Objectives: The incidence of soft tissue sarcomas (STSs) among older patients is increasing. Although surgical treatment of elderly patients with STS has been reported to improve their prognosis, most of these studies included patients with STS aged <85 years. This study aimed to analyze the clinical features and prognostic factors of STS in elderly patients aged ≥90 years. Subject and Methods: We retrospectively identified patients aged ≥90 years with STS who were treated at our two hospitals between 1994 and 2022. Data on clinical information and detailed assessments were collected. We evaluated the features and factors affecting the prognosis of patients with older-extremity STS. In addition, we compared the clinical courses and results of patients treated with surgery and radiotherapy for primary tumors. Results: Among 454 patients with STS, 16 were aged ≥90 years. Kaplan-Meier curves for overall survival showed a significantly poorer prognosis in patients who did not receive surgical treatment (p = 0.0348) and those who received radiotherapy (p = 0.0070). Moreover, we investigated the difference in prognosis between surgical treatment and radiotherapy, excluding two cases with distant metastasis at initial diagnosis and one case with no treatment. Kaplan-Meier curves for overall survival showed a significantly better prognosis in patients who underwent surgical treatment (p = 0.0161). Univariate analysis revealed that only primary tumor size was a significant predictor of poor prognosis (p = 0.0426). Conclusion: In patients with STS aged ≥90 years old, aggressive surgical treatment may improve the prognosis more than radiotherapy.

Highlight of the Study

  • This study investigated the clinical features and prognostic factors of soft tissue sarcoma (STS) in elderly patients aged ≥90 years.

  • Among 454 patients with STS, 16 were aged ≥90 years (3.5%).

  • Aggressive surgical treatment, rather than radiotherapy, may improve the prognosis in elderly patients aged ≥90 years.

The proportion of the elderly population in developed countries is increasing rapidly. According to the United Nations, the most significant increase is expected to occur in Japan [1]. The proportion of Japanese citizens aged >65 years has reached 29% by 2022, and it is expected to increase to 36% by 2050. In recent years, the incidence of soft tissue sarcoma (STS) in older patients has been increasing, and older age has been reported as one of the factors indicating a poor prognosis [2]. Although radical resection is important in the treatment of STS, a less aggressive treatment is sometimes selected for elderly patients because of comorbidities and decreased performance status. However, in recent years, the surgical treatment of elderly patients with STS has been reported to improve their prognoses. Most of these studies included patients with STS aged ≥65 years, ≥70 years, and at most ≥80 years [2‒9]. Furthermore, a few reports on patients with STS aged ≥85 years have also indicated that surgical treatment improves prognosis [10, 11].

Recent reports indicate that surgical treatment improves the prognosis of femoral neck fractures, even in patients aged ≥90 years [12]. Due to the aging population in Japan, patients with STS aged ≥90 years accounted for approximately 1.0% of all patients with STS in 2009; however, the proportion of patients in this age group increased to 2.5% in 2021 [13, 14]. Aggressive treatment was often not administered to patients with STS aged ≥90 years. Nevertheless, as the population continues to age, consideration of treatment strategies for elderly individuals with STS becomes critical. This study aimed to analyze the clinical features and prognostic factors of STS in elderly patients aged ≥90 years.

Subjects

We retrospectively identified patients aged ≥90 years with STS involving the extremities or trunk who were treated at our two hospitals between 1994 and 2022. Patient records were searched to collect data, including age, sex, histological subtype, malignancy, anatomical tumor location, size, period from onset to consultation, presence or absence of unplanned excision, metastasis at diagnosis, the American Society of Anesthesiologists physical status (ASA-PS) classification system [15], primary tumor treatment, local and distant relapse, follow-up period, and outcomes. Soft tissue sarcoma specimens were classified using the French Federation of Cancer Center Sarcoma Group system, which includes mitotic index, necrosis extension, and histological differentiation [16]. Additionally, we collected information on the type of local therapy and surgical margins (Enneking staging system) of patients who underwent surgery [17]. In the absence of any events, patients were de-identified at the last follow-up.

We evaluated the features of patients aged ≥90 years and the factors affecting the prognosis of extremity older patients. In addition, we compared the clinical courses and results of patients treated with surgery versus those treated with radiation therapy for primary tumors.

This study was approved by the Institutional Review Board for Clinical Research at Akita University (Approval No. 2149) and was conducted in accordance with the 1975 Declaration of Helsinki and its 1983 revision. Informed consent was obtained from all the patients.

