Objective: We evaluated the usefulness of human epididymis protein 4 (HE4), a tumor marker, during and after treatment in patients with ovarian cancer (OC). Methods: We included Japanese patients newly diagnosed with OC treated at the National Cancer Center Hospital between 2014 and 2021. The HE4 levels were measured in the serum stored during diagnosis. To evaluate the concordance between HE4 and the imaging results, we employed sequential pairs of blood sampling points and the results of imaging examinations. We compared the timing of the elevated HE4 levels, imaging diagnoses, and elevated cancer antigen 125 (CA125) levels in patients with recurrence. The Ethics Review Committee of our institution (2021-056) reviewed this study. Results: Forty-eight patients with epithelial OC were eligible for enrollment. The sensitivity, specificity, and positive and negative predictive values of HE4 (criterion, 70 pmol/L) for disease progression during the follow-up period were 79.4%, 59.1%, 32.5%, and 92.0%, respectively (time point, n=317). We evaluated the relationship between HE4 and CA125 variability and disease status (recurrence or no recurrence). For recurrence, the sensitivity and negative predictive value of HE4 (criterion, 70 pmol/L), CA125 (criterion, 35 U/mL), and combination of HE4 and CA125 were 77.8%, 85.2%, and 92.6% and 75.0%, 82.6%, and 88.9%, respectively (n=48). Among the 27 patients who exhibited recurrence, 16 and nine showed earlier increased HE4 levels than the relevant imaging and CA125 levels, respectively. Conclusion HE4 may be a valuable marker for follow-up during and after OC therapy. A complementary role for HE4 and CA125 measurements was suggested for follow-up observations.

OBJECTIVE: To treat advanced ovarian cancer, interval debulking surgery (IDS) is performed after 3 cycles each of neoadjuvant chemotherapy (NAC) and postoperative chemotherapy (IDS group). If we expect that complete resection cannot be achieved by IDS, debulking surgery is performed after administering additional 3 cycles of chemotherapy without postoperative chemotherapy (Add-C group). We evaluated the survival outcomes of the Add-C group and determined their serum cancer antigen 125 (CA125) levels to predict complete surgery. METHODS: A retrospective chart review of all stage III and IV ovarian, fallopian tube, and peritoneal cancer patients treated with NAC in 2007–2016 was conducted. RESULTS: About 117 patients comprised the IDS group and 26 comprised the Add-C group. Univariate and multivariate analyses revealed that Add-C group had an equivalent effect on progression-free survival (PFS; p=0.09) and overall survival (OS; p=0.94) compared with the IDS group. Multivariate analysis revealed that patients who developed residual disease after surgery had worse PFS (hazard ratio [HR]=2.18; 95% confidence interval [CI]=1.45–3.28) and OS (HR=2.33; 95% CI=1.43–3.79), and those who received <6 cycles of chemotherapy had worse PFS (HR=5.30; 95% CI=2.56–10.99) and OS (HR=3.05; 95% CI=1.46–6.38). The preoperative serum CA125 cutoff level was 30 U/mL based on Youden index method. CONCLUSIONS: Administering 3 additional cycles of chemotherapy followed by debulking surgery exhibited equivalent effects on survival as IDS followed by 3 cycles of postoperative chemotherapy. Preoperative serum CA125 levels of ≤30 U/mL may be a useful predictor of achieving complete surgery.
CA-125 Antigen ; Cytoreduction Surgical Procedures ; Disease-Free Survival ; Drug Therapy ; Fallopian Tubes ; Female ; Humans ; Methods ; Multivariate Analysis ; Neoadjuvant Therapy ; Ovarian Neoplasms ; Retrospective Studies

