Hua Tu

Sentinel-Lymph-Node Biopsy Alone or with Lymphadenectomy in Cervical Cancer

Limited data are available on survival outcomes after sentinel-lymph-node biopsy alone as compared with lymphadenectomy in cervical cancer. In this multicenter, randomized, noninferiority trial, we enrolled patients with cervical cancer that was stage IA1 (with lymphovascular invasion), IA2, IB1, or IIA1 according to 2009 International Federation of Gynecology and Obstetrics criteria. Sentinel-lymph-node biopsy was performed at the time of surgery and was followed by examination of frozen sections. Patients who had negative sentinel lymph nodes were intraoperatively assigned in a 1:1 ratio not to undergo pelvic lymphadenectomy (the biopsy-only group) or to undergo lymphadenectomy (the lymphadenectomy group). All the patients underwent hysterectomy, and adjuvant therapy was provided according to a unified protocol. The primary end point was disease-free survival at 3 years, with a prespecified noninferiority margin of 5 percentage points in the upper limit of the confidence interval for the difference between the lymphadenectomy group and the biopsy-only group. Secondary end points included retroperitoneal nodal recurrence, cancer-specific survival, and surgical complications. A total of 838 patients underwent randomization: 420 patients were assigned to the biopsy-only group and 418 to the lymphadenectomy group. The median follow-up was 62.8 months. The 3-year disease-free survival was 94.6% in the lymphadenectomy group and 96.9% in the biopsy-only group (difference, -2.3 percentage points; 95% confidence interval [CI], -5.0 to 0.5; P<0.001 for noninferiority); the 3-year cancer-specific survival was 99.2% in the biopsy-only group and 97.8% in the lymphadenectomy group (hazard ratio for death from cancer in competing-risks analysis, 0.37; 95% CI, 0.15 to 0.95). Retroperitoneal nodal recurrences occurred in no patients in the biopsy-only group and in 9 patients (2.2%) in the lymphadenectomy group. The biopsy-only group had a lower incidence of lymphocyst than the lymphadenectomy group (8.3% vs. 22.0%; P<0.001), as well as a lower incidence of lymphedema (5.2% vs. 19.1%; P<0.001), paresthesia (4.0% vs. 8.4%; P = 0.009), and pain (2.6% vs. 7.9%; P = 0.001). In patients with early-stage cervical cancer, sentinel-lymph-node biopsy alone was noninferior to lymphadenectomy with respect to disease-free survival and was associated with fewer complications. (Funded by Guangzhou Municipal Science and Technology and others; PHENIX ClinicalTrials.gov number, NCT02642471.).

Perineural Invasion Should Be Regarded as an Intermediate-Risk Factor for Recurrence in Surgically Treated Cervical Cancer: A Propensity Score Matching Study

Background. Perineural invasion (PNI) is considered as a poor prognostic factor in cervical cancer, but there has been no postoperative adjuvant therapy for it, because whether it belongs to high- or intermediate-risk factors has not been determined, this study intends to provide evidences to solve this problem. Methods. We conducted a retrospective analysis of cervical cancer patients who underwent radical surgery and be reported PNI from January 2012 to June 2017 at the Sun Yat-sen University Cancer Center. After 1 : 1 propensity score matching (PSM), a group of patients without PNI was matched according to the clinical pathological features. Postoperative pathological parameters and prognosis were evaluated between the PNI and the matched groups. Results. 1836 patients were screened, of which 162 (8.8%) diagnosed as stages IB1 to IIB reported PNI. Comparing to the matched group, more PNI (+) patients had deep outer cervix stromal invasion, cervical tunica adventitia invasion, positive lymph nodes, and positive margins. Among patients without high-risk factors, PNI (+) patients had worse 3-year overall survival (90.8% vs. 98.1%, P = 0.02 ), PNI (+) patients with single intermediate-risk factor and PNI (-) patients who meet with SEDLIS criteria had similar progress free survival ( P = 0.63 ) and overall survival ( P = 0.63 ), even similar survival curves. Conclusion. PNI is related to a worse overall survival among cervical cancer patients without high-risk factors and play the role as an intermediate-risk factor.