Statistical Analysis

All continuous variables were expressed as mean ± standard deviation. A Cox proportional hazards model was used to identify factors affecting prognosis. The curve for overall survival was drawn according to the Kaplan-Meier method, and differences were analyzed using the generalized Wilcoxon test. Statistical significance was defined as a p value of <0.05.

Among the 454 patients with STS, 16 (3.5%) with a mean age of 91.6 years (90–94 years) were aged ≥90 years and were included in this study. The clinicodemographic characteristics of the patients are shown in Table 1. Undifferentiated pleomorphic sarcoma (UPS) was the most common histological subtype (n = 9), followed by dedifferentiated liposarcoma (n = 2). Among the histological subtypes, 1 patient each had pleomorphic liposarcoma, myxofibrosarcoma, synovial sarcoma, leiomyosarcoma, and a malignant peripheral nerve sheath tumor. The median period from onset to consultation was 25.7 ± 35.5 months (0–108 months), and the mean follow-up was 14.9 ± 12.5 months (2–50 months). Inappropriate excision was performed in 4 patients (25%). The primary tumors occurred in the thigh (n = 6), lower leg (n = 3), upper arm (n = 2), forearm (n = 2), back (n = 2), and knee (n = 1). The mean tumor size for all patients was 89.1 ± 41.7 mm (40–168 mm), and the FNCLCC classifications were Grade I for 3 patients, Grade II for 5 patients, and Grade III for 8 patients.

Table 1.

Clinical data of 16 patients aged ≥90 years with soft tissue sarcoma

Number 16 
Age, years 91.6±1.5 
Sex – male/female 5/11 
Histological subtype 
 Undifferentiated pleomorphic sarcoma 
 Dedifferentiated liposarcoma 
 Pleomorphic liposarcoma 
 Myxofibrosarcoma 
 Synovial sarcoma 
 Leiomyosarcoma 
 Malignant peripheral nerve sheath tumor 
Size, mm 89.1±41.7 
Period from onset to consultation, months 25.7±35.5 
Past inappropriate excision – present/none 4/12 
Location – extremity/axial 14/2 
FNCLCC classification – grade I/II/III 3/5/8 
All distant metastasis – present/none 5/11 
 Distant metastasis at diagnosis 
 Distant metastasis after diagnosis 
ASA-physical status classification system – I/II/III/IV/v 0/10/6/0/0 
Surgical treatment for primary tumor – present/none 10/6 
 Surgical margin – adequate/inadequate 10/0 
Local recurrence after surgical treatment – present/none 4/6 
Radiotherapy – present/none 7/9 
 Radiotherapy for primary tumor 
 Radiotherapy for non-primary tumor 
Chemotherapy – present/none 1/15 
 Chemotherapy for primary tumor 
 Chemotherapy for non-primary tumor 
Surgical treatment for local recurrence and distant metastasis 
Follow-up period, months 14.9±12.5 
Outcome at the last follow-up – NED/AWD/DOD 8/2/6 
Number 16 
Age, years 91.6±1.5 
Sex – male/female 5/11 
Histological subtype 
 Undifferentiated pleomorphic sarcoma 
 Dedifferentiated liposarcoma 
 Pleomorphic liposarcoma 
 Myxofibrosarcoma 
 Synovial sarcoma 
 Leiomyosarcoma 
 Malignant peripheral nerve sheath tumor 
Size, mm 89.1±41.7 
Period from onset to consultation, months 25.7±35.5 
Past inappropriate excision – present/none 4/12 
Location – extremity/axial 14/2 
FNCLCC classification – grade I/II/III 3/5/8 
All distant metastasis – present/none 5/11 
 Distant metastasis at diagnosis 
 Distant metastasis after diagnosis 
ASA-physical status classification system – I/II/III/IV/v 0/10/6/0/0 
Surgical treatment for primary tumor – present/none 10/6 
 Surgical margin – adequate/inadequate 10/0 
Local recurrence after surgical treatment – present/none 4/6 
Radiotherapy – present/none 7/9 
 Radiotherapy for primary tumor 
 Radiotherapy for non-primary tumor 
Chemotherapy – present/none 1/15 
 Chemotherapy for primary tumor 
 Chemotherapy for non-primary tumor 
Surgical treatment for local recurrence and distant metastasis 
Follow-up period, months 14.9±12.5 
Outcome at the last follow-up – NED/AWD/DOD 8/2/6 

Values are expressed as number of patients or mean ± SD with ranges.

FNCLCC, French Federation of Cancer Center Sarcoma Group; NED, no evidence of disease; ASA, American Society of Anesthesiologists; AWD, alive with disease; DOD, died of disease.

