Correspondence to Meng Qiu; [email protected]
STRENGTHS AND LIMITATIONS OF THIS STUDY
We systematically analysed one of the largest cohorts of carcinosarcoma (CS) patients in a population-level cancer registry.
The clinicopathological and treatment features of CS differed from those of other common subtypes at each site.
Pulmonary CS had the worst survival compared with CS at other sites. Radiotherapy did not exert positive effects on these patients. More attention should be paid to the effective treatment for them.
Several clinical variables, such as tumour stage and grade, have very extensive definitions in all primary tumours, unavoidably leading to imprecise comparisons.
The details of the systemic treatment such as the treatment sequences and drug names are lacking.
Introduction
Carcinosarcoma (CS) is a rare but exceedingly aggressive tumour characterised by high metastasis rates and poor prognosis. Since Virchow et al first reported it in 1863, a growing number of researchers have described it in the genitourinary tract, digestive tract, breast, lung and other sites of the body.1 The incidence of CS and correlated cancers is highly variable and relies on the anatomical sites, ranging from extremely infrequent in the skin to as much as approximately 5%–10% of grades III–IV uterine corpus tumours.2 In the uterus and adnexa, CS is grouped as (malignant) mixed Müllerian tumours (MMMTs).3 Breast CS and pulmonary CS are classified as metaplastic carcinoma and sarcomatoid carcinoma, respectively.4 5 Histologically, CS consists of malignant sarcomatous (mesenchymal) and carcinomatous (epithelial) cells. According to the sarcomatous component, the subtypes are divided into homologous (emanating from the primary tumour site) and heterologous (not deriving from the primary tumour site).6
Prior research has proposed three main hypotheses to explain the aetiology of CS.7 These are the collision, combination and conversion theories. The collision theory suggests that CS arises from two distinct neoplasms (carcinoma and sarcoma), which accidentally appear and merge. In the combination theory, a transformed progenitor cell is hypothesised to differentiate these two components. Based on the conversion theory, a carcinoma experiences an epithelial-mesenchymal transition (EMT), resulting in an admixed cancer consisting of both epithelioid and spindle-like cells. This theory plays a dominant role in the histogenic process of CS. Several critical EMT-related markers, including E-cadherin, the transcription factors ZEB1 and Snail, are expressed in CS.2
At present, the accurate diagnosis of CS is challenging, which could be influenced by the multiple tumour differentiation tendencies, few tissue samples and atypical cell morphology. The available evidence about the treatment of CS is from limited trials and case series. The consensus that surgical resection is for early-stage patients has been generally established. It is also widely acknowledged that platinum-based chemotherapy combined with ifosfamide and paclitaxel is effective.8 However, mixed results were demonstrated in the advantages of radiotherapy on overall survival (OS).9 10 Due to the ambiguous treatment options and the invasive histological features of CS, patients suffer a poor prognosis, with a 5-year OS of 12.85% in stage IV.11 Therefore, it is necessary to recognise the features of this scarce histological type comprehensively. The Surveillance, Epidemiology and End Results (SEER) database, one of the population-based cancer registries, encompasses approximately 30% of the USA with widespread capture of different histological cases.12 Nonetheless, because of the anatomic diversity of origin in CS, previous studies based on the SEER database usually focused on a single organ, rendering the understanding of CS fragmentary and deficient.13–16 This study intended to describe a standardised and systematic characterisation of demographical and clinicopathological peculiarities of CS across common locations compared with nonvariant histological subtypes.
Materials and methods
Data source and patient selection
This study was abstracted from the National Cancer Institute’s SEER database of nine cancer registries from 1975 to 2018. CS was identified by the International Classification of Disease for Oncology 0–3 classification as 8980/3 (CS, NOS) and 8981/3 (CS, embryonal type). Patients with a first or only diagnosis of CS were included to conduct incidence-related analysis. Then, we excluded patients with T0 stage or tumour in situ. Patients without complete race and survival information (survival status and time) were not included. We selected the top five anatomic CS for further analysis, and we compared each anatomic CS with the most common subtypes at this site. The final recruited patients underwent baseline comparison analysis and survival analysis.
Variables and endpoints
All available variables about CS were recorded and analysed, including patient demographics (age, gender, race and marital status), tumour information (grade and stage) and cancer-related therapy (surgery, radiation therapy and chemotherapy). The primary endpoint was cancer-specific survival (CSS). It was defined as death from CS. Relative survival (RS) was defined as the ratio of observed survival to expected survival.
Statistical analysis
Data from the SEER database (SEER*Stat V.8.3.9) were analysed with EmpowerStats (X&Y Solutions, Boston, Massachusetts, USA) and R software (V.4.1) for statistical analysis. The incidence is per 100 000 and adjusted by age with its variable recode less than 1 year old to the 2000 US standard population. The annual percent change (APC) and the average APC (AAPC) were calculated from the incidence by Joinpoint Trend Analysis Software (V.4.9.0.0, March 2021, National Cancer Institute). Age-standardised CSS and RS were calculated by using SEER*Stat V.8.3.9. We used Origin Pro 2021 software (OriginLab, Northampton, Massachusetts, USA) to produce graphs. Descriptive analyses were conducted to delineate the baseline features and the intergroup discrepancies. Categorical and continuous variables were analysed by χ2 and t-tests. The former variables were documented as frequencies and proportions. The latter variables were expressed as the means and SD. We recognised the risk factors associated with CSS by univariate and multivariate Cox proportional hazards models. The Kaplan-Meier (K-M) method with a log-rank test was performed to estimate the CSS rate. A p<0.05 in a two-tailed test was identified as statistically significant.
Patient and public involvement
Patients and the public were not involved in the design or planning of the study.
Results
The site and geographical distribution of CS
The study flow chart is shown in figure 1. Generally, the sites for these 5042 patients were located throughout the body (figure 2). In this study, CS was most common in the genital system (79.5%), among which the corpus/cervix accounted for the majority (nearly 80%), followed by the ovary/fallopian tube (18.2%, 731/4008). Thoracic CS comprised 9.6% of all CS. Among them, lung CS and breast CS occupied a large proportion. Additionally, no more than 5% of CS occurred in the urinary system, almost all in the bladder. Abdomen CS covered 3.1% of all CS, with nearly one-third located in the liver/gallbladder. Only approximately 1% of CS was presented in bone, skin, secretory glands or head and neck. We selected the top five anatomic CS for further analysis.
