Utility of molecular subtypes and genetic alterations for evaluating clinical outcomes in 1029 patients with endometrial cancer.

BACKGROUND: We investigated the utility of a molecular classifier tool and genetic alterations for predicting prognosis in Japanese patients with endometrial cancer. METHODS: A total of 1029 patients with endometrial cancer from two independent cohorts were classified into four molecular subtype groups. The primary and secondary endpoints were relapse-free survival (RFS) and overall survival (OS), respectively. RESULTS: Among the 265 patients who underwent initial surgery, classified according to immunohistochemistry, patients with DNA polymerase epsilon exonuclease domain mutation had an excellent prognosis (RFS and OS), patients with no specific molecular profile (NSMP) and mismatch repair protein deficiency had an intermediate prognosis, and those with protein 53 abnormal expression (p53abn) had the worst prognosis (P < 0.001). In the NSMP group, mutant KRAS and wild-type ARID1A were associated with significantly poorer 5-year RFS (41.2%) than other genomic characteristics (P < 0.001). The distribution of the subtypes differed significantly between patients with recurrence/progression and classified by sequencing (n = 764) and patients who underwent initial surgery (P < 0.001). Among patients with recurrence/progression, 51.4% had the opportunity to receive molecular targeted therapy. CONCLUSIONS: A molecular classifier is a useful tool for determining prognosis and eligibility for molecularly targeted therapy in patients with endometrial cancer.

Utility of the revised FIGO2023 staging with molecular classification in endometrial cancer.

OBJECTIVES: Molecular classification was introduced in endometrial cancer staging following the transition of the International Federation of Gynecology and Obstetrics (FIGO) 2008 to FIGO2023. In the early stages, p53 abnormal endometrial carcinoma with myometrial involvement was upstaged to stage IICm, in addition to the downstaging of POLE mutation endometrial cancer to stage IAm. This study compared the goodness of fit and discriminatory ability of FIGO2008, FIGO2023 without molecular classification (FIGO2023), and FIGO2023 with molecular classification (FIGO2023m); no study has been externally validated to date. METHODS: The study included 265 patients who underwent initial surgery at the National Cancer Center Hospital between 1997 and 2019 and were pathologically diagnosed with endometrial cancer. The three classification systems were compared using Harrell's concordance index (C-index), Akaike information criterion (AIC), and time-dependent receiver operating characteristic (ROC) curves. A higher C-index score and a lower AIC value indicated a more accurate model. RESULTS: Among the three classification systems, FIGO2023m had the lowest AIC value (FIGO2023m: 455.925; FIGO2023: 459.162; FIGO2008: 457.901), highest C-index (FIGO2023m: 0.768; FIGO2023: 0.743; FIGO2008: 0.740), and superior time-dependent ROC curves within 1 year after surgical resection. In the stage IIIC, patients with p53 abnormalities had considerably lower 5-year overall survival than those with a p53 wild-type pattern (24.3% vs. 83.7%, p = 0.0005). CONCLUSIONS: FIGO2023m had the best discriminatory ability compared with FIGO2008 and FIGO2023. Even in advanced stages, p53 status was a poor prognostic factor. When feasible, molecular subtypes can be added to the staging criteria to allow better prognostic prediction in all stages.

Endometrioid Endometrial Carcinoma With NKX3.1 Expression in a Transgender Man: A Case Report.

Endometrial cancer in transgender men is rare, and its histopathologic features remain unknown. A 30-yr-old transgender man with an intrauterine tumor, an ovarian mass, and a 2-yr history of testosterone use was referred to us for treatment. The presence of the tumors was confirmed via imaging, and the intrauterine tumor was identified as an endometrial endometrioid carcinoma via endometrial biopsy. The patient underwent hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and lymph node dissection. Pathologic examination revealed grade 3 endometrioid endometrial carcinoma, and the synchronous endometrial and ovarian tumors were collectively characterized as primary endometrial carcinoma. Metastatic carcinomas were discovered in both ovaries and the omentum, pelvic peritoneum, and a para-aortic lymph node. On immunohistochemistry, the tumor cells diffusely expressed p53, retained expression of PTEN, ARID1A, PMS2, and MSH6, and focally expressed estrogen receptors, androgen receptors, and NKX3.1. NKX3.1 was also expressed in glandular structures within the exocervical squamous epithelium. Prostate-specific antigen and prostatic acid phosphatase were focally positive. In conclusion, we describe a transgender man with NKX3.1-expressing endometrioid endometrial carcinoma who provides valuable suggestions regarding the effects of testosterone on endometrial cancer and appropriate gynecological care for transgender men.

