In LACC, lymphatic spread typically occurs in a stepwise progression. The pattern of nodal metastasis tends to progress in a contiguous and predictable manner, starting from the lower pelvis to the upper pelvis, followed by the PANs. The regional pelvic lymph nodes become involved before the common iliac and para-aortic nodal chain and skip metastases are rare [11, 12]. In 2018, the clinical staging was revised by the FIGO Committee, and the most significant change in the existing staging system was the incorporation of nodal spread status as stage IIIC. Aslan et al. reported positive pelvic LNs in 138/154 (74.6%), positive pelvic and para-aortic LNs in 43/154 (23.3%), and positive para-aortic LNs only in 4/154 (2.2%) of the stage ⅢC1 and ⅢC2 cervical cancer patients . Patients with pelvic lymph node involvement are at a risk of occult PAN metastasis. Therefore, our prospective study only included patients with pelvic lymph node metastases diagnosed with PET-CT.
Radiographic and surgical examinations to diagnose lymph node metastasis have conflicting results. Radiographic assessment is useful, but it has low sensitivity. The criteria for lymph node involvement in CT and MRI are based on size and morphology. A node is suspicious when its shape is spherical, and the smallest diameter is greater than 10 mm. Analysis of the outcome data from the GOG trials (GOG85, GOG120, and GOG165) showed a better prognosis for patients who underwent surgical exclusion of PAN involvement compared to those who underwent radiographic determination . The results of a meta-analysis showed that both MRI and CT have low sensitivity (55.5% and 57.5%, respectively) . In a meta-analysis conducted by Kang et al., the sensitivity of PET reached 73%. However, in patients with negative morphological imaging, the sensitivity of PET-CT for the detection of microscopic lymph node metastases was much lower (almost 34%) . Another meta-analysis reported that the pooled estimates for sensitivity and specificity of PET-CT were 0.71 (95% confidence interval [CI] = 0.54–0.83) and 0.97 (95% CI = 0.93–0.98), respectively, . In our study, the sensitivity and specificity of PET-CT were 66.7% and 90.9%, respectively. In other words, 30% of the patients who underwent extended radiation for PAN metastasis diagnosed with PET-CT were over-treated. Further, 10% of the patients who did not undergo extended radiation for PAN negative diagnosed with PET-CT were under-treated.
Gouy et al. reported that the proportion of PANs showing no uptake on PET or PET-CT but were proven to be positive by histological analysis (false-negative rate) was 12%, and the proportion of pelvic nodes with uptake on PET or PET-CT at the time of lymphadenectomy was 22% . The present study also includes one false-negative case (Case 10, Fig. 1–B) and one false-positive case (Case 6, Fig. 1–A) with PET-CT. In this study, Case 10 had a high SCC antigen level (31.7 ng/mL) despite having the smallest tumor size (39 mm). The smallest size of pelvic lymph node metastases was 12 mm, and the SUVmax was 5.2. In Case 6, the SCC antigen level was low (3.4 ng/mL) despite the bulky tumor size (60 mm). The smallest size of pelvic lymph node metastases was 8 mm, and the SUVmax was 3.5. Since this study is the small number of cases, the risk of false-negatives and false-positives was unknown. Large pelvic lymph node metastases (with the smallest diameter 18 mm, 24 mm, and 26 mm) were not associated with the risk of PA lymph node metastases. The SCC antigen levels of three patients with PA lymph node metastases determined by pathological assessment were high (31.7 ng/mL, 52.5 ng/mL, 104.5 ng/mL). Our study hypothesizes that the SCC antigen level is related to PA lymph node metastases, but does not show this conclusively. Since the false-negative rate of radiographic assessment is high (33.3% in this study), laparoscopic surgical PAN staging can identify the false-negative cases of PET-CT imaging.
In our study, three patients diagnosed with PA lymph node metastases by pathological staging were treated with Ex-CCRT. These PANs were low-volume disease (≤ 5 mm). Further, Gouy et al. reported the same survival rate for patients with PAN metastases ≤ 5 mm and patients without PAN involvement. In these cases, when imaging results are negative or inconclusive, surgery remains the best means to detect nodal disease definitively . Therefore, if PA lymph node metastases with PET-CT were less than 5 mm, surgical staging could be helpful as a prognostic factor. Moreover, the absence of false-positive cases could prevent unnecessary radiation therapy, as in Case 6 of the present study.
Our surgical procedure is a laparoscopic retroperitoneal approach, similar to previous studies . The median number of lymph nodes retrieved was 19 (range, 6–36), which is more than that in the previous study. The median time in the initiation of radiotherapy was 13 days (range, 11–17 days). When there are no complications intraoperatively, CCRT can be started earlier than laparotomy. Furthermore, the incidence of complications such as gastrointestinal ulcers, perforation, and ileus increases with an extended radiation field. The usefulness of IMRT has been reported earlier . Although side effects could be reduced by IMRT in the future, laparoscopic retroperitoneal PAN with less intestinal obstruction than transperitoneal laparotomy should be the standard treatment worldwide.
In the present study, three patients (21.4%) had lymphocysts that needed CT-guided drainage; one case was symptomatic. Lymphocysts are common (11–27%), especially after retroperitoneal lymphadenectomy . Our institution performs a similar surgery for endometrial cancer, and lymphocysts have occurred in only 2.5% (1/40) of the cases. The decrease in the occurrence of lymphocysts in these cases was due to minimum opening of the posterior peritoneum. CCRT had to be delayed in these three cases; therefore, we should be careful while making the incision larger.
Most cases of PA lymph node metastases are diagnosed using CT or PET-CT. In Japan, this is the first report of a surgical assessment using laparoscopic retroperitoneal approach, before administration of CCRT. The strength of our prospective study was the use of laparoscopic retroperitoneal para-aortic lymphadenectomy for LACC with pelvic lymph node metastases diagnosed with PET-CT, which is a more appropriate eligibility criterion than those used in previous retrospective reports. The identification of a false-positive case of PET-CT prevented the overtreatment of the patient. The limitation of our study was the small number of cases because it was a single-institution study. In the future, we will conduct a multi-institution study of LACC with pelvic lymph node metastases.