Enlarge this image.Figure 2. Distribution of carcinosarcoma in the SEER database spanning 1975-2018, with a total of 5042 cases. SEER, Surveillance, Epidemiology and End Results.
Regarding geographical distribution, Atlanta showed the highest age-adjusted incidence of 0.7 per 100 000, followed by Seattle (Puget Sound) at 0.6 per 100 000 and Utah and Detroit (Metropolitan) at 0.5 per 100 000. The remaining regions, including San Francisco-Oakland SMSA, Connecticut, Hawaii, Iowa and New Mexico, showed the same incidence of 0.4 per 100 000 (figure 3A). We also presented the rates in each registry stratified by race, sex and age (figure 3B). In Atlanta, the majority of CS patients were black, female and aged over 60 years old.
Enlarge this image.Figure 3. (A) Age-adjusted incidence rates for carcinosarcoma across the nine SEER registries during 1975-2018. (B) The carcinosarcoma incidence rates in each registry stratified by race, sex and age. SEER, Surveillance, Epidemiology and End Results.
Incidence trends of CS
The long-term trends in morbidity of CS are described in figure 4. Of CS in five common primary sites, uterine CS persistently presented the highest age-adjusted rate from 1975 to 2018, with a peak of 0.65% in 2018 (figure 4A). Joinpoint regression showed four inflexion points in uterine CS (1990, 1993, 2004, 2008). From 2004 to 2018, the incidence rate of uterine CS experienced a sustained increase, with the highest growth rate at 20.91% (95% CI 4.1% to 40.4%) per year between 2004 and 2008. One inflexion point was shown in ovary/fallopian tube CS (1987). Its incidence rates increased by 5.2% (95% CI 4.1% to 6.3%) per year from 1981 to 2018. Although pulmonary, bladder and breast CS seemed to present relatively stable age-adjusted rates of no more than 0.07% (figure 4A), the trends were decreasing over the past years, significantly in pulmonary CS (AAPC: −1.5%; 95% CI −2.5% to −0.5%).
Enlarge this image.Figure 4. Trends in annual carcinosarcoma incidence (SEER 1975-2018). (A) Age-adjusted rate stratified by primary site. (B) Age-adjusted rate stratified by age. (C) Age-adjusted rate stratified by sex. (D) Age-adjusted rate stratified by race. (E) Age-adjusted rate stratified by stage. SEER, Surveillance, Epidemiology and End Results.
The morbidity of CS increased with age, and the incidence in different age groups varied between 1974 and 2018 (figure 4B). The overall trend was significantly upward in patients over 80 years, with an AAPC of 1.8% (95% CI 0.2% to 3.5%). For gender, females presented higher rates than males, with an increased rate of 3.94% (95% CI 3.31% to 4.56%) per year from 1975 to 2018 (figure 4C). The prevalence rate in black populations maintained an upward trend of 3.66% (95% CI 2.5% to 4.9%) annually, with the highest rate at 1.9% in 2018 (figure 4D). We also calculated the age-adjusted rates stratified by stage (figure 4E). CS cases with distant metastasis presented the highest age-adjusted rates among the three-stage groups from 1998 to 2018 (AAPC 2.8%, 95% CI 1.1% to 4.6%).
The baseline characteristics of the included CS
The characteristics of all CS patients are shown in table 1. For the most part, it was more common for CS to occur in elderly married Caucasians. Pulmonary and bladder CS were prone to appear in males. Histologically, CS was universally poorly differentiated or undifferentiated at almost all sites. Lymph node metastasis was uncommon in all CS. However, ovary/fallopian tube CS was most often detected at an advanced stage. In terms of treatments, most patients with CS received surgery, particularly breast or bladder CS patients. Radiotherapy was primarily applied in uterine CS patients. Nearly half of CS patients received chemotherapy, with most patients receiving chemotherapy in the ovary/fallopian tube and breast.
Table 1The baseline characteristics of the included carcinosarcoma patients
| Variables | Total | Corpus/cervix | Ovary/fallopian Tube | Lung | Bladder | Breast | Other | P value |
| N (%) | 5042 | 3168 (62.83%) | 731 (14.50%) | 282 (5.59%) | 188 (3.73%) | 150 (2.98%) | 523 (10.37%) | |
| Age | <0.001 | |||||||
| 70 (1.39%) | 31 (0.98%) | 13 (1.78%) | 3 (1.06%) | 1 (0.53%) | 12 (8.00%) | 10 (1.91%) | ||
| 1143 (22.67%) | 654 (20.64%) | 219 (29.96%) | 59 (20.92%) | 19 (10.11%) | 60 (40.00%) | 132 (25.24%) | ||
| 2981 (59.12%) | 1955 (61.71%) | 403 (55.13%) | 188 (66.67%) | 105 (55.85%) | 61 (40.67%) | 269 (51.43%) | ||
| 848 (16.82%) | 528 (16.67%) | 96 (13.13%) | 32 (11.35%) | 63 (33.51%) | 17 (11.33%) | 112 (21.41%) | ||
| Sex | <0.001 | |||||||
| 4526 (89.77%) | 3168 (100.00%) | 731 (100.00%) | 113 (40.07%) | 64 (34.04%) | 150 (100.00%) | 300 (57.36%) | ||
| 516 (10.23%) | 0 (0.00%) | 0 (0.00%) | 169 (59.93%) | 124 (65.96%) | 0 (0.00%) | 223 (42.64%) | ||
| Race | <0.001 | |||||||
| 3838 (76.12%) | 2268 (71.59%) | 608 (83.17%) | 239 (84.75%) | 168 (89.36%) | 119 (79.33%) | 436 (83.37%) | ||
