Management and Prognosis of Patients with Recurrent or Persistent/Progressive Uterine Carcinosarcoma
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patients
2.2. Primary Therapy and Adjuvant Choice
2.3. Recurrent Patterns
2.4. Statistics
3. Results
3.1. Patients Characteristics and Survival
3.2. Factors Influencing CSS and SAR
3.3. Long-Term Survivors
3.4. Molecular Medicine
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Cantrell, L.A.; Blank, S.V.; Duska, L.R. Uterine carcinosarcoma: A review of the literature. Gynecol. Oncol. 2015, 137, 581–588. [Google Scholar] [CrossRef]
- Matsuo, K.; Ross, M.S.; Machida, H.; Blake, E.A.; Roman, L.D. Trends of uterine carcinosarcoma in the United States. J. Gynecol. Oncol. 2018, 29, e22. [Google Scholar] [CrossRef] [Green Version]
- Liao, C.-I.; Caesar, M.A.; Lee, D.; Chan, A.; Darcy, K.M.; Tian, C.; Kapp, D.S.; Chan, J.K. Increasing incidence of uterine carcinosarcoma: A United States Cancer Statistics study. Gynecol. Oncol. Rep. 2022, 40, 100936. [Google Scholar] [CrossRef]
- Bansal, N.; Herzog, T.J.; Seshan, V.E.; Schiff, P.B.; Burke, W.M.; Cohen, C.J.; Wright, J.D. Uterine carcinosarcomas and grade 3 endometrioid cancers: Evidence for distinct tumor behavior. Obstet. Gynecol. 2008, 112, 64–70. [Google Scholar] [CrossRef]
- Nama, N.; Cason, F.D.; Misra, S.; Hai, S.; Tucci, V.; Haq, F.; Love, J.; Ullah, A.; Peterson, P.; Grishko, F.F.; et al. Carcinosarcoma of the Uterus: A Study From the Surveillance Epidemiology and End Result (SEER) Database. Cureus 2020, 12, e10283. [Google Scholar] [CrossRef]
- Toboni, M.D.; Crane, E.K.; Brown, J.; Shushkevich, A.; Chiang, S.; Slomovitz, B.M.; Levine, D.A.; Dowdy, S.C.; Klopp, A.; Powell, M.A.; et al. Uterine carcinosarcomas: From pathology to practice. Gynecol. Oncol. 2021, 162, 235–241. [Google Scholar] [CrossRef]
- de Jong, R.A.; Nijman, H.W.; Wijbrandi, T.F.; Reyners, A.K.; Boezen, H.M.; Hollema, H. Molecular markers and clinical behavior of uterine carcinosarcomas: Focus on the epithelial tumor component. Mod. Pathol. 2011, 24, 1368–1379. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chiang, C.Y.; Huang, H.J.; Chang, W.Y.; Yang, L.Y.; Wu, R.C.; Wang, C.C.; Tung, H.J.; Chao, A.; Lai, C.H. Adjuvant therapy and prognosis in uterine carcinosarcoma. J. Formos. Med. Assoc. 2021, 120, 1977–1987. [Google Scholar] [CrossRef]
- Silverberg, S.G.; Major, F.J.; Blessing, J.A.; Fetter, B.; Askin, F.B.; Liao, S.-Y.; Miller, A. Carcinosarcoma (Malignant Mixed Mesodermal Tumor) of the Uterus: A Gynecologic Oncology Group Pathologic Study of 203 Cases. Int. J. Gynecol. Pathol. 1990, 9, 1–19. [Google Scholar] [CrossRef] [PubMed]
- Network, N.C.C. Uterine Neoplasms (Version 1. 2022). Available online: https://www.nccn.org/professionals/physician_gls/pdf/uterine.pdf (accessed on 24 January 2022).