Clinical impact of genetic alterations of CTNNB1 in patients with grade 3 endometrial endometrioid carcinoma.

To identify prognostic factors in patients with grade 3 (high-grade) endometrial endometrioid carcinoma, we evaluated the spectrum of genomic alterations and examined whether previously reported molecular subtypes of endometrial carcinoma were adapted to clinical outcome prediction. Seventy-five Japanese patients with grade 3 endometrial endometrioid carcinoma, who underwent a potentially curative resection procedure between 1997 and 2018 at the National Cancer Center Hospital, were included. We classified the patients into four risk groups of the disease based on the Proactive Molecular Risk Classifier for Endometrial Cancer. Genomic alterations in PTEN, ARID1A, TP53, and PIK3CA were detected in more than 30% of the patients. Overall survival and recurrence-free survival of patients with genomic alterations in CTNNB1 were poorer than those of patients with wild-type CTNNB1 (p = 0.006 and p = 0.004, respectively). Compared with that of alterations prevalent in Caucasians, the frequency of genomic alterations in POLE and TP53 was higher in our study than in The Cancer Genome Atlas dataset (p = 0.01 and p = 0.01, respectively). The tendency for recurrence-free survival in the POLE exonuclease domain mutation group was better than that in the TP53 mutation and mismatch repair-deficient groups (p = 0.08 and p = 0.07, respectively), consistent with the Proactive Molecular Risk Classifier for Endometrial Cancer risk classifier definition. The CTNNB1 mutation is a potential novel biomarker for the prognosis of patients with grade 3 endometrial endometrioid carcinoma, and prognosis classification using Proactive Molecular Risk Classifier for Endometrial Cancer may help screen Japanese patients with the disease.

Gross mucinous multinodular appearance aids in the identification of ovarian metastases in low-grade appendiceal mucinous neoplasms during intraoperative consultation.

Ovarian metastases of low-grade appendiceal mucinous neoplasms (LAMNs) show grossly abundant nodular mucous cells, with a gross mucinous multinodular appearance and a histological resemblance to primary ovarian mucinous tumors (POMTs). This study aimed to elucidate the utility of gross features including the gross mucinous multinodular appearance and available clinical information at the time of intraoperative consultation, in distinguishing the ovarian metastases of LAMNs from POMTs or the ovarian metastases of colorectal cancer (CRC). In total, 776 patients with primary ovarian tumor and 68 patients with ovarian metastases underwent intraoperative consultation during 1998-2018. Of the total cases, 4 ovarian metastases of LAMNs, 19 ovarian metastases of CRC, and 50 POMTs (36 borderline tumors and 14 carcinomas) were identified. The gross features including the gross mucinous multinodular appearance were analyzed based on the gross photographs obtained before formalin fixation and the available clinical information collected during intraoperative consultation. The analysis indicated that the ovarian metastases of LAMNs significantly presented with gross mucinous multinodular appearance (4/4 vs. 0/50, P < 0.0001), extraovarian disease (4/4 vs. 2/50, P < 0.0001), ovarian surface involvement (3/4 vs. 2/50, P = 0.0016), and abnormal appendix (4/4 vs. 0/50, P < 0.0001) as compared to POMT. Moreover, the gross mucinous multinodular appearance was a distinguishable feature between the ovarian metastases of LAMNs and ovarian metastases of CRC (4/4 vs. 0/19, P = 0.0001). Based on these results, we proposed an algorithm to diagnose ovarian tumors using the gross mucinous multinodular appearance. Thus, recognizing unique gross features including the gross mucinous multinodular appearance would be useful for both pathologists and surgeons to accurately diagnose ovarian metastases of LAMNs during intraoperative consultation.

Feasibility of initial treatment in elderly patients with ovarian cancer in Japan: a retrospective study.

