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Copyright (c) 2022 Slovenian Medical Journal. This work is licensed under a
Creative Commons Attribution-NonCommercial 4.0 International License.
The outcome of primary retroperitoneal sarcoma 
patients treated at sarcoma referral centre: the Institute 
of Oncology Ljubljana experience
Primarni retroperitonealni sarkomi: preživetje bolnikov, zdravljenih na Onkološkem 
inštitutu Ljubljana, referenčnem centru za sarkome
Marko Novak,1 Naja Bohanec,2 Andraž Perhavec,1,3 Sonja Kramer,1 Darja Eržen1
Abstract
Background: Retroperitoneal sarcomas are extremely rare, therefore, patients should be treated at sarcoma referral cen-
tre. Surgery is the mainstay of treatment. Compartmental resection is proposed as the best surgical approach.
Methods: The Institute of Oncology Ljubljana is the only referral centre for these patients in Slovenia. Data for all con-
secutive patients surgically treated from January 1999 to June 2020 for primary localized retroperitoneal sarcoma were 
extracted from a prospective surgical database. The patient outcome, quality of surgery, and postoperative adverse events 
were analysed.
Results: A hundred patients were eligible for the study. Their median age was 62 years. The median tumor size was 
21.5 cm. Dedifferentiated liposarcoma was the most common histology (39%). Compartmental resection was performed 
in 24% and multivisceral resection in 25%. 29% of patients had postoperative complication grade 3a or higher according 
to Clavien-Dindo classification and 58.6% (17/29) of them required reoperation. The 30-day and 90-day mortality rate was 
3% and 5%, respectively. The median follow-up was 55.1 months. The 5-year overall survival was 67.8%. The 5-year crude 
cumulative incidence of local recurrence and distant metastases were 16.9% and 21.4%, respectively. ASA score and blood 
loss during surgery were significant prognostic factors of overall survival.
Conclusion: Retroperitoneal sarcomas belong to the group of rare cancers. We achieve very good results in the treatment 
of retroperitoneal sarcoma patients and outcomes are comparable to other referral centres. Our results also confirm the 
crucial role of sarcoma referral centre in the management and treatment of these patients.
1 Department of Surgical Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia
2 Statistics and modeling, Novartis, Mengeš, Slovenia
3 Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
Correspondence / Korespondenca: Marko Novak, e: mnovak@onko-i.si
Key words: sarcoma; retroperitoneum; referral centre; treatment
Ključne besede: sarkom; retroperitonej; referenčni center; zdravljenje
Received / Prispelo: 10. 1. 2021 | Accepted / Sprejeto: 2. 8. 2021
Cite as / Citirajte kot: Novak M, Bohanec N, Perhavec A, Kramer S, Eržen D. The outcome of primary retroperitoneal sarcoma patients 
treated at sarcoma referral centre: the Institute of Oncology Ljubljana experience. Zdrav Vestn. 2022;91(3–4):100–7. DOI: https://doi.
org/10.6016/ZdravVestn.3211
eng slo element
en article-lang
10.6016/ZdravVestn.3211 doi
10.1.2021 date-received
2.8.2021 date-accepted
Cytology, oncology, cancerology Citologija, onkologija, kancerologija discipline
Original scientific article Izvirni znanstveni članek article-type
The outcome of primary retroperitoneal 
sarcoma patients, treated in a sarcoma referral 
centre: the Institute of Oncology Ljubljana 
experience
Primarni retroperitonealni sarkomi: preživetje 
bolnikov, zdravljenih na Onkološkem inštitutu 
Ljubljana, referenčnem centru za sarkome
article-title
Outcome of retroperitoneal sarcoma patients 
treated at the Institute of Oncology Ljubljana
Retroperitonealni sarkomi: preživetje po zdravl-
jenju na Onkološkem inštitutu Ljubljana alt-title
sarcoma, retroperitoneum, referral centre, 
treatment
sarkom, retroperitonej, referenčni center, zdravl-
jenje kwd-group
The authors declare that there are no conflicts 
of interest present.