- Yamada, S.D.; Burger, R.A.; Brewster, W.R.; Anton, D.; Kohler, M.F.; Monk, B.J. Pathologic variables and adjuvant therapy as predictors of recurrence and survival for patients with surgically evaluated carcinosarcoma of the uterus. Cancer 2000, 88, 2782–2786. [Google Scholar] [CrossRef]
- Pezzicoli, G.; Moscaritolo, F.; Silvestris, E.; Silvestris, F.; Cormio, G.; Porta, C.; D’Oronzo, S. Uterine carcinosarcoma: An overview. Crit. Rev. Oncol. Hematol. 2021, 163, 103369. [Google Scholar] [CrossRef] [PubMed]
- Matsuzaki, S.; Klar, M.; Matsuzaki, S.; Roman, L.D.; Sood, A.K.; Matsuo, K. Uterine carcinosarcoma: Contemporary clinical summary, molecular updates, and future research opportunity. Gynecol. Oncol. 2021, 160, 586–601. [Google Scholar] [CrossRef]
- Fleming, G.F. Second-Line Therapy for Endometrial Cancer: The Need for Better Options. J. Clin. Oncol. 2015, 33, 3535–3540. [Google Scholar] [CrossRef]
- Pecorelli, S. Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium. Int. J. Gynecol. Obstet. 2009, 105, 103–104. [Google Scholar] [CrossRef]
- Wu, T.I.; Hsu, K.H.; Huang, H.J.; Hsueh, S.; Chou, H.H.; Tsai, C.S.; Ho, K.C.; Chao, A.; Chang, T.C.; Lai, C.H. Prognostic factors and adjuvant therapy in uterine carcinosarcoma. Eur. J. Gynaecol. Oncol. 2008, 29, 483–488. [Google Scholar]
- Guttmann, D.M.; Li, H.; Sevak, P.; Grover, S.; Jacobson, G.; Feldman, A.; Rubin, S.; Chu, C.; Bhatia, S.; Elshaikh, M.A.; et al. The Impact of Adjuvant Therapy on Survival and Recurrence Patterns in Women With Early-Stage Uterine Carcinosarcoma: A Multi-institutional Study. Int. J. Gynecol. Cancer 2016, 26, 141–148. [Google Scholar] [CrossRef]
- Odei, B.; Boothe, D.; Suneja, G.; Werner, T.L.; Gaffney, D.K. Chemoradiation Versus Chemotherapy in Uterine Carcinosarcoma: Patterns of Care and Impact on Overall Survival. Am. J. Clin. Oncol. 2018, 41, 784–791. [Google Scholar] [CrossRef]
- Zhao, F.; Tan, P.; Wang, C.; Ji, X.; Chen, A. Effect of adjuvant therapy on the prognosis in stage I/II uterine carcinosarcoma: A meta-analysis. J. Obstet. Gynaecol. Res. 2021, 47, 2473–2480. [Google Scholar] [CrossRef]
- Powell, M.A.; Filiaci, V.L.; Hensley, M.L.; Huang, H.Q.; Moore, K.N.; Tewari, K.S.; Copeland, L.J.; Secord, A.A.; Mutch, D.G.; Santin, A.; et al. Randomized Phase III Trial of Paclitaxel and Carboplatin Versus Paclitaxel and Ifosfamide in Patients with Carcinosarcoma of the Uterus or Ovary: An NRG Oncology Trial. J. Clin. Oncol. 2022, 40, 968–977. [Google Scholar] [CrossRef]
- Ebata, T.; Yonemori, K.; Nishikawa, T.; Sudo, K.; Shimomura, A.; Noguchi, E.; Fujiwara, Y.; Kato, T.; Hasegawa, K.; Fujiwara, K.; et al. Treatment Outcome of Second-Line Chemotherapy for Gynecologic Carcinosarcoma. Oncology 2020, 98, 699–705. [Google Scholar] [CrossRef]
- Matsuo, K.; Ross, M.S.; Yunokawa, M.; Johnson, M.S.; Machida, H.; Omatsu, K.; Klobocista, M.M.; Im, D.D.; Satoh, S.; Baba, T.; et al. Salvage chemotherapy with taxane and platinum for women with recurrent uterine carcinosarcoma. Gynecol. Oncol. 2017, 147, 565–571. [Google Scholar] [CrossRef] [PubMed]
- Ohtake, Y.; Sudo, K.; Kojima, Y.; Seo, T.; Okuma, H.; Nishikawa, T.; Uno, M.; Uehara, T.; Ishikawa, M.; Tanioka, M.; et al. Ifosfamide and Paclitaxel for Recurrent or Metastatic Uterine Carcinosarcoma. Gan Kagaku Ryoho 2019, 46, 1525–1529. [Google Scholar]
