Clinical Presentation, Treatment Outcomes, and Resistance-related Factors in South American Women with Low-risk Postmolar Gestational Trophoblastic Neoplasia

Ramírez, Luz Angela Correa; Maestá, Izildinha; Bianconi, María Inés; Jankilevich, Gustavo; Otero, Silvina; Mejía, Carlos Raúl Villegas; Cortés-Charry, Rafael; Elias, Kevin M.; Horowitz, Neil S.; Seckl, Michael; Berkowitz, Ross S.

doi:10.1055/s-0042-1748974

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Revista Brasileira de Ginecologia e Obstetrícia

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Sumário

Original Article • Rev Bras Ginecol Obstet. 44 (08) • 2022 • https://doi.org/10.1055/s-0042-1748974 copy

Clinical Presentation, Treatment Outcomes, and Resistance-related Factors in South American Women with Low-risk Postmolar Gestational Trophoblastic Neoplasia

Apresentação clínica, resultados do tratamento e fatores relacionados à resistência em mulheres sul-americanas com neoplasia trofoblástica gestacional pós-molar de baixo risco

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Objective

There are few multinational studies on gestational trophoblastic neoplasia (GTN) treatment outcomes in South America. The purpose of this study was to assess the clinical presentation, treatment outcomes, and factors associated with chemoresistance in low-risk postmolar GTN treated with first-line single-agent chemotherapy in three South American centers.

Methods

Multicentric, historical cohort study including women with International Federation of Gynecology and Obstetrics (FIGO)-staged low-risk postmolar GTN attending centers in Argentina, Brazil, and Colombia between 1990 and 2014. Data were obtained on patient characteristics, disease presentation, and treatment response. Logistic regression was used to assess the relationship between clinical factors and resistance to first-line single-agent treatment. A multivariate analysis of the clinical factors significant in univariate analysis was performed.

Results

A total of 163 women with low-risk GTN were included in the analysis. The overall rate of complete response to first-line chemotherapy was 80% (130/163). The rates of complete response to methotrexate or actinomycin-D as first-line treatment, and actinomycin-D as second-line treatment postmethotrexate failure were 79% (125/157), 83% (⅚), and 70% (23/33), respectively. Switching to second-line treatment due to chemoresistance occurred in 20.2% of cases (33/163). The multivariate analysis demonstrated that patients with a 5 to 6 FIGO risk score were 4.2-fold more likely to develop resistance to first-line single-agent treatment (p= 0.019).

Conclusion

1) At presentation, most women showed clinical characteristics favorable to a good outcome, 2) the overall rate of sustained complete remission after first-line single-agent treatment was comparable to that observed in developed countries, 3) a FIGO risk score of 5 or 6 is associated with development of resistance to first-line single-agent chemotherapy.

Keywords
low-risk gestational trophoblastic neoplasia; molar pregnancy; South America; chemotherapy; resistance-related factors

Variables	Summary
Age (years)	28.0 (21.0, 33.0)
Gravidity	2.0 (1.0, 3.0)
Parity	1.0 (0.0, 1.0)
Molar histology
Partial	27 (16.6%)
Complete	136 (83.4%)
HM evacuation-GTN diagnosis interval (months)	2.3 (1.6, 3.6)
GTN diagnosischemotherapy initiation interval (days)	2.0 (0.0–6.0)
Pre-treatment hCG	7,442 (1,693, 29,227)
Pre-treatment hCG
< 1,000	31 (19.0%)
1,000 < 10,000	60 (36.8%)
10,000–99,999	62 (38.0%)
≥ 100,000	10 (6.2%)
Metastatic disease at presentation	51 (31.2%)
FIGO stage
1	112 (68.7%)
2	3 (1.8%)
3	48 (29.4%)
FIGO risk score	3.0 (1.0, 4.0)
FIGO risk score
0–2	81 (49.7%)
3–4	61 (37.5%)
5–6	21 (12.8%)
Number of first-line chemotherapy cycles	4.0 (3.0, 7.0)
Total number of chemotherapy cycles to remission	5.0 (3.0–8.0)
Time to hCG remission (weeks)	12.5 (7.7, 19.0)
Switch to second-line treatment	33 (20.2%)
Switch to third-line treatment	2 (1.2%)
Surgery after chemoresistance	11 (6.74%)
Survival rate	163 (100.0%)

Variables	OR	95% CI		P
Age (years)	0.98	0.94	1.03	0.488
Gravidity	0.79	0.58	1.08	0.146
Parity	0.80	0.55	1.18	0.260
Complete mole	0.87	0.32	2.36	0.780
HM evacuation - GTN diagnosis interval (months)	0.97	0.82	1.16	0.740
GTN diagnosis-chemotherapy initiation interval (days)	0.97	0.92	1.03	0.327
Pretreatment hCG	1.00	1.00	1.00	0.020
Pretreatment hCG (Reference ≤ 1,000)				0.140
[1,000–10,000)	0.45	0.14	1.43	0.178
[10,000–100,000)	1.09	0.39	3.04	0.863
≥ 100,000	2.29	0.50	10.45	0.286
Metastatic disease at presentation	1.26	0.55	2.85	0.584
FIGO stage (reference = 1)				0.715
2	2.17	0.19	25.03	0.536
3	1.29	0.57	2.94	0.547
FIGO risk score	1.43	1.10	1.86	0.007
FIGO risk score (reference = 0–2)
3–4	0.91	0.36	2.28	0.833
5–6	5.75	2.03	16.31	0.001
Number of first-line chemotherapy cycles	1.05	0.94	1.17	0.405
Total number of chemotherapy cycles to remission	1.32	1.16	1.49	< 0.001
Time to hCG remission (weeks)	1.07	1.03	1.11	0.001

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[1] Address for correspondence Izildinha Maesta, Distrito de Rubião Júnior, S/N, 18618-970, Botucatu, SP, Brazil (i.maesta@unesp.br).