The value of hysterectomy in the management of gestational trophoblastic neoplasia: a retrospective analysis.

This single-center, retrospective study enrolled patients with uterine-confined or isolated lung metastatic gestational trophoblastic disease (GTD) who underwent hysterectomy between January 2014 and December 2023. The exclusion criteria were as follows: (1) patients who did not undergo total hysterectomy; (2) patients with brain or other visceral metastases; (3) those with incomplete clinical data; and (4) those with a follow-up duration of less than 6 months. The study protocol was approved by the Institutional Review Board (IRB: 20240165), and the requirement for informed consent was waived due to the retrospective nature of the research. Disease staging was conducted in accordance with the International Federation of Gynecology and Obstetrics (FIGO) 2000 criteria. Risk categorization was performed using the FIGO-modified WHO prognostic scoring system, classifying patients into low-risk (score 0–6), high-risk (score 7–12), and ultra-high-risk (score ≥ 13) groups [ 20 ]. Given the elevated risk of resistance to single-agent chemotherapy among patients with scores of 5–6 [ 18 ], the low-risk category was further subdivided into ultra-low-risk (score 0–4) and low-risk (score 5–6). First-line chemoresistance was defined as either a plateau (three consecutive human Chorionic Gonadotropin [hCG] measurements with ≤ 10% variation) or a rise in hCG levels after at least two consecutive courses of chemotherapy [ 21 , 22 ]. Chemotherapy served as the primary treatment, with regimens tailored to disease stage and risk category. Low-risk patients received single-agent chemotherapy, including methotrexate, actinomycin-D, or 5-fluorouracil. High-risk patients were treated with multi-agent regimens such as EMA-CO, EMA/EP, or TP/TE (paclitaxel, cisplatin/paclitaxel, etoposide). Hysterectomy was considered in patients who had completed childbearing, presented with uncontrolled uterine bleeding, exhibited chemoresistance, experienced disease recurrence, or had a histologic diagnosis of PSTT or ETT, given their relative chemoresistance. Demographic, clinical, treatment, and outcome data were retrospectively collected from electronic medical records. Variables consisted of hysterectomy indications, FIGO 2000 stage, WHO risk score, histologic diagnosis, preoperative and postoperative chemotherapy regimens, number of chemotherapy cycles to remission, and prognostic outcomes. Patients were stratified by the timing of hysterectomy into first line (primary surgical intervention) and non-first line (surgery after other treatments) groups. Follow-up was conducted through outpatient visits or telephone interviews until May 31, 2024. Continuous variables are expressed as median and interquartile range (IQR), and categorical variables as frequencies and percentages. Group comparisons between patients receiving first-line and non-first-line hysterectomy were performed using appropriate statistical methods, with a two-sided p-value < 0.05 considered statistically significant. All analyses were conducted using IBM SPSS Statistics version 27.0.

