1Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
2Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul, Korea
Copyright © 2023 by the Korean Cancer Association
This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Ethical Statement
The Institutional Review Board of the Seoul National University Hospital (SNUH) approved this retrospective cohort study (No. H-2106-007-1233). The study was performed in accordance with the principles of the Declaration of Helsinki, and the requirement for informed consent was waived.
Author Contributions
Conceived and designed the analysis: Kim SI, Lee M.
Collected the data: Kim SI, Lim H, Lee M.
Contributed data or analysis tools: Kim SI, Lim H, Chung HH, Kim JW, Park NH, Song YS, Lee M.
Performed the analysis: Kim SI, Lee M.
Wrote the paper: Kim SI, Lim H, Kim HS, Chung HH, Kim JW, Park NH, Song YS, Lee M. Lee M.
Conflicts of Interest
Conflict of interest relevant to this article was not reported.
Characteristic | Total (n=262) | BRCA mutation (n=91) | BRCA wild-type (n=171) | p-value |
---|---|---|---|---|
Platinum-free interval (mo) | ||||
Median (range) | 13.8 (6.0–172.3) | 15.2 (6.1–133.7) | 13.2 (6.0–172.3) | 0.115 |
≥ 6 and < 12 | 106 (40.5) | 28 (30.8) | 78 (45.6) | 0.020 |
≥ 12 | 156 (59.5) | 63 (69.2) | 93 (54.4) | |
Age at recurrence, mean±SD (yr) | 57.1±9.6 | 55.9±8.3 | 57.6±10.2 | 0.146 |
CA-125 at recurrence (IU/mL) | ||||
Median (range)a) | 95.5 (2.2–8,320.0) | 96.0 (2.2–6,290.0) | 95.5 (2.5–8,320.0) | 0.541 |
Ascites > 500 mL at recurrence | ||||
No | 225 (85.9) | 80 (87.9) | 145 (84.8) | 0.490 |
Yes | 37 (14.1) | 11 (12.1) | 26 (15.2) | |
AGO score | ||||
Negative | 100 (38.2) | 34 (37.4) | 66 (38.6) | 0.845 |
Positive | 162 (61.8) | 57 (62.6) | 105 (61.4) | |
Secondary treatment | ||||
Chemotherapy only | 182 (69.5) | 67 (73.6) | 115 (67.3) | 0.286 |
Secondary CRS | 80 (30.5) | 24 (26.4) | 56 (32.7) | |
Residual tumor at secondary CRS | ||||
Complete resection | 66 (25.2) | 22 (24.2) | 44 (25.7) | 0.364 |
< 1 cm | 8 (3.1) | 1 (1.1) | 7 (4.1) | |
≥ 1 cm | 6 (2.3) | 1 (1.1) | 5 (2.9) | |
Complete resection rate (%)b) | 82.5 | 91.7 | 78.6 | 0.209 |
Second-line chemotherapy | ||||
Paclitaxel-Carboplatin-BEV | 97 (37.0) | 18 (19.8) | 79 (46.2) | 0.001 |
Gemcitabine-Carboplatin-BEV | 3 (1.1) | 0 | 3 (1.8) | |
Paclitaxel-Carboplatin | 91 (34.7) | 45 (49.5) | 46 (26.9) | |
PLD-Carboplatin | 44 (16.8) | 16 (17.6) | 28 (16.4) | |
Docetaxel-Carboplatin | 12 (4.6) | 5 (5.5) | 7 (4.1) | |
Gemcitabine-Carboplatin | 9 (3.4) | 4 (4.4) | 5 (2.9) | |
Belotecan-Cisplatin | 4 (1.5) | 3 (3.3) | 1 (0.6) | |
Topotecan-Cisplatin | 1 (0.4) | 0 | 1 (0.6) | |
Irinotecan-Cisplatin | 1 (0.4) | 0 | 1 (0.6) | |
Second-line chemotherapy cycles | ||||
Median (range) | 6 (2–12) | 6 (2–12) | 6 (2–12) | 0.812 |
< 6 | 33 (12.6) | 15 (16.5) | 18 (10.5) | 0.382 |
6 | 186 (71.0) | 62 (68.1) | 124 (72.5) | |
≥ 7 | 43 (16.4) | 14 (15.4) | 29 (17.0) | |