PURPOSE: The purpose of this study was to evaluate the real world situation and clarify the problem in initial treatment for elderly patients with ovarian cancer in Japan. METHODS: We used the ovarian cancer database, containing all patients diagnosed and treated with International Federation of Gynecology and Obstetrics Stage I-IV ovarian cancer at the National Cancer Center Hospital in Japan from June 2008 to April 2013. Patients were stratified into two groups based on age: an elderly group, aged 70 years or older, and a younger group, aged below 70 years. We retrospectively assessed the rate of receiving standard therapy, and the feasibility and safety of chemotherapy compared with younger patients. RESULTS: In total, 244 patients (elderly group, 36 patients; younger group, 208 patients) were analyzed. A significantly lower proportion of elderly patients than younger patients received standard therapy (15.7% vs. 32.5%, p = 0.026). Even for the elderly group, 95% patients underwent surgery in our institution. Conversely the rate of patients receiving nonstandard chemotherapy in the elderly group was significantly higher than in the younger group (30.5% vs. 9.6%, p = 0.01). CONCLUSIONS: This study clarified the type of treatment being performed in the field, and the proportion of elderly ovarian cancer patients receiving standard therapy compared with younger patients in Japan. In addition, the actual situation of elderly patients in Japan might be different from that in Western countries. We need to evaluate the appropriate treatment for elderly patients in Japan.

Laparoscopic Posterior Pelvic Exenteration with Radical Vulvectomy for Intestinal-type Vulvar Adenocarcinoma.

Vulvar intestinal adenocarcinoma is a rare malignancy. The most significant predictor of advanced vulvar cancer is achieving complete resection, although determining the optimal treatment for this rare histologic type remains uncertain. We report the case of a 63-year-old woman with a primary vulvar tumor suspected of having rectal invasion and inguinal lymph node metastases based on preoperative magnetic resonance imaging and computed tomography scans. To achieve complete resection of stage IIIC intestinal-type vulvar adenocarcinoma, we performed a laparoscopic posterior pelvic exenteration (PPE) and radical vulvectomy, along with bilateral inguinal lymph node dissection. This case report highlights the use of a novel hybrid procedure that combines laparoscopic PPE with radical vulvectomy and bilateral inguinal lymph node dissection for vulvar adenocarcinoma of the intestinal type. Laparoscopic PPE can be considered a minimally invasive approach for vulvar tumor when complete resection is achievable with an appropriate safety margin.

Ovarian Mucinous Tumor Presenting Atypical Lobular Endocervical Glandular Hyperplasia-Like Appearance in a Patient With Germline STK11 p.F354L Variant: A Case Report.

Peutz-Jeghers syndrome (PJS) is associated with female genital lesions, such as cervical gastric-type adenocarcinoma and lobular endocervical glandular hyperplasia (LEGH). However, ovarian mucinous borderline tumors (OMBT) with atypical LEGH-like histology have not been described. The patient was a 60-year-old female with PJS clinically diagnosed at 23 years old with gastrointestinal polyposis. Abdominal distension was noted, and computed tomography scan revealed bilateral breast masses, multiple lung nodules, and a multicystic ovarian tumor. A needle biopsy revealed invasive ductal carcinoma of the breast. For the ovarian tumor, simple hysterectomy and bilateral salpingo-oophorectomy were performed. The left ovarian tumor was 25 × 20 × 12 cm in size and a multicystic tumor containing yellowish mucus without a solid part. Histologically, the cyst wall was covered with mucus cells with focal mild-to-moderate cellular atypia, forming LEGH-like architectures. The glandular cells were immunohistochemically positive for MUC5AC, MUC6 (focal), HIK1083 (focal), and HNF4α. Stromal invasion was not observed. Cervical lesions were not observed. The final pathological diagnosis was OMBT showing atypical LEGH morphology. Targeted sequencing of nontumor tissues revealed the germline STK11 p.F354L variant. Six months later, peritoneal dissemination of adenocarcinoma showing features similar to those of the ovarian tumor was observed, and the patient died of the disease. In summary, we report a case of OMBT with an atypical LEGH-like appearance in a patient with germline STK11 p.F354L variant. This case provides us with unresolved questions regarding the pathogenicity of this STK11 variant and the malignant potential of OMBT with this unusual morphology.

Ovarian Mesonephric-Like Adenocarcinoma With Recurrent Liver Metastases: A Case Report with Analysis of Therapeutic Molecular Targets.