A total of 96 patients underwent hysterectomy for GTD. The median age was 44.5 years (IQR: 31–50), with 55% ( n  = 53) aged 18–45 years. The primary indications for surgery were non–fertility-sparing management, primary treatment of GTD, and chemoresistant disease (Supplementary Table 1). Among patients opting for non–fertility-sparing surgery (median age: 49.5 years [IQR: 45.8–51.2]), 98% ( n  = 47) had at least one child (median parity: 1 [IQR: 1–1.3]). Two unique cases included hysterectomy after two failed hysteroscopic procedures and surgery for concurrent hydatidiform mole with symptomatic adenomyosis. Histopathological analysis categorized the specimens into three groups: GTN (57%, n  = 55), encompassing choriocarcinoma, invasive hydatidiform mole (IHM), or undefined GTN; intermediate trophoblastic tumors (ITTs; 31%, n  = 30), PSTT(26%, n  = 25) and ETT(5%, n  = 5); and hydatidiform mole (12%, n  = 11), including complete, partial, and residual unspecified subtypes (Supplementary Table 1). Among the 55 GTN patients, risk stratification according to the FIGO-modified WHO system was as follows: 55% ( n  = 30) ultra-low risk, 27% ( n  = 15) low risk, 16% ( n  = 9) high risk, and 2% ( n  = 1) ultra-high risk. Patients aged > 45 years and those with a prior hydatidiform mole history were predominantly in the ultra-low and low-risk groups. Pretreatment serum hCG levels showed a median of 39,060 IU/L (IQR: 5,071–189,545), with higher median values correlated with increasing risk category (Table  1 ). The overall survival rate was 95% (52/55), excluding three patients lost to follow-up. Recurrence was documented in three patients (two ultra-low risk, one low-risk). Table 1 The clinical characteristics of 55 GTN patients with different WHO risk score Variables Ultra-low risk ( N  = 30) Low risk ( N  = 15) High risk ( N  = 9) Ultra-high risk ( N  = 1) Total ( N  = 55) Age median (Q1-Q3), year 49.5 (43.5–51.25.5.25) 48 (44–50) 41(37–49) 29 48 (41–50)  45, n (%) 20(61) 9(27) 4(12) 0(0) 33(60) Pretreatment hCG median (Q1-Q3), IU/L 13,133 (3315–81850.25.25) 100,000 (25000–270000) 122,970 (13019.5–451485.5) 16,403 39,060 (5071–189545) Antecedent pregnancy, n (%)  Term 0(0) 1(50) 0(0) 1(50) 2(4)  Hydatidiform mole 28(64) 12(27) 4(9) 0(0) 44(80)  Abortion 2(25) 1(13) 5(62) 0(0) 8(15)  None 0(0) 1(100) 0(0) 0(0) 1(2) Site of metastasis, n (%)  None 20(59) 9(26) 5(15) 0(0) 34(62)  Lung 10(48) 6(29) 4(19) 1(4) 21(38) FIGO Stage, n (%)  I 20(67) 7(23) 3(10) 0(0) 30 (55)  III 10(40) 8(32) 6(24) 1(4) 25 (46) Recurrent, n (%)  Yes 2(67) 1(33) 0(0) 0(0) 3(6)  No 25(51) 14(29) 9(18) 1(2) 49(89)  Unknown 3(100) 0(0) 0(0) 0(0) 3(6) Prognostic outcome, n (%)  Alive 27(52) 15(29) 9(17) 1(2) 52(95)  Mortality 0(0) 0(0) 0(0) 0(0) 0(0)  Loss to follow-up 3(100) 0(0) 0(0) 0(0) 3(6) Chemotherapy before hysterectomy, n (%)  Yes 7(33) 7(33) 6(29) 1(5) 21(38)  No 23(68) 8(24) 3(9) 0(0) 34(62) Chemotherapy regimen before hysterectomy, n (%)  MTX 4 (57) 2 (29) 1 (14) 0(0) 7 (13)  MTX+Actd 2(50) 2 (50) 0(0) 0(0) 4(7)  MTX + EMA-CO 0(0) 0(0) 1 (100) 0(0) 1(2)  MTX+Actd + EMA-CO 1 (50) 1 (50) 0(0) 0(0) 2 (4)  