Management and Prognosis of Patients with Recurrent or Persistent/Progressive Uterine Carcinosarcoma

Round 1

Reviewer 1 Report

The study includes a large number of patients with UCS - 168 cases. The authors investigate survivival after recurrence (SAR)  and cancer-after-survival (CAR). Information is provided on risk factors associated with recurrence. The study aims to explore patients with recurrent  or persistent/progressive disease and focus on salvage treatment, which is a valuable aspect of this paper. Salvage therapy includes radio/chemo-therapy which improves SAR. The results are well-presented in the tables and figures. The paper is significant as it looks at molecular factors including CA-125, as well as estrogen and progesterone receptor. The fact that the majority of patients in the study had advanced stages of cancer and recurrences with disseminated disease is particularly interesting from a treatment perspective. Novel therapies applied in the first salvage plan included immunotherapy (Olaparib & Pembrolizumab). From a clinical point of view the study is valuable as it researches the angle of new target therapies.

 

Author Response

Thanks for your positive opinion. Since salvage treatment data is valuable for those patients, we would like to see more novel attempts in future publication.

Reviewer 2 Report

Excellent investigation!

Author Response

Thanks for your interest in our work. 

Reviewer 3 Report

The bottom line conclusion of this work is that 2nd line treatment for recurrent or persistant uterine carcinosarcoma is worth while. 

The relatively small number of cases precludes stage and recurrence-pattern specific analysis. 

Also the relatively high fraction of ER/PR positive tumors raises the concern that G3 endometrial are included in this cohort. I have liked to see that an independent pathologist has revised all slides, not only the pathology reports, and confirmed the diagnoses according to most recent diagnostic criteria.

Author Response

1. A gynecologic pathologist (R.C.W.) has reviewed all patients’ tissue slides to confirm the diagnosis according to the most recent diagnostic criteria. The relevant sentence has been added to the manuscript (lines 79-81).
2. The relatively high fraction of ER/PR in our article (36.4% for ER and 33.8% for PR, table 1) is an interesting topic. The positive rate of ER/PR may be affected by 1) the fraction of carcinoma component in the tissue block chosen for immunostaining [1], and 2) the cutoff for positivity of ER/PR. Currently, there is no consensus on the cutoff for endometrial cancer. Following the ASCO/CAP guideline for breast cancer, we have chosen 1% as the cutoff for endometrial cancer, which may have resulted in a higher fraction of ER/PR in our study. In the very first paper that investigated hormone receptors in UCS, 36.4% of cases expressed at least one hormonal receptor (27.3% for ER and 27.3% for PR) [2]. A recently published abstract reported a positive rate of 22.8% for ER and 17.2% for PR in a cohort of 1,144 UCS [3]. Both studies chose 10% as the cutoff for positivity. We believe the relatively high fraction of ER/PR positivity in our study is mainly attributable to the lower cutoff used (1% vs 10%). The explanation has been added in lines 274-281.

Reference

1. 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. American Journal of Obstetrics & Gynecology 2009, 200, 457.e451-457.e455, doi:10.1016/j.ajog.2008.12.012.
2. 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, doi:10.1136/jcp.50.4.328.
3. 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. Journal of Clinical Oncology 2021, 39, 5588-5588, doi:10.1200/JCO.2021.39.15_suppl.5588.