Ovarian mesonephric-like adenocarcinoma (MLA) is a rare cancer subtype. We describe a patient with ovarian MLA wherein liver metastases developed 1 month after surgery. A phenotypic analysis of the tumor was performed to identify molecular therapeutic targets. A 53-year-old woman, without any symptoms, underwent uterine cancer screening. Transvaginal ultrasonography revealed an ovarian mass, and subsequent pelvic magnetic resonance imaging showed a 13 × 10 cm multicystic ovarian lesion with a solid part. No extra ovarian lesions were observed and a staging laparotomy was performed. Pathological examination revealed an MLA of the left ovary (stage IC1). The tumor comprised tumor cells in a tubular pattern with intraluminal eosinophilic material, as well as mixed glandular and papillary, cord-like, and solid patterns. Endometriosis was also observed. Immunohistochemically, the tumor cells were positive for PAX8, GATA3 (focal), TTF1 (focal), and CD10 (luminal) and negative for the estrogen receptor, progesterone receptor, and WT1. One month after surgery, computed tomography revealed multiple liver metastases. Additional immunohistochemistry for therapeutic targets revealed that the tumor cells were weakly positive for human epidermal growth factor receptor 2 (focal; score 1+), pan-tropomyosin receptor kinase-negative, programmed death-ligand 1-negative, and PMS2 and MSH6 intact. The companion homologous recombination deficiency test (MyChoice®) showed homologous recombination repair proficiency. These findings suggest that poly(ADP-ribose) polymerase inhibitors and immune checkpoint inhibitors may not be effective treatment options. A literature review revealed that data on therapeutic targets in MLA are scarce. In summary, we report a patient with ovarian MLA showing an aggressive clinical course and the phenotypic analysis of the tumor may contribute to the identification of therapeutic targets for MLA.

Mismatch Repair Protein Expression in Endometrial Cancer: Assessing Concordance and Unveiling Pitfalls in Two Different Immunohistochemistry Assays.

This study aimed to compare the concordance and interchangeability of the Dako/Agilent and Ventana/Roche mismatch repair (MMR) immunohistochemistry (IHC) assays commonly used in pathology. It also aimed to provide diagnostic insights by examining the frequency and characteristics of the dot-like artifact observed in MLH1 M1 clone staining in endometrial cancer. Fifty endometrial cancer cases with MMR deficiency, excised between 2011 and 2018, were included in the study. IHC was performed using primary antibody clones from Ventana/Roche (MLH1, clone M1; MSH2, G219-1129; MSH6, SP93; PMS2, A16-4) and Dako/Agilent (MLH1, ES05; MSH2, FE11; MSH6, EP49; PMS2, EP51). Both assays were conducted using respective autostainers. The Dako/Agilent assay showed a loss of MLH1 in 26 cases, MSH2 in 12 cases, MSH6 in 23 cases, and PMS2 in 28 cases. The two assays had a complete agreement in MMR protein expression or loss. The dot-like artifact in MLH1 M1 clone staining was observed in 77% (20/26) of cases, predominantly in the surface area of the tumor, ranging from 5% to 40% (median: 10%). These findings highlight the high concordance between the MMR-IHC assays and emphasize the importance of considering the dot-like artifact in MLH1 M1 clone staining when diagnosing endometrial cancer with MMR deficiency.

Adenoid Basal Carcinoma with Adenoid Cystic Carcinoma Component of the Uterine Cervix: A Case Report and Literature Review.

Adenoid basal carcinoma (ABC) is rare cancer with a favorable prognosis. However, some ABCs are associated with other histological types, such as squamous cell carcinoma. Here, we present a case of a mixed tumor of ABC and adenoid cystic carcinoma (ACC) of the cervix, with a detailed immunohistochemical study and literature review. We describe a case of a 66-year-old woman who underwent cervical cancer screening that led to the detection of a 0.7 cm nodular lesion. Cervical punch biopsies revealed a high-grade squamous intraepithelial lesion. Cervical conization revealed a mixed carcinoma composed of ABC and ACC, showing stromal invasion, lymphovascular invasion, and positive resection margins. Immunohistochemically, the ACC components were positive for KIT and αSMA and negative for NKX3.1. The tumor presented with proficient mismatch repair (MMR) and was negative for HER2, PD-L1, and TRKA (NTRK1). Subsequent radical hysterectomy with pelvic lymph node dissection revealed the presence of residual tumor cells in the cervix. Our literature review identified six similar cases, including one patient who died of disease recurrence. We report a rare tumor comprising both ABC and ACC. Prognostic data on mixed tumors are scarce; however, given the aggressive nature of ACC, attention should be paid to the detection of mixed tumors. Since ABC and ACC histology may overlap, adequate sampling and IHC for detecting ACC would be helpful.

Uterine Leiomyosarcoma Masquerading as a Malignant Perivascular Epithelioid Cell Tumor: A Diagnostic Challenge.