EMA-CO 0(0) 1 (20) 3(60) 1(20) 5 (9)  None 23(68) 8(24) 3(9) 0(0) 34(62)  Others # 0(0) 1 (50) 1 (50) 0(0) 2(4) Chemotherapy after hysterectomy, n (%)  Yes 27(53) 15(29) 8(16) 1(2) 51(93)  No 3(75) 0(0) 1(25) 0(0) 4(7)  Number of post-hysterectomy chemotherapy cycles to remission median (Q1-Q3) 2 (1–4) 3 (2–4) 2 (0.5–5.5) 2 2 (1–4)  Number of chemotherapy cycles to remission median (Q1-Q3) 2(1–6) 5(3.5–7.5) 6(4–8) 6 4(1–7) Chemotherapy regimen after hysterectomy, n (%)  MTX 19(73) 7 (27) 0(0) 0(0) 26 (47)  Actd 1 (50) 1 (50) 0(0) 0(0) 2 (4)  MTX+Actd 4 (57) 2 (29) 1 (14) 0(0) 7 (13)  MTX+Actd + EMA-CO 0(0) 1 (100) 0(0) 0(0) 1(2)  EMA-CO 2(18) 4 (36) 4(36) 1(9) 11 (20)  EP-EMA 0(0) 0(0) 3(100) 0(0) 3(6)  None 3(75) 0(0) 1 (25) 0(0) 4(7)  Others & 1 (100) 0(0) 0(0) 0(0) 1(2) MTX  methotrexate, Actd actinomycin-D, VCR vincristine, EMA-CO etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine, EP-EMA etoposide, cisplatin, etoposide, methotrexate and actinomycin-D, TP paclitaxel, cisplatin, hCG human chorionic gonadotropin # one patient sequentially received chemotherapy with TP, EMA-CO regimen pre-hysterectomy; One patient sequentially received chemotherapy with MTX, 5-FU combined with VCR and KSM, 5-FU combined with KSM, and the EMA-CO regimen pre-hysterectomy & The patient was sequentially treated with the EMA-CO regimen, followed by EP, in combination with sintilimab and bevacizumab The clinical characteristics of 55 GTN patients with different WHO risk score MTX  methotrexate, Actd actinomycin-D, VCR vincristine, EMA-CO etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine, EP-EMA etoposide, cisplatin, etoposide, methotrexate and actinomycin-D, TP paclitaxel, cisplatin, hCG human chorionic gonadotropin # one patient sequentially received chemotherapy with TP, EMA-CO regimen pre-hysterectomy; One patient sequentially received chemotherapy with MTX, 5-FU combined with VCR and KSM, 5-FU combined with KSM, and the EMA-CO regimen pre-hysterectomy & The patient was sequentially treated with the EMA-CO regimen, followed by EP, in combination with sintilimab and bevacizumab Metastases were present in 21 GTN patients (38%), with the lungs being the most common site across all risk groups (Table  1 ). Patients with metastatic disease who underwent primary hysterectomy required more chemotherapy cycles to achieve remission (median: 3 cycles [IQR: 1–7]) compared to their non-metastatic counterparts (median: 2 cycles [IQR: 1–3]). Of 21 patients receiving preoperative chemotherapy, 52% ( n  = 11) started with single-agent regimens, with three patients (one per risk stratum) requiring escalation to multi-agent therapy due to resistance (Table  1 ). Postoperatively, 51 patients received chemotherapy, predominantly with single-agent regimens (69%, n  = 35). The median total chemotherapy cycles to remission were 2 (IQR: 1–6) for ultra-low risk and 5 (IQR: 3.5–7) for low-risk patients. One high-risk patient achieved sustained remission with hysterectomy alone, without adjuvant chemotherapy. Comparative analysis revealed significant differences between the first-line ( n  = 34) and non-first