Uterine sarcomas are rare, heterogeneous malignant tumours of several histologic types originating from mesenchymal tissues of the uterus. The most common histologic types are carcinosarcoma, leiomyosarcoma, and endometrial stromal sarcoma, accounting for 90% of uterine sarcomas. To date, no effective treatment has been found to achieve a high rate of cure or prolong survival. Although complete surgical excision of the tumour is the only curative treatment modality, the rarity of these tumours and their diversity of histologic types have precluded the development of standard surgical strategies. Surgery may also be optimal for recurrent uterine sarcomas, but indications for secondary surgical treatment have not been established. Here, we describe recent changes in, and updates of, the surgical treatment of the three most common types of malignant uterine sarcomas.
Introduction
Uterine sarcomas are highly malignant tumours of the uterus that originate from mesenchymal tissues, including uterine smooth muscle, endometrial stroma, and supporting tissue. These tumours are relatively rare, accounting for about 3% of all uterine malignancies. They are heterogeneous, consisting of several histologic types. The three most common histologic types, accounting for 90% of all uterine sarcomas, are carcinosarcoma, leiomyosarcoma (LMS), and endometrial stromal sarcoma (ESS), listed in decreasing order of incidence.
Because of the rarity and diversity of histologic types, a treatment strategy unique to each has not been established. In addition, these tumours were surgically staged by the International Federation of Obstetrics and Gynecology (FIGO) staging system for endometrial adenocarcinoma, because no FIGO staging system unique to each type of uterine sarcoma had been established. The recent development of a new FIGO staging system unique to each type of uterine sarcoma has allowed each type to be treated separately ( Table 1 ).
| (1) Leiomyosarcomas and endometrial stromal sarcomas* | |
| Stage | Definition |
| I | Tumor limited to uterus |
| IA | ≤5 cm |
| IB | >5 cm |
| II | Tumor extends to the pelvis |
| IIA | Adnexal involvement |
| IIB | Tumor extends to extrauterine pelvic tissue |
| III | Tumor invades abdominal tissues (not just protruding into the abdomen). |
| IIIA | One site |
| IIIB | >One site |
| IIIC | Metastasis to pelvic and/or para-aortic lymph nodes |
| IV | Tumor invades bladder and/or rectum |
| IVA | |
| IVB | Distant metastasis |
| (2) Adenosarcomas | |
| Stage | Definition |
| I | Tumor limited to uterus |
| IA | Tumor limited to endometrium/endocervix with no myometrial invasion |
| IB | Less than or equal to half myometrial invasion |
| IC | More than half myometrial invasion |
| II | Tumor extends to the pelvis |
| IIA | Adnexal involvement |
| IIB | Tumor extends to extrauterine pelvic tissue |
| III | Tumor invades abdominal tissues (not just protruding into the abdomen). |
| IIIA | One site |
| IIIB | >One site |
| IIIC | Metastasis to pelvic and/or para-aortic lymph nodes |
| IV | Tumor invades bladder and/or rectum |
| IVA | |
| IVB | Distant metastasis |
| (3) Carcinosarcomas | |
| Carcinosarcomas should be staged as carcinomas of the endometrium. | |
Surgery, including hysterectomy and resection of disease, is the mainstay of treatment for uterine sarcomas, regardless of histologic type. Complete surgical excision is the only curative treatment modality currently known. It has been difficult, however, to establish a surgical strategy for each type of uterine sarcoma because of a lack of randomised-controlled trials to determine the extent and efficacy of surgical treatment. To date, no effective adjuvant therapy has been found to prolong the survival of women with uterine sarcomas. Moreover, the efficacy of primary chemotherapy, radiation therapy, combinations of both, and hormone therapy has not been determined. In this review, we describe recent changes in, and updates of, surgical treatments of the three most common histologic types of malignant uterine sarcomas.
Surgical treatment of uterine carcinosarcoma
Uterine carcinosarcoma is frequently diagnosed by endometrial biopsy because women usually present with vaginal bleeding and an endometrial mass, with about 40% having tumours in the cervical canal caused by their exophytic growth. Therefore, most women with uterine carcinosarcoma can undergo planned surgical treatment according to the preoperative staging of the tumour and determination of lymph-node involvement. Simple hysterectomy has been recommended for women with stage I uterine carcinosarcoma because no survival differences in stage I patients who underwent simple versus radical hysterectomy were found. Radical hysterectomy can be considered for women whose tumours have spread to the cervix or parametrial tissue.