Surgical treatment of the primary tumor was performed in 10 patients (62.5%), and adequate tumor-free margins were achieved in 100% of cases. Adjuvant therapy for surgical margin was not conducted in all patients. Radiotherapy for the primary tumor was performed in 5 patients (31.3%) and did not include heavy-ion radiation, proton beam radiation, or radiotherapy plus surgery. Chemotherapy was not used for the primary tumor in any of the subjects; however, pazopanib was used for distant metastasis in 1 case. Local recurrence occurred in 4 patients, with 1 patient undergoing surgical resection and 2 patients receiving radiotherapy. Distant metastases developed in 5 patients (31.2%), and 2 of these patients were present at diagnosis. All 5 cases had metastases to the lungs, and one case also had lymph node metastases. The patient outcomes were as follows: no evidence of disease in 8 patients, alive with disease in 2 patients, and 6 patients died because of their original disease. None of the patients died of complications during the perioperative period.

Kaplan-Meier curves for overall survival showed a significantly poorer prognosis in patients who did not receive surgical treatment (p = 0.0348) and those who received radiotherapy (p = 0.0070) (Fig. 1). Moreover, we investigated the difference in prognosis between surgical treatment (n = 10) and radiotherapy (n = 3) in 13 cases, excluding two cases where distant metastasis had occurred at the initial diagnosis, which is considered to have a significant impact on prognosis, and one case with no surgical treatment or radiotherapy. Kaplan-Meier curves for overall survival showed a significantly better prognosis in patients who underwent surgical treatment (p = 0.0161) (Fig. 2). However, univariate analysis revealed that only the size of the primary tumor was a significant predictor of poor prognosis (p = 0.0426), and the treatment method was not mentioned as a significant factor influencing prognosis (Table 2).

Fig. 1.

Kaplan-Meier overall OS curves according to surgical treatment (a) and radiotherapy (b) for all patients. A significant difference was observed between the two groups (p = 0.0348 and p = 0.007, respectively).

Fig. 1.

Kaplan-Meier overall OS curves according to surgical treatment (a) and radiotherapy (b) for all patients. A significant difference was observed between the two groups (p = 0.0348 and p = 0.007, respectively).

Close modal
Fig. 2.

Kaplan-Meier overall survival curves according to surgical treatment, excluding those with distant metastases at initial diagnosis and those without any treatment. A significant difference was observed between the two groups (p = 0.0161).

Fig. 2.

Kaplan-Meier overall survival curves according to surgical treatment, excluding those with distant metastases at initial diagnosis and those without any treatment. A significant difference was observed between the two groups (p = 0.0161).

Close modal
Table 2.

Univariate analysis of factors affecting prognosis

VariablesOR95% CIp value
Age 1.181 0.507–2.751 0.7005 
Sex – female 0.283 0.051–1.587 0.1515 
Size 1.037 1.001–1.075 0.0426 
Period from onset to consultation 1.016 0.986–1.047 0.2861 
Past inappropriate excision 0.573 0.100–3.292 0.5325 
Histological grade – high 0.909 0.261–3.169 0.8815 
ASA-physical status classification system 0.646 0.104–4.037 0.6406 
Surgical treatment for primary tumor 0.143 0.017–1.233 0.0768 
All distant metastasis 2.918 0.525–16.217 0.2210 
Distant metastasis at diagnosis 5.826 0.789–43.035 0.0841 
VariablesOR95% CIp value
Age 1.181 0.507–2.751 0.7005 
Sex – female 0.283 0.051–1.587 0.1515 
Size 1.037 1.001–1.075 0.0426 
Period from onset to consultation 1.016 0.986–1.047 0.2861 
Past inappropriate excision 0.573 0.100–3.292 0.5325 
Histological grade – high 0.909 0.261–3.169 0.8815 
ASA-physical status classification system 0.646 0.104–4.037 0.6406 
Surgical treatment for primary tumor 0.143 0.017–1.233 0.0768 
All distant metastasis 2.918 0.525–16.217 0.2210 
Distant metastasis at diagnosis 5.826 0.789–43.035 0.0841 

OR, odds ratio; 95% CI, 95% confidence interval.

This study showed that surgical treatment may have a better prognosis than radiation therapy for patients with STS aged ≥90 years. Regarding factors associated with poor prognosis, although it has not been shown whether surgical treatment improves prognosis, there is some recognition of this tendency. Previous reports on elderly patients with STS have shown that aggressive surgical treatment may improve the prognosis [2‒11]. However, few reports have examined STS patients aged ≥90 years, and the only report evaluating this group did not evaluate the impact of surgical treatment on prognosis [18]. Therefore, this is the first report to examine the effects of surgical treatment on STS patients aged >90 years. Although this study has the disadvantage of a small number of cases, we submit that it furnishes useful information.