- Ansink, A.C.; Cross, P.A.; Scorer, P.; de Barros Lopes, A.; Monaghan, J.M. The hormonal receptor status of uterine carcinosarcomas (mixed müllerian tumours): An immunohistochemical study. J. Clin. Pathol. 1997, 50, 328–331. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jones, N.L.; Wu, S.; Xiu, J.; Rocconi, R.P.; Erickson, B.K.; Thaker, P.H.; Brown, J.; Herzog, T.J.; Holloway, R.W.; Korn, W.M.; et al. Association of the presence of estrogen and progesterone receptors in uterine carcinosarcoma with improved survival and increased immunogenicity. J. Clin. Oncol. 2021, 39, 5588. [Google Scholar] [CrossRef]
- Huang, G.S.; Arend, R.C.; Li, M.; Gunter, M.J.; Chiu, L.G.; Horwitz, S.B.; Goldberg, G.L. Tissue microarray analysis of hormonal signaling pathways in uterine carcinosarcoma. Am. J. Obstet. Gynecol. 2009, 200, 457.E1–457.E4575. [Google Scholar] [CrossRef] [Green Version]
- Liang, A.L.; Katebi Kashi, P.; Hopkins, M.; Beavis, A.; Gaillard, S.; Shih, I.M.; Fader, A.N. Progestin and aromatase inhibitor therapy in recurrent, estrogen/progestin receptor positive uterine carcinosarcoma: A case report. Gynecol. Oncol. Rep. 2021, 38, 100877. [Google Scholar] [CrossRef]
- Edmondson, R.J.; O’Connell, R.L.; Banerjee, S.; Mileshkin, L.; Sykes, P.; Beale, P.; Fisher, A.; Bonaventura, A.; Millan, D.; Nottley, S.; et al. Phase 2 study of anastrozole in rare cohorts of patients with estrogen receptor/progesterone receptor positive leiomyosarcomas and carcinosarcomas of the uterine corpus: The PARAGON trial (ANZGOG 0903). Gynecol. Oncol. 2021, 163, 524–530. [Google Scholar] [CrossRef]
- Cherniack, A.D.; Shen, H.; Walter, V.; Stewart, C.; Murray, B.A.; Bowlby, R.; Hu, X.; Ling, S.; Soslow, R.A.; Broaddus, R.R.; et al. Integrated Molecular Characterization of Uterine Carcinosarcoma. Cancer Cell 2017, 31, 411–423. [Google Scholar] [CrossRef] [Green Version]
- Gotoh, O.; Sugiyama, Y.; Takazawa, Y.; Kato, K.; Tanaka, N.; Omatsu, K.; Takeshima, N.; Nomura, H.; Hasegawa, K.; Fujiwara, K.; et al. Clinically relevant molecular subtypes and genomic alteration-independent differentiation in gynecologic carcinosarcoma. Nat. Commun. 2019, 10, 4965. [Google Scholar] [CrossRef] [Green Version]
- Travaglino, A.; Raffone, A.; Raimondo, D.; Arciuolo, D.; Angelico, G.; Valente, M.; Scaglione, G.; D’Alessandris, N.; Casadio, P.; Inzani, F.; et al. Prognostic value of the TCGA molecular classification in uterine carcinosarcoma. Int. J. Gynaecol. Obstet. 2021, 158, 13–20. [Google Scholar] [CrossRef]
- Travaglino, A.; Raffone, A.; Gencarelli, A.; Mollo, A.; Guida, M.; Insabato, L.; Santoro, A.; Zannoni, G.F.; Zullo, F. TCGA Classification of Endometrial Cancer: The Place of Carcinosarcoma. Pathol. Oncol. Res. 2020, 26, 2067–2073. [Google Scholar] [CrossRef] [PubMed]
- Segura, S.E.; Pedra Nobre, S.; Hussein, Y.R.; Abu-Rustum, N.R.; Weigelt, B.; Soslow, R.A.; DeLair, D.F. DNA Mismatch Repair-deficient Endometrial Carcinosarcomas Portend Distinct Clinical, Morphologic, and Molecular Features Compared With Traditional Carcinosarcomas. Am. J. Surg. Pathol. 2020, 44, 1573–1579. [Google Scholar] [CrossRef] [PubMed]
- Jenkins, T.M.; Hanley, K.Z.; Schwartz, L.E.; Cantrell, L.A.; Stoler, M.H.; Mills, A.M. Mismatch Repair Deficiency in Uterine Carcinosarcoma: A Multi-institution Retrospective Review. Am. J. Surg. Pathol. 2020, 44, 782–792. [Google Scholar] [CrossRef]
- Kucukgoz Gulec, U.; Kilic Bagir, E.; Paydas, S.; Guzel, A.B.; Gumurdulu, D.; Vardar, M.A. Prognostic significance of programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) expression in uterine carcinosarcoma. Eur. J. Obstet. Gynecol. Reprod. Biol. 2020, 244, 51–55. [Google Scholar] [CrossRef] [Green Version]