line ( n  = 6) hysterectomy groups (Table  2 ). The first-line group was older (median age: 50 vs. 43 years; P  = 0.003), had higher FIGO stages ( P  = 0.005), and more frequently underwent non–fertility-sparing surgery ( P  < 0.001) and received postoperative multi-agent chemotherapy ( P  < 0.001). Most importantly, the first-line group required significantly fewer total chemotherapy cycles to achieve remission (median: 2 [IQR: 1–4] vs. 7 [IQR: 5–9]; P  < 0.001). Table 2 Characteristics of 55 GTN patients treated with or without first-line hysterectomy Variables First-line hysterectomy P value Yes ( N  = 34) No ( N  = 21) Age median (Q1-Q3), year 50(45.75–51.25) 43(36.5–48.5) 0.003  45 26 (79) 7 (21) Gravidity median (Q1-Q3) 5 (4–5) 5(4–7) 0.452 Parity median (Q1-Q3) 1 (1–2) 1 (1–2) 0.152 Indication hysterectomy < 0.001  Non-fertility-sparing operation 27 (71) 11 (29)  Chemo-resistant disease 0 (0) 8 (100)  Hemorrhage 7 (78) 2 (22)  Pretreatment hCG median (Q1-Q3), IU/L 32,030 (3532–138789) 45,777 (12975.8–270000.8) 0.215 Antecedent pregnancy, n (%) 0.2  Term 0 (0) 2 (100)  Hydatidiform mole 29 (66) 15 (34)  Abortion 4 (50) 4 (50)  None 1 (100) 0 (0)  Largest uterine tumor size, cm median (Q1-Q3)* 4.3 (2.4–7.6) 3.2 (2.5–6.4) 0.592 Site of metastasis, n (%) 0.044  None 25 (74) 9 (26)  Lung 9 (43) 12 (57) Uterine pathological diagnosis, n (%) 0.446  IHMs 21 (62) 13 (38)  Choriocarcinoma 3 (43) 4 (57)  undefined GTN 10 (71) 4(29) FIGO Stage, n (%) 0.005  I 24 (80) 6 (20)  III 10 (40) 15 (60) Risk Classification, n (%) 0.047  Ultra-low risk 23 (77) 7 (23)  Low risk 8 (53) 7 (47)  High risk 3 (33) 6 (67)  Ultra-high risk 0 (0) 1 (100) Recurrent, n (%) 0.314  Yes 1 (33) 2 (67)  No 32 (65) 17 (35)  Unknown 1 (33) 2 (67) Prognostic outcome, n (%) 0.551  Alive 33 (63) 19 (37)  Mortality 0 (0) 0 (0)  Loss to follow-up 1 (33) 2 (67) Chemotherapy after hysterectomy, n (%) 0.286  Yes 30 (59) 21 (41)  No 4 (100) 0 (0) Chemotherapy regimen after hysterectomy, n (%) < 0.001  MTX 22 (85) 4 (15)  Actd 0 (0) 2 (100)  MTX+Actd 6 (86) 1 (14)  MTX+Actd + EMA-CO 0 (0) 1 (100)  EMA-CO 2 (18) 9 (82)  None 4 (100) 0 (0)  Others # 0 (0) 4 (100)  Number of post-hysterectomy chemotherapy cycles to remission median (Q1-Q3) 2 (1–4) 2 (2–4) 0.42  Number of chemotherapy cycles to remission median (Q1-Q3) 2 (1–4) 7 (5–9) < 0.001 *Information available for 51 patients # one patient sequentially received chemotherapy with TP，EMA-CO regimen pre-hysterectomy; One patient sequentially received chemotherapy with MTX, 5-FU combined with VCR and KSM, 5-FU combined with KSM, and the EMA-CO regimen pre-hysterectomy Characteristics of 55 GTN patients treated with or without first-line hysterectomy *Information available for 51 patients # one patient sequentially received chemotherapy with TP，EMA-CO regimen pre-hysterectomy; One patient sequentially received chemotherapy with MTX, 5-FU combined with VCR and KSM, 5-FU combined with KSM, and the EMA-CO regimen pre-hysterectomy Among 34 patients, 31 had low-risk, non-metastatic GTN. Three of these patients (all FIGO stage I, risk score 2) achieved complete remission with