It is assumed that elderly patients aged ≥90 years have more complications than younger patients, and the risk of surgical treatment is higher. In the current study, we evaluated ASA-PS, a risk assessment tool for general anesthesia surgery. Among the 10 patients who underwent surgical treatment, the ASA-PS was 2 in 8 patients and 3 in 2 patients. In contrast, among the 3 patients who received radiotherapy without distant metastases at the initial diagnosis, ASA-PS was 2 in 1 case and 3 in 2 cases. Among the surgical cases, a high proportion involved low-risk patients with ASA-PS 2; however, patients with ASA-PS 3 also underwent surgical treatment in some cases. In contrast, even though the ASA-PS score was 2, surgery was not performed in some cases. In a previous report examining patients aged ≥90 years, 60.2% underwent surgical treatment, which was lower than that in other age groups [18]. In our study, surgical treatment was performed on 62.5% of the patients, a similar proportion. In patients aged ≥90 years, doctors or families of patients may often choose radiotherapy instead of active treatment simply by taking age into account. Older age has been reported as one of the factors indicating a poor prognosis in patients with STS [2]. Similarly, a report examining STS in patients aged ≥90 years showed a poor prognosis, especially in patients who did not receive surgical treatment [18]. In contrast, in this study, age ≥90 years was not cited as a factor for poor prognosis. Our previous study, which examined patients aged ≥85 years, showed that the prognosis was worse in this age group; however, it also demonstrated no difference in prognosis between patients who received surgical treatment and younger patients [11]. The results of previous studies may be affected by the fact that aggressive surgical treatment is not performed in elderly patients aged ≥90 years.

Previous reports examining patients with STS aged ≥90 years have indicated that UPS is the most common histological subtype (35.4%), often occurring in the extremities (59.3%) and head and neck (15.9%) [18]. Similarly, in our study, UPS was the most common histological subtype (56.3%). Regarding the site of occurrence, none of our cases involved the head and neck; however, a similar trend was observed, with an overwhelming majority of cases occurring in the extremities (87.5%).

In the present study, 3.5% of all patients with STS were aged ≥90 years. In a previous report, 113 of 12,835 patients with STS were aged ≥90 years, accounting for 0.88% [18]. In addition, in the 16-year STS case registration from 2006 to 2021 in Japan, 274 of 25,956 STS cases were aged ≥90 years, accounting for 1.06% [14]. Compared with these reports, our cases had an overwhelmingly higher proportion of patients aged ≥90 years. The population over the age of 65 in Akita and Hokkaido, northern regional prefectures, already showed high elderly population rates of 38.6 and 32.8% in 2022, respectively. This is mainly because the survey was conducted in two prefectures with the highest aging rates in Japan. In countries where population aging is expected to progress in the future, we believe it is necessary to conduct research targeting elderly people, as in this study.

One of the main limitations of this study was the small number of patients. Additionally, among the patients treated with radiotherapy, only three had no distant metastases at the initial diagnosis. As various factors influence the prognosis of STS, more cases are needed to perform detailed analyses that consider these factors. Therefore, further detailed studies with a larger number of patients are required.

This is the first study to examine the clinical features and prognostic factors of elderly STS patients aged ≥90 years. Even in patients with STS in the same age group, aggressive surgical treatment may improve the prognosis rather than radiotherapy. In developed countries, where the population is aging in the future, research targeting excessively elderly people will be necessary; therefore, conducting further research with a larger number of cases is necessary.

This study protocol was reviewed and approved by the Institutional Review Board for Clinical Research at Akita University (Approval No. 2149).

The authors have no conflicts of interest to declare.

No funding was received.

T.H., E.M., Y.T., and M.N.: planning and revision of research; T.H., E.M., N.H., M.Y., M.E., and S.J.: clinical data collection; T.H.: data analyses and manuscript preparation; and Y.T. and M.N.: manuscript review.

All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding author.

