Implications of para-aortic lymph node metastasis in patients with endometrial cancer without pelvic lymph node metastasis

Yukiharu Todo,Sho Takeshita,Kazuhira Okamoto,Katsushige Yamashiro,Hidenori Kato 대한부인종양학회 2017 Journal of Gynecologic Oncology Vol.28 No.5

Objective: The aim of this study was to confirm the incidence and implications of a lymphaticspread pattern involving para-aortic lymph node (PAN) metastasis in the absence of pelviclymph node (PLN) metastasis in patients with endometrial cancer. Methods: We carried out a retrospective chart review of 380 patients with endometrial cancertreated by surgery including PLN dissection and PAN dissection at Hokkaido Cancer Centerbetween 2003 and 2016. We determined the probability of PAN metastasis in patients withoutPLN metastasis and investigated survival outcomes of PLN−PAN+ patients. Results: The median numbers of PLN and PAN removed at surgery were 41 (range: 11–107)and 16 (range: 1–65), respectively. Sixty-four patients (16.8%) had lymph node metastasis,including 39 (10.3%) with PAN metastasis. The most frequent lymphatic spread pattern wasPLN+PAN+ (7.9%), followed by PLN+PAN− (6.6%), and PLN−PAN+ (2.4%). The probabilityof PAN metastasis in patients without PLN metastasis was 2.8% (9/325). The 5-year overallsurvival rates were 96.5% in PLN−PAN−, 77.6% in PLN+PAN−, 63.4% in PLN+PAN+, and53.6% in PLN−PAN+ patients. Conclusion: The likelihood of PAN metastasis in endometrial cancer patients withoutPLN metastasis is not negligible, and the prognosis of PLN−PAN+ is likely to be poor. The implications of a PLN−PAN+ lymphatic spread pattern should thus be taken intoconsideration when determining patient management strategies

Isolated tumor cells and micrometastases in regional lymph nodes in stage I to II endometrial cancer

Yukiharu Todo,Hidenori Kato,Kazuhira Okamoto,Shinichiro Minobe,Katsushige Yamashiro,Noriaki Sakuragi 대한부인종양학회 2016 Journal of Gynecologic Oncology Vol.27 No.1

Objective: The aim of this study was to clarify the clinical significance of isolated tumor cells (ITCs) or micrometastasis (MM) in regional lymph nodes in patients with International Federation of Gynecology and Obstetrics (FIGO) stage I to II endometrial cancer. Methods: In this study, a series of 63 patients with FIGO stage I to II were included, who had at least one of the following risk factors for recurrence: G3 endometrioid/serous/clear cell adenocarcinomas, deep myometrial invasion, cervical involvement, lympho-vascular space invasion, and positive peritoneal cytology. These cases were classified as intermediate-risk endometrial cancer. Ultrastaging by multiple slicing, staining with hematoxylin and eosin and cytokeratin, and microscopic examination was performed on regional lymph nodes that had been diagnosed as negative for metastases. Results: Among 61 patients in whom paraffin-embedded block was available, ITC/MM was identified in nine patients (14.8%). Deep myometrial invasion was significantly associated with ITC/MM (p=0.028). ITC/MM was an independent risk factor for extrapelvic recurrence (hazard ratio, 17.9; 95% confidence interval [CI], 1.4 to 232.2). The 8-year overall survival (OS) and recurrence-free survival (RFS) rates were more than 20% lower in the ITC/MM group than in the node-negative group (OS, 71.4% vs. 91.9%; RFS, 55.6% vs. 84.0%), which were statistically not significant (OS, p=0.074; RFS, p=0.066). Time to recurrence tended to be longer in the ITC/MM group than in the node-negative group (median, 49 months vs. 16.5 months; p=0.080). Conclusions: It remains unclear whether ITC/MM have an adverse influence on prognosis of intermediate-risk endometrial cancer. A multicenter cooperative study is needed to clarify the clinical significance of ITC/MM.