| 811 (16.08%) | 629 (19.85%) | 64 (8.76%) | 30 (10.64%) | 13 (6.91%) | 20 (13.33%) | 55 (10.52%) | ||
| 393 (7.79%) | 271 (8.55%) | 59 (8.07%) | 13 (4.61%) | 7 (3.72%) | 11 (7.33%) | 32 (6.12%) | ||
| Marital status | 0.006 | |||||||
| 4103 (81.38%) | 2556 (80.68%) | 588 (80.44%) | 249 (88.30%) | 165 (87.77%) | 116 (77.33%) | 429 (82.03%) | ||
| 720 (14.28%) | 474 (14.96%) | 113 (15.46%) | 28 (9.93%) | 17 (9.04%) | 26 (17.33%) | 62 (11.85%) | ||
| 219 (4.34%) | 138 (4.36%) | 30 (4.10%) | 5 (1.77%) | 6 (3.19%) | 8 (5.33%) | 32 (6.12%) | ||
| Grade | <0.001 | |||||||
| 128 (2.54%) | 91 (2.87%) | 9 (1.23%) | 8 (2.84%) | 1 (0.53%) | 5 (3.33%) | 14 (2.68%) | ||
| 2404 (47.68%) | 1549 (48.90%) | 379 (51.85%) | 93 (32.98%) | 96 (51.06%) | 106 (70.67%) | 181 (34.61%) | ||
| 2510 (49.78%) | 1528 (48.23%) | 343 (46.92%) | 181 (64.18%) | 91 (48.40%) | 39 (26.00%) | 328 (62.72%) | ||
| Stage | <0.001 | |||||||
| 1639 (32.51%) | 1259 (39.74%) | 64 (8.76%) | 50 (17.73%) | 45 (23.94%) | 103 (68.67%) | 118 (22.56%) | ||
| 1523 (30.21%) | 998 (31.50%) | 121 (16.55%) | 84 (29.79%) | 105 (55.85%) | 31 (20.67%) | 184 (35.18%) | ||
| 1531 (30.36%) | 792 (25.00%) | 533 (72.91%) | 58 (20.57%) | 27 (14.36%) | 10 (6.67%) | 111 (21.22%) | ||
| 349 (6.92%) | 119 (3.76%) | 13 (1.78%) | 90 (31.91%) | 11 (5.85%) | 6 (4.00%) | 110 (21.03%) | ||
| T stage | <0.001 | |||||||
| 786 (15.59%) | 628 (19.82%) | 81 (11.08%) | 9 (3.19%) | 19 (10.11%) | 10 (6.67%) | 39 (7.46%) | ||
| 573 (11.36%) | 323 (10.20%) | 159 (21.75%) | 28 (9.93%) | 14 (7.45%) | 17 (11.33%) | 32 (6.12%) | ||
| 3683 (73.05%) | 2217 (69.98%) | 491 (67.17%) | 245 (86.88%) | 155 (82.45%) | 123 (82.00%) | 452 (86.42%) | ||
| N stage | <0.001 | |||||||
| 1015 (20.13%) | 695 (21.94%) | 179 (24.49%) | 23 (8.16%) | 31 (16.49%) | 23 (15.33%) | 64 (12.24%) | ||
| 353 (7.00%) | 260 (8.21%) | 55 (7.52%) | 17 (6.03%) | 3 (1.60%) | 4 (2.67%) | 14 (2.68%) | ||
| 3674 (72.87%) | 2213 (69.85%) | 497 (67.99%) | 242 (85.82%) | 154 (81.91%) | 123 (82.00%) | 445 (85.09%) | ||
| M stage | <0.001 | |||||||
| 1155 (22.91%) | 797 (25.16%) | 202 (27.63%) | 28 (9.93%) | 33 (17.55%) | 25 (16.67%) | 70 (13.38%) | ||
| 266 (5.28%) | 195 (6.16%) | 41 (5.61%) | 14 (4.96%) | 2 (1.06%) | 2 (1.33%) | 12 (2.29%) | ||
| 3621 (71.82%) | 2176 (68.69%) | 488 (66.76%) | 240 (85.11%) | 153 (81.38%) | 123 (82.00%) | 441 (84.32%) | ||
| Surgery | <0.001 | |||||||
| 4424 (87.74%) | 2846 (89.84%) | 692 (94.66%) | 199 (70.57%) | 181 (96.28%) | 143 (95.33%) | 363 (69.41%) | ||
| 618 (12.26%) | 322 (10.16%) | 39 (5.34%) | 83 (29.43%) | 7 (3.72%) | 7 (4.67%) | 160 (30.59%) | ||
| Radiation | <0.001 | |||||||
| 1759 (34.89%) | 1358 (42.87%) | 43 (5.88%) | 103 (36.52%) | 37 (19.68%) | 55 (36.67%) | 163 (31.17%) | ||
| 3283 (65.11%) | 1810 (57.13%) | 688 (94.12%) | 179 (63.48%) | 151 (80.32%) | 95 (63.33%) | 360 (68.83%) | ||
| Chemotherapy | <0.001 | |||||||
| 2492 (49.42%) | 1579 (49.84%) | 565 (77.29%) | 72 (25.53%) | 36 (19.15%) | 77 (51.33%) | 163 (31.17%) | ||
| 2550 (50.58%) | 1589 (50.16%) | 166 (22.71%) | 210 (74.47%) | 152 (80.85%) | 73 (48.67%) | 360 (68.83%) |
Prognostic factors and survival of CS
For all CS patients, age over 80, black race, grades III–IV disease, advanced stage and no treatment were significantly associated with decreased CSS (online supplemental table S1). For site-specific survival, breast CS showed the greatest prognosis (online supplemental table S1 and figure S1 A), followed by uterine, bladder, adnexa and lung CS. Regardless of the histological type at each site, CS appeared to have the worst outcome (online supplemental figure S1B–F). The stratified K-M analysis between the primary site and prognosis is shown in online supplemental figure S2. However, only pulmonary CS showed significantly worse survival in multivariate analysis. The CSS and RS of CS are summarised in online supplemental table S2. In the overall CS population, the median CSS and RS were 26.73 and 22.84 months, and the 5-year CSS and RS rates were 37.30% and 34.90%, respectively. According to the primary site, breast CS had the longest 5-year CSS of 61.40% (95% CI 50.3% to 70.8%) and 5-year RS of 57.30% (95% CI 45.60% to 67.40%), while lung CS had the shortest median CSS (9.92 months) and RS (9.14 months).
Corpus/cervix cancer
For corpus/cervix cancer, the common features were age 60–80 years old and married white. Early TNM stage also presented in endometrioid carcinoma (EC), adenocarcinoma (AC) and squamous cell carcinoma (SC) of corpus/cervix cancer. Specifically, uterine CS preferred a more advanced grade (48.90%, p<0.001). In addition, radiotherapy (61.23% and 42.87%) and chemotherapy (49.84% and 25.40%) accounted for the majority of uterine CS and SC patients, respectively (online supplemental table S3).
Black race (HR 1.20, 95% CI 1.06 to 1.36) and patients without receiving therapy were significantly associated with a lower survival benefit of CSS (online supplemental table S1).