Objective: This study aimed to investigate the prognosis of patients with intermediate-risk cervical cancer and to evaluate the necessity of adjuvant therapy. Methods: We conducted a retrospective chart review of patients with stage IB–II cervical cancer who underwent type III radical hysterectomy with pelvic lymphadenectomy between 2008 and 2017. In our institution, radical hysterectomy is performed as an open surgery and not as a minimally invasive surgery, and adjuvant therapy is not administered to patients with intermediate-risk cervical cancer. The intermediate-risk group included patients with 2 or more of the following factors: tumor size >4 cm, stromal invasion >1/2, and lymphovascular stromal invasion. Intermediaterisk patients with squamous cell carcinoma were included in the I-SCC group, whereas those with endocervical adenocarcinoma, usual type, or adenosquamous carcinoma were included in the I-Adeno group. Results: There were 34 and 18 patients in the I-SCC and I-Adeno groups, respectively. The 5-year recurrence-free survival (RFS) and overall survival rates in the I-SCC group were 90.5% (95% confidence interval [CI], 85.3–95.7%) and 100% (95% CI, 100%), respectively, whereas those in the I-Adeno group were 54.9% (95% CI, 42.0–67.9%) and 76.1% (95% CI, 63.7–88.4%), respectively. Multivariate analysis revealed that endocervical adenocarcinoma, usual type, or adenosquamous carcinoma, and tumor size >4 cm had worse RFS. Conclusion The I-SCC group had good prognosis without adjuvant therapy; therefore, adjuvant therapy may be omitted in these patients. In contrast, the I-Adeno group had poor prognosis without adjuvant therapy; therefore, adjuvant therapy should be considered in their treatment.

Objective: This study aimed to investigate the prognosis of patients with intermediate-risk cervical cancer and to evaluate the necessity of adjuvant therapy. Methods: We conducted a retrospective chart review of patients with stage IB–II cervical cancer who underwent type III radical hysterectomy with pelvic lymphadenectomy between 2008 and 2017. In our institution, radical hysterectomy is performed as an open surgery and not as a minimally invasive surgery, and adjuvant therapy is not administered to patients with intermediate-risk cervical cancer. The intermediate-risk group included patients with 2 or more of the following factors: tumor size >4 cm, stromal invasion >1/2, and lymphovascular stromal invasion. Intermediaterisk patients with squamous cell carcinoma were included in the I-SCC group, whereas those with endocervical adenocarcinoma, usual type, or adenosquamous carcinoma were included in the I-Adeno group. Results: There were 34 and 18 patients in the I-SCC and I-Adeno groups, respectively. The 5-year recurrence-free survival (RFS) and overall survival rates in the I-SCC group were 90.5% (95% confidence interval [CI], 85.3–95.7%) and 100% (95% CI, 100%), respectively, whereas those in the I-Adeno group were 54.9% (95% CI, 42.0–67.9%) and 76.1% (95% CI, 63.7–88.4%), respectively. Multivariate analysis revealed that endocervical adenocarcinoma, usual type, or adenosquamous carcinoma, and tumor size >4 cm had worse RFS. Conclusion The I-SCC group had good prognosis without adjuvant therapy; therefore, adjuvant therapy may be omitted in these patients. In contrast, the I-Adeno group had poor prognosis without adjuvant therapy; therefore, adjuvant therapy should be considered in their treatment.

Objective: Folate receptor α (FRα) is a membrane protein expressed in various solid tumors but has limited expression in normal cells. Therefore, FRα is an attractive target for cancer treatment. This study aimed to investigate the relationship between FRα expression and the clinicopathological characteristics and survivals of cervical cancer. Methods: This retrospective study included patients with cervical cancer who underwent primary surgery between 2000 and 2020 at our institution. Immunohistochemical staining of FRα was performed using an anti-folate-binding protein/FBP antibody. FRα-positive staining was defined as ≥5% of tumor staining and FRα-high as ≥50% tumor staining with ≥2+ intensity. The association between FRα expression and survival was assessed using multivariate Cox regression analysis, adjusting for established prognostic factors. Results: Overall, 123 patients were identified, and 140 tumor samples, including 17 paired primary and metastatic samples, were evaluated. As histological types, 67 patients had squamous cell carcinoma (SCC), and 56 patients had non-SCC. All primary tumors were FRα-positive. High FRα expression was observed in 25% of the cases and differed according to histology (SCC vs. non-SCC, 14.9% vs. 37.5%, p=0.004). FRα expression was significantly higher in metastatic tumors than in primary (170 [IQR, 140–205] vs. 125 [IQR, 110–150], p=0.0006). High FRα expression was significantly associated with worse overall survival (hazard ratio, 6.73; 95% confidence interval, 2.21–20.53; p=0.001). Conclusion In cervical cancer, FRα expression was elevated in metastatic tumors and high expression was associated with a worse prognosis. Our study supports the development of FRα-targeted therapy for advanced cervical cancer.