Background: Ovarian clear cell carcinoma (CCC) is often diagnosed at stage I. However, because of the poor prognosis of recurrent cases, even for stage Ia CCC, treatment strategies such as expansion of fertility-sparing treatment and omission of adjuvant chemotherapy have been carefully discussed in recent years. We previously reported the possibility of the maximum standardized uptake value (SUVmax) as a biomarker of CCC prognosis prediction at all stages. In this study, we confirmed differences in SUVmax within stage I CCC and considered treatment strategies. Methods: We selected all 31 patients with ovarian CCC stage I who underwent fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) before treatment between 2006 and 2013 at our institution. This retrospective study was based on their medical records. Results: Clinical tumor stage was Ia in 13 patients, and Ic in 18 (Ic (b) in 11, and Ic (1) + Ic (2) in seven). There were no differences in serum CA125 level, maximum tumor diameter or mural nodules. Median SUVmax was significantly higher in stage Ic (5.87) than stage Ia (3.08) cases ( P = 0.02). Progression-free survival was longer in the low SUVmax group than the high SUVmax group ( P = 0.08). Conclusions: SUVmax for primary lesions in CCC was significantly higher in stage Ic than stage Ia. As SUVmax represents a prognostic factor in stage I CCC, these findings may suggest SUVmax as an indicator for the application of fertility-sparing surgery and omission of adjuvant chemotherapy for stage Ia CCC.
Approximately 8000 patients are diagnosed annually with epithelial ovarian cancer and the number has increased in recent years in Japan. Ovarian clear cell carcinoma (CCC) is the second most common histological type after serous adenocarcinoma in Japan. The biological characteristics of epithelial ovarian cancer are known to differ depending on histological type. Serous adenocarcinoma is often diagnosed at advanced stages III and IV; however, CCC is often diagnosed at stage I because of the association of endometriosis with severe adhesion to neighboring organs [
For this study, we selected all Japanese patients with ovarian CCC stage I who underwent FDG-PET/CT prior to treatment in our hospital between January 2006 and December 2013 (n = 31). When ovarian cancer was suspected following analysis of patient history and ultrasound and pelvic examinations, FDG-PET/CT was undertaken to enable pretreatment evaluation. CCC was histologically confirmed by surgery. This retrospective comparative study was based on patient medical records for serum CA125 level, FDG-PET/CT (SUVmax) and MRI findings and histopathological diagnosis, and treatment course. For the study of SUVmax as a biomarker to predict prognosis, patients who could be tracked over 3months after their first treatment were divided into two groups based on the median SUVmax to compare survival. Statistical analysis was performed using the Mann-Whitney U test, log-rank test and Pearson’s correlation coefficient, and the level of statistical significance was P < 0.05. However, the numerical value was listed when a trend was apparent even if P < 0.09. As a retrospective and observational study, cancers were staged according to the Federation of Gynecology and Obstetrics (FIGO) 1988 staging system (
Details of the scanning were previously reported [
Median patient age was 54 years (range, 34 - 73 years). Clinical tumor stage was Ia in 13 patients, and Ic in 18 (Ic (b) in 11, and Ic (1) + I (2) in seven) (
STAGE I: Tumor confined to ovaries | ||
---|---|---|
Ia | Tumor limited to 1 ovary, capsule intact, no tumor on surface, negative washings/ascites. | |
Ib | Tumor involves both ovaries otherwise like IA. | |
Ic | Tumor involves 1 or both ovaries with any of the following: capsule rupture, tumor on surface, positive washings/ascites. | |
Ic (a) | Capsule rupture before surgery | |
Ic (b) | Surgical spill | |
Ic (1) | Malignant cells in the peritoneal washings. | |
Ic (2) | Malignant cells in the ascites |
n (%) | ||
---|---|---|
Age (median) | 54 (34 - 73) | |
Stage | Ia | 13 (42%) |
Ic(b) | 11 (35%) | |
Ic(1) | 1 (3%) | |
Ic(2) | 6 (20%) | |
Unilateral | 31 (100%) | |
Endometriosis coexist* | 26 (84%) |
*pathological findings.