Ovary/fallopian tube cancer
In general, three types of ovary/fallopian tube cancer, including serous cystadenocarcinoma, EC and CS, were all primarily presented in married white patients (online supplemental table S4). Elderly patients (age 60–80 years old) were more likely to have CS and serous cystadenocarcinoma than EC (age 40–60 years old). EC patients mostly received radiotherapy (7.57%), while the other two types received chemotherapy more (serous cystadenocarcinoma: 80.85%; CS: 77.29%).
Patients aged over 60 years old, advanced stage and without surgery or chemotherapy seemed to suffer worse outcomes (online supplemental table S1).
Lung cancer
All three types of lung tumours were more common in elderly and married white male patients (online supplemental table S5). A higher proportion of advanced T stage was shown in the lung CS patients than in the other subtypes. CS patients were more likely to be treated with surgery but less likely to be accepted for chemotherapy or radiotherapy.
For the prognostic factors, male sex (HR 1.45, 95% CI 1.08 to 1.94), advanced stage and radiotherapy (HR 0.60, 95% CI 0.42 to 0.86) were associated with poor prognosis. Receiving surgery and chemotherapy were associated with a better prognosis (online supplemental table S1).
Bladder cancer
Regardless of the type of pathology, the incidence of bladder cancer was higher in married white males (online supplemental table S6). Compared with transitional cell carcinoma (TCC) and AC (26.42% and 23.10%), CS was more frequent in older (>80) patients (33.51%). TCC was mainly in the localised stage (51.31%), while CS and AS were more often in the regional stage (55.85%% and 42.78%). Furthermore, surgery was more frequently applied in CS patients, while fewer CS patients received adjuvant therapy. Only the advanced stage was an independent predictor of poor prognosis (online supplemental table S1).
Breast cancer
CS, invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) patients were all mostly 60–80 years, white married females (online supplemental table S7). Compared with IDC and ILC, CS was more likely to be found with grades III–IV (70.67%), localised stage (68.67%) and T3–T4 stage (11.33%). In addition, more CS patients were treated with chemotherapy (51.33%) than the other two types of breast cancer (33.37% and 27.72%).
After multivariable analysis, we found that regional or distant metastasis was associated with a poorer prognosis (online supplemental table S1).
Discussion
CS is a rare and biphasic malignancy characterised by coexisting epithelial and mesenchymal compositions. Our study based on the SEER database intended to demonstrate the epidemiological, site-specific clinical and prognostic features of CS. Comparative analysis was also conducted between CS and major non-variant histological types.
Epidemiology
Our results showed that nearly 80% of CS occurred in the genitourinary system, especially the female reproductive system, including the uterus and adnexa. CS usually originates from gynaecological tumours but also appears in any anatomic site. The incidence of uterine CS has continued to grow in the past 20 years. One contributing factor Matsuo et al found was obesity, which has continued to rise in the USA.17 Nearly 40% of people over 60 years old were evaluated to be obese in 2015–2016.18 The increased risk of endometrial cancer was associated with obesity, which increased EMT in endometrial tumours and further formed uterine CS.17 In addition, uterine CS shared other risk factors with endometrial carcinoma, including tamoxifen use, excessive oestrogen exposure and nulliparity.19 Our study also showed that black individuals presented the highest age-adjusted rate of CS, suggesting possible demographic trends in the future. Previous studies reported that black women suffered a higher incidence of invasive histological subtypes such as CS than white women.20 The differences could be attributed to molecular factors, socioeconomic status and the time and type of treatment.21 Black patients had higher frequencies of TP53 and some DNA mismatch gene mutations.22 23 In addition, the rates of distant metastasis in CS have progressively increased, stressing the importance of prevention and early diagnosis. Notably, Atlanta was the area with the highest incidence from 1975 to 2018. This registry collected information on residents in metropolitan Atlanta (countries: Gwinnett, Fulton, DeKalb, Cobb and Clayton) and its adjacent rural regions. The geographical variations in CS incidence might be ascribed to the different demographic characteristics (age, race and sex) and environmental risk factors (alcohol use, smoking and obesity). We found that women, the elderly and the black population accounted for the largest proportion in Atlanta, which could lead to the highest incidence.
Clinicopathological and treatment characteristics of CS
CS in different sites has similar and specific clinicopathological and treatment features. Without respect to the anatomic locations, our findings showed that the shared features of CS included age between 60 and 80, white race, married status, grades III–IV, N0/M0 stage and surgical treatment. In particular, pulmonary and bladder CS more frequently occurred in men and were diagnosed with regional stage. Distant metastasis was mostly found in the ovary/fallopian tube CS. Radiotherapy was more commonly applied in uterine and breast CS. Adnexa and breast CS cases were prone to receive chemotherapy.
Concerning uterine CS, it showed a more advanced grade, predominantly in site or localised stage, than the other three types of uterine cancer. The biological behaviour of uterine CS relies on epithelial characteristics instead of stromal elements.7 24 Nearly 95% of sarcoma components reported in uterine CS were grade IV, and over 50% of uterine CS were diagnosed in early stage (I–II).24 Similarly, the majority of uterine CS cases were localised diseases in our results. In cases where the epithelial components presented as clear cell, serous and grade III endometrioid in type, a higher metastasis frequency was reported.25 However, a stage shift with rising nodal metastasis and declining distant metastasis has recently appeared in uterine CS.24 26 Notably, our results showed that ovarian CS had higher rates of distant metastasis than uterine CS. High distant metastasis in ovary CS precluded thorough lymph node dissections. As a result, significantly less lymphadenectomy was performed in cases with ovary CS than in those with uterine CS.26 In addition, uterine CS displayed a higher radiosensitivity than other uterine sarcomas, while ovary CS cases extensively existed as an intra-abdominal disease.27 Therefore, the approach of adjuvant therapy presented a preference for these two CS types in our results. Radiotherapy was linked with improved disease-free survival (DFS) in uterine CS.28 Platinum-based chemotherapy regimens are regarded as the optimal treatment for ovarian CS.27
In terms of pulmonary and bladder CS, males played a dominant part with male‒female sex ratios of 4:1 and 2:1, respectively.16 29 30 Sex-related living habits (smoking and drinking) and biological differences (DNA damage susceptibility) may explain this preference. In contrast with non-small cell lung cancer, pulmonary CS presented a lower incidence of lymph node metastasis and a higher rate of surgical resection in our results. This is in line with the classic statement that lung CS seldom metastasizes via the lymphatic system.31
Breast CS, a breast metaplastic carcinoma, also displays more aggressive characteristics than IDC or ILC carcinoma. It has been reported that breast CS resembles triple-negative and poorly differentiated breast cancer.32 Lymphatic and bloodstream metastasis were found in breast CS, while the incidence of lymphatic metastasis was lower than that in IDC, in accordance with the sarcoma phenotype.33 It has been reported that breast CS commonly presents as a large, painful breast mass, so breast-conserving surgery is not the preferred approach.5 Multidisciplinary therapies are required for breast CS. Mastectomy followed by adjuvant chemoradiotherapy was recommended in most reported cases and could improve 5-year OS.34 This might explain why our results showed that radiotherapy and chemotherapy both accounted for a large proportion of breast CS.
