites when controlling for year of diagnosis (Table
Univariate and multivariate Cox-proportional hazards models in a population of Kaposi’s sarcoma patients diagnosed at Mount Sinai Medical Center in Miami Beach, FL, USA.
Variable | Hazard ratio |
|
---|---|---|
Age | ||
>50 | 0.91 (0.60, 1.21) | 0.66 |
<50* | 1 | |
Year of diagnosis | ||
1997–2007 | 0.38 (0.24, 0.60) |
<0.0001 |
1987–1996* | 0.33 (0.19, 0.55)** |
<0.0001 |
Sex | ||
Male | 0.94 (0.69, 1.19) | 0.84 |
Female* | 1 | |
Ethnicity | ||
Hispanic, white | 0.52 (0.36, 0.68) |
0.01 |
Non-Hispanic, white* | 0.55 (0.33, 0.90)** |
0.02 |
Smoking | ||
Current | 0.62 (0.46, 0.77) | 0.17 |
Former | 1.06 (0.73, 1.39) | 0.82 |
Nonsmoker* | 1 | |
Site of initial presentation | ||
Skin | 0.69 (0.49, 0.88) | 0.22 |
Nonskin* | 1 | |
Stage | ||
Regional | 1.14 (0.83, 1.45) | 0.68 |
Distant | 1.48 (0.99, 1.96) | 0.07 |
Local* | 1 | |
Chemotherapy | 1.27 (0.92, 1.62) | 0.43 |
No chemotherapy* | 1 | |
Radiation | 1.01 (0.67, 1.34) | 0.98 |
No radiation* | 1 | |
HIV status | ||
Positive | 1.02 (0.67, 1.36) | 0.91 |
Negative* | 1 |
*Reference level.
**Significant variables based on multivariate analysis.
As with earlier case series and reported epidemiological data [
An unexpected finding in our series was the higher five-year survival rate among the Hispanic white population. We initially hypothesized this difference was due to an older non-Hispanic white population with multiple comorbidities and a Hispanic white population with greater access to healthcare, supportive services, and community resources. Upon further data analysis, as opposed to non-Hispanic white patients, a significant majority of the Hispanic white patients were less than 50 years old. Despite a relatively small patient population, we suspect the difference in five-year survival was, in part, due to a younger, healthier Hispanic white KS population. However, an underlying genetic polymorphism contributing to improved survival must be considered, as there is evidence that differences in KS survival among ethnic groups can be explained by a TP53 polymorphism at codon 72 [
Consistent with previous literature [
Similar to earlier studies, the majority of patients in our study were diagnosed between 1987 and 1996, corresponding with the peak of the HIV epidemic [
The patients in our study population with distant disease at diagnosis had a significantly shorter survival compared to patients with local and regional disease at diagnosis. However, patients with regional disease had essentially the same survival as those with local disease only. These findings reflect the strengths and limitations of the SEER local/regional/distant KS classification scheme. All of our patients were classified based on this system, which was amended twice during the course of our study period [
We hypothesized that those patients given chemotherapy and/or radiation would have longer survival times. However, our data revealed a trend toward worsening survival among patients receiving chemotherapy. This unusual finding may in part be explained by the fact that patients receiving chemotherapy were more likely to have advanced and bulky disease at diagnosis. Since there were no National Comprehensive Cancer Network (NCCN) guidelines for disease management, decisions to treat patients with chemotherapy were left to physician’s discretion. Similar to several other malignancies, the major goals of KS treatment involve symptom palliation, prevention of disease progression, and attempts to improve survival [
Another possible explanation for the lack of significant survival benefit with chemoradiation techniques was the difference in chemotherapy treatment and radiation techniques offered to the patient population. Treatment for KS changed over the past 30 years and patients diagnosed and treated in the 2000s were treated much differently than those in the 1980s and 1990s. Currently, treatment options for localized cutaneous KS lesions include surgery [
Currently accepted indications for systemic chemotherapy for KS include widespread skin involvement, extensive skin involvement unresponsive to other therapies, extensive extremity edema, symptomatic visceral organ involvement, and immune reconstitution syndrome. Pegylated liposomal doxorubicin and liposomal doxorubicin have been established as first-line treatments for KS, unless there is a cardiac contraindication [
Based on the results of our study, we believe that each patient’s treatment should be individualized, taking into account immune status, tumor bulk, ethnic status, comorbidities, and quality-of-life measures. Large randomized studies are needed to compare currently accepted treatment options. In addition to survival studies incorporating new treatment guidelines [
One of the major limitations of our study was the inability to obtain CD4 counts and HIV viral loads for HIV-positive patients. We were also unable to obtain patients’ HAART treatment history. Due to these limitations, we were unable to reach conclusions regarding KS survival and degree of immunosuppression from HIV/AIDS. From the data obtained from this study, we believe that tumor databases, when dealing with HIV-associated malignancies, need to include information regarding patient’s HIV status and treatment. This information will be useful not only for future KS studies, but also for the treatment planning of patients.
Another limitation of our study was our inability to determine cause of death of our patients. Due to this limitation, we were unable to draw conclusions regarding whether patients died from KS versus other disease processes. This information would have been useful in the elderly and post-HAART HIV patients where we suspect many succumbed to disease processes unrelated to KS.
Our decision to create the timeframes (1987–1996 and 1997–2007) was not arbitrary. The United States Federal Drug Administration approved the first protease inhibitor, saquinavir, on December 6, 1995 [
We were unable to report on the type of chemotherapy or radiation used in the treatment of our KS patients. These data were not recorded in the cancer database during the 1980s and 1990s. As was previously mentioned, KS treatment greatly improved over the course of the study timeframe. Therefore, consolidating all radiation and chemotherapy regimens prohibited conclusions regarding efficacy.
Our study did not distinguish between subtypes of KS, including those associated with organ transplants. However, we assumed that the total number of patients from this group was negligible, because our hospital did not perform solid organ or stem cell transplants.
This large retrospective study provides further insight into the epidemiology, staging, treatment, and prognosis of KS. The majority of KS patients identified were young, nonsmoking, HIV-positive, non-Hispanic white males diagnosed during the peak of the HIV epidemic. There were no significant differences in survival among patients based on sex, HIV status, or radiation received. There was a trend towards an improved survival among patients who were older, currently smoking, had localized stage at diagnosis, and had received no chemotherapy. Hispanic white patients had superior outcomes compared with non-Hispanic whites. Patients diagnosed from 1997 to 2007 had superior outcomes compared to those diagnosed from 1987 to 1996.
The authors declare that they have no conflict of interests.
The authors acknowledge the critical review and editorial assistance of Richard L. Theriault, D.O., M.B.A., F.A.C.P., Professor of Medicine, MD Anderson Cancer Center, Houston, TX, USA.