Maintenance therapy | ||||
Two categories | ||||
No | 133 (50.8) | 41 (45.1) | 92 (53.8) | 0.178 |
Yes | 129 (49.2) | 50 (54.9) | 79 (46.2) | |
Three categories | ||||
No | 133 (50.8) | 41 (45.1) | 92 (53.8) | < 0.001 |
BEV | 90 (34.4) | 16 (17.6) | 74 (43.3) | |
PARPi | 39 (14.9) | 34 (37.4) | 5 (2.9) | |
Four categories | ||||
No | 133 (50.8) | 41 (45.1) | 92 (53.8) | < 0.001 |
BEV | 90 (34.4) | 16 (17.6) | 74 (43.3) | |
OLA | 32 (12.2) | 30 (33.0) | 2 (1.2) | |
NIRA | 7 (2.7) | 4 (4.4) | 3 (1.8) |
Value are presented as number (%) unless otherwise indicated. AGO, Arbeitsgemeinschaft Gynäkologische Onkologie; BEV, bevacizumab; CA-125, cancer antigen 125; CRS, cytoreductive surgery; NIRA, niraparib; OLA, olaparib; PARPi, poly(ADP-ribose) polymerase inhibitor; PLD, pegylated liposomal doxorubicin; SD, standard deviation.
a) Missing data: 10,
b) Among the patients who received secondary CRS.
Patients’ characteristics at the time of primary treatment
Characteristic | Total (n=262) | BRCA mutation (n=91) | BRCA wild-type (n=171) | p-value |
---|---|---|---|---|
Age at initial diagnosis, mean±SD (yr) | 54.6±9.9 | 53.5±8.4 | 55.2±10.6 | 0.150 |
Histology | ||||
Two categories | ||||
High-grade serous | 218 (83.2) | 81 (89.0) | 137 (80.1) | 0.067 |
Non-high grade serous | 44 (16.8) | 10 (11.0) | 34 (19.9) | |
In detail | ||||
High-grade serous | 218 (83.2) | 81 (89.0) | 137 (80.1) | 0.046 |
Low-grade serous | 6 (2.3) | 0 | 6 (3.5) | |
Endometrioid | 17 (6.5) | 5 (5.5) | 12 (7.0) | |
Mucinous | 5 (1.9) | 1 (1.1) | 4 (2.3) | |
Clear cell | 10 (3.8) | 0 | 10 (5.8) | |
Mixed | 4 (1.5) | 3 (3.3) | 1 (0.6) | |
Others | 2 (0.8) | 1 (1.1) | 1 (0.6) | |
FIGO stage | ||||
I | 15 (5.7) | 2 (2.2) | 13 (7.6) | 0.199 |
II | 20 (7.6) | 5 (5.5) | 15 (8.8) | |
III | 140 (53.4) | 50 (54.9) | 90 (52.6) | |
IV | 87 (33.2) | 34 (37.4) | 53 (31.0) | |
Primary treatment | ||||
Upfront CRS | 186 (71.0) | 62 (68.1) | 124 (72.5) | 0.457 |
NAC-interval CRS | 76 (29.0) | 29 (31.9) | 47 (27.5) | |
Residual tumor at first CRS | ||||
Complete resection | 185 (70.6) | 64 (70.3) | 121 (70.8) | 0.942 |
Residual disease | 77 (29.4) | 27 (29.7) | 50 (29.2) | |
BEV at first-line chemotherapy | ||||
No | 237 (90.5) | 82 (90.1) | 155 (90.6) | 0.889 |
Yes | 25 (9.5) | 9 (9.9) | 16 (9.4) | |
BRCA testing methods | ||||
Germline only | 155 (59.2) | 65 (71.4) | 90 (52.6) | 0.013 |
Somatic only | 27 (10.3) | 6 (6.6) | 21 (12.3) | |
Both | 80 (30.5) | 20 (22.0) | 60 (35.1) | |
BRCA mutational status | ||||
BRCA1 mutation | 70 (26.7) | 70 (76.9) | 0 | < 0.001 |
BRCA2 mutation | 21 (8.0) | 21 (23.1) | 0 | |
Mutations in both genes | 0 | 0 | 0 | |
Wild-type | 171 (65.3) | 0 | 171 (100) |
Values are presented as number (%) unless otherwise indicated. BEV, bevacizumab; CRS, cytoreductive surgery; FIGO, International Federation of Gynecology and Obstetrics; NAC, neoadjuvant chemotherapy; SD, standard deviation.