Prognosis of CS
Regardless of the various primary sites, a highly aggressive course was the most important clinical feature shared in CS. We compared CS with the common histological type in each location. The results indicated that CS patients suffered from the poorest prognosis, which could be attributed to EMT. It is universally acknowledged that complete EMT leads to the occurrence of the sarcoma component of CS.2 In many carcinomas, EMT is involved in increased invasiveness, metastatic potential and chemoresistance.35 Nonetheless, the genetic characteristics and molecular pathways associated with EMT in CS differed in anatomical sites. Uterine CS was found with abnormal p53 staining and defective mismatch repair (MMR). However, MMR deficiency is not common in extrauterine CS.35 In uterine CS, the Akt/β-catenin pathway activated Slug, restraining the expression of E-cadherin (an epithelial phenotype marker), further promoting tumour invasion and metastasis. Moreover, the Wnt signalling pathway was dysregulated.36 Instead, pulmonary CS was launched by the upregulated c-Jun pathway and the consecutively overexpressed fascin and vimentin (cytoskeletal proteins).37 These differences might be associated with the prognosis of CS in distinct sites.
In our study, we found that the prognosis of CS differed from that of anatomic sites. Breast CS had the best prognosis, with a 5-year CSS rate of 61.4%. Pulmonary CS suffered the worst CSS in the multivariate analysis. Several studies have reported comparisons between different sites of CS. Garg et al found that the survival of ovary CS was worse than that of uterine CS in K-M analysis (16 months vs 25 months, p<0.01), whereas the results were opposite after stratification by stage.26 Ovary CS presented a superior prognosis than uterine CS in regional and distant diseases,26 38 which was in line with our subgroup analysis. However, other studies did not reach significant results.39 40 The differences in genetic features between uterine and ovarian CS might be connected with prognosis. It was reported that TP53 expression was lower in ovarian CS than uterine CS (30% vs 75%).41 Moreover, HMGA protein, which participates in the tumourigenic process by activating and sustaining EMT, displayed consistently higher levels in uterine CS than in ovarian CS. In addition, Growdon et al42 found that PI3K/Akt/mTOR pathway (PIK3CA) and/or MAPK cascade (KRAS and NARS) mutations were exclusive to uterine CS instead of other gynaecological origin CS, which may implicate a more aggressive clinical course and shorter survival. We found that breast CS presented the greatest survival in each subgroup. A prior study compared the genetic landscape between breast CS and the uterine CS gene by performing whole-exome sequencing.43 The results showed that uterine CS differed from breast CS based on more frequent PPP2R1A and FBXW7 mutations and HER2 amplification, which increased tumour invasion and poor prognosis. This implied the notion that these tumours were more than mere phenotypes of the same histological subtype in distinct sites.
The lung seemed to be the worst anatomic site of CS in our study. Lung or bronchus tumours are the leading cause of cancer death regardless of sex and age in the USA.44 In contrast to uterine CS, the poor prognosis of pulmonary CS depends on malignant mesenchymal elements.45 It features easy relapse after surgical resection and resistance to radiotherapy and chemotherapy.46 The Mayo Clinic conducted a study and showed that the 5-year preoperative and postoperative survival for pulmonary CS patients was 21.3% and 28.7%, respectively, with an average postoperative survival of 9 months.47 The genomic alterations of pulmonary CS have been identified by using next-generation sequencing analysis.48 The Lyst gene, which is associated with life-threatening diseases, has been found in these patients. In addition, approximately one-fourth of pulmonary CS patients had significant PD-L1 expression, which was involved in aggressive pathological features and tumour mutation burden (especially KRAS mutation).49 Identifying prognostic discrepancies at primary sites would lay a foundation for therapy and follow-up strategies.
Prognostic factors of CS
We also explored the prognostic factors of CS in the five most common primary sites, which did not suggest significant differences. Black race, advanced stage and no treatment were associated with poor prognosis in all site CS. Several public databases, such as the National Cancer Database and California Cancer Registry database, have shown that uterine and ovarian CS in black women manifested higher incidence and mortality than their white counterparts.20 50 Long et al51 suggested that black patients had a lower socioeconomic status, which led to a therapeutic delay and high expression of HER2 in cancer. These were further linked with worse prognosis and treatment resistance.
Moreover, several studies have reported the unique prognostic factors of ovary CS.52 53 A recent meta-analysis,54 which included eight studies of gynaecological CS, showed that heterologous component presence indicated worse OS after excluding the confounding factors. Previous research55 56 demonstrated that the primary tumour with over 25% sarcoma component and abundant small vessels would suffer poor survival. Besides, serous epithelial components in tumour presented more aggressive behaviours than non-serous components.25 Compared with other gynaecological tumours, ovarian CS had higher p53 overexpression, which adversely affected the outcome.57 58 Except for the well-acknowledged prognostic factors, such as age over 65 and suboptimal surgical excision, high Ki67 index in ovarian CS was associated with lower 5-year survival.59 PD-L1 negative expression and increased CD8+tumour-infiltrating lymphocytes (TILs) from ovarian CS patients showed remarkable value in predicting superior prognosis,60 suggesting the effectiveness of immunotherapy.61
In particular, we found that radiotherapy might be a significant risk factor for pulmonary CS. Several studies also came to the same conclusion by analysing the SEER database,15 62 suggesting resistance to radiation of pulmonary CS. A real-world study in the larger context of pulmonary sarcomatoid carcinoma indicated that no survival benefits of radiotherapy were found in these patients who were treated with a complete surgery section.29 Moreover, Sun et al15 found that patients with lung sarcomatoid carcinoma could significantly benefit from chemotherapy, which was consistent with our results.