- Yano, M.; Aso, S.; Sato, M.; Aoyagi, Y.; Matsumoto, H.; Nasu, K. Pembrolizumab and Radiotherapy for Platinum-refractory Recurrent Uterine Carcinosarcoma With an Abscopal Effect: A Case Report. Anticancer Res. 2020, 40, 4131–4135. [Google Scholar] [CrossRef]
- Zhu, B.; Liu, Y.; Li, J.; Diao, L.; Shao, L.; Han-Zhang, H.; Zhang, L.; Kang, Q.; Yang, W. Exceptional Response of Cryoablation Followed by Pembrolizumab in a Patient with Metastatic Cervical Carcinosarcoma with High Tumor Mutational Burden: A Case Report. Oncologist 2020, 25, 15–18. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bhangoo, M.S.; Boasberg, P.; Mehta, P.; Elvin, J.A.; Ali, S.M.; Wu, W.; Klempner, S.J. Tumor Mutational Burden Guides Therapy in a Treatment Refractory POLE-Mutant Uterine Carcinosarcoma. Oncologist 2018, 23, 518–523. [Google Scholar] [CrossRef] [Green Version]
- Makker, V.; Colombo, N.; Casado Herráez, A.; Santin, A.D.; Colomba, E.; Miller, D.S.; Fujiwara, K.; Pignata, S.; Baron-Hay, S.; Ray-Coquard, I.; et al. Lenvatinib plus Pembrolizumab for Advanced Endometrial Cancer. N. Engl. J. Med. 2022, 386, 437–448. [Google Scholar] [CrossRef]
- Hunt, J.T.; Chambers, L.M.; Yao, M.; Joehlin-Price, A.; Debernardo, R.; Rose, P.G. Lenvatinib plus pembrolizumab in patients with advanced or recurrent uterine carcinosarcoma. Gynecol. Oncol. Rep. 2021, 37, 100840. [Google Scholar] [CrossRef]
- Ray-Coquard, I.L.; Leary, A.; Bigot, F.; Montane, L.; Fabbro, M.; Hardy-Bessard, A.-C.; Selle, F.; Chakiba, C.; Lortholary, A.; Berton, D.; et al. ROCSAN trial (GINECO-EN203b/ENGOT-EN8): A multicentric randomized phase II/III evaluating dostarlimab in combination with niraparib versus niraparib alone compared to chemotherapy in the treatment of endometrial/ovarian carcinosarcoma after at least one line of platinum based chemotherapy. J. Clin. Oncol. 2021, 39, TPS5604. [Google Scholar] [CrossRef]
- Lorusso, D.; Ferrandina, G.; Colombo, N.; Pignata, S.; Pietragalla, A.; Sonetto, C.; Pisano, C.; Lapresa, M.T.; Savarese, A.; Tagliaferri, P.; et al. Carboplatin-paclitaxel compared to Carboplatin-Paclitaxel-Bevacizumab in advanced or recurrent endometrial cancer: MITO END-2—A randomized phase II trial. Gynecol. Oncol. 2019, 155, 406–412. [Google Scholar] [CrossRef] [PubMed]
- Aghajanian, C.; Filiaci, V.; Dizon, D.S.; Carlson, J.W.; Powell, M.A.; Secord, A.A.; Tewari, K.S.; Bender, D.P.; O’Malley, D.M.; Stuckey, A.; et al. A phase II study of frontline paclitaxel/carboplatin/bevacizumab, paclitaxel/carboplatin/temsirolimus, or ixabepilone/carboplatin/bevacizumab in advanced/recurrent endometrial cancer. Gynecol. Oncol. 2018, 150, 274–281. [Google Scholar] [CrossRef] [PubMed]
- Mackay, H.J.; Buckanovich, R.J.; Hirte, H.; Correa, R.; Hoskins, P.; Biagi, J.; Martin, L.P.; Fleming, G.F.; Morgan, R.; Wang, L.; et al. A phase II study single agent of aflibercept (VEGF Trap) in patients with recurrent or metastatic gynecologic carcinosarcomas and uterine leiomyosarcoma. A trial of the Princess Margaret Hospital, Chicago and California Cancer Phase II Consortia. Gynecol. Oncol. 2012, 125, 136–140. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Campos, S.M.; Brady, W.E.; Moxley, K.M.; O’Cearbhaill, R.E.; Lee, P.S.; DiSilvestro, P.A.; Rotmensch, J.; Rose, P.G.; Thaker, P.H.; O’Malley, D.M.; et al. A phase II evaluation of pazopanib in the treatment of recurrent or persistent carcinosarcoma of the uterus: A gynecologic oncology group study. Gynecol. Oncol. 2014, 133, 537–541. [Google Scholar] [CrossRef] [Green Version]