Sentinel lymph node biopsy versus pelvic lymphadenectomy in early-stage cervical cancer: a multi-center randomized trial (PHENIX/CSEM 010)

There is no accepted strategy for applying sentinel lymph node (SLN) biopsy as an alternative to pelvic lymphadenectomy in cervical cancer. It is unclear whether and when pelvic lymphadenectomy can be safely replaced by SLN biopsy alone. To comprehensively compare the oncological outcomes of SLN biopsy with pelvic lymphadenectomy in patients with and without SLN metastasis. It is hypothesized that the oncological outcomes provided by SLN biopsy are non-inferior to those of pelvic lymphadenectomy in patients with clinically early-stage cervical cancer if risk-adapted adjuvant treatments are given. All eligible patients will undergo SLN biopsy at the start of surgery. The resected SLNs will be submitted for frozen section examination. and patients will be triaged into the PHENIX-I (SLN-negative) or PHENIX-II (SLN-positive) cohort. In each cohort of this trial, patients will be randomized in a 1:1 ratio into the experimental (SLN biopsy alone) or reference (pelvic lymphadenectomy) arm. Radical hysterectomy will be performed for all patients, and adjuvant treatments will be planned according to post-operative pathological factors. Patients aged between 18 and 65 years with histologically confirmed, untreated stage IA1 (lymphovascular space involvement), IA2, IB1, and IB2 cervical squamous carcinoma, adenocarcinoma, or adenosquamous carcinoma. The primary endpoint is disease-free survival. Estimated sample sizes of 830 and 250 are required to fulfill the study objectives of PHENIX-I and II, respectively. As of May 2020, more than 600 eligible patients have been enrolled. Enrollment is expected to be completed by December 2022, and presentation of results is expected in 2026. NCT02642471.

Neoadjuvant chemotherapy followed by radical surgery versus concurrent chemoradiotherapy in patients with FIGO stage IIB cervical cancer: the CSEM 006 study

Concurrent chemoradiotherapy is the first-line treatment for FIGO stage IIB cervical cancer. Neoadjuvant chemotherapy followed by radical surgery may provide another treatment option. To compare the therapeutic outcomes of neoadjuvant chemotherapy followed by surgery with cisplatin-based concurrent chemoradiotherapy for stage IIB cervical cancer. We hypothesize that the therapeutic effect of neoadjuvant chemotherapy combined with surgery and risk-adapted adjuvant treatment will be superior to that of concurrent chemoradiotherapy in stage IIB cervical cancer. Patients with stage IIB cervical cancer will be randomized 1:1 to neoadjuvant chemotherapy followed by surgery (Arm A) or concurrent chemoradiotherapy (Arm B). In arm A, patients will receive three cycles of paclitaxel and cisplatin followed by a type C radical hysterectomy and pelvic ±paraaortic lymphadenectomy. Patients showing progression after neoadjuvant chemotherapy will be referred to concurrent chemoradiotherapy. Adjuvant therapy will be recommended according to the presence of pathological risks. In Arm B, all patients will receive definitive concurrent chemoradiotherapy, including external beam pelvic radiotherapy combined with concurrent weekly cisplatin followed by brachytherapy. Patients between 18 and 60 years with histologically confirmed, untreated stage IIB cervical squamous carcinoma, adenocarcinoma, or adeno-squamous carcinoma. The primary endpoint is 2-year disease-free survival. An estimated sample size of 240 is required to fulfill the study objectives. As of February 2020, 115 eligible patients from four institutions have been enrolled. Enrollment is expected to be completed by December 2022. ClinicalTrials. gov identifier: NCT02595554.