Uterine sarcomas with myomelanocytic differentiation have been reported to be diagnostically challenging. We report a case of uterine leiomyosarcoma with extensive perivascular epithelioid cell tumor (PEComa)-like areas and extrauterine metastases. The patient was a 49-year-old gravida 3 para 2 Japanese woman with no relevant medical history. She noticed a vaginal mass with bleeding. Imaging examination revealed a uterine tumor and multiple liver and lung metastases. The vaginal tumor (3.5 cm) was resected and diagnosed as a malignant PEComa based on morphology and myomelanocytic marker expression. Clinically used targeted sequencing (FoundationOneCDx™) revealed gene alterations in RB1, TP53, and ATRX but not TSC1/2. Despite administration of an mTOR inhibitor, the tumor size increased, and subsequently, hysterectomy was performed to relieve the symptoms. The uterine tumor was composed of conventional leiomyosarcoma showing RB1 loss, wild-type TP53 staining, and retained ATRX expression, as well as adjacent predominant PEComa-like components with RB1 loss, TP53 overexpression, and ATRX loss, identical to the characteristics of the vaginal tumor. In the uterine tumor, both HMB-45 and MITF were weak to moderately positive for approximately 40% of tumor cells while Melan-A was negative. The tumor was finally diagnosed as leiomyosarcoma with PEComa-like features. This case exemplifies the tumorigenesis of diagnostically challenging tumors with myomelanocytic differentiation and demonstrates the importance of integrating multiple types of information, including genomic profiling, in making a correct diagnosis leading to appropriate treatment.

Genetic features of endometrioid-type endometrial carcinoma arising in uterine adenomyosis.

This study aimed to clarify the genetic features of endometrioid-type endometrial cancer arising in adenomyosis (EC-AIA) using targeted sequencing and immunohistochemistry (IHC) for both carcinoma and adjacent adenomyosis tissues. We identified three endometrioid-type EC-AIAs in 689 patients with endometrial cancer; two exhibited grade 3 endometrioid carcinoma. IHC revealed retained expression of PMS2, MSH6, ARID1A, and PAX2. Two of them showed diffuse strong p53 expression only in the carcinoma. PTEN expression was lost in carcinoma of only one of these cases. Carcinoma had many gene mutations than adjacent adenomyosis in all cases. KRAS and TP53 mutations were found in two of them. The other patient had mutations in KRAS, PIK3CA, and PPP2R1A. They were classified as two "p53-mutated" and one "non-specific molecular profile." These molecular alterations in endometrioid-type EC-AIA imply similar carcinogenesis to a subset of endometrial endometrioid carcinoma and might be used as targets of liquid biopsy after further validation.

Gastric-type cervical adenocarcinoma with squamous differentiation: buried in adenosquamous carcinomas?

Gastric-type adenocarcinoma (GAS) of the cervix is a human papilloma virus (HPV)-independent, aggressive, and chemo-resistant adenocarcinoma. However, although the histopathological features of GAS have been extensively investigated, squamous differentiation has not been mentioned. This study aimed to elucidate the frequency of GAS with squamous differentiation and describe their clinicopathological characteristics. We retrospectively evaluated 78 patients with GAS (n = 13) and adenosquamous carcinoma (n = 65) diagnosed between 2000 and 2020. Two patients with GAS with squamous differentiation were identified. Both tumors showed advanced stage (pT2bN1) and had predominant GAS and merged squamous cell carcinoma components without p16-block positivity and HPV DNA. Gastric-type adenocarcinoma in situ was confirmed in both cases. Some cases of GAS could show squamous differentiation mimicking the usual, HPV-associated, adenosquamous carcinoma. GAS with squamous differentiation is recognized as an HPV-independent cancer.

Diagnostic Discordance in Intraoperative Frozen Section Diagnosis of Ovarian Tumors: A Literature Review and Analysis of 871 Cases Treated at a Japanese Cancer Center.