- Nishikawa, T.; Hasegawa, K.; Yabuno, A.; Yoshida, H.; Yasuda, M.; Kozawa, E.; Fujiwara, K. Pazopanib as a second line treatment for uterine and ovarian carcinosarcoma: A single institutional study. J. Gynecol. Oncol. 2017, 28, e25. [Google Scholar] [CrossRef] [Green Version]
- Chandran, E.A.; Kennedy, I. Significant Tumor Response to the Poly (ADP-ribose) Polymerase Inhibitor Olaparib in Heavily Pretreated Patient With Ovarian Carcinosarcoma Harboring a Germline RAD51D Mutation. JCO Precis. Oncol. 2018, 2, 1–4. [Google Scholar] [CrossRef]
- Tymon-Rosario, J.R.; Manara, P.; Manavella, D.D.; Bellone, S.; Hartwich, T.M.P.; Harold, J.; Yang-Hartwich, Y.; Zipponi, M.; Choi, J.; Jeong, K.; et al. Homologous recombination deficiency (HRD) signature-3 in ovarian and uterine carcinosarcomas correlates with preclinical sensitivity to Olaparib, a poly (adenosine diphosphate [ADP]- ribose) polymerase (PARP) inhibitor. Gynecol. Oncol. 2022, 166, 117–125. [Google Scholar] [CrossRef]
- Rottmann, D.; Snir, O.L.; Wu, X.; Wong, S.; Hui, P.; Santin, A.D.; Buza, N. HER2 testing of gynecologic carcinosarcomas: Tumor stratification for potential targeted therapy. Mod. Pathol. 2020, 33, 118–127. [Google Scholar] [CrossRef]
- Jenkins, T.M.; Cantrell, L.A.; Stoler, M.H.; Mills, A.M. HER2 Overexpression and Amplification in Uterine Carcinosarcomas With Serous Morphology. Am. J. Surg. Pathol. 2022, 46, 435–442. [Google Scholar] [CrossRef]
- Fader, A.N.; Roque, D.M.; Siegel, E.; Buza, N.; Hui, P.; Abdelghany, O.; Chambers, S.K.; Secord, A.A.; Havrilesky, L.; O’Malley, D.M.; et al. Randomized Phase II Trial of Carboplatin-Paclitaxel Versus Carboplatin-Paclitaxel-Trastuzumab in Uterine Serous Carcinomas That Overexpress Human Epidermal Growth Factor Receptor 2/neu. J. Clin. Oncol. 2018, 36, 2044–2051. [Google Scholar] [CrossRef] [Green Version]
- Maruthi, V.K.; Khazaeli, M.; Jeyachandran, D.; Desouki, M.M. The Clinical Utility and Impact of Next Generation Sequencing in Gynecologic Cancers. Cancers 2022, 14, 1352. [Google Scholar] [CrossRef] [PubMed]
Variable | Total (n = 98) | Isolated (n = 14) | Disseminated (n = 84) | p-Value 1 | |||
---|---|---|---|---|---|---|---|
n | % | n | % | n | % | ||
Age, years (median, range) | 60.0 (32.3, 86.2) | 58.6 (34.6, 80.3) | 60.0 (32.3, 86.2) | 0.768 | |||
CA-125, U/mL (median, range) at recurrence | 49.8 (5.5, 3533.3) | 19.9 (6.0, 136.7) | 65.0 (5.5, 3533.3) | 0.026 | |||
Time to treatment failure, months (median, range) | 8.1 (0.0, 89.1) | 16.2 (6.6, 89.1) | 7.4 (0.0, 68.5) | 0.001 | |||
Stage | 0.509 | ||||||
I | 20 | (20.4) | 3 | (21.4) | 17 | (20.2) | |
II | 6 | (6.1) | 2 | (14.3) | 4 | (4.8) | |
III | 35 | (35.7) | 5 | (35.7) | 30 | (35.7) | |
IV | 37 | (37.8) | 4 | (28.6) | 33 | (39.3) | |
Estrogen receptor | 0.354 | ||||||
Negative | 49 | (63.6) | 10 | (76.9) | 39 | (60.9) | |
Positive | 28 | (36.4) | 3 | (23.1) | 25 | (39.1) | |
Progesterone receptor | 0.752 | ||||||
Negative | 51 | (66.2) | 8 | (61.5) | 43 | (67.2) | |
Positive | 26 | (33.8) | 5 | (38.5) | 21 | (32.8) | |
Primary treatment | 0.702 | ||||||
Surgery | 85 | (86.7) | 12 | (85.7) | 73 | (86.9) | |
Neoadjuvant chemotherapy | 8 | (8.3) | 2 | (14.3) | 6 | (7.1) | |
Chemotherapy | 2 | (2.0) | 0 | (0) | 2 | (2.4) | |
Radiotherapy | 1 | (1.0) | 0 | (0) | 1 | (1.2) | |
Chemoradiation | 1 | (1.0) | 0 | (0) | 1 | (1.2) | |
Hormone therapy | 1 | (1.0) | 0 | (0) | 1 | (1.2) | |
Adjuvant treatment | 0.434 | ||||||
No | 18 | (18.4) | 2 | (14.3) | 16 | (19.0) | |
Radiotherapy | 7 | (7.1) | 0 | (0) | 7 | (8.3) | |