Avtorji so izjavili, da ne obstajajo nobeni 
konkurenčni interesi. conflict
year volume first month last month first page last page
2022 91 3 4 100 107
name surname aff email
Marko Novak 1 mnovak@onko-i.si
name surname aff
Naja Bohanec 2
Andraž Perhavec 1,3
Sonja Kramer 1
Darja Eržen 1
eng slo aff-id
Department of Surgical 
Oncology, Institute of Oncology 
Ljubljana, Ljubljana, Slovenia
Oddelek za kirurško onkologijo, 
Onkološki inštitut Ljubljana, 
Ljubljana, Slovenija
1
Statistics and modeling, 
Novartis, Mengeš, Slovenia
Statistika in modeliranje, 
Novartis, Mengeš, Slovenija 2
Faculty of Medicine, University 
of Ljubljana, Ljubljana, Slovenia
Medicinska fakulteta, Univerza v 
Ljubljani, Ljubljana, Slovenija 3
Slovenian Medical Journallovenian Medical Journal
101
ORIGINAL SCIENTIFIC ARTICLE
The outcome of primary retroperitoneal sarcoma patients treated at sarcoma referral centre
1 Introduction
Retroperitoneal sarcomas (RPS) are extremely ra-
re. According to the literature, the incidence is 0.3–
0.4/100,000 inhabitants (1), which means 6–8 patients 
per year for Slovenia. Surgery is the mainstay of treatment 
of RPS patients. Compartmental resection offers the best 
option for local control and the potential cure to the pa-
tients (2). This surgical procedure involves removing the 
tumour along with the colon, kidney, and psoas fascia 
or muscle. If during surgery the tumour is estimated to 
involve other organs, the compartmental resection is ex-
tended to multivisceral resection. In this case, the tumour 
is removed together with the colon, kidney, psoas fascia 
or muscle and all the organs involved. We speak of prima-
ry localized RPS if the patient has not yet been operated 
on and the disease has not spread.
Local recurrence of the disease is possible as a recur-
rence at the site of the primary tumour in the retroperi-
toneum and/or in other areas of the abdomen and/or as 
peritoneal sarcomatosis. In the case of liver metastases, 
which are classified as distant, the disease is defined as 
metastatic.
The benefit of preoperative radiotherapy for local re-
currence in patients with primary localized RPS is still in 
the research phase and is therefore not routinely recom-
mended in treatment guidelines. EORTC 62092 (STRASS 
1) was the only prospective phase III randomized study 
comparing the impact of preoperative radiotherapy and 
surgery versus surgery alone on local recurrence (3). The 
benefit of preoperative radiotherapy in various histolog-
ical subtypes of RPS was not confirmed, it was indicated 
Izvleček
Izhodišča: Retroperitonealni sarkomi so izredno redki, zato naj zdravljenje bolnikov z retroperitonealnimi sarkomi poteka 
v referenčnem centru. Temeljno zdravljenje je kirurško. Priporočen tip operacije je kompartment resekcija.
Metode: Onkološki inštitut Ljubljana je edini referenčni center za sarkome v Sloveniji. V raziskavo so bili vključeni bolniki 
s primarnim lokaliziranim retroperitonealnim sarkomom, zdravljeni pri nas v obdobju od januarja 1999 do junija 2020. 
Opredelili smo preživetje, kakovost kirurškega zdravljenja in zaplete.
Rezultati: Vključenih je bilo 100 bolnikov. Srednja starost je bila 62 let. Srednja velikost tumorja je bila 21,5 cm. Najpogostejši 
histološki podtip je bil dediferenciran liposarkom (39 %). Kompartment resekcija je bila opravljena v 24 %, multivisceralna 
resekcija pa v 25 %. Zaplete po posegu je imelo po klasifikaciji Clavien-Dindo stopnje 3a ali višje 29 % bolnikov, pri 58,6 % 
(17/29) je bila potrebna ponovna operacija. Zgodnja in pozna smrtnost po operaciji sta bili 3 % in 5 %. Srednji čas sledenja 
je bil 55,1 mesecev. 5-letno celokupno preživetje je bilo 67,8 %. Kumulativna verjetnost za lokalno ponovitev bolezni po 5 
letih je bila 16,9 %, za oddaljene zasevke pa 21,4 %. Ocena ASA in izguba krvi med operacijo sta bila neodvisna napovedna 
dejavnika celokupnega preživetja.