For breast and bladder CS, our results did not show any prognostic indicators due to the limited sample size. Similar to our results, a previous study confirmed that stage was the most significant predictive factor for survival in bladder CS.30 Since bladder CS usually invades the lamina propria, which means coexisting carcinous and sarcomatous degeneration in the mucosa and underlying submucosal stroma, respectively, radical cystectomy seems to be the preferred method for bladder CS.63 However, the therapeutic effects of adjuvant therapy remain controversial in bladder CS. In terms of breast CS, other insurance status, comorbidity index, surgical margin, T stage and therapeutic strategy were significantly linked with OS.64 Among them, there is no consensus on the role of adjuvant chemotherapy in breast CS.65
Some limitations of this study should not be omitted. First, several essential clinical variables, such as tumour grade and stage, have very extensive definitions in all primary tumours, unavoidably leading to imprecise comparisons. Besides, considering the rarity of CS, misclassification in a fraction of tumours could not be excluded reliably.
Conclusion
Overall, CS is a rare but highly aggressive disease, regardless of the primary site. We showed that elderly individuals, black population and Atlanta region presented the highest age-adjusted rate of CS. The rate of distant metastasis was also increasing, mainly in adnexa CS. Uterine, adnexal and breast CS presented differences in adjuvant therapy. Pulmonary CS seemed insensitive to radiotherapy and had the poorest prognosis. Anatomic sites of CS played a pivotal role in prognosis, and future studies should focus on the predictive and stratified biomarkers in different sites of CS at the genomic and molecular levels.
The authors are grateful to all the staff at the National Cancer Institute (USA) for their contribution to the SEER programme.
Data availability statement
Data are available on reasonable request. The datasets for this study can be obtained from the corresponding author on any reasonable request. All free text entered below will be published.
Ethics statements
Patient consent for publication
Not applicable.
L-ST, Y-WZ and J-LW contributed equally.
Contributors All authors contributed to this manuscript. Y-WZ and MQ conceptualised the study. L-ST and J-LW helped in the literature search and writing—original draft preparation. G-XZ and C-HX contributed to writing—review and editing. J-YL and MQ supervised the study. All authors have read and agreed to the published version of the manuscript. MQ is responsible for the overall content as guarantor.
Funding This study was supported by the Sichuan Science and Technology Department Key Research and Development Project (2019YFS0539), 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University (ZYJC18022 and ZYJC21017) and the National Clinical Research Center for Geriatrics (West China Hospital, Z2018B12).
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.
1 Sasamoto S, Aoki T, Tashiro Y, et al. Experience of the Pancreas Duodenectomy for so-called Carcinosarcoma of the common bile duct:a case report and review of literature. Int Cancer Conf J 2021; 10: 134–8. doi:10.1007/s13691-020-00462-y
2 Pang A, Carbini M, Moreira AL, et al. Carcinosarcomas and related cancers: tumors caught in the act of epithelial-Mesenchymal transition. J Clin Oncol 2018; 36: 210–6. doi:10.1200/JCO.2017.74.9523
3 Prat J. FIGO staging for uterine Sarcomas. Int J Gynaecol Obstet 2009; 104: 177–8. doi:10.1016/j.ijgo.2008.12.008
4 Travis WD, Brambilla E, Nicholson AG, et al. The 2015 world health organization classification of lung tumors: impact of genetic, clinical and Radiologic advances since the 2004 classification. J Thorac Oncol 2015; 10: 1243–60. doi:10.1097/JTO.0000000000000630
5 Salemis NS. Metaplastic carcinoma of the breast with Mesenchymal differentiation (Carcinosarcoma). A unique presentation of an aggressive malignancy and literature review. Breast Dis 2018; 37: 169–75. doi:10.3233/BD-170313
6 Leskela S, Pérez-Mies B, Rosa-Rosa JM, et al. Molecular basis of tumor heterogeneity in endometrial Carcinosarcoma. Cancers (Basel) 2019; 11: 964. doi:10.3390/cancers11070964
7 Somarelli JA, Boss M-K, Epstein JI, et al. Garcia-Blanco MA: Carcinosarcomas: tumors in transition? Histol Histopathol 2015; 30: 673–87. doi:10.14670/HH-30.673
8 Otsuki A, Watanabe Y, Nomura H, et al. Paclitaxel and carboplatin in patients with completely or Optimally Resected Carcinosarcoma of the uterus A phase II trial by the Japanese uterine sarcoma group and the Tohoku gynecologic cancer unit. Int J Gynecol Cancer 2015; 25: 92–7. doi:10.1097/IGC.0000000000000302
9 Manzerova J, Sison CP, Gupta D, et al. Adjuvant radiation therapy in uterine Carcinosarcoma: A population-based analysis of patient demographic and clinical characteristics, patterns of care and outcomes. Gynecol Oncol 2016; 141: 225–30. doi:10.1016/j.ygyno.2016.02.013
10 Nemani D, Mitra N, Guo M, et al. Assessing the effects of Lymphadenectomy and radiation therapy in patients with uterine Carcinosarcoma: A SEER analysis. Gynecol Oncol 2008; 111: 82–8. doi:10.1016/j.ygyno.2008.05.016
11 George EM, Herzog TJ, Neugut AI, et al. Carcinosarcoma of the ovary: natural history, patterns of treatment, and outcome. Gynecol Oncol 2013; 131: 42–5. doi:10.1016/j.ygyno.2013.06.034
12 Park HS, Lloyd S, Decker RH, et al. Overview of the surveillance, epidemiology, and end results database: evolution, data variables, and quality assurance. Curr Probl Cancer 2012; 36: 183–90. doi:10.1016/j.currproblcancer.2012.03.007
13 Nama N, Cason FD, Misra S, et al. Carcinosarcoma of the uterus: A study from the surveillance epidemiology and end result (SEER) database. Cureus 2020; 12: e10283. doi:10.7759/cureus.10283
14 Lin S, Liu C, Tao Z, et al. Clinicopathological characteristics and survival outcomes in breast Carcinosarcoma: A SEER population-based study. The Breast 2020; 49: 157–64. doi:10.1016/j.breast.2019.11.008
15 Sun L, Dai J, Wang X, et al. Pulmonary Carcinosarcoma: analysis from the surveillance, epidemiology and end results database. Interact Cardiovasc Thorac Surg 2020; 30: 4–10. doi:10.1093/icvts/ivz215
16 Liu L, Zhu J, Tian Y. Carcinosarcoma is an aggressive subtype of bladder cancer: A population-based study. Cancer Med 2022; 11: 2216–23. doi:10.1002/cam4.4611 Available: https://onlinelibrary.wiley.com/toc/20457634/11/11
17 Matsuo K, Ross MS, Machida H, et al. Trends of uterine Carcinosarcoma in the United States. J Gynecol Oncol 2018; 29. doi:10.3802/jgo.2018.29.e22
18 Hales CM, Carroll MD, Fryar CD, et al. Prevalence of obesity among adults and youth: United States, 2015-2016. NCHS Data Brief 2017; 2017: 1–8.
