DISCUSSION
In the present study, the clinical characteristics and treatment
outcomes of 71 patients with recurrent uterine leiomyosarcoma treated at
our institution were analyzed. To our knowledge, the current study is
one of the largest studies to evaluate the clinical characteristics and
treatment outcomes of women with recurrent uLMS in a single center to
data. We found that secondary cytoreductive surgery is an important
treatment choice for recurrent uLMS and time to fist recurrence within
12 months is an independent predictor of decreased 5-year OS in patients
who received SCS. These findings suggested that it’s important to
identify the suitable candidate for SCS.
Uterine leiomyosarcoma is the most frequent malignant gynecologic
mesenchymal tumor, often develops distant metastases and local
recurrence.(Mbatani et al , 2018) Because of their low incidence
and the lack of prospective studies, it is very difficult to reach
conclusions as to the best disease management recommendations for
recurrent uLMS. Treatment recommendations are made according to the site
and nature of the recurrence for recurrent
uLMS. Emerging evidence suggested
that optimal surgical resection for
recurrent uLMS may provide an
opportunity for long-term survival in a select patient
population.(Leitao et al , 2002; Giuntoli et al , 2007;
Bacalbasa et al , 2015; Villalaín-González et al , 2017;
Nakamura et al , 2018; Bizzarri et al , 2019; Cybulskaet al , 2019) The survival advantage was seen not only in patents
with pulmonary metastases but also patients with extrapulmonary
metastases.(Giuntoli et al , 2007) In the present study, we found
secondary cytoreduction surgery in patients with first recurrent uLMS
was associated with a significant improvement in overall survival.
Recently, some studies showed cytoreductive surgery and hyperthermic
intraperitoneal chemotherapy (CRS/HIPEC) was a promising treatment
modality for uterine sarcoma patients with peritoneal dissemination.6–8 It’s important to identify the suitable candidate
for SCS.
The time to first recurrent since initial diagnosis
affects the survival. Patients with
uLMS who experience longer time to recurrence may have improved survival
outcomes following metastasectomy.(Leitao et al , 2002) In the
present study, patients experienced first recurrence after initial
diagnoses within 12 months had a significantly worse 5-year OS than
those after 12 months, which was an independent predictor of worse
survival.
Site governs local control, distant recurrence-free and disease-specific
survival for completely resected locally recurrent sarcoma without
metastasis.(Stojadinovic et al , 2002) Patients with single site
recurrence are more likely to receive SCS and achieve a complete
resection with no residual disease than those with multiple sites
recurrences. We found patients with multiple recurrent locations were
more likely to receive systematic therapy and had a worse survival,
which in accordance with other
studies. Similarly, patients with residual tumors after cytoreductive
surgery had a tendency towards a worse survival than those without in
the present study.
Furthermore, Bartosch et al found the most frequent distant metastatic
sites were lung (67.7%).(Bartosch et al , 2017) We found lung was
also the most common distant metastatic site in our study. But it’s not
that bad for some patients, especially for those with lung-only
recurrence. We found patients with lung-only recurrence had a tendency
towards better 5-year OS than those without.
uLMS also have a high tendency for local recurrent in pelvic and
abdominal cavity after initial treatment. Since it is difficult to
discriminate between benign uterine fibroids and uterine sarcomas
preoperatively, most uterine sarcomas are often found incidentally after
primary hysterectomy or myomectomy.(Hosh et al , 2016) Tumor
fragmentation/morcellation might be used which was associated with
significantly higher risk of recurrence and a nearly 4-fold increase in
peritoneal recurrence.(Pedra Nobre et al , 2021) Since nearly all
patients received primary myomectomy in other centers, we could not
determining how many patients received morcellation clearly in the
present study.
Radiotherapy can be recommended for
patients with recurrent uterine sarcoma based on tumor resectability and
patients’ prior radiotherapy exposure. For patients with local
recurrent, all recurrences are localized either in the vagina or in or
directly proximal to the vaginal stump that is negative for distant
metastatic disease. Radiotherapy or surgery treatment are reasonable
choices. Concurrent radiotherapy shows good local effectiveness with a
good long-term survival for local recurrence.(Kortmann et al ,
2006) A combined modality approach with perioperative EBRT, surgery, and
IORT for locally advanced or recurrent uterine sarcoma resulted in
excellent local disease control with acceptable toxicity, even in
patients with positive resection margins. (Barney et al , 2012)
8.5% patients had vaginal cuff recurrent in our study and 3 of them
received pelvic radiotherapy in our study.
Further adjuvant systemic therapy should be considered for patients with
recurrent leiomyosarcoma after initial surgical treatment or
radiotherapy. Systemic therapy is also important medical choice for
patients with distant metastasis.
Leoimyosarcoma is extremely aggressive and responds poorly to
traditional chemotherapeutics. Docetaxel/gemcitabine, doxorubicin, and
ifosfamide are all reasonable options for advanced or recurrent disease
with response rates ranging from 17% to 36%.(Seddon et al ,
2017; Mbatani et al , 2018) Gemcitabine and docetaxel have
demonstrated the highest objective response rates as first-line or
second-line treatment for metastatic disease, with an OS of 14.7 months
in second-line treatment.(Hensley et al , 2008)
Gemcitabine-docetaxel remains a standard first-line treatment for
uLMS.(Hensley et al , 2015) Recently, new drugs such as
trabectedin and eribulin have showed promising therapeutic effect for
patients with recurrent uLMS. (Pautier et al , 2015; Schöffskiet al , 2016) The most common chemotherapy regimens for recurrent
uLMS were doxorubicin-based regimens and docetaxel/gemcitabine in our
study.
Target therapy are important choice for patients with recurrent
sarcoma. In recent years, targeted
therapies such as pazopanib and olaratumab achieved a highly significant
improvement in survival for patients with metastatic uLMS.(van der Graafet al , 2012; Tap et al , 2016) Larotrectinib is highly
active treatment especially for patients with TRK fusions.(Hong et
al , 2020) The potential role of immunotherapy is being assessed in
current uLMS clinical trials. Doxorubicin in combination with
pembrolizumab is a promising combination worthy of further study,
especially in certain sarcoma subtypes.(Pollack et al , 2020;
Livingston et al , 2021) Endocrine therapy is also an important
treatment for recurrent sarcoma. Aromatase inhibitors can be considered
for ER/PR-expressing uLMS.(George et al , 2014)
There are two limitations to our study. The current study was
retrospective, and the primary treatment was not assigned at randomized.
All patients with recurrent uLMS in this study came from our single
center. Therefore, caution is required when interpreting our results.