Patients’ characteristics at the time of recurrence and during secondary treatment
Characteristic | Total (n=262) | BRCA mutation (n=91) | BRCA wild-type (n=171) | p-value |
---|---|---|---|---|
Platinum-free interval (mo) | ||||
Median (range) | 13.8 (6.0–172.3) | 15.2 (6.1–133.7) | 13.2 (6.0–172.3) | 0.115 |
≥ 6 and < 12 | 106 (40.5) | 28 (30.8) | 78 (45.6) | 0.020 |
≥ 12 | 156 (59.5) | 63 (69.2) | 93 (54.4) | |
Age at recurrence, mean±SD (yr) | 57.1±9.6 | 55.9±8.3 | 57.6±10.2 | 0.146 |
CA-125 at recurrence (IU/mL) | ||||
Median (range) |
95.5 (2.2–8,320.0) | 96.0 (2.2–6,290.0) | 95.5 (2.5–8,320.0) | 0.541 |
Ascites > 500 mL at recurrence | ||||
No | 225 (85.9) | 80 (87.9) | 145 (84.8) | 0.490 |
Yes | 37 (14.1) | 11 (12.1) | 26 (15.2) | |
AGO score | ||||
Negative | 100 (38.2) | 34 (37.4) | 66 (38.6) | 0.845 |
Positive | 162 (61.8) | 57 (62.6) | 105 (61.4) | |
Secondary treatment | ||||
Chemotherapy only | 182 (69.5) | 67 (73.6) | 115 (67.3) | 0.286 |
Secondary CRS | 80 (30.5) | 24 (26.4) | 56 (32.7) | |
Residual tumor at secondary CRS | ||||
Complete resection | 66 (25.2) | 22 (24.2) | 44 (25.7) | 0.364 |
< 1 cm | 8 (3.1) | 1 (1.1) | 7 (4.1) | |
≥ 1 cm | 6 (2.3) | 1 (1.1) | 5 (2.9) | |
Complete resection rate (%) |
82.5 | 91.7 | 78.6 | 0.209 |
Second-line chemotherapy | ||||
Paclitaxel-Carboplatin-BEV | 97 (37.0) | 18 (19.8) | 79 (46.2) | 0.001 |
Gemcitabine-Carboplatin-BEV | 3 (1.1) | 0 | 3 (1.8) | |
Paclitaxel-Carboplatin | 91 (34.7) | 45 (49.5) | 46 (26.9) | |
PLD-Carboplatin | 44 (16.8) | 16 (17.6) | 28 (16.4) | |
Docetaxel-Carboplatin | 12 (4.6) | 5 (5.5) | 7 (4.1) | |
Gemcitabine-Carboplatin | 9 (3.4) | 4 (4.4) | 5 (2.9) | |
Belotecan-Cisplatin | 4 (1.5) | 3 (3.3) | 1 (0.6) | |
Topotecan-Cisplatin | 1 (0.4) | 0 | 1 (0.6) | |
Irinotecan-Cisplatin | 1 (0.4) | 0 | 1 (0.6) | |
Second-line chemotherapy cycles | ||||
Median (range) | 6 (2–12) | 6 (2–12) | 6 (2–12) | 0.812 |
< 6 | 33 (12.6) | 15 (16.5) | 18 (10.5) | 0.382 |
6 | 186 (71.0) | 62 (68.1) | 124 (72.5) | |
≥ 7 | 43 (16.4) | 14 (15.4) | 29 (17.0) | |
Maintenance therapy | ||||
Two categories | ||||
No | 133 (50.8) | 41 (45.1) | 92 (53.8) | 0.178 |
Yes | 129 (49.2) | 50 (54.9) | 79 (46.2) | |
Three categories | ||||
No | 133 (50.8) | 41 (45.1) | 92 (53.8) | < 0.001 |
BEV | 90 (34.4) | 16 (17.6) | 74 (43.3) | |
PARPi | 39 (14.9) | 34 (37.4) | 5 (2.9) | |
Four categories | ||||
No | 133 (50.8) | 41 (45.1) | 92 (53.8) | < 0.001 |
BEV | 90 (34.4) | 16 (17.6) | 74 (43.3) | |
OLA | 32 (12.2) | 30 (33.0) | 2 (1.2) | |
NIRA | 7 (2.7) | 4 (4.4) | 3 (1.8) |
Value are presented as number (%) unless otherwise indicated. AGO, Arbeitsgemeinschaft Gynäkologische Onkologie; BEV, bevacizumab; CA-125, cancer antigen 125; CRS, cytoreductive surgery; NIRA, niraparib; OLA, olaparib; PARPi, poly(ADP-ribose) polymerase inhibitor; PLD, pegylated liposomal doxorubicin; SD, standard deviation.