Carcinosarcoma rapidly spreads to the adnexa, lymph nodes and peritoneal surfaces, with 32–61% of women having extrauterine disease during staging. Many women who are clinically thought to have disease confined to the uterus are found to have extrauterine disease after surgical staging. About 12–23% of women with carcinosarcoma apparently confined to the uterus were found to have adnexal involvement, and 23% had occult metastases, suggesting that bilateral salpingo-oophorectomy should be part of surgical management for carcinosarcoma, even in women with apparently early disease.
Lymph-node metastasis is also frequent in carcinosarcoma. About 14–38% of women with carcinosarcoma confined to the uterus are upstaged to stage IIIc because of occult lymph-node metastasis after lymph-node dissection. The frequency and pattern of lymph-node metastasis of carcinosarcoma is similar to that of high-risk endometrial adenocarcinoma ( Table 2 ). Therefore, pelvic and para-aortic lymph-node dissection is recommended for surgical treatment of carcinosarcoma, as it is for endometrial adenocarcinoma. Because sampling of pelvic and para-aortic lymph nodes may miss microscopic or occult lymph-node metastases in women with clinically early stage carcinosarcoma, systematic lymph-node dissection is recommended rather than sampling or removal of enlarged lymph nodes. In addition, the number of lymph nodes retrieved in early stage carcinosarcoma has been found to correlate with the risk of recurrence and survival. Because about 50% of women with pelvic lymph-node metastasis also had para-aortic lymph-node metastasis, and about 7% of women had para-aortic without pelvic lymph-node metastasis, para-aortic lymph-node dissection should also be included in the surgical treatment of carcinosarcoma. Although lymph-node dissection improves surgical staging and provides prognostic information on women with apparently early stage carcinosarcoma, it is still unclear whether lymph-node dissection improves patient survival. Several retrospective studies have indicated the importance of lymph-node removal on the survival of women with early stage uterine carcinosarcoma. Because surgical extirpation is the most important aspect of treatment, removal of occult lymph-node metastases may also improve prognosis. In addition, the removal of occult lymph-node metastases may render women more susceptible to cure by adjuvant therapy. Further evaluation is warranted.
| Author | Year | N | FIGO stage | Lymph-node dissection or sampling ( N ) | Lymph-node metastasis | |
|---|---|---|---|---|---|---|
| N | (%) | |||||
| Ayhan et al. | 1997 | 28 | I–II | 14 | 4 | 28.5 |
| Park et al. | 2010 | 41 | I–II | 41 | 13 | 31.7 |
| Nemani et al. | 2008 | 1855 | I–III | 965 | 119 | 14 |
| Inthasorn et al. | 2002 | 37 | I–IV | 20 | 7 | 35 |
| Callister et al. | 2004 | 300 | I–IV | 124 | 33 | 26.6 |
| Galaal et al. | 2009 | 93 | I–IV | 34 | 13 | 38.2 |
| Total | 2354 | 1196 | 189 | 15.8 | ||
Positive peritoneal washings have been reported in 19–44% of women with carcinosarcoma, with a rate as high as 29% in women with apparently early diease. Positive peritoneal washings are also of prognostic value in carcinosarcoma, further indicating the need for multiple peritoneal washing cytology during the surgical treatment of carcinosarcoma. The roles of omentectomy and multiple peritoneal biopsies in women with early stage carcinosarcoma are unclear, as they have never been evaluated. As omentectomy is a recommended staging procedure for women with high-risk endometrial cancers, including papillary serous and clear-cell carcinomas, it should also be carried out for women with early stage carcinosarcoma. If gross extrauterine disease is encountered during surgery, complete debulking surgery, similar to surgery for epithelial ovarian cancer, is recommended.
Although laparoscopy for surgical staging of women with early stage uterine carcinosarcoma has not been fully evaluated, there is no evidence that laparoscopy has an adverse affect on patient outcomes. All surgical staging procedures can be safely carried out using laparoscopy in women with early stage uterine carcinosarcoma.