BACKGROUND: This study examined the accuracy and pitfalls associated with frozen section diagnosis of primary ovarian tumors and ovarian metastases based on the 2014 World Health Organization classification (WHO) criteria and proposed improvements from a pathologist's perspective. METHODS: We microscopically reviewed 871 cases of primary ovarian tumor (N = 802) and ovarian metastasis (N = 69) and compared the results of frozen sections with the final diagnosis. Malignant potential concordance (benign, borderline, or malignant) and specific discordant diagnosis rates were analyzed. Finally, we conducted a unique literature review of specific diagnostic errors in the frozen section diagnosis of primary ovarian tumors. RESULTS: Of 802 primary ovarian tumors, 50 (6.2%) cases showed discordant diagnoses in which mucinous carcinoma (40.5%), low-grade serous carcinoma (LGSC; 31.3%), and mucinous borderline tumor (18.4%) were frequently misinterpreted. Of 69 ovarian metastases, all 4 cases of low-grade appendiceal mucinous neoplasm (LAMN) were misdiagnosed as primary ovarian mucinous tumor. A literature review revealed that mucinous/serous borderline tumor or carcinoma accounted for approximately 70% of 217 reported discordant diagnoses. CONCLUSION: In the present study, the concordance rate of malignant potential of the tumor was comparable to that previously reported. Even in the 2014 WHO classification, primary ovarian mucinous borderline tumor/carcinoma and LGSC still comprised the majority of discordant cases. Grossing methods that reduce sampling error are required. LAMN was frequently misinterpreted as a benign or borderline ovarian mucinous tumor. To prevent this error, a differential algorithm integrating clinical information and gross findings should be developed.

Clear Cell Carcinoma of the Cervix With OHVIRA Syndrome: A Rare Case Report.

Obstructed hemivagina and ipsilateral renal agenesis (OHVIRA) syndrome is a rare Mullerian duct anomaly characterized by an obstructed hemivagina, ipsilateral renal agenesis, and uterine didelphys. There are only a few published case reports of OHVIRA syndrome, and cases of OHVIRA syndrome associated with cancer have rarely been reported. In fact, there is only one published report of a case with clear cell carcinoma (CCC) of the cervix. Here, we report a case of CCC of the cervix with OHVIRA syndrome that underwent abdominal radical hysterectomy; we also provide a short literature review of this topic. A 52-year-old woman presented with abnormal vaginal bleeding for 1 month 2 years after menopause. A pelvic examination and preoperative imaging showed uterine didelphys, an obstructed hemivagina with a mass measuring approximately 2 cm located in her left cervix, and an absence of her left kidney. A colposcopy biopsy reported CCC of the cervix. Clinical staging classified her with stage IB1 disease. Abdominal radical hysterectomy was performed. Her left ectopic ureter led to the left cervix and opened in the endometrium, resulting in a so-called ectopic ureter. Macroscopic examination of the excised specimens showed two cervixes, two corpora of the uterus, and a tumor measuring 1.0 × 2.0 cm on the left cervix. In addition to typical OHVIRA symptoms including uterine didelphys, obstructed hemivagina, and renal agenesis, several anatomical variants were present. The current case included those variants as well as an atrophic kidney with an ectopic ureter to the obstructed hemivagina. Based on the results of our case, clinicians should be aware of the risks of cancer and anatomical variants associated with OHVIRA syndrome.

Platinum-free interval affects efficacy of following treatment for platinum-refractory or -resistant ovarian cancer.

BACKGROUND/OBJECTIVE: Platinum-refractory or -resistant ovarian cancer (PRROC) is associated with poor prognosis and low response to further chemotherapy. We investigated predictors of effectiveness of following treatments for PRROC. PATIENTS AND METHODS: We included 380 patients diagnosed with stage I-IV ovarian, fallopian tube, or primary peritoneal cancer, who were treated at the National Cancer Center Hospital in Japan from January 2007 to December 2014 and recurred after initial treatment, who had a platinum-refractory or -resistant relapses and received chemotherapy, in this single-center, retrospective study. We investigated factors related to response to following treatment, and to progression-free survival (PFS). RESULTS: Among 183 patients (48%) who suffered recurrences, 62 (34%) developed PRROC after chemotherapy. In multivariate analysis, platinum-free interval (PFI) < 3 months was independently associated with progressive disease (odds ratio [OR] 6.043, 95% confidence interval [CI] 1.485-24.595, P = 0.012). Median PFS was 139 days (95% CI 19.4-258) among patients with PFI > 3 months, but was 57 days (95% CI 34.7-79.2) among those with PFI < 3 months. In multivariate analysis, two factors, performance status (PS) 1-2 (HR 1.915, 95% CI 1.074-3.415, P = 0.028) and PFI < 3 months (HR 1.943, 95% CI 1.109-3.403, P = 0.02), were independently associated with worse PFS. CONCLUSIONS: PS 1-2 and PFI < 3 months were significant predictors of poor response to following treatment for PRROC. Risks and benefits of treatment should be frankly discussed with patients who have these characteristics.