a)Missing data: 10,
b)Among the patients who received secondary CRS.
Factors associated with progression-free survival
Characteristic | Univariate analysis | Multivariate analysis | ||||
---|---|---|---|---|---|---|
|
|
|||||
HR | 95% CI | p-value | aHR | 95% CI | p-value | |
Platinum-free interval (mo) | ||||||
|
||||||
≥ 6 and < 12 | 1 | - | - | 1 | - | - |
|
||||||
≥ 12 | 0.523 | 0.391–0.699 | < 0.001 | 0.571 | 0.421–0.773 | < 0.001 |
|
||||||
CA-125 at recurrence (IU/mL) | ||||||
|
||||||
< 95 | 1 | - | - | 1 | - | - |
|
||||||
≥ 95 | 1.710 | 1.274–2.293 | < 0.001 | 1.593 | 1.176–2.158 | 0.003 |
|
||||||
Histology | ||||||
|
||||||
High-grade serous | 1 | - | - | 1 | - | - |
|
||||||
Non-high grade serous | 0.707 | 0.478–1.045 | 0.082 | 0.743 | 0.492–1.120 | 0.156 |
|
||||||
BRCA mutational status | ||||||
|
||||||
Wild-type | 1 | - | - | 1 | - | - |
|
||||||
Mutation | 0.789 | 0.585–1.065 | 0.122 | 0.816 | 0.596–1.119 | 0.207 |
|
||||||
Secondary CRS | ||||||
|
||||||
No | 1 | - | - | 1 | - | - |
|
||||||
Yes | 0.521 | 0.378–0.720 | < 0.001 | 0.566 | 0.397–0.807 | 0.002 |
|
||||||
Maintenance therapy | ||||||
|
||||||
No | 1 | - | - | 1 | - | - |
|
||||||
Yes | 0.587 | 0.437–0.787 | < 0.001 | 0.489 | 0.357–0.669 | < 0.001 |
aHR, adjusted hazard ratio; CA-125, cancer antigen 125; CI, confidence interval; CRS, cytoreductive surgery; HR, hazard ratio.
Values are presented as number (%) unless otherwise indicated. BEV, bevacizumab; CRS, cytoreductive surgery; FIGO, International Federation of Gynecology and Obstetrics; NAC, neoadjuvant chemotherapy; SD, standard deviation.
Value are presented as number (%) unless otherwise indicated. AGO, Arbeitsgemeinschaft Gynäkologische Onkologie; BEV, bevacizumab; CA-125, cancer antigen 125; CRS, cytoreductive surgery; NIRA, niraparib; OLA, olaparib; PARPi, poly(ADP-ribose) polymerase inhibitor; PLD, pegylated liposomal doxorubicin; SD, standard deviation. Missing data: 10, Among the patients who received secondary CRS.
aHR, adjusted hazard ratio; CA-125, cancer antigen 125; CI, confidence interval; CRS, cytoreductive surgery; HR, hazard ratio.