Zaključek: Retroperitonealni sarkomi sodijo med redke vrste raka. Naši rezultati zdravljenja bolnikov z retroperitoneal-
nimi sarkomi so zelo dobri in primerljivi z rezultati drugih referenčnih centrov iz tujine. Potrjujejo tudi ključno vlogo refe-
renčnega centra pri obravnavi in zdravljenju teh bolnikov.
only in well-differentiated liposarcoma. The effect of che-
motherapy on local recurrence or distant metastases in 
these patients has not been explored in the research.
The purpose of our study was to determine the param-
eters of survival, quality of surgical treatment and compli-
cations after surgical treatment of patients with RPS who 
underwent surgery at the Institute of Oncology Ljubljana 
(IOL). We wanted to compare our results with the results 
of some reference centres with a similar number of cases.
2 Methods
We analyzed data from patients treated at the IOL for 
primary localized RPS between January 1999 and June 
2020. The primary objective of the study was to determine 
overall survival (OS) and the five-year cumulative inci-
dence of local disease recurrence and distant metastases. 
Secondary objectives were to define the quality of surgi-
cal treatment, complications after surgical treatment, and 
prognostic factors of OS by multivariate analysis. The In-
stitutional Review Board (KSOPKR-0020-2020) and the 
IOL Ethical Commission (ERID 0023-2020) approved the 
study.
The quality of surgical treatment was assessed by ana-
lyzing the status of surgical margins, duration of surgery, 
blood loss during surgery, complications, duration of hos-
pitalization, and mortality after surgery. To identify pos-
sible independent prognostic factors for OS, the analysis 
included the ASA classification and blood loss during the 
surgical procedure. The ASA classification summarizes 
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the American Society of Anaesthesiologists’ scale for cat-
egorizing the patient’s physiological status prior to sur-
gery (4). Tumour grade was based on the FNCLCC grad-
ing system (fr. Fédération Nationale des Centers de Lutte 
Contre le Cancer) (5,6).
2.1 Statistical Methods
The main objective of the study was to identify OS, 
local recurrence of the disease, and the occurrence of dis-
tant metastases. OS was defined as the time from surgery 
to the time of death or truncation, regardless of the cause 
of death. The survival curve was constructed using the 
Kaplan-Meier method. Local recurrence of the disease 
and the occurrence of distant metastases were defined by 
competing risk analysis and status analysis with the as-
sessment of cumulative incidence.
In the competing risk analysis, the cumulative inci-
dence of local recurrence of the disease, the occurrence 
of distant metastases, and death without recurrence of 
the disease or metastases were assessed. The first of these 
events was analyzed; however, the events did not coin-
cide. In the status analysis, the probability of individual 
statuses over time was estimated. The analysis included 
local recurrence status, occurrence of distant metastases, 
local recurrences and distant metastases together (LR + 
DM), and deaths. Cox proportional hazards model was 
used to identify possible independent prognostic factors 
for OS. Results were defined as statistically significant if 
the p value was less than 0.05.
3 Results
During the period covered by the study, 134 patients 
underwent surgery for RPS at IOL. Patients who had 
undergone operations with primary metastatic disease 
(n=6), patients with residual sarcoma after being operat-
ed on in another hospital (n=14), and those who came 
for treatment due to recurrent RPS (n=14) were excluded 
from the study. The study thus included 100 patients who 
underwent surgery for primary localized RPS (Figure 
1). The median age of patients at diagnosis was 62 years. 
Half of the patients were diagnosed due to a palpable tu-
mour in the abdomen (n=49), 23% (n=23) due to other 
health problems, and in 28% (n=28) of cases the tumour 
was detected by chance during imaging tests. Weight loss 
was reported by 41% (n=41) of patients. Prior to surgery, 
fine needle aspiration biopsy was performed in 60% of 
patients (n=60), core needle biopsy in 23% (n=23), and 
both (n=11) were performed in 11% of patients. Only 
6% (n=6) of patients underwent surgery without tumour 
biopsy before surgery.