Pretreatment risk factors for parametrial involvement in FIGO stage IB1 cervical cancer

Hiroyuki Yamazaki,Yukiharu Todo,Kazuhira Okamoto,Katsushige Yamashiro,Hidenori Kato 대한부인종양학회 2015 Journal of Gynecologic Oncology Vol.26 No.4

Objective: All patients with stage IB1 cervical cancer do not need to undergo parametrectomy. Some low-risk criteria for parametrial involvement (PI) have been proposed based on pathological findings. The aim of this study was to determine pretreatment risk factors for PI in stage IB1 cervical cancer. Methods: We retrospectively reviewed 115 patients with stage IB1 cervical cancer who underwent radical hysterectomy or radical trachelectomy. Magnetic resonance imaging (MRI) was performed and serum concentrations of squamous cell carcinoma antigen (SCC-Ag) and cancer antigen 125 (CA-125) were determined in all patients before initial treatment. The following pretreatment factors were investigated: histological variant, maximum tumor diameter, tumor volume (volume index), pelvic lymph node enlargement, and serum tumor markers. Logistic regression analysis was used to select the independent risk factors for PI. Results: Eighteen of the 115 patients (15.7%) were pathologically diagnosed with PI. Multivariate analysis confirmed the following independent risk factors for PI: MRI-based tumor diameter ≥25 mm (odds ratio [OR], 9.9; 95% confidence interval [CI], 2.1 to 48.1), MRI-based volume index ≥5,000 mm3 (OR, 13.3; 95% CI, 1.4 to 125.0), and positive serum tumor markers SCC-Ag ≥1.5 ng/mL or CA-125 ≥35 U/mL (OR, 5.7; 95% CI, 1.3 to 25.1). Of 53 patients with no risk factors for PI, none had PI. Conclusion: Less radical surgery may become one of the treatment options for stage IB1 cervical cancer patients with MRIbased tumor diameter <25 mm, MRI-based volume index <5,000 mm3, and negativity for SCC-Ag and CA-125.

Incidence of metastasis in circumflex iliac nodes distal to the external iliac nodes in cervical cancer

Sho Takeshita,Yukiharu Todo,Kazuhira Okamoto,Satoko Sudo,Katsushige Yamashiro,Hidenori Kato 대한부인종양학회 2016 Journal of Gynecologic Oncology Vol.27 No.4

Objective: A causal relationship between removal of circumflex iliac nodes distal to the external iliac nodes (CINDEIN) and lower leg edema has been recently suggested. The aim of this study was to elucidate the incidence of CINDEIN metastasis in cervical cancer. Methods: A retrospective chart review was carried out for 531 patients with cervical cancer who underwent lymph node dissection between 1993 and 2014. CINDEIN metastasis was pathologically identified by microscopic investigation. After 2007, sentinel lymph node biopsy was performed selectively in patients with non-bulky cervical cancer. The sentinel node was identified using 99mTc-phytate and by scanning the pelvic cavity with a γ probe. Results: Two hundred and ninety-seven patients (55.9%) underwent CINDEIN dissection and 234 (44.1%) did not. The percentage of International Federation of Gynecology and Obstetrics stage IIb to IV (42.4% vs. 23.5%, p<0.001) was significantly higher in patients who underwent CINDEIN dissection than those who did not. CINDEIN metastasis was identified in 1.9% overall and in 3.4% of patients who underwent CINDEIN dissection. For patients with stage Ia to IIa disease, CINDEIN metastasis was identified in 0.6% overall and in 1.2% of patients who underwent CINDEIN dissection. Of 115 patients with sentinel node mapping, only one (0.9%) had CINDEIN detected as a sentinel node. In this case, the other three lymph nodes were concurrently detected as sentinel lymph nodes. Conclusion: CINDEIN dissection can be eliminated in patients with stage Ia to IIa disease. CINDEIN might not be regional lymph nodes in cervical cancer.