1.
United Nations
.
Dept. Of economic and social affairs. Population division
. In:
World population ageing: 1950-2050
.
New York, N.Y.
:
United Nations
;
2002
.
2.
Lahat
G
,
Dhuka
AR
,
Lahat
S
,
Lazar
AJ
,
Lewis
VO
,
Lin
PP
, et al
.
Complete soft tissue sarcoma resection is a viable treatment option for select elderly patients
.
Ann Surg Oncol
.
2009
;
16
(
9
):
2579
86
.
3.
Osaka
S
,
Sugita
H
,
Osaka
E
,
Yoshida
Y
,
Ryu
J
.
Surgical management of malignant soft tissue tumours in patients aged 65 years or older
.
J Orthop Surg
.
2003
;
11
(
1
):
28
33
.
4.
Buchner
M
,
Bernd
L
,
Zahlten-Hinguranage
A
,
Sabo
D
.
Primary malignant tumours of bone and soft tissue in the elderly
.
Eur J Surg Oncol
.
2004
;
30
(
8
):
877
83
.
5.
Tsuda
Y
,
Ogura
K
,
Kobayashi
E
,
Hiruma
T
,
Iwata
S
,
Asano
N
, et al
.
Impact of geriatric factors on surgical and prognostic outcomes in elderly patients with soft-tissue sarcoma
.
Jpn J Clin Oncol
.
2017
;
47
(
5
):
422
9
.
6.
Lev
D
,
Pollock
RE
.
Managing elderly soft tissue sarcoma patients-should age drive treatment
.
Ann Surg Oncol
.
2010
;
17
(
7
):
1725
6
.
7.
Boden
RA
,
Clark
MA
,
Neuhaus
SJ
,
A'hern
JR
,
Thomas
JM
,
Hayes
AJ
.
Surgical management of soft tissue sarcoma in patients over 80 years
.
Eur J Surg Oncol
.
2006
;
32
(
10
):
1154
8
.
8.
Al-Refaie
WB
,
Habermann
EB
,
Dudeja
V
,
Vickers
SM
,
Tuttle
TM
,
Jensen
EH
, et al
.
Extremity soft tissue sarcoma care in the elderly: insights into the generalizability of NCI Cancer Trials
.
Ann Surg Oncol
.
2010
;
17
(
7
):
1732
8
.
9.
Yoneda
Y
,
Kunisada
T
,
Naka
N
,
Nishida
Y
,
Kawai
A
,
Morii
T
, et al
.
Favorable outcome after complete resection in elderly soft tissue sarcoma patients: Japanese Musculoskeletal Oncology Group study
.
Eur J Surg Oncol
.
2014
;
40
(
1
):
49
54
.
10.
Okamoto
M
,
Yoshimura
Y
,
Aoki
K
,
Kito
M
,
Tanaka
A
,
Suzuki
S
, et al
.
Clinical outcomes of patients 80 years of age and older with soft tissue sarcoma
.
J Orthop Sci
.
2017
;
22
(
5
):
951
7
.
11.
Tsuchie
H
,
Emori
M
,
Nagasawa
H
,
Miyakoshi
N
,
Murahashi
Y
,
Mizushima
E
, et al
.
The prognostic significance of surgical treatment for excessive elderly patients with soft tissue sarcoma
.
Int J Clin Oncol
.
2018
;
23
(
4
):
775
82
.
12.
Liu
Y
,
Zhang
CW
,
Zhao
XD
.
Long-term survival of femoral neck fracture patients aged over ninety years: arthroplasty compared with nonoperative treatment
.
BMC Musculoskelet Disord
.
2020
;
21
(
1
):
217
.
13.
Japanese Orthopedic Association Musculoskeletal Tumor Committee
.
Soft tissue tumor registry in Japan 2009
.
Tokyo
:
National Cancer Center
;
2011
.
14.
Japanese Orthopedic Association Musculoskeletal Tumor Committee
.
Soft tissue tumor registry in Japan 2021
.
Tokyo
:
National Cancer Center
;
2023
.
15.
Hackett
NJ
,
De Oliveira
GS
,
Jain
UK
,
Kim
JY
.
ASA class is a reliable independent predictor of medical complications and mortality following surgery
.
Int J Surg
.
2015
;
18
:
184
90
.
16.
Coindre
JM
,
Terrier
P
,
Bui
NB
,
Bonichon
F
,
Collin
F
,
Le Doussal
V
, et al
.
Prognostic factors in adult patients with locally controlled soft tissue sarcoma. A study of 546 patients from the French Federation of Cancer Centers Sarcoma Group
.
J Clin Oncol
.
1996
;
14
(
3
):
869
77
.
17.
Enneking
WF
,
Spanier
SS
,
Goodman
MA
.
A system for the surgical staging of musculoskeletal sarcoma
.
Clin Orthop Relat Res
.
1980
;
153
:
106
20
.
18.
Basse
C
,
Italiano
A
,
Penel
N
,
Mir
O
,
Chemin
C
,
Toulmonde
M
, et al
.
Sarcomas in patients over 90: natural history and treatment-A nationwide study over 6 years
.
Int J Cancer
.
2019
;
145
(
8
):
2135
43
.