Benedetta Guani

External beam radiotherapy boost versus surgical debulking followed by radiotherapy for the treatment of metastatic lymph nodes in cervical cancer: A systematic review and meta-analysis

We aimed to assess disease-free survival (DFS), overall survival (OS) and treatment-related toxicity of two therapeutic strategies for treating bulky lymph nodes on imaging in patients with locally advanced cervical cancer (LACC): radiotherapy boost versus surgical debulking followed by radiotherapy. We performed a systematic review of studies published up to October 2023. We selected studies including patients with LACC treated by external beam radiotherapy (EBRT) boost or lymph node debulking followed by EBRT (with or without boost). We included two comparative (included in the meta-analysis) and nine non-comparative studies. The estimated 3-year recurrence rate was 28.2% (95%CI:18.3-38.0) in the EBRT group and 39.9% (95%CI:22.1-57.6) in the surgical debulking plus EBRT group. The estimated 3-year DFS was 71.8% and 60.1%, respectively (p = 0.19). The estimated 3-year death rate was 22.2% (95%CI:11.2-33.2) in the EBRT boost group and 31.9% (95%CI:23.3-40.5) in the surgical debulking plus EBRT group. The estimated 3-year OS was 77.8% and 68.1%, respectively (p = 0.04). No difference in lymph node recurrence between the two comparative studies (p = 0.36). The meta-analysis of the two comparative studies showed no DFS difference (p = 0.13) but better OS in the radiotherapy boost group (p = 0.006). The incidence of grade≥3 toxicities (ranging 0-50%) was not different between the two approaches in the two comparative studies (p = 0.31). No DFS and toxicity difference when comparing EBRT boost with surgical debulking of enlarged lymph nodes and EBRT in patients with cervical cancer was evident. Radiotherapy boost had better OS. Further investigation is required to better understand the prognostic role of surgical lymph node debulking in light of radiotherapy developments.

ASO Author Reflections: Validation Based on Low-Volume Metastasis of the Sentinel Lymph Node Biopsy in Early-Stage Cervical Cancer

Histopathologic Validation of the Sentinel Node Technique for Early-Stage Cervical Cancer Patients

Abstract Background The sentinel lymph node (SLN) biopsy may be an alternative to systematic lymphadenectomy in early cervical cancer. The SLN biopsy is less morbid and has been shown to have high sensitivity for metastasis detection. However, the sensitivity of the SLN technique might be overevaluated because SLNs are examined with ultra-staging, and non-sentinel nodes usually are examined only with routine techniques. This study aimed to validate the negative predictive value (NPV) of the SLN technique by the ultra-staging of SLNs and non-sentinel nodes (NSLNs). Methods The SENTICOL 1 study data published in 2011 were used. All nodes (i.e., SLNs and NSLNs) were secondarily subjected to ultra-staging. The ultra-staging consisted of sectioning every 200 µm, in addition to immunohistochemistry. Moreover, the positive slides and 10% of the negative slides were reviewed. Results The study enrolled 139 patients, and SLNs were detected in 136 (97.8%) of these patiets. Bilateral SLNs were detected in 104 (76.5%) of the 136 patients. A total of 2056 NSLNs were identified (median, 13 NSLNs per patient; range 1–54). Of the 136 patients with SLNs, 23 were shown to have positive SLNs after serial sectioning and immunohistochemical staining. The NSLNs were metastatic in six patients. In the case of bilateral SLN detection, the NPV was 100%, with no false-negatives (FNs). Conclusions The pelvic SLN technique is safe and trustworthy for determining the nodal status of patients with early-stage cervical cancer. In the case of optimal mapping with bilateral detection, the NPV was found to be 100%.

Laparoscopic vaginal radical trachelectomy in the post-LACC era: step-by-step surgical procedure

Survival after sentinel lymph node biopsy for early cervical cancers: a systematic review and meta-analysis

Sentinel lymph node biopsy represents an alternative to pelvic lymphadenectomy for lymph node staging of early-stage cervical carcinoma, but prospective evidence on long-term oncological safety of sentinel lymph node biopsy alone versus pelvic lymphadenectomy is missing. To investigate, with this meta-analysis, the impact of sentinel lymph node biopsy alone versus pelvic lymphadenectomy on survival for patients with early-stage cervical cancer. A systematic literature review was performed. We excluded studies in which pelvic lymphadenectomy was systematically performed after every sentinel lymph node biopsy, including only articles where pelvic lymphadenectomy was performed because sentinel lymph node biopsy was not conclusive. A meta-analysis was carried out combining 5-year disease-free survival and overall survival rates with a random and fixed effect model. Heterogeneity was tested using the Cochran Χ The search of databases and registers found 927 items and six articles (two retrospective and four prospective). The median time of follow-up was 34.8 months (range 13-53). Overall common effect disease-free survival was 98% while random effect disease-free survival was 94%. Overall heterogeneity was 77%. A subgroup analysis was applied, dividing studies into one group including sentinel lymph node biopsy negative data only (common effect disease-free survival 91%; random effect disease-free survival 90%), and one group with a negative and positive sentinel lymph node biopsy (common effect disease-free survival 98%; random effect disease-free survival 96%). In the analysis of overall survival, positive and negative sentinel lymph node biopsy cases were examined together (common and random effect overall survival 99%). Ultrastaging did not affect disease-free survival (common and random effect disease-free survival 92% in the ultrastaging group vs common effect disease-free survival 99% and random effect disease-free survival 96% in the non-ultrastaging group). Both 5-year disease-free survival and overall survival rate after sentinel lymph node biopsy alone are higher than 90% and do not differ from pelvic lymphadenectomy survival data. Ultrastaging did not impact survival.

Consensus on surgical technique for sentinel lymph node dissection in cervical cancer

The purpose of this study was to establish a consensus on the surgical technique for sentinel lymph node (SLN) dissection in cervical cancer. A 26 question survey was emailed to international expert gynecological oncology surgeons. A two-step modified Delphi method was used to establish consensus. After a first round of online survey, the questions were amended and a second round, along with semistructured interviews was performed. Consensus was defined using a 70% cut-off for agreement. Twenty-five of 38 (65.8%) experts responded to the first and second rounds of the online survey. Agreement ≥70% was reached for 13 (50.0%) questions in the first round and for 15 (57.7%) in the final round. Consensus agreement identified 15 recommended, three optional, and five not recommended steps. Experts agreed on the following recommended procedures: use of indocyanine green as a tracer; superficial (with or without deep) injection at 3 and 9 o'clock; injection at the margins of uninvolved mucosa avoiding vaginal fornices; grasping the cervix with forceps only in part of the cervix is free of tumor; use of a minimally invasive approach for SLN biopsy in the case of simple trachelectomy/conization; identification of the ureter, obliterated umbilical artery, and external iliac vessels before SLN excision; commencing the dissection at the level of the uterine artery and continuing laterally; and completing dissection in one hemi-pelvis before proceeding to the contralateral side. Consensus was also reached in recommending against injection at 6 and 12 o'clock, and injection directly into the tumor in cases of the tumor completely replacing the cervix; against removal of nodes through port without protective maneuvers; absence of an ultrastaging protocol; and against modifying tracer concentration at the time of re-injection after mapping failure. Recommended, optional, and not recommended steps of SLN dissection in cervical cancer have been identified based on consensus among international experts. These represent a surgical guide that may be used by surgeons in clinical trials and for quality assurance in routine practice.