Chemotherapy + radiotherapy | 40 | (40.8) | 9 | (64.3) | 31 | (36.9) | |
Chemotherapy | 32 | (32.7) | 3 | (21.4) | 29 | (34.5) | |
Hormone therapy | 1 | (1.0) | 0 | (0) | 1 | (1.2) | |
Adjuvant chemotherapy regimen | 0.560 | ||||||
No chemotherapy | 27 | (27.6) | 2 | (14.3) | 25 | (29.8) | |
Platinum + Paclitaxel | 32 | (32.7) | 5 | (35.7) | 27 | (32.1) | |
Platinum + Ifosfamide | 13 | (13.3) | 3 | (21.4) | 10 | (11.9) | |
PAC or PC/PAI/PA | 13 | (13.3) | 1 | (7.1) | 12 | (14.3) | |
Adrimycin + Ifosfamide | 5 | (5.1) | 1 | (7.1) | 4 | (4.8) | |
Other | 8 | (8.2) | 2 | (14.3) | 6 | (7.1) | |
Radiotherapy field failure | 0.728 | ||||||
Non-infield failure | 77 | (78.6) | 12 | (85.7) | 65 | (77.4) | |
Infield failure | 21 | (21.4) | 2 | (14.3) | 19 | (22.6) |
Variable | Total (n = 98) | Isolated (n = 14) | Disseminated (n = 84) | p-Value 1 | |||
---|---|---|---|---|---|---|---|
n | % | n | % | n | % | ||
Salvage treatment (First-line after primary treatment failed) 2 | 0.002 | ||||||
Supportive care | 34 | (36.2) | 1 | (7.7) | 33 | (40.7) | |
CT alone +/− HT or target therapy | 22 | (23.4) | 1 | (7.7) | 21 | (25.9) | |
RT alone +/− HT or target therapy | 9 | (9.6) | 4 | (30.8) | 5 | (6.2) | |
Surgery +/− CT or RT or CRT or target | 13 | (13.8) | 2 | (15.4) | 11 | (13.6) | |
CRT +/− HT or target | 9 | (9.6) | 2 | (15.4) | 7 | (8.6) | |
HT alone | 7 | (7.4) | 3 | (23.1) | 4 | (4.9) | |
Salvage chemotherapy regimen (First-line after primary treatment failed) | 0.930 | ||||||
Not receive chemotherapy | 58 | (61.7) | 9 | (69.2) | 49 | (60.5) | |
Paclitaxel +/− carboplatin/cisplatin | 10 | (10.6) | 2 | (15.4) | 8 | (9.9) | |
Ifosfamide +/− carboplatin/cisplatin | 2 | (2.1) | 0 | (0) | 2 | (2.5) | |
Doxorubicin/Lipodoxorubicin +/− carboplatin/cisplatin/Ifosfamide | 7 | (7.4) | 1 | (7.7) | 6 | (7.4) | |
Platinum only | 7 | (7.4) | 0 | (0) | 7 | (8.6) | |
Others | 10 | (10.6) | 1 | (7.7) | 9 | (11.1) | |
Salvage target and immunotherapy (First-line after primary treatment failed) | 0.436 | ||||||
Did not receive target/immunotherapy | 85 | (90.4) | 12 | (92.3) | 73 | (90.1) | |
Pazopanib | 4 | (4.3) | 0 | (0) | 4 | (4.9) | |
Bevacizumab | 2 | (2.1) | 0 | (0) | 2 | (2.5) | |
Olaparib | 1 | (1.1) | 1 | (7.7) | 0 | (0) | |
Pembrolizumab | 1 | (1.1) | 0 | (0) | 1 | (1.2) | |
Bevacizumab + Pembrolizumab | 1 | (1.1) | 0 | (0) | 1 | (1.2) |
Univariate Analysis | Multivariate Analysis 1 | ||||
---|---|---|---|---|---|
Variable | n | HR (95% CI) | p-Value | HR (95% CI) | p-Value |
Age | |||||
≤60 years | 48 | Ref | |||
>60 years | 50 | 1.29 (0.84, 1.99) | 0.239 | ||
Stage | |||||
I-II | 26 | Ref | |||
III-IV | 72 | 1.42 (0.87, 2.31) | 0.163 | ||
CA-125 at recurrence | |||||
≤35 | 34 | Ref | |||
>35 | 48 | 1.13 (0.70, 1.82) | 0.617 | ||
Estrogen receptor | |||||
Negative | 49 | Ref | |||
Positive | 28 | 0.87 (0.53, 1.43) | 0.576 | ||
Progesterone receptor | |||||
Negative | 51 | Ref | |||
Positive | 26 | 0.76 (0.46, 1.26) | 0.284 | ||
Adjuvant treatment | |||||
No | 18 | Ref | |||
Radiotherapy | 7 | 1.48 (0.60, 3.62) | 0.394 | ||
Chemoradiotherapy | 40 | 0.57 (0.31, 1.03) | 0.060 | ||
Chemotherapy | 32 | 0.94 (0.51, 1.72) | 0.843 | ||
Hormone therapy | 1 | 1.45 (0.19, 11.10) | 0.720 | ||
Time to treatment failure | |||||
≤6 months | 31 | Ref | Ref | ||
>6 months | 67 | 0.23 (0.14, 0.36) | 0.000 | 0.30 (0.18, 0.52) | <0.001 |
Salvage treatment (first-line after primary treatment failed) | |||||
Supportive care | 34 | Ref | Ref | ||