surgery alone (Table  3 ). The remaining 30 patients (88%) received postoperative chemotherapy (median: 4 cycles [IQR: 1.25–6.25]). Treatment intensity differed by subgroup: ultra-low risk patients received a median of 3 cycles (74% with single-agent methotrexate), while low-risk patients received a median of 5 cycles (Table  3 ). Table 3 Clinical characteristics of 34 GTN patients who underwent first-line hysterectomy with different WHO risk score Variables Ultra-low risk ( N  = 23) Low risk ( N  = 8) High risk ( N  = 3) Age median (Q1-Q3), year 50(45–51) 49.5(47.5–52) 46(39.5–49.5)  45, n (%) 17(65) 7(27) 2(8) Gravidity median (Q1-Q3) 5(4–5) 4.5(3–6.5.5) 5(3.5–5.5) Parity median (Q1-Q3) 1(1–1) 1(1–2) 1(1–1.5.5) Pretreatment hCG median (Q1-Q3), IU/L 10,707(2912–90626) 95,842(17500–227672) 122,970(63991–127443) Antecedent pregnancy, n (%)  Abortion 2(50) 1(25) 1(25)  Hydatidiform mole 21(72) 6(21) 2(7)  None 0(0) 1(100) 0(0)  Mean largest uterine tumor size, cm median (Q1-Q3)* 3.5(2.3–6.2) 5.7(3.7–9.95) 7.4(6.2–8.2) Site of metastasis, n (%)  None 16(64) 7(28) 2(8)  Lung 7(78) 1(11) 1(11) Uterine pathological diagnosis, n (%)  IHMs 13(62) 6(29) 2(9)  Choriocarcinoma 0(0) 2(67) 1(33)  undefined GTN 10(100) 0(0) 0(0) FIGO Stage, n (%)  I 16(67) 7(29) 1(4)  III 7(70) 1(10) 2(20) Recurrent, n (%)  Yes 1(100) 0(0) 0(0)  No 21(66) 8(25) 3(9)  Unknown 1(100) 0(0) 0(0) Prognostic outcome, n (%)  Alive 22(67) 8(24) 3(9)  Mortality 0(0) 0(0) 0(0)  Unknown 1(100) 0(0) 0(0) Chemotherapy after hysterectomy, n (%)  Yes 20(67) 8(27) 2(6)  No 3(75) 0(0) 1(25) Chemotherapy regimen after hysterectomy, n (%)  MTX 17(77) 5(23) 0(0)  MTX+Actd 3(60) 2(40) 0(0)  EMA-CO 0(0) 1(50) 1(50)  None 3(75) 0(0) 1(25)  Number of post-hysterectomy chemotherapy cycles to remission median (Q1-Q3) 1(1–3) 3.5(1.5–4.5) 4(2–5)  Number of chemotherapy cycles to remission median (Q1-Q3) 1(1–3) 3.5(1.5–4.5) 4(2–5) *Information available for 32 patients Clinical characteristics of 34 GTN patients who underwent first-line hysterectomy with different WHO risk score *Information available for 32 patients Six patients underwent surgery after 1–2 cycles of single-agent methotrexate (Table  4 ). This subgroup (all with invasive mole; median age 46.5 years [IQR: 43.5–51]) required a median total of 4.5 (IQR: 3.25–5.75) chemotherapy cycles for remission. Separately, one high-risk choriocarcinoma patient achieved remission after hysterectomy (following 8 methotrexate cycles) and 2 additional postoperative cycles. Table 4 Clinical characteristics of 21 GTN patients who underwent non-first-line hysterectomy with different WHO risk score Variables Ultra-low risk N  = 7 Low risk N  = 7 High risk N  = 6 Utra-high risk N  = 1 Age median (Q1-Q3), year 43(38–50.5.5) 45(41–46.5.5) 40(37–49) 29 18–45, n (%) 4(29) 5(36) 4(29) 1(7) > 45, n (%) 3(43) 2(29) 2(29) 0(0) Gravidity median (Q1-Q3) 4(4–6) 5(3.5–9.5) 5(5–6) 2 Parity median (Q1-Q3) 2(1–2) 1(1–2) 1(1–2) 1 Indication hysterectomy, n (%)  Non-fertility-sparing operation  3(27)  5(45)  2(18)  1(9)  Chemo-resistant disease  3(38)  2(25)  3(38)  0(0)  Hemorrhage  1(50)  0(0)  1(50)  0(0)  