Surgical treatment of uterine leiomyosarcoma
The mainstay of surgical treatment for uterine LMS is simple hysterectomy. In postmenopausal women, bilateral salpingo-oophorectomy is recommended. The incidence of occult ovarian metastasis, however, in women with early stage LMS has been found to range from 3.4% to 3.9%, and most macroscopic ovarian metastases are associated with either macroscopic lymph-node metastasis or other macroscopic extrauterine disease. In addition, the preservation of ovarian tissues does not seem to increase the risk of recurrence, indicating that ovarian tissues can be preserved in premenopausal women unless these tissues show macroscopic involvement. Furthermore, in one study, bilateral salpingo-oophorectomy was found to have a negative effect on survival in women with LMS.
In contrast to uterine carcinosarcoma, the utility of additional surgical staging procedures in women with early-stage uterine LMS is unclear. Retroperitoneal spread seems to be less frequent in uterine LMS than in other types of uterine sarcomas. Occult lymph-node metastasis was found in only 0–3.7% of women with early stage LMS, although one study reported that this frequency was 75% ( Table 3 ). In other studies, lymph-node metastasis was observed only in women with peritoneal spread or was almost always associated with other extrauterine disease ( Table 3 ). Therefore, lymph-node dissection is not recommended for women with early stage LMS. The low incidence of lymph-node metastasis in these women is similar to that of lymph-node metastasis observed in women with LMS of other soft tissues, and in those with other soft tissue sarcomas, in which lymph-node dissection is not routinely recommended. Lymph-node metastasis in women with uterine LMS has been associated with poorer survival, and women with metastasis to two or more lymph nodes had poorer survival than did women with metastasis to a single lymph node. However, the removal of lymph nodes with microscopic metastases and lymph-node dissection itself seems to be of no clinical benefit. Lymph-node dissection in women with lymph-node metastasis or in those with apparently early stage LMS did not have a therapeutic benefit in previous studies. These findings suggest that lymph-node dissection should be considered only in women found to have macroscopic lymph-node metastasis or extrauterine disease during surgery.
| Author | Year | N | Lymph-node dissection or sampling ( N ) | Overall lymph–node metastasis | Early stage ( N ) | Occult lymph–node metastasis | ||
|---|---|---|---|---|---|---|---|---|
| N | % | N | % | |||||
| Chen et al. | 1989 | 20 | 4 | 3 | 75 | 4 | 3 | 75 |
| Major et al. | 1993 | 59 | 57 | 2 | 3.5 | 57 | 2 | 3.5 |
| Goff et al. | 1993 | 21 | 15 | 4 | 26.7 | 9 | 0 | 0 |
| Gadducci et al. | 1996 | 126 | 7 | 2 | 29 | 4 | 0 | 0 |
| Ayhan et al. | 1997 | 63 | 34 | 3 | 8.8 | 27 | 1 | 3.7 |
| Leitao et al. | 2003 | 37 | 37 | 3 | 8.1 | 27 | 0 | 0 |
| Giuntoli et al. | 2003 | 208 | 36 | 4 | 11 | NR | NR | NR |
| Wu et al. | 2006 | 51 | 21 | 0 | 0 | 12 | 0 | 0 |
| Park et al. | 2008 | 46 | 11 | 0 | 0 | NR | NR | NR |
| Kapp et al. | 2008 | 1396 | 348 | 23 | 6.6 | NR | 0 | 0 |
| Koivisto-Korander et al. | 2008 | 39 | 15 | 0 | 0 | NR | NR | NR |
| Total | 2066 | 585 | 44 | 7.5 | 140 | 6 | 4.3 | |
The roles of peritoneal washing cytology, peritoneal biopsies and omentectomy have not been fully evaluated in women with uterine LMS. Because uterine LMS usually spreads haematogenously rather than via a retroperitoneal or transperitoneal route, these surgical staging procedures seem to be less important in women with early stage disease. If extrauterine disease is encountered during surgery, complete debulking surgery is warranted. The lung is one of the most frequent sites of haematogenous metastases in women with uterine LMS. Resection of isolated lung metastases has been found to prolong survival and should be considered.