The most common histological subtype was dediffer-
entiated liposarcoma (39%). The median tumour size was 
21.5 cm. In all operations, we managed to achieve macro-
scopic complete resection, in 74% (n=74) with negative 
margins. Compartmental resection was performed in 
24% (n=24) and multivisceral resection in 25% (n=25) of 
patients. Only in two patients (2%) the tumour was re-
moved without a simultaneous resection of a larger organ. 
Organ removal by frequency: kidney 56%, colon 55%, 
adrenal gland 40%, psoas fascia 31%, psoas muscle 26%, 
diaphragm 19%, small intestine 12%, spleen and distal 
part of the pancreas 10%, inferior vena cava 8% and liver 
resection 5%. The median number of resected organs in 
surgery was four. On average, surgery lasted 7.5 hours, 
median time was seven hours (range 1.3–19.0). The mean 
blood loss during surgery was 3260 ml and the median 
value was 1330 ml (range 100–32000).
The median time of hospitalization after surgery was 
20.5 days (range 5–102) and in the intensive care unit 
it was eight days (range 0–55). According to the Cla-
vien-Dindo classification, complications after surgery, 
grade 3a or higher, were experienced by 29% (n=29) of 
patients and 17 patients (17/29; 58.6%) required reopera-
tion. The most common complications were: ileus (n=7), 
sepsis (n=6), retroperitoneal abscess (n=5), bleeding 
(n=4), abdominal abscess (n=3), anastomotic dehiscence 
(n=2), and intestinal gangrene (n=1). Within 30 days af-
ter surgery, three patients died (3%), and within 90 days 
after surgery, five patients died (5%). Most of the data are 
shown in Table 1.
Figure 1: Selection of patients with primary localized 
retroperitoneal sarcoma included in the study.
Legend: RPS – retroperitoneal sarcoma.
Operated on for RPS
134
Primary RPS 
100
With metastatic disease – 6
With residual RPS – 14
With recurrent RPS – 14
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ORIGINAL SCIENTIFIC ARTICLE
The outcome of primary retroperitoneal sarcoma patients treated at sarcoma referral centre
Legend: BMI – body mass index;  ASA –  American Society 
of Anesthesiologists classification; FNCLCC –  fr. Fédération 
Nationale des Centres de Lutte Contre Le Cancer; G – tumour 
grade; AJCC – American Joint Committee on Cancer.
Characteristics Number (% as well)
Gender
Male 55
Female 45
Median age at diagnosis (age, range) 62 (24 – 84)
<50 years 23
≥50 years 77
Mean BMI (kg/m2) 26.9
Weight loss before treatment 41
ASA score
 ASA 1 21
 ASA 2 49
 ASA 3 26
 ASA 4 4
Histological subtype
Dedifferentiated liposarcoma 39
Well-differentiated liposarcoma 22
Leiomyosarcoma 16
Solitary fibrous tumour 9
Other tumours 14
Average tumour size (cm) 23.4
Median tumour size (cm, range) 21.5 (3–80)
Tumour grade (FNCLCC system)
G1 35
G2 18
G3 35
No data 12
AJCC staging (8th edition)
IA 1
IB 47
IIIA 7
IIIB 45
Table 1: Demographic, pathological and clinical data.
Characteristics Number (% as well)
Postoperative complications (Clavien-Dindo classification)
3a 7
3b 9
4 8
5 5
Preoperative treatment  
No 94
Chemotherapy 1
Radiotherapy 3
Chemotherapy and radiotherapy 2
Postoperative treatment  
No 90
Chemotherapy 1
Radiotherapy 7
Chemotherapy and radiotherapy 2
Status at the last documentation review
Alive 61
Dead 39
Local recurrence
No 75
Yes 25
Distant metastasis
No 71
Yes 29
The median postoperative follow-up time was 55.1 
months (range 1–223). 39 patients died. The correspond-
ing five-year OS was 67.8% (Figure 2). 25 patients had 
local recurrence and 29 patients had distant metastases. 
14 patients had local recurrence alone, six patients had 
local recurrence and then distant metastases, three pa-
tients had distant metastases and then local recurrence, 
two patients had local recurrence and concurrent distant 
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metastases and 18 patients had distant metastases alone. 