Pretreatment hCG median (Q1-Q3), IU/L  16081.1(7470.8–31641.5.8.5)  225,000(45184–536070.5.5)  176,399(21027–632970)  16,403 Antecedent pregnancy, n (%)  Abortion 0(0) 0(0) 4(100) 0(0)  Hydatidiform mole, n (%) 7(47) 6(40) 2(13) 0(0)  Term 0(0) 1(50) 0(0) 1(50)  Mean largest uterine tumor size, cm median (Q1-Q3) * 2.5(2–2.85.85) 4.55(3.2–5.3) 7.4(3.1–7.8) 6.4 Site of metastasis, n (%)  None 4(44) 2(22) 3(33) 0(0)  Lung 3(25) 5(42) 3(25) 1(8) Uterine pathological diagnosis, n (%)  IHMs 6(46) 5(38) 2(15) 0(0)  Choriocarcinoma 0(0) 1(25) 3(75) 0(0)  undefined GTN 1(25) 1(25) 1(25) 1(25) FIGO Stage, n (%)  I 4(67) 0(0) 2(33) 0(0)  III 3(20) 7(47) 4(27) 1(7) Recurrent, n (%)  Yes 1(50) 1(50) 0(0) 0(0)  No 4(24) 6(35) 6(35) 1(6)  Lost to follow-up 2(100) 0(0) 0(0) 0(0) Prognostic outcome, n (%)  Alive 5(26) 7(37) 6(32) 1(5)  Lost to follow-up 2(100) 0(0) 0(0) 0(0) Chemotherapy regimen before hysterectomy, n (%)  MTX 4(57) 2(29) 1(14) 0(0)  MTX+Actd 2(50) 2(50) 0(0) 0(0)  MTX+Actd + EMA-CO 1(50) 1(50) 0(0) 0(0)  EMA-CO 0(0) 1(20) 3(60) 1(20)  MTX + EMA-CO 0(0) 0(0) 1(100) 0(0)  TP + EMA-CO 0(0) 0(0) 1(100) 0(0)  Others # 0(0) 1(100) 0(0) 0(0) Chemotherapy regimen after hysterectomy, n (%)  MTX 2(50) 2(50) 0(0) 0(0)  Actd 1(50) 1(50) 0(0) 0(0)  MTX+Actd 1(100) 0(0) 0(0) 0(0)  MTX+Actd + EMA-CO 0(0) 1(100) 0(0) 0(0)  EMA-CO 2(22) 3(33) 3(33) 1(11)  Others & 1(25) 0(0) 3(75) 0(0)  Number of pre-hysterectomy chemotherapy cycles median (Q1-Q3) 2(1.5–5.5) 5(3–8) 4(3–8) 4  Number of post-hysterectomy chemotherapy cycles to remission median (Q1-Q3) 4(2.5–5.5) 2(2–3) 2(1–3) 2  Number of chemotherapy cycles to remission median (Q1-Q3) 7(5.5–10.5) 7(5.5–9.5) 7.5(6–9) 6 * Information available for 19 patients # one patient sequentially received chemotherapy with TP, EMA-CO regimen pre-hysterectomy; One patient sequentially received chemotherapy with MTX, 5-FU combined with VCR and KSM, 5-FU combined with KSM, and the EMA-CO regimen pre-hysterectomy & The patient was sequentially treated with the EMA-CO regimen, followed by EP, in combination with sintilimab and bevacizumab Clinical characteristics of 21 GTN patients who underwent non-first-line hysterectomy with different WHO risk score * Information available for 19 patients # one patient sequentially received chemotherapy with TP, EMA-CO regimen pre-hysterectomy; One patient sequentially received chemotherapy with MTX, 5-FU combined with VCR and KSM, 5-FU combined with KSM, and the EMA-CO regimen pre-hysterectomy & The patient was sequentially treated with the EMA-CO regimen, followed by EP, in combination with sintilimab and bevacizumab The cohort included 30 ITT patients (median age: 29.5 years). Metastatic disease was present in 30% ( n  = 9), primarily pulmonary, with four patients (13%) having FIGO stage IV disease (one death) (Supplementary Table 2). Primary hysterectomy was performed in 77% ( n  = 23), all of whom were alive and recurrence-free. The seven patients receiving perioperative chemotherapy predominantly had multi-agent regimens. Recurrence occurred in four patients (13%), resulting in an overall survival rate of 93% (28/30).