19 Kanthan R, Senger J-LB, Diudea D. Malignant mixed Mullerian tumors of the uterus: histopathological evaluation of cell cycle and apoptotic regulatory proteins. World J Surg Oncol 2010; 8: 60. doi:10.1186/1477-7819-8-60
20 Baskovic M, Lichtensztajn DY, Nguyen T, et al. Racial disparities in outcomes for high-grade uterine cancer: A California cancer Registry study. Cancer Med 2018; 7: 4485–95. doi:10.1002/cam4.1742
21 Lee JW, Ouh YT, Chang HK, et al. Trends in gynecologic Carcinosarcoma based on analysis of the surveillance epidemiology end result (SEER) database. J Clin Med 2023; 12: 1188. doi:10.3390/jcm12031188
22 Guttery DS, Blighe K, Polymeros K, et al. Racial differences in endometrial cancer molecular portraits in the cancer genome Atlas. Oncotarget 2018; 9: 17093–103. doi:10.18632/oncotarget.24907
23 Dubil EA, Tian C, Wang G, et al. Racial disparities in molecular subtypes of endometrial cancer. Gynecol Oncol 2018; 149: 106–16. doi:10.1016/j.ygyno.2017.12.009
24 Matsuzaki S, Klar M, Matsuzaki S, et al. Uterine Carcinosarcoma: contemporary clinical summary, molecular updates, and future research opportunity. Gynecol Oncol 2021; 160: 586–601. doi:10.1016/j.ygyno.2020.10.043
25 Cicin İ, Özatlı T, Türkmen E, et al. Predictive and Prognostic factors in ovarian and uterine Carcinosarcomas. Balkan Med J 2016; 33: 517–24. doi:10.5152/balkanmedj.2016.151268
26 Garg G, Shah JP, Kumar S, et al. Ovarian and uterine Carcinosarcomas: a comparative analysis of Prognostic variables and survival outcomes. Int J Gynecol Cancer 2010; 20: 888–94. doi:10.1111/IGC.0b013e3181dc8292
27 Pacaut C, Bourmaud A, Rivoirard R, et al. Uterine and ovary Carcinosarcomas: outcome, prognosis factors, and adjuvant therapy. Am J Clin Oncol 2015; 38: 272–7. doi:10.1097/COC.0b013e3182979b27
28 Vordermark D, Medenwald D, Izaguirre V, et al. The role of postoperative radiotherapy for Carcinosarcoma of the uterus. Cancers (Basel) 2020; 12: 3573. doi:10.3390/cancers12123573
29 Lin Y, Yang H, Cai Q, et al. Characteristics and Prognostic analysis of 69 patients with pulmonary Sarcomatoid carcinoma. Am J Clin Oncol 2016; 39: 215–22. doi:10.1097/COC.0000000000000101
30 Wang J, Wang FW, Lagrange CA, et al. Clinical features of Sarcomatoid carcinoma (Carcinosarcoma) of the urinary bladder: analysis of 221 cases. Sarcoma 2010; 2010: 454792. doi:10.1155/2010/454792
31 Janssen JP, Mulder JJ, Wagenaar SS, et al. Primary sarcoma of the lung: a clinical study with long-term follow-up. Ann Thorac Surg 1994; 58: 1151–5. doi:10.1016/0003-4975(94)90476-6
32 Yakan S, Sarı E, Erkan N, et al. Breast Carcinosarcomas. J Breast Health 2014; 10: 161–5. doi:10.5152/tjbh.2014.2197
33 McKinnon E, Xiao P. Metaplastic carcinoma of the breast. Arch Pathol Lab Med 2015; 139: 819–22. doi:10.5858/arpa.2013-0358-RS
34 Park HS, Park S, Kim JH, et al. Lee K-S: Clinicopathologic features and outcomes of Metaplastic breast carcinoma: comparison with invasive Ductal carcinoma of the breast. Yonsei Med J 2010; 51: 864–9. doi:10.3349/ymj.2010.51.6.864
35 Kunc M, Gabrych A, Rękawiecki B, et al. Immunohistochemical evaluation of mismatch repair proteins and P53 expression in Extrauterine Carcinosarcoma/Sarcomatoid carcinoma. Wo 2020; 24: 1–4. doi:10.5114/wo.2020.94718
36 Saegusa M, Hashimura M, Kuwata T, et al. Requirement of the AKT/beta-Catenin pathway for uterine Carcinosarcoma genesis, Modulating E-Cadherin expression through the Transactivation of slug. Am J Pathol 2009; 174: 2107–15. doi:10.2353/ajpath.2009.081018
37 Blaukovitsch M, Halbwedl I, Kothmaier H, et al. Sarcomatoid Carcinomas of the lung--are these Histogenetically heterogeneous tumors Virchows Arch 2006; 449: 455–61. doi:10.1007/s00428-006-0256-8
38 Rauh-Hain JA, Shoni M, Schorge JO, et al. Prognostic determinants in patients with uterine and ovarian Carcinosarcoma. J Reprod Med 2013; 58: 297–304.