In the competing risk analysis, the five-year cumulative 
incidence of local recurrence was 16.9%, for distant me-
tastases 21.4%, and for death without local recurrence 
and distant metastases 9.12% (Figure 3). In the status 
analysis, the cumulative incidence of death after five years 
was 32.1% and the probability of the patient remaining 
disease-free after five years was 52.6% (Figure 4).
The Cox model of multivariate analysis included 
two variables: ASA score and blood loss during surgery. 
Figure 2: Overall survival curve.
Follow-up period (months)
0.0
0.2
0.4
0.6
0.8
1
0 50 100 150 200
O
ve
ra
ll 
su
rv
iv
al
Figure 3: Graphical representation of competing risk analysis.
Follow-up period (months)
0.00
0.05
0.10
0.15
0.20
0.25
0 50 100 150
Cu
m
ul
at
iv
e 
in
ci
de
nc
e
Death without recurrence or metastases
Distant metastasis
Local recurrence
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ORIGINAL SCIENTIFIC ARTICLE
The outcome of primary retroperitoneal sarcoma patients treated at sarcoma referral centre
Three coefficients were identified as statistically signifi-
cant: ASA 3, ASA 4, and blood loss during surgery. The 
coefficient for patients with ASA 3 is statistically signif-
icant with p=0.002, hazard ratio 6.3 (95% CI: 1.9-20.7), 
which means that these patients are 6.3 times more at 
risk of death than patients from the ASA 1 group. The co-
efficient for patients with ASA 4 is statistically significant 
with p=0.006, hazard ratio 8.8 (95% CI: 1.9-41.8), which 
means that these patients are 8.8 times more at risk of 
death than patients from the ASA 1 group. Coefficient 
for blood loss during surgery is statistically significant 
with p=0.040, hazard ratio 1.05 (95% CI: 1.0-1.1), which 
means that each additional litre of blood lost during sur-
gery increases the risk of death by 5% (Table 2).
During this period, During this period, 9 patients 
with primary localized RPS were not surgically treated. 
In five, the risk of death during and after surgery was 
considered too high due to comorbidities, two were re-
jected due to old age, in one, the tumour was assessed as 
unresectable, and one patient refused surgery. Two were 
treated with palliative radiotherapy, and symptomatic 
and supportive treatment led by a chosen physician with 
the option of consulting with a palliative care team was 
suggested to the others.
4 Discussion
The care of sarcoma patients is differently organized 
around the world. Patients should be managed by a 
multidisciplinary team before starting treatment. Most 
Figure 4: Graphic representation of status analysis.
Legend: LR + DM – llocal recurrence + distant metastasis.
Follow-up period (months)
0.00
0.01
0.02
0.03
0.04
0.05
0.06
0 50 100 150
Pr
op
or
tio
n 
of
 p
at
ie
nt
s
Local recurrence
Death
Distant metastasis
LR + DM
Legend: IC – confidence interval for the risk relationship; ASA – American Society of Anesthesiologists classification.
Variable Hazard ratio Lower limit 95% CI Upper limit 95% CI P-value
ASA 2 1.50 0.42 5.23 0.527
ASA 3 6.30 1.91 20.70 0.002
ASA 4 8.81 1.86 41.81 0.006
Blood loss 1.05 1.00 1.09 0.040
Table 2: Multivariate analysis of overall survival.
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patients with limb and trunk sarcomas are operated on 
by orthopaedists, while patients with RPS are operated 
on by abdominal surgeons, both focused on sarcoma sur-
gery. Reference centres in which the same team operates 
on patients with tumours in all anatomic locations are 
rare. According to the recommendations of the European 
Cancer Organisation published in 2017, an institution is 
considered to be a reference centre if it treats at least 100 
new cases of patients with soft tissue and bone sarcoma 
per year (7). A sarcoma surgeon should perform at least 
2–3 sarcoma surgeries per month (7). Villano et al. pub-
lished an article in 2019 in which the limit for optimal 
treatment of these patients was identified as at least 13 
RPS surgeries per year in the reference centre (8). The 
centre that meets this condition was declared “a high-vol-
ume retroperitoneal sarcoma centre”.