Gestational trophoblastic disease (GTD) comprises a spectrum of rare pregnancy-related disorders, ranging from benign partial and complete hydatidiform moles to malignant forms such as invasive mole, choriocarcinoma, placental site trophoblastic tumor (PSTT), and epithelioid trophoblastic tumor (ETT). While fertility-sparing surgery is standard for molar pregnancies [ 1 ], hysterectomy offers a definitive option for patients not desiring fertility preservation, with near-100% survival in non-metastatic disease [ 2 – 5 ] and reduces subsequent neoplasia risk in high-risk hydatidiform mole patients [ 6 ]. In acute settings, such as uterine rupture complicated by shock, hysterectomy becomes a necessary and life-saving intervention [ 7 ]. Chemotherapy remains the cornerstone for gestational trophoblastic neoplasia (GTN), tailored to the World Health Organization (WHO) risk score. Low-risk patients (score < 6) typically receive single-agent methotrexate or actinomycin D, with remission rates ranging from 53% to 94% [ 8 , 9 ]. However, efficacy declines with higher risk scores (5–6) [ 9 – 13 ]. High-risk patients (score ≥ 7) receive multi-agent regimens such as EMA/CO (etoposide, methotrexate, actinomycin, cyclophosphamide, and vincristine), yet 30–40% develop resistance or relapse [ 14 , 15 ]. Salvage therapies like EMA/EP (etoposide, methotrexate, actinomycin, etoposide and cisplatin) or FAEV (floxuridine, dactinomycin, etoposide, and vincristine) are associated with significant toxicities, including myelosuppression in over one-quarter of patients [ 16 , 17 ]. To address the clinical challenges of chemotherapy toxicity and resistance, a clearer understanding of the role of hysterectomy is needed. While not routinely recommended for low-risk GTN, it can reduce chemotherapy exposure in stage I disease and achieve complete remission in over 80% of selected cases, including chemoresistant ones [ 18 , 19 ]. Its utility appears limited in high-risk metastatic disease [ 13 ]. This study retrospectively evaluates clinical outcomes of GTD patients undergoing hysterectomy, aiming to clarify its role in individualized management across disease types and risk profiles.

In our retrospective review of 96 GTD patients treated with hysterectomy, patients who underwent first-line hysterectomy required a median of only 2 total chemotherapy cycles to achieve remission, which was significantly fewer than the median of 7 cycles required by those undergoing surgery after failed chemotherapy ( P  < 0.001). This chemotherapy-sparing benefit was most pronounced in low-risk patients, in whom primary surgery alone was curative in a subset, effectively de-escalating treatment. Moreover, hysterectomy proved to be a definitive intervention for chemoresistant trophoblastic tumors. Overall, the treatment strategy incorporating hysterectomy was associated with a high overall survival rate of 95% in the malignant cohort. Among the 55 patients diagnosed with GTN, the majority were classified as ultra-low and low risk, aligning with previous studies showing that older patients and those with a history of hydatidiform mole pregnancies often present with less aggressive disease [ 2 , 4 ]. The recurrence rate was low, with only two ultra-low risk and one low-risk patient experiencing disease relapse during follow-up. Despite the higher pre-treatment serum hCG levels correlating with increasing GTN risk scores, the overall survival rate remained excellent, with 95% of patients alive at the last follow-up. This further highlights the success of risk-based treatment strategies in managing GTN. For patients with metastatic GTN, the lungs were the most common site of metastasis, consistent with existing literature. Although these patients required more chemotherapy cycles compared to those with localized disease, the survival outcomes were favorable [ 23 , 24 ]. Nine patients with metastatic GTN who underwent primary hysterectomy required median of 3 cycles (IQR: 1–7) of chemotherapy postoperatively to achieve remission, while those with localized disease needed fewer cycles (median: 2 cycles [IQR: 1–3]). These findings underscore the potential benefit of early hysterectomy in reducing the burden of chemotherapy, especially for patients with metastatic disease, by offering a direct reduction of tumor burden. Chemotherapy remains a critical component of GTN treatment, and our findings mirror previous studies in highlighting the role of single-agent chemotherapy, particularly MTX, as a first-line treatment for low-risk patients [ 9 ]. In our cohort, 52% (11/21) of patients who received chemotherapy before hysterectomy were treated with single-agent regimens. However, due