39 Ureyen I, Karalok A, Cirik DA, et al. Uterine and ovarian Carcinosarcomas: do they behave similarly? J Obstet Gynaecol Can 2017; 39: 559–63. doi:10.1016/j.jogc.2017.03.098
40 Jonson AL, Bliss RL, Truskinovsky A, et al. Jr.: clinical features and outcomes of uterine and ovarian Carcinosarcoma. Gynecol Oncol 2006; 100: 561–4. doi:10.1016/j.ygyno.2005.09.017
41 Brunetti M, Agostini A, Staurseth J, et al. Molecular characterization of Carcinosarcomas arising in the uterus and Ovaries. Oncotarget 2019; 10: 3614–24. doi:10.18632/oncotarget.26942
42 Growdon WB, Roussel BN, Scialabba VL, et al. Tissue-specific signatures of activating Pik3Ca and RAS mutations in Carcinosarcomas of gynecologic origin. Gynecol Oncol 2011; 121: 212–7. doi:10.1016/j.ygyno.2010.11.039
43 Moukarzel LA, Ferrando L, Da Cruz Paula A, et al. The genetic landscape of Metaplastic breast cancers and uterine Carcinosarcomas. Mol Oncol 2021; 15: 1024–39. doi:10.1002/1878-0261.12813
44 Siegel RL, Miller KD, Wagle NS. Cancer statistics, 2023. CA: A Cancer Journal for Clinicians 2023; 73: 17–48. doi:10.3322/caac.21763
45 Huwer H, Kalweit G, Straub U, et al. Pulmonary Carcinosarcoma: diagnostic problems and determinants of the prognosis. Eur J Cardiothorac Surg 1996; 10: 403–7. doi:10.1016/s1010-7940(96)80105-9
46 Cen Y, Huang Z, Ren J, et al. The characteristic of tumor immune Microenvironment in pulmonary Carcinosarcoma. Immunotherapy 2020; 12: 323–31. doi:10.2217/imt-2019-0123
47 Panagiotopoulos N, Patrini D, Adams B, et al. Key features in the management of pulmonary Carcinosarcoma. Case Rep Pulmonol 2016; 2016: 2020146. doi:10.1155/2016/2020146
48 Li F, Hu S, Kong K, et al. Next-generation sequencing analysis identified Genomic alterations in pathological Morphologies of 3 cases of pulmonary Carcinosarcoma. Onco Targets Ther 2020; 13: 7963–72. doi:10.2147/OTT.S264617
49 Lococo F, Torricelli F, Rossi G, et al. Inter-relationship between PD-L1 expression and clinic-pathological features and driver gene mutations in pulmonary Sarcomatoid Carcinomas. Lung Cancer 2017; 113: 93–101. doi:10.1016/j.lungcan.2017.09.009
50 Rojas C, Tian C, Powell MA, et al. Racial disparities in uterine and ovarian Carcinosarcoma: A population-based analysis of treatment and survival. Gynecol Oncol 2020; 157: 67–77. doi:10.1016/j.ygyno.2020.01.017
51 Long B, Liu FW, Bristow RE. Disparities in uterine cancer epidemiology, treatment, and survival among African Americans in the United States. Gynecol Oncol 2013; 130: 652–9. doi:10.1016/j.ygyno.2013.05.020
52 Boussios S, Karathanasi A, Zakynthinakis-Kyriakou N, et al. Ovarian Carcinosarcoma: Current developments and future perspectives. Crit Rev Oncol Hematol 2019; 134: 46–55. doi:10.1016/j.critrevonc.2018.12.006
53 Rauh-Hain JA, Birrer M, Del Carmen MG. Carcinosarcoma of the ovary, Fallopian tube, and Peritoneum: Prognostic factors and treatment modalities. Gynecol Oncol 2016; 142: 248–54. doi:10.1016/j.ygyno.2016.06.003
54 Kim Y, Kang GH, Kim H. Kim H: Prognostic significance of heterologous component in Carcinosarcoma of the gynecologic organs: a systematic review and meta-analysis. J Gynecol Oncol 2023; 34. doi:10.3802/jgo.2023.34.e73
55 Athavale R, Thomakos N, Godfrey K, et al. The effect of epithelial and Stromal tumor components on FIGO stages III and IV ovarian Carcinosarcomas treated with primary surgery and chemotherapy. Int J Gynecol Cancer 2007; 17: 1025–30. doi:10.1111/j.1525-1438.2007.00919.x
56 Näyhä V, Stenbäck F. Angiogenesis and expression of angiogenic agents in uterine and ovarian carcinosarcomas. APMIS 2008; 116: 107–17. doi:10.1111/j.1600-0463.2008.00757.x Available: https://onlinelibrary.wiley.com/toc/16000463/116/2
57 Cantrell LA, Van Le L. Carcinosarcoma of the ovary a review. Obstet Gynecol Surv 2009; 64: 673–80. doi:10.1097/OGX.0b013e3181b8aff3
58 Zorzou M-P, Markaki S, Rodolakis A, et al. Papadimitriou CA: Clinicopathological features of ovarian Carcinosarcomas: a single institution experience. Gynecol Oncol 2005; 96: 136–42. doi:10.1016/j.ygyno.2004.09.051
59 Ariyoshi K, Kawauchi S, Kaku T, et al. Prognostic factors in ovarian Carcinosarcoma: a Clinicopathological and immunohistochemical analysis of 23 cases. Histopathology 2000; 37: 427–36. doi:10.1046/j.1365-2559.2000.01015.x
60 Ordner J, Gutierrez Amezcua JM, Marcus A, et al. Programmed death ligand 1 (PD-L1) expression and Cd8 + tumor-infiltrating lymphocyte-based tumor immune Microenvironment classification in gynecologic Carcinosarcoma: Prognostic impact and implications for therapy. Int J Gynecol Pathol 2023; 42: 364–75. doi:10.1097/PGP.0000000000000890
61 Daniyal M, Polani AS, Canary M. Ovarian Carcinosarcoma and response to Immunotherapy. Cureus 2023; 15: e37149. doi:10.7759/cureus.37149
62 Zhang MY, Tang LS, Qin ZJ, et al. Clinical features and Prognostic factors of pulmonary Carcinosarcoma: A Nomogram development and validation based on surveillance epidemiology and end results database. Front Med (Lausanne) 2022; 9: 988830. doi:10.3389/fmed.2022.988830
63 Wright JL, Black PC, Brown GA, et al. Differences in survival among patients with Sarcomatoid carcinoma, Carcinosarcoma and urothelial carcinoma of the bladder. J Urol 2007; 178: 2302–6; doi:10.1016/j.juro.2007.08.038
64 Kennedy WR, Gabani P, Acharya S, et al. Clinical outcomes and patterns of care in the treatment of Carcinosarcoma of the breast. Cancer Med 2019; 8: 1379–88. doi:10.1002/cam4.1942
65 Bae SY, Lee SK, Koo MY, et al. The prognoses of Metaplastic breast cancer patients compared to those of triple-negative breast cancer patients. Breast Cancer Res Treat 2011; 126: 471–8. doi:10.1007/s10549-011-1359-8
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; Yu-Wen, Zhou 2 ; Jia-Ling, Wang 1 ; Guo-Xu, Zhang 1 ; Chen-Hao, Xu 1 ; Ji-Yan, Liu 2
; Qiu, Meng 3 1 West China Hospital of Sichuan University, Chengdu, China
2 Department of Biotherapy, West China Hospital of Sichuan University, Chengdu, China
3 Department of Abdominal Oncology, West China Hospital of Sichuan University, Chengdu, China