IOL was founded in 1938, and the multidisciplinary 
team for sarcomas in 1975. It is the only reference centre 
for sarcoma patients in Slovenia. There are currently 23 
doctors on the team. We treat patients with soft tissue 
and bone tumours/sarcomas in anatomic locations and 
propose a diagnostic and treatment plan. At IOL, patients 
with sarcomas of the soft tissues of the limbs, trunk, su-
perficial part of the head and neck, and with visceral, 
retroperitoneal and pelvic sarcomas are operated on. 
Patients with sarcomas in the ORL area, central nervous 
system and the chest are operated on by appropriate spe-
cialists. According to the Cancer Registry, the incidence 
of patients with soft tissue sarcomas was highest in 2015, 
when 112 cases were recorded (9). At the IOL, about 90 
new cases are dealt with per year and about 60–70 sarco-
ma surgeries are performed, of which (only) five are due 
to primary RPS. A sarcoma surgeon performs at least two 
surgeries a month.
In our series, the five-year OS rate is 67.8%, cumula-
tive incidence of local recurrence after five years is 16.9%, 
and of distant metastases it is 21.4%. 29% of patients in 
our series had serious postoperative complications, ear-
ly postoperative mortality was 3%, and late mortality 
was 5%. The data can be compared with the results of 
the largest retrospective study to date, which included 
1,007 patients treated in centres with a high number of 
patients. The five-year OS rate was 67%, the five-year cu-
mulative incidence of local recurrence was 25.9%, and of 
distant metastases it was 21.0% (10). In the same series, 
the complication rate was 16.4% and postoperative ear-
ly mortality was 1.8% (11). Reports of reference centres 
similar to ours in the number of patients treated with 
primary RPS are rare. In an article, written in 2019, Ma-
linka et al. from the Charité Clinic in Berlin reported the 
results of the treatment of 61 patients (12). The five-year 
OS rate was 58% and the five-year local disease recur-
rence rate was 41%. The postoperative complication rate 
was 31% and the 90-day mortality rate was 3%. Similar 
results as reported by us were reported in an article pub-
lished in 2018 by Snow et al. from the MacCallum Centre 
in Melbourne (13). 88 patients with primary RPS were 
operated on. The five-year OS rate was 66%, the five-year 
local disease recurrence rate was 35%, and the five-year 
distant metastases rate was 29%. In the future, we want to 
reduce the complication rate and shorten hospital stays. 
There are no recommendations in the form of guidelines 
for enhanced recovery of patients with RPS after surgery 
(ERAS) (14).
In a multivariate analysis, the ASA score and blood 
loss during surgery proved to be an independent pre-
dictor of OS. In addition to age, the ASA score is a key 
parameter for deciding whether a patient is fit for sur-
gery. Patients with localized RPS from groups ASA 1 and 
2 are operated without restraint if the tumour is remov-
able (resectable). However, the final decision regarding 
surgery in the ASA 3 and 4 group of patients also takes 
into account the size, location and histological subtype of 
the tumour. The final decision regarding the operation is 
made at the anaesthesiology-surgical tumour board. In 
the analyzed period, five patients were rejected, although 
their tumour was resectable. Dealing with groups ASA 3 
and 4 by means of the multivariate analysis is important, 
as patients in this group are expected to have poorer sur-
vival than in groups ASA 1 and 2.
Membership in the international Transatlantic Aus-
tralasian Retroperitoneal Sarcoma Working Group 
(TARPSWG), led by dr. Gronchi from Milan, gives us 
the opportunity for education, international cooperation 
and participation in research. Thus, we get to know this 
rare disease better in the desire to provide our patients 
with the best possible treatment.
5 Conclusion
Our results in the treatment of RPS patients are very 
good and comparable to the results of other reference 
centres. However, we would like patients with retroper-
itoneal tumours, where sarcoma is suspected, to be re-
ferred to us for diagnosis and treatment without prior 
surgery, because only then do they have the opportunity 
for optimal treatment.
Conflict of interest
None declared.
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The outcome of primary retroperitoneal sarcoma patients treated at sarcoma referral centre
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