J Cancer Res Clin Oncol (1992) 118:635-636 C ilcer esearch Clinical @neology �9 Springer-Verlag 1992

Evaluation of different staging systems for Kaposi's sarcoma in HIV-infected patients Andrea Antinori, Immacolata Izzi, Adviana Ammassari, Gaetano Camilli, Rita Murri, and Enrica Tamburrini

Clinic of Infectious Diseases, Universit~t Cattolica del Sacro Cuore

Received 17 February 1992/Accepted 6 May i992

Summary. The records of 49 consecutive AIDS patients with Kaposi ' s sarcoma were analysed retrospectively to assess the prognostic value of the four staging systems proposed for epidemic Kaposi ' s sarcoma. The classifica- tions by Krigel and Mitsuyasu do not describe exactly the characteristics o f the disease, and do not give enough in- format ion on survival. Our study confirms that CD4 § cell depletion, systemic symptoms and opportunistic in- fections at diagnosis are the major prognostic factors and influence survival to a great extent, as shown by Krown and Chachoua.

Key words: H I V - AIDS - Kaposi ' s sarcoma - Staging systems - Survival

Introduction

The importance of a staging system that reliably predicts favourable and unfavourable outcomes of Kaposi ' s sar- coma has increased in recent years since the number of patients with Kaposi ' s sarcoma has risen because of AIDS.

Four major forms of classic Kaposi ' s sarcoma are gen- erally recognized, as proposed by Taylor (Taylor et al. 1971); however, no prognostic information can be gained f rom this classification based on clinical aspects only. More recent studies (Hymes et al. 1981; Fr iedman-Kien et al. 1982) showed that clinical features of the epidemic Kaposi ' s sarcoma (EKS) were peculiar and that factors other than the extent o f tumour may have prognostic value and influence survival. In addition, a uniform stag-

Abbreviations: EKS, epidemic Kaposi's sarcoma; OI, opportunistic infections; SS, systemic symptoms Correspondence to: A. Antinori, Clinic of Infectious Diseases, Uni- versitfi Cattolica del Sacro Cuore, L.go A. Gemelli 8~)0168 Roma, Italy

ing classification would also be of benefit to evaluate dif- ferent therapeutic protocols.

Patients and methods

We analysed retrospectively the records of AIDS patients with Ka- posi's sarcoma to assess the prognostic value of the four staging sys- tems proposed for EKS from 1983 through 1989 (Krigel et al 1983; Mitsuyasu and Groopman 1984; Krown et al. 1989; Chachoua et al. 1989).

For each patient we collected the following data: sex, HIV trans- mission modality, date of EKS diagnosis, age at onset, extent of tu- mour, and CD4 § cell count at diagnosis and previous/concomitant opportunistic infections (OI) or systemic symptoms (SS). Survival time was calculated from diagnosis of EKS until death or 15 Oc- tober 1991. We used Kaplan-Meier plots for survival analysis and the Wilcoxon test for comparison of groups. The independent effect on survival oftumour extent, CD4 + count and OI + SS as covariates was measured using the Cox proportional hazard model.

A group of 55 patients with EKS (54 male, 1 female) were fol- lowed at our clinic from 1985 to 30 September 1991; 42 were homo- sexuals, 8 were intravenous drug abusers, 5 heterosexuals. Their mean age at onset was 37.8 years (range 22-54). Six patients were lost at follow-up, leaving 49 evaluable cases in the study.

Results and discussion

The distribution of patients in each staging system and their survival time are shown in Table 1.

For the sake of clarity, the classifications of Krigel and Mitsuyasu and of Krown and Chachoua will be discussed together being based on similar criteria.

The classifications by Krigel and Mitsuyasu are based on the extent o f disease, and patients are grouped accord- ing to the presence or absence of SS or OI. In our popu- lation, no patient was in Krigel 's stage I I (cutaneous lo- cally aggressive disease) and in Mitsuyasu's stage I I I (vis- ceral involvement only). Although the tack of patients in these groups could be due to our small sample size, the practicability of maintaining these two stages in an ideal EKS classification can be questioned. When patients

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Table 1. Distribution of patients in the different staging systems a

Krigel 1983 Mitsuyasu 1984 Krown 1989

A B A B 0 1

Chachoua 1989

I 7 (356) 5 (138) I 7 (329) 6 (138) T 32 (365) II - - II 7 (591) 1 (109) I 6 (_)b III 18 (591) 7 (189) III - - S 19 (621) IV 4 (360) 8 (253) IV 15 (695) 13 (253)

17 (621) 43 (356) 30 (256)

I II III IV

3 (_)b 18 (591) 7 (253)

21 (256)

IB vs IIIA IB vs IVA I0 vs I1 II vs III (P = 0.0001) (P = 0.0002) (P = 0.04) (P = 0.001)

IB vs IIA SO vs S1 II vs IV (e = 0.0078) (P = 0.0006) (e = 0.0009)

a Median survival time is indicated in parenthesis. A, patients without systemic symptoms; B, patients with systemic symptoms b All patients alive

were stratified according to tumour stages, no correlation between stage, roughly corresponding to the bulk of the tumour, and survival time was observed. In fact, patients classified in Krigel 's stage I I IA and in Mitsuyasu's stage IVA showed a longer survival time than those in the other stages. On the other hand, a significantly longer survival time was observed in EKS patients without SS (group A) than in those with SS (group B); the probabil i ty of sur- vival at I year was 64% for group A and 26% for group B ( P = 0.0002). We therefore conclude that survival time is strongly influenced by the presence or absence of SS or OI rather than by the extent of turnout.

The patients were more equally distributed in the stages of the systems proposed by Krown and Chachoua. These classifications are based on the severity of immu- nodeficiency (CD4 § cell count) and the presence of SS or previous/concomitant OI. As an additional parameter , Krown includes a measure of tumour extent. In our pop- ulation, patients classified in the groups I0 or SO ("good risk") by Krown showed a significantly longer survival time than those in the groups 11 or SI ("poor risk"). No significant difference in survival time was observed be- tween patients in Krown 's stages TO and T1. Moreover, when patients were stratified according to Chachoua 's system, which does not consider tumour extent as a vari- able, survival time was longer in groups I and II than in groups I I I or IV. The importance of OI is highlighted by stratifying the patients in two groups. For patients with OI the propor t ion of surviving at 1 year was 26% com- pared to 67% of those without OI (P=0.01) . Cox re- gression analysis confirmed the independent effects, as covariates, of the CD4 § count (P = 0.001) and of OI + SS (corresponding to S of Krown 's staging system) ( P = 0.002), but not of the extent of tumour (P = 0.40), on sur- vival.

In conclusion, in agreement with the results of previ- ous studies (Chachoua et al. 1989; Mitsuyasu et al. 1986; Mitsuyasu 1987; Taylor et al. 1986; Antinori et al. 1991), our retrospective analysis shows that CD4 + cell deple-

tion, OI and SS are the major prognostic factors in EKS. The staging systems of Krown and Chachoua seem to be the most suitable for prospective studies, particularly when the assessment of the efficacy of new therapeutic protocols is the main objective.

R e f e r e n c e s

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Chachoua A, Krigel R, Lafleur F, Ostreicher R, Speer M, Lauben- stein L, Wernz J, Rubenstein P, Zang E, Friedman-Kien A (1989) Prognostic factors and staging classification of patients with epidemic Kaposi's sarcoma. J Clin Oncol 7:774-780

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