Therapeutic significance of full lymphadenectomy in early-stage ovarian clear cell carcinoma

Hiroyuki Yamazaki,Yukiharu Todo,Chisa Shimada,Sho Takeshita,Shinichiro Minobe,Kazuhira Okamoto,Katsushige Yamashiro,Hidenori Kato 대한부인종양학회 2018 Journal of Gynecologic Oncology Vol.29 No.2

Objectives: This study evaluated the therapeutic significance of full lymphadenectomy in early-stage ovarian clear cell carcinoma (OCCC). Methods: We retrospectively reviewed records of 127 consecutive patients with pT1/pT2 and M0 OCCC who were treated between January 1995 and December 2015. We compared survival outcomes between those who did and did not undergo para-aortic lymph node dissection (PAND), and analyzed independent prognostic factors (Cox proportional hazards model with backward stepwise elimination). Results: Of the 127 patients, 36 (28%) did not undergo lymphadenectomy; 12 (10%) patients underwent pelvic lymph node dissection (PLND) only; and 79 (62%) patients underwent both PLND and PAND. Of the 91 patients with lymphadenectomy, 11 (12%) had lymph node metastasis (LNM). The PAND− and PAND+ groups did not significantly differ in age, distribution of pT status, radiologically enlarged lymph nodes, positive peritoneal cytology, capsule rupture, peritoneal involvement, and combined chemotherapy. Cox regression multivariate analysis confirmed that older age (hazard ratio [HR]=2.1; 95% confidence interval [CI]=1.0–4.3), LNM (HR=4.4; 95% CI=1.7–11.6), and positive peritoneal cytology (HR=4.2; 95% CI=2.1–8.4) were significantly and independently related to poor disease-specific survival (DSS), but implementation of both PLND and PAND (HR=0.4; 95% CI=0.2–0.8) were significantly and independently related to longer DSS. Conclusion: Although few in number, there are some patients with early-stage OCCC who can benefit from full lymphadenectomy. Its therapeutic role should be continuously investigated in OCCC patients at potential risk of LNM.

A prediction model of survival for patients with bone metastasis from uterine cervical cancer

Hiroko Matsumiya,Yukiharu Todo,Kazuhira Okamoto,Sho Takeshita,Hiroyuki Yamazaki,Katsushige Yamashiro,Hidenori Kato 대한부인종양학회 2016 Journal of Gynecologic Oncology Vol.27 No.6

Objective: The aim of the study was to establish a predictive model of survival period afterbone metastasis from cervical cancer. Methods: A total of 54 patients with bone metastasis from cervical cancer were included in thestudy. Data at the time of bone metastasis diagnosis, which included presence of extraskeletalmetastasis, performance status, history of any previous radiation or chemotherapy, thenumber of bone metastases, onset period, and treatment were collected. Survival data wereanalyzed using Kaplan-Meier method and Cox proportional hazards model. Results: The median survival period after diagnosis of bone metastasis was 22 weeks (5months). The 26- and 52-week survival rates after bone metastasis were 36.5% and 15.4%,respectively. Cox regression analysis showed that extraskeletal metastasis (hazard ratio [HR],6.1; 95% CI, 2.2 to 16.6), performance status of 3 to 4 (HR, 7.8; 95% CI, 3.3 to 18.2), previousradiation or chemotherapy (HR, 3.3; 95% CI, 1.4 to 7.8), multiple bone metastases (HR, 1.9;95% CI, 1.0 to 3.5), and a bone metastasis-free interval of <12 months (HR, 2.5; 95% CI, 1.2to 5.3) were significantly and independently related to poor survival. A prognostic score wascalculated by adding the number of each significant factor. The 26-week survival rates afterdiagnosis of bone metastasis were 70.1% in the group with a score ≤2, 46.7% in the groupwith a score of 3, and 12.5% in the group with a score ≥4 (p<0.001). Conclusion: This scoring system provided useful prognostic information on survival ofpatients with bone metastasis of cervical cancer.