CT alone +/− HT or target | 22 | 0.24 (0.13, 0.44) | 0.000 | 0.29 (0.15, 0.53) | <0.001 |
RT alone +/− HT or target | 9 | 0.11 (0.04, 0.31) | 0.000 | 0.26 (0.10, 0.72) | 0.010 |
Surgery +/- CT/RT/CRT or target | 13 | 0.24 (0.11, 0.50) | 0.000 | 0.44 (0.21, 0.93) | 0.033 |
CRT +/− HT or target | 9 | 0.23 (0.10, 0.53) | 0.000 | 0.17 (0.07, 0.41) | <0.001 |
HT alone | 7 | 0.16 (0.05, 0.46) | 0.001 | 0.34 (0.11, 1.01) | 0.053 |
Recurrence in previous RT field | |||||
No | 77 | Ref | |||
Yes (infield failure) | 21 | 0.91 (0.53, 1.56) | 0.739 | ||
Recurrent/progressive disease pattern | |||||
Isolated | 14 | Ref | Ref | ||
Disseminated | 84 | 4.82 (2.27, 10.25) | 0.000 | 4.01 (1.55, 10.33) | 0.004 |
Univariate Analysis | Multivariate Analysis 1 | ||||
---|---|---|---|---|---|
Variable | n | HR (95% CI) | p-Value | HR (95% CI) | p-Value |
Age | |||||
≤60 years | 48 | Ref | |||
>60 years | 50 | 1.06 (0.70, 1.63) | 0.773 | ||
Stage | |||||
I-II | 26 | Ref | |||
III-IV | 72 | 1.39 (0.86, 2.27) | 0.182 | ||
CA-125 at recurrence | |||||
≤35 | 34 | Ref | |||
>35 | 48 | 1.28 (0.79, 2.06) | 0.316 | ||
Estrogen receptor | |||||
Negative | 49 | Ref | |||
Positive | 28 | 0.99 (0.60, 1.62) | 0.957 | ||
Progesterone receptor | |||||
Negative | 51 | Ref | |||
Positive | 26 | 0.76 (0.46, 1.26) | 0.287 | ||
Time to treatment failure | |||||
≤6 months | 31 | Ref | |||
>6 months | 67 | 0.52 (0.33, 0.81) | 0.004 | ||
Salvage treatment (first-line after primary treatment failed) | |||||
Supportive care | 34 | Ref | Ref | ||
CT alone +/− HT or target | 22 | 0.41 (0.23, 0.71) | 0.001 | 0.41 (0.24, 0.72) | 0.002 |
RT alone +/− HT or target | 9 | 0.15 (0.06, 0.39) | <0.001 | 0.27 (0.10, 0.71) | 0.008 |
Surgery +/− CT/RT/CRT or target | 13 | 0.35 (0.17, 0.73) | 0.005 | 0.52 (0.25, 1.09) | 0.085 |
CRT +/− HT or target | 9 | 0.28 (0.13, 0.61) | 0.002 | 0.33 (0.15, 0.75) | 0.008 |
HT alone | 7 | 0.28 (0.11, 0.72) | 0.009 | 0.52 (0.19, 1.41) | 0.201 |
Recurrence in previous RT field | |||||
No | 77 | Ref | |||
Yes (infield failure) | 21 | 0.86 (0.51, 1.45) | 0.581 | ||
Recurrent/progressive disease pattern | |||||
Isolated | 14 | Ref | Ref | ||
Disseminated | 84 | 4.58 (2.22, 9.45) | 0.000 | 3.94 (1.67, 9.31) | 0.002 |
No. | Age | FIGO Stage | Primary Treatment | CA125 2 | TTF | Site of Recurrence/Pattern | Salvage Therapy | SAR | CSS | Status |
---|---|---|---|---|---|---|---|---|---|---|
1 | 55.6 | IA | Comprehensive surgical staging 1 | 3.99 | 2.50 | Lung, pelvis, and vagina/disseminated pattern | CRT to pelvis and lung (ifosfamide + cisplatin) | 168.2 | 170.7 | DWOD (colon cancer) |
2 | 52.4 | II | CPSS + CT (cisplatin + paclitaxel) | 6.0 | 19.02 | Lung/solitary pattern | VATS resection of lung tumor | 144.7+ | 163.7 | NED |
3 | 34.6 | IIIB | CPSS + CRT (ifosfamide + cisplatin) | 99.7 | 80.3 | Left pelvic recurrence, extended to int. and ext. iliac LN and caused hydronephrosis (infield failure)/solitary pattern | Hormone therapy (anastrozole and megestrol acetate for ER3+, PR3+) | 101.4 | 181.7 | DOD |
4 | 49.9 | IIIC2 | CPSS + CT (PAC) | NA | 8.2 | Neck LN/solitary pattern | RT to neck LN | 88.0 | 96.2 | DWOD (unknown) |
5 | 68.4 | IA | CPSS + CT (cisplatin + paclitaxel) | 6.2 | 16.9 | Vagina/solitary pattern | Vaginectomy and vaginal stump RT | 79.3+ | 96.2 | NED |
6 | 65.7 | IIIA | CPSS + CRT (ifosfamide+ doxorubicin) | 9.5 | 15.5 | Lung/solitary pattern | RT to lung nodule | 53.9+ | 69.4 | NED |
No | Age | FIGO Stage | Primary Treatment | IHC Markers | TTF | Site of Recurrence/Pattern | Salvage Therapy | SAR | CSS | Status |