to chemotherapy resistance, a small subset of low-risk patients required a switch to multi-agent chemotherapy. Post-hysterectomy, the majority of patients (69%, n = 35) continued on single-agent chemotherapy, further demonstrating the efficacy of this approach in managing low to ultra-low risk GTN. Interestingly, one high-risk patient achieved remission without chemotherapy, suggesting that hysterectomy alone may be curative in select high-risk cases, particularly when disease is confined to the uterus. Regarding first-line hysterectomy outcomes, our study identified 34 patients who underwent this procedure, primarily among those with low-risk, non-metastatic GTN. Remarkably, three patients achieved complete remission without the need for additional chemotherapy or experiencing relapse. These findings are in line with Bolze et al.’s retrospective analysis, which found that hysterectomy in low-risk, non-metastatic patients significantly reduce the need for salvage chemotherapy [ 18 ]. Additionally, the reduction in chemotherapy cycles not only lowers the risk of chemotherapy-related side effects but also improves patients’ quality of life and overall prognosis. Our study strengthens the argument for considering hysterectomy as a first-line treatment option in carefully selected low-risk patients. For non-first-line hysterectomy, six patients underwent the procedure after receiving 1–2 cycles of single-agent MTX regimens. These patients had invasive hydatidiform moles (IHMs) and a median age of 46.5 years (IQR: 43.5–51), with the majority opting for surgery to avoid further chemotherapy. The median number of chemotherapy cycles required for remission in these patients was 4.5 (IQR: 3.25–5.75), which is consistent with prior reports indicating that chemotherapy alone may not always be sufficient in cases of invasive disease. The absence of recurrence in five out of six patients further supports the role of hysterectomy in managing chemotherapy-resistant or invasive disease, particularly in patients who no longer wish to preserve fertility. Among the 30 patients with ITTs, our study highlighted the challenges associated with treating metastatic disease. Despite aggressive chemotherapy and surgery, one patient with FIGO stage IV disease succumbed to the disease, emphasizing the poor prognosis associated with advanced-stage ITTs. However, the overall survival rate among ITTs patients was 93%, with the majority achieving long-term remission following a combination of hysterectomy and multi-agent chemotherapy. These results align with current recommendations advocating for aggressive multimodal treatment in patients with advanced-stage GTN. This study provides a comprehensive, retrospective analysis of the clinical outcomes associated with total hysterectomy across the histologic spectrum of GTD at a single institution. By evaluating both first-line and non-first-line surgical strategies, it offers practical insights into the role of hysterectomy within individualized treatment algorithms. However, key limitations stem from its retrospective nature. These include the potential for ascertainment and selection bias, as treatment allocation was not randomized. Furthermore, inherent to the retrospective design is the issue of incomplete or missing data; specific metrics, particularly on surgical risks, perioperative complications, and long-term morbidity, were not systematically recorded, precluding a comprehensive risk-benefit analysis. The single-center design may also affect generalizability. To address these gaps and strengthen the evidence base, future prospective, multi-center studies are strongly recommended. Such research should prioritize the standardized collection of surgical safety data, enabling a more balanced and comprehensive risk-benefit assessment of hysterectomy in the management of GTD.

In conclusion, our study confirms that hysterectomy plays a pivotal role in the management of GTD, particularly in older patients, those with non-fertility-sparing needs, and in cases of chemotherapy-resistant disease. For patients with low-risk GTN, timely hysterectomy can reduce the need for prolonged chemotherapy, thereby minimizing the side effects associated with systemic treatment. Moreover, our findings reinforce the importance of individualized treatment strategies based on risk stratification, which can lead to excellent long-term outcomes even in patients with metastatic or invasive disease. Future studies should focus on optimizing the timing and patient selection for hysterectomy to further improve outcomes and reduce treatment burden in GTD patients.

Supplementary Material 1. Supplementary Material 1.