Prognostic factors for patients with cervical cancer treated with concurrent chemoradiotherapy:a retrospective analysis in a Japanese cohort

Daisuke Endo,Yukiharu Todo,Kazuhira Okamoto,Shinichiro Minobe,Hidenori Kato,Noriaki Nishiyama 대한부인종양학회 2015 Journal of Gynecologic Oncology Vol.26 No.1

Objective: Concurrent chemoradiotherapy (CCRT) is the primary treatment for locally advanced cervical cancer. We studied prognostic factors for patients treated with CCRT. Methods: We retrospectively reviewed records of 85 consecutive patients with cervical cancer who were treated with CCRT between 2002 and 2011, with external beam radiation therapy, intracavitary brachytherapy, and platinum-based chemotherapy. Survival data were analyzed with Kaplan-Meier methods and Cox proportional hazard models. Results: Of the 85 patients, 69 patients (81%) had International Federation of Gynecology and Obstetrics (FIGO) stage III/IV disease; 25 patients (29%) had pelvic lymph node enlargement (based on magnetic resonance imaging), and 64 patients (75%) achieved clinical remission following treatment. Median maximum tumor diameter was 5.5 cm. The 3- and 5-year overall survival rates were 60.3% and 55.5%, respectively. Cox regression analysis showed tumor diameter >6 cm (hazard ratio [HR], 2.3; 95% confidence interval [CI], 1.2 to 4.6), pelvic lymph node enlargement (HR, 2.2; 95% CI, 1.1 to 4.5), and distant metastasis (HR, 10.0; 95% CI, 3.7 to 27.0) were significantly and independently related to poor outcomes. Conclusion: New treatment strategies should be considered for locally advanced cervical cancers with tumors >6 cm and radiologically enlarged pelvic lymph nodes.

Long-term survival of patients with recurrent endometrial stromal sarcoma: a multicenter, observational study

Hiroyuki Yamazaki,Yukiharu Todo,Kenrokuro Mitsube,Hitoshi Hareyama,Chisa Shimada,Hidenori Kato,Katsushige Yamashiro 대한부인종양학회 2015 Journal of Gynecologic Oncology Vol.26 No.3

Objective: The aim of this study was to evaluate the clinical behavior and management outcome of recurrent endometrial stromal sarcoma (ESS). Methods: A retrospective review of charts of 10 patients with recurrent ESS was performed and relapse-free interval, relapse site, treatment, response to treatment, duration of follow-up and clinical outcome extracted. Survival outcome measures used were post-relapse survival which was defined as the time from first evidence of relapse to death from any cause. Living patients were censored at the date of last follow-up. Results: The median age and median relapse-free interval at the time of initial relapse were 51.5 years and 66.5 months, respectively. The number of relapses ranged from one to five. Sixteen surgical procedures for recurrent disease included nine (56.0%) complete resections. There was no statistically significant difference between initial recurrent tumors and second/ subsequent recurrent tumors in the rate of complete surgery (44.4% vs. 71.4%, respectively, p=0.36). Of the eleven evaluable occasions when hormonal therapy was used for recurrent disease, disease control was achieved in eight (72.7%). There was no difference between initial recurrent tumors and second/subsequent recurrent tumors in disease control rate by hormonal therapy (85.7% vs. 50.0%, respectively, p=0.49). The 10-year post-relapse survival rate was 90.0% and the overall median postrelapse survival 119 months (range, 7 to 216 months). Conclusion: Post-relapse survival of patients with ESS can be expected to be >10 years when treated by repeated surgical resection and hormonal therapy or both.