---|---|---|---|---|---|---|---|---|---|---|
1 | 62.4 | IVB | NACT + IDS + post-operative CRT (lipodox + ifoasfamide) | ER (−) PR(−) P53(+) MMR-p PDL1(+) BRCA1 somatic deletion | 17.4 | 1st rec: Left inguinal LN (solitary pattern) 2nd rec: Right pelvic LN, ext. iliac | (1) RT to inguinal LN → CR maintenance with Olaparib (2) Pembrolizumab | 14.7 | 32.0 | DOD |
2 | 61.9 | IA | Comprehensive surgical staging (malignant ascites) + CT (TP) | ER (−) PR(−) P53(+) MMR-p PDL1 (−) | 20.4 | 1st rec: Peritoneal carcinomatosis (disseminated pattern) 2nd rec: progressive with ometum cake and subdiaphragm seeding | (1) Cisplatin, bevacizumab, pembrolizumab →oral cyclophosphamide, tamoxifen, lenvatinib (2) RT to lower pelvis + TPB + oral palbociclib | 21.4 | 41.8 | DOD |
3 | 69.0 | IIIA | Hysterectomy at another hospital, refused adjuvant therapy. | ER (−) PR(+) P53(+) 1 | 3.7 | Peritoneal carcinomatosis, bone metastasis /disseminated pattern | RT to pelvic tumor, with Cisplatin, bevacizumab → 5-FU + bevazumab | 2.9 | 6.6 | DOD |
4 | 77.4 | IVB | CRT (TPB) | ER (−) PR(−) P53(−) MMR-p | 3.5 | 1st rec: Pelvic tumor, supraclavicular and axillary LN (disseminated pattern) 2nd rec: Progressive disease | (1) CT with Bevacizumab + oral tegafur, etoposide (2) paclitaxel + bevacizumab, Topotecan | 6.4 | 9.9 | DOD |
5 | 37.1 | IVB | Comprehensive surgical staging + CT (TP) | ER (−) PR(−) 1 | 7.1 | Peritoneal carcinomatosis, neck and axillary LN, PALN, skin and breast nodule (disseminated pattern) | Lipodox+ Pembrolizumab → TP | 2.2 | 9.3 | DOD |
6 | 70.4 | IB | Comprehensive surgical staging + CRT (TP) | ER (−) PR(−) P53(−) MMR-d PDL1 (−) | 16.0 | 1st rec: Lung and brain /disseminated pattern 2nd rec: New lung nodules | (1) RT to brain and lung, with CT AI, then maintenance with Pazopanib (2) Pembrolizumab | 13.1 | 29.1 | DOD |
7 | 61.0 | IIIA | Comprehensive surgical staging + CRT (TP) | ER (+) PR(+) P53(+) MMR-p | 13.4 | Malignant pleural effusion /disseminated pattern | TP, then maintained on oral pazopanib + cyclophosphamide | 10.3 | 23.7 | DOD |
8 | 50.3 | IIIC2 | Comprehensive surgical staging + CRT (TP) | ER (−) PR(−) P53(+) MMR-p | 12.9 | Lung and bone/disseminated pattern | VATS lobectomy for lung metastasis, then oral pazopanib | 2.0 | 14.8 | DOD |
9 | 48.4 | IVB | Comprehensive surgical staging + CRT (TP) | ER (+) PR(+) MMR-p PDL1 (−) | 5.9 | Peritoneal carcinomatosis, liver metastasis/disseminated pattern | RT to liver, oral letrozole, megace, and pazopanib | 6.3 | 12.3 | DOD |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Tung, H.-J.; Chiang, C.-Y.; Chang, W.-Y.; Wu, R.-C.; Huang, H.-J.; Yang, L.-Y.; Lin, C.-Y.; Wang, C.-C.; Chao, A.; Lai, C.-H. Management and Prognosis of Patients with Recurrent or Persistent/Progressive Uterine Carcinosarcoma. Curr. Oncol. 2022, 29, 7607-7623. https://doi.org/10.3390/curroncol29100601
Tung H-J, Chiang C-Y, Chang W-Y, Wu R-C, Huang H-J, Yang L-Y, Lin C-Y, Wang C-C, Chao A, Lai C-H. Management and Prognosis of Patients with Recurrent or Persistent/Progressive Uterine Carcinosarcoma. Current Oncology. 2022; 29(10):7607-7623. https://doi.org/10.3390/curroncol29100601
Chicago/Turabian StyleTung, Hsiu-Jung, Chi-Yuan Chiang, Wei-Yang Chang, Ren-Chin Wu, Huei-Jean Huang, Lan-Yan Yang, Chiao-Yun Lin, Chun-Chieh Wang, Angel Chao, and Chyong-Huey Lai. 2022. "Management and Prognosis of Patients with Recurrent or Persistent/Progressive Uterine Carcinosarcoma" Current Oncology 29, no. 10: 7607-7623. https://doi.org/10.3390/curroncol29100601