Uterine LMS is frequently diagnosed after surgery for presumed uterine leiomyoma because no specific symptoms, signs, tumour markers or diagnostic modality can preoperatively differentiate LMS from uterine leiomyoma. Therefore, many women with early stage LMS undergo tumour morcellation. This may adversely affect treatment outcomes, as higher recurrence rates and poorer survival have been observed in women who have undergone tumour morcellation. Therefore, women with early stage uterine LMS require complete tumour excision and also en-bloc resection without injury to the tumour. If the women are referred for further management after surgery, including tumour morcellation for presumed uterine leiomyoma or adenomyosis, complete hysterectomy is recommended in women who have undergone conservative surgery at initial operation. Restaging operations, however, are not recommended in women who have undergone initial total hysterectomy unless there is definite evidence of residual disease.
Surgical treatment of uterine carcinosarcoma
Uterine carcinosarcoma is frequently diagnosed by endometrial biopsy because women usually present with vaginal bleeding and an endometrial mass, with about 40% having tumours in the cervical canal caused by their exophytic growth. Therefore, most women with uterine carcinosarcoma can undergo planned surgical treatment according to the preoperative staging of the tumour and determination of lymph-node involvement. Simple hysterectomy has been recommended for women with stage I uterine carcinosarcoma because no survival differences in stage I patients who underwent simple versus radical hysterectomy were found. Radical hysterectomy can be considered for women whose tumours have spread to the cervix or parametrial tissue.
Carcinosarcoma rapidly spreads to the adnexa, lymph nodes and peritoneal surfaces, with 32–61% of women having extrauterine disease during staging. Many women who are clinically thought to have disease confined to the uterus are found to have extrauterine disease after surgical staging. About 12–23% of women with carcinosarcoma apparently confined to the uterus were found to have adnexal involvement, and 23% had occult metastases, suggesting that bilateral salpingo-oophorectomy should be part of surgical management for carcinosarcoma, even in women with apparently early disease.
Lymph-node metastasis is also frequent in carcinosarcoma. About 14–38% of women with carcinosarcoma confined to the uterus are upstaged to stage IIIc because of occult lymph-node metastasis after lymph-node dissection. The frequency and pattern of lymph-node metastasis of carcinosarcoma is similar to that of high-risk endometrial adenocarcinoma ( Table 2 ). Therefore, pelvic and para-aortic lymph-node dissection is recommended for surgical treatment of carcinosarcoma, as it is for endometrial adenocarcinoma. Because sampling of pelvic and para-aortic lymph nodes may miss microscopic or occult lymph-node metastases in women with clinically early stage carcinosarcoma, systematic lymph-node dissection is recommended rather than sampling or removal of enlarged lymph nodes. In addition, the number of lymph nodes retrieved in early stage carcinosarcoma has been found to correlate with the risk of recurrence and survival. Because about 50% of women with pelvic lymph-node metastasis also had para-aortic lymph-node metastasis, and about 7% of women had para-aortic without pelvic lymph-node metastasis, para-aortic lymph-node dissection should also be included in the surgical treatment of carcinosarcoma. Although lymph-node dissection improves surgical staging and provides prognostic information on women with apparently early stage carcinosarcoma, it is still unclear whether lymph-node dissection improves patient survival. Several retrospective studies have indicated the importance of lymph-node removal on the survival of women with early stage uterine carcinosarcoma. Because surgical extirpation is the most important aspect of treatment, removal of occult lymph-node metastases may also improve prognosis. In addition, the removal of occult lymph-node metastases may render women more susceptible to cure by adjuvant therapy. Further evaluation is warranted.
| Author | Year | N | FIGO stage | Lymph-node dissection or sampling ( N ) | Lymph-node metastasis | |
|---|---|---|---|---|---|---|
| N | (%) | |||||
| Ayhan et al. | 1997 | 28 | I–II | 14 | 4 | 28.5 |
| Park et al. | 2010 | 41 | I–II | 41 | 13 | 31.7 |
| Nemani et al. | 2008 | 1855 | I–III | 965 | 119 | 14 |
| Inthasorn et al. | 2002 | 37 | I–IV | 20 | 7 | 35 |
| Callister et al. | 2004 | 300 | I–IV | 124 | 33 | 26.6 |
| Galaal et al. | 2009 | 93 | I–IV | 34 | 13 | 38.2 |
| Total | 2354 | 1196 | 189 | 15.8 | ||
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