Lymphadenectomy can be omitted for low-risk endometrial cancer based on preoperative assessments

Takashi Mitamura,Hidemichi Watari,Yukiharu Todo,Tatsuya Kato,Yosuke Konno,Masayoshi Hosaka,Noriaki Sakuragi 대한부인종양학회 2014 Journal of Gynecologic Oncology Vol.25 No.4

Objective: According to the International Federation of Gynecology and Obstetrics staging, some surgeons perform lymphadenectomy in all patients with early stage endometrial cancer to enable the accurate staging. However, there are some risks to lymphadenectomy such as lower limb lymphedema. The aim of this study was to investigate whether preoperative assessment is useful to select the patients in whom lymphadenectomy can be safely omitted. Methods: We evaluated the risk of lymph node metastasis (LNM) using LNM score (histological grade, tumor volume measured in magnetic resonance imaging [MRI], and serum CA-125), myometrial invasion and extrautrerine spread assessed by MRI. Fifty-six patients of which LNM score was 0 and myometrial invasion was less than 50% were consecutively enrolled in the study in which a lymphadenectomy was initially intended not to perform. We analyzed several histological findings and investigated the recurrence rate and overall survival. Results: Fifty-one patients underwent surgery without lymphadenectomy. Five (8.9%) who had obvious myometrial invasion intraoperatively underwent systematic lymphadenectomy. One (1.8%) with endometrial cancer which was considered to arise from adenomyosis had para-aortic LNM. Negative predictive value of deep myometrial invasion was 96.4% (54/56). During the mean follow-up period of 55 months, one patient with deep myometrial invasion who refused an adjuvant therapy had tumor recurrence. The overall survival rate was 100% during the study period. Conclusion: This preoperative assessment is useful to select the early stage endometrial cancer patients without risk of LNM and to safely omit lymphadenectomy.

Risk stratification models for para-aortic lymph node metastasis and recurrence in stage IB–IIB cervical cancer

Koji Matsuo,Muneaki Shimada,Tsuyoshi Saito,Kazuhiro Takehara,Hideki Tokunaga,Yoh Watanabe,Yukiharu Todo,Kenichirou Morishige,Mikio Mikami,Toru Sugiyama 대한부인종양학회 2018 Journal of Gynecologic Oncology Vol.29 No.1

Objective: To examine the surgical-pathological predictors of para-aortic lymph node (PAN) metastasis at radical hysterectomy, and for PAN recurrence among women who did not undergo PAN dissection at radical hysterectomy. Methods: This is a retrospective analysis of a nation-wide cohort study of surgically-treated stage IB–IIB cervical cancer (n=5,620). Multivariate models were used to identify independent surgical-pathological predictors for PAN metastasis/recurrence. Results: There were 120 (2.1%) cases of PAN metastasis at surgery with parametrial involvement (adjusted odds ratio [aOR]=1.65), deep stromal invasion (aOR=2.61), ovarian metastasis (aOR=3.10), and pelvic nodal metastasis (single-node aOR=5.39 and multiple-node aOR=33.5, respectively) being independent risk factors (all, p<0.05). Without any risk factors, the incidence of PAN metastasis was 0.9%, while women exhibiting certain risk factor patterns (>20% of the study population) had PAN metastasis incidences of ≥4%. Among 4,663 clinically PAN-negative cases at surgery, PAN recurrence was seen in 195 (4.2%) cases that was significantly higher than histologically PAN-negative cases (2.5%, p=0.046). In clinically PAN-negative cases, parametrial involvement (adjusted hazard ratio [aHR]=1.67), lympho-vascular space invasion (aHR=1.95), ovarian metastasis (aHR=2.60), and pelvic lymph node metastasis (single-node aHR=2.49 and multiple-node aHR=8.11, respectively) were independently associated with increased risk of PAN recurrence (all, p<0.05). Without any risk factors, 5-year PAN recurrence risk was 0.8%; however, women demonstrating certain risk factor patterns (>15% of the clinically PAN-negative population) had 5-year PAN recurrence risks being ≥8%. Conclusion: Surgical-pathological risk factors proposed in this study will be useful to identify women with increased risk of PAN metastasis/recurrence.