There were no differences in serum CA125 level, maximum tumor diameter and mural nodules based on MRI in pathological specimens between stage Ia and Ic (
The median period from the examination of FDG-PET/CT to surgery was 17.9 days. Median ± standard error of SUVmax for primary lesions was 4.36 ± 0.43 in all 31 patients. Median ± standard error of SUVmax by clinical stage was 3.08 ± 0.49 in stage Ia, and 5.87 ± 0.59 in stage Ic, including 5.4 ± 0.50 in Ic (b) and 6.55 ± 0.78 in Ic (1) + Ic (2). SUVmax tended to increase in proportion to stage, and was significantly higher in stage Ic than Ia (P = 0.02) (
The median duration of follow-up was 60.4 months (range, 2.3 - 104 months).We divided the patients into two groups according to median SUVmax to compare progression-free survival (PFS). PFS tended to be longer in the low SUVmax group than the high SUVmax group (P = 0.08) (
Approximately 8000 patients are diagnosed with epithelial ovarian cancer each year, of which approximately 4000 patients die, and the number has increased in recent years in Japan. More than half of ovarian cancers are diagnosed at advanced stages III and IV with poor prognosis. Although the introduction of multidrug chemotherapy and molecular-targeted agents has improved survival, the five-year survival rate of advanced ovarian cancer is
Stage Ia | Stage Ic | |||||
---|---|---|---|---|---|---|
Serum | CA125 (U/ml) | 25.8 | (12 - 139) | 38.45 | (8 - 3935) | N.S |
MRI | Tumor size (cm) | 10 | (4.2 - 18) | 10 | (5.3 - 15) | N.S |
Solid part (cm) | 3 | (2 - 10) | 5.1 | (1 - 10.1) | N.S | |
Pathological | Tumor size (cm) | 10.5 | (5 - 23) | 15 | (6.5 - 19) | N.S |
findings | Solid part (cm) | 6.7 | (1.5 - 10) | 6 | (1 - 15) | N.S |
*median (range).
still 30% to 40%. Prognostic factors of advanced cancer are known to be clinical stage, maximum residual tumor size after surgery, CCC histological type and mucinous carcinoma, older age, and poor performance status [
Conversely, stage I ovarian cancer localized to the ovary accounts for approximately 40% of all ovarian cancers and has a relatively good prognosis. According to the report by the Japan Society of Obstetrics and Gynecology, the five-year survival rate is 95.5% for stage Ia, 79.4% for stage Ic (a), 93.4% for stage Ic (b), 72.9% for stage Ic (1), and 81.4% for stage Ic (2) cases [
Endometriosis is known to be associated with CCC. The most important MRI finding to indicate malignancy accompanying endometriotic cysts of the ovary is the presence of mural nodules protruding from the cyst wall. Tanaka et al. reported that the mean maximum cyst diameter was 7.8 cm (range, 3.2 - 14.2 cm) in benign cases and 11.2 cm (range, 4.0 - 19.2 cm) in malignant cases [
In general, malignant tumors have enhanced glucose metabolism, and FDG-PET/CT exploiting this characteristic has become common in recent years for diagnosis of malignant tumors [
In this study, we compared the SUVmax of primary tumors at stage I CCC, in which expansion of the indication for fertility-sparing treatment and omission of adjuvant chemotherapy have been discussed. SUVmax was significantly higher in stage Ic than stage Ia, which indicated that biological characteristics such as glucose metabolism differed even within stage I. These results are considered to support the omission of adjuvant chemotherapy and fertility-sparing surgery for stage Ia CCC in the future from the perspective of glucose metabolism. We acknowledge that there are several limitations to our study. First, the number of patients was relatively small. Second, this was a retrospective study at a single institution; however, conversely, because SUV is a semi- quantitative index and may vary from one PET center to another, a single institution study was a strong point. A larger number of patients and longer-term follow-up would improve the quality of our data, and further confirmation by a prospective trial could reinforce our findings. The possibility of SUVmax as a biomarker for treatment strategy decision needs to be further investigated.
This research was partly supported by the Practical Research for Innovative Cancer Control from Japan Agency for Medical Research and Development (AMED).
The authors declare that they have no conflict of interest.
This article does not include any studies performed on human participants or animals.
Formal consent is not required for this type of study.
HaruhisaKonishi,KazuhiroTakehara,ShinichiOkame,MasaakiKomatsu,YukoShiroyama,TakashiYokoyama,YoshifumiSugawara,11, (2016) Prognostic Significance of Fluorodeoxyglucose Positron Emission Tomography Maximum Standardized Uptake Value in Stage I Ovarian Clear Cell Carcinoma: A Retrospective Observational Study. Open Journal of Obstetrics and Gynecology,06,136-143. doi: 10.4236/ojog.2016.62017