Long-term outcomes of individualized management after sentinel lymph-node biopsy for vulvar cancer

The management for patients with vulvar cancer after sentinel lymph-node biopsy (SLNB) remains controversial. The aim of this study was to investigate the long-term outcomes of individualized management after SLNB for early stage vulvar cancer. The medical records of patients with vulvar cancer treated by surgery involving SLNB between 2004 and 2019 were retrospectively reviewed. During this period, the inguinofemoral lymphadenectomy (IL) were performed with individualized strategy, while the postoperative intensity-modulated radiotherapy was planned with a consistent policy. We identified 138 patients with at least one sentinel node detected, of whom 64 underwent further IL while 74 had SLNB only. Nodal metastases (pN+) were confirmed in 22 patients with IL and 16 without. Radiotherapy was scheduled with the dose of 60-70 Gy for all pN+ patients and finally completed in 15 with IL and 15 without. The median follow-up time was 56 months (6-156 months). Recurrence was observed in 24 patients, of whom 10 were pN- at primary treatment. The 3-year overall survival (OS) was 97.2, 95.2, 68.3, and 71.8%; 3-year disease-free survival (DFS) was 94.5, 91.4, 60.2, and 59.2%, respectively, for patients with pN- and IL, pN- and SLNB, pN+ and IL, and pN+ and SLNB. Neither OS nor DFS showed significant difference between SLNB and IL in pN- (P = 0.564 for OS, P = 0.423 for DFS), or pN + patients (P = 0.920 for OS, P = 0.862 for DFS). With appropriate adjuvant radiotherapy, SLNB alone provided similar long-term survival compared with IL for both patients with and without sentinel node metastasis.

Proposal for modified inguinofemoral lymphadenectomy derived from investigation of anatomic distribution of sentinel and metastatic nodes in vulvar cancer

AbstractObjectiveWe aimed to develop a less invasive inguinofemoral lymphadenectomy (IFL) approach for vulvar cancer based on the investigation of the anatomic distribution of sentinel and metastatic nodes.MethodsPatients with vulvar cancer treated by surgery between 1995 and 2019 were retrospectively reviewed. A seven‐field method was adopted to assign the anatomic locations for lymph nodes removed via IFL or sentinel node biopsy. Only patients with nodal metastasis or sentinel nodes were included.ResultsA total of 102 patients with eligible data were analyzed. Nodal metastasis was confirmed in 118 groins undergoing IFL; sentinel node detection succeeded in 46 groins. The medial‐inguinal field had the highest rate of nodal metastasis involvement (59.3%, 70/118) and sentinel nodes present (73.9%, 34/46). The inferior‐femoral field was involved only in one groin with quadruple‐field metastases. The lateral‐inguinal field was not involved in any groin. Neither the lateral‐inguinal nor the inferior‐femoral field presented sentinel nodes.ConclusionThe lateral‐inguinal and inferior‐femoral fields of the groins have a low risk of developing nodal metastasis. Therefore, a modified IFL preserving these fields can be established to reduce surgical morbidity without sacrificing its therapeutic effect.

Sentinel Lymph Node Biopsy Versus Pelvic Lymphadenectomy in Early-stage Cervical Cancer (PHENIX/CSEM 010)

The diagnostic value of sentinel lymph node biopsy in early-stage cervical cancer has been well studied. However, there were no randomized controlled study on comparing the long-term outcomes of sentinel lymph node biopsy and conventional procedure. The investigators perform a phase III, randomized controlled trial to determine whether pelvic lymphadenectomy can be replaced by sentinel lymph node biopsy in surgical treatment for patients with early-stage cervical cancer.

Neoadjuvant Chemotherapy and Radical Surgery in Stage IIB Cervical Cancer

Neoadjuvant chemotherapy (NACT) and radical surgery (RS) may have a possible better outcome to concurrent chemoirradiation (CCRT) in stage IIB cervical cancer. We try to verify such a hypothesis in terms of survival and treatment related morbidity.