Pelvic Recurrence Rate Research Articles

Value of surgery combined chemotherapy and radiation therapy in locally advanced neuroendocrine carcinoma of the cervix: a single-center retrospective cohort study

Objective: To evaluate the surgery combined chemotherapy and radiation in locally advanced neuroendocrine carcinoma of the cervix (NECC) . Methods: This is a single-center retrospective cohort study. Locally advanced NECC patients admitted to Peking Union Medical College Hospital, Chinese Acadmy of Medical Sciences from January 2011 to April 2022 were enrolled. They were divided into concurrent chemoradiotherapy group, and surgery combined with chemotherapy and radiation group. The Kaplan-Meier method was used to analyze the progression free survival (PFS), overall survival (OS), recurrence rate, and mortality rate. Results: (1) Forty-six cases were included, 22 in concurrent chemoradiotherapy group, 24 in surgery combined chemotherapy and radiation group. With 16 patients (35%, 16/46) received neoadjuvant chemotherapy (NACT), the NACT effective rate was 15/16. (2) The median follow-up time was 27.5 months (range: 10-106 months), with 26 (57%, 26/46) experienced recurrences. There were 4 (9%, 4/46) pelvic recurrences and 25 (54%, 25/46) distant recurrences, and 3 (7%, 3/46) both pelvic and distant recurrences. Compared with concurrent chemoradiotherapy group, surgery combined chemotherapy and radiation group had lower pelvic recurrence rate [14% (3/22) vs 4% (1/24); χ2=1.296, P=0.255] but without statistic difference. Both groups had similar distant recurrence rate [55% (12/22) vs 54% (13/24); χ2=0.001, P=0.979] and overall recurrence rate [59% (13/22) vs 54% (13/24); χ2=0.113, P=0.736]. (3) During the follow-up period, 22 cases (48%, 22/46) died, with 11 cases (50%, 11/22) in concurrent chemoradiotherapy group and 11 cases (46%, 11/24) in surgery combined chemotherapy and radiation group, without significant difference (χ2=0.080, P=0.777). The postoperative 3-year and 5-year OS rates were 62.3% and 36.9%. Compared with concurrent chemoradiotherapy group, the patients in surgery combined chemotherapy and radiation group showed an extended trend in PFS (17.0 vs 32.0 months) and OS (37.0 vs 50.0 months) but without statistic differences (P=0.287, P=0.125). Both groups had similar 3-year OS rate (54.2% vs 69.9%; P=0.138) and 5-year OS rate (36.1% vs 38.8%; P=0.217). Conclusions: Our study supports the multi-modality treatment strategy (including surgery, chemotherapy and radiation) as an important component in the treatment of locally advanced NECC. The combination of surgery, chemotherapy and radiation seems to have advantages in the treatment of locally advanced NECC, but needs to be confirmed by further multicenter studies.

Salvage Treatment of Recurrent or Persistent Anal Squamous Cell Carcinoma: The Role of Multi-modality Therapy

BackgroundThe standard treatment for recurrent or persistent anal squamous cell carcinoma is surgical salvage, but disease control and survival are suboptimal. Patients/MethodsPatients treated for recurrent or persistent anal squamous cell carcinoma at our institution from 2002 to 2022 were included. Patients were classified by type of salvage treatment received: surgery alone vs. reirradiation followed by surgery and by whether they received intraoperative radiation at the time of surgery. Clinical and pathologic variables were collected and assessed for association with risk of second local recurrence and death from any cause. ResultsSixty four patients were included; 55(85.9%) were treated with surgery alone and 9 (14.1%) were treated with reirradiation followed by surgery. Median (IQR) follow up from the time of salvage treatment was 40.0 (20.3-68.0) months. The 3-year cumulative incidence of second local recurrence (95% CI) after salvage surgery was 36% (24%-48%); 39% (26%-52%) for patients treated with surgery alone and 15% (0.46%-51%) for patients treated with reirradiation followed by surgery. Factors associated with increased second local recurrence after salvage surgery included a locoregional recurrence, lymphovascular space invasion and positive surgical margins. The 3-year overall survival (95% CI) after salvage surgery was 70% (59%-83%); 68% (7%-56%) after surgery alone and 89% (10.5%-70.6%) after reirradiation followed by surgery. Factors associated with worse overall survival included male sex, a larger recurrent tumor and positive surgical margins. ConclusionsApproximately 60% of patients achieved pelvic control after salvage therapy for recurrent or persistent anal squamous cell carcinoma. Although receipt of reirradiation and intraoperative radiation were not associated with improved second local recurrence or overall survival in our cohort, patients with positive surgical margins and lymphovascular space invasion on surgical pathology had higher rates of pelvic recurrence after salvage surgery and may benefit from escalated salvage therapy.

Statement of the Uterus Commission of the Gynecological Oncology Working Group (AGO) on Surgical Therapy for Patients with Stage IA2-IIB1 Cervical Cancer.

The presentation of the results of the prospective randomized international multicenter study AGO-OP.8 - CCTG CX.5 - SHAPE at the annual conference of the American Society of Clinical Oncology (ASCO) in 2023 will affect the surgical treatment of early-stage cervical cancer. In the SHAPE study, simple total hysterectomy (experimental arm) was found to be non-inferior to radical hysterectomy (standard arm) to treat patients with early-stage cervical cancer (FIGO stages [2018] IA2 - IB1 ≤ 2 cm with an infiltration depth of < 1 cm); after 3years' follow-up the pelvic recurrence rate was 2.52% (experimental arm) compared to 2.17% (standard arm) with no statistically significant difference with regards to recurrence-free survival and overall survival rates. After weighing up the results of the SHAPE study published at the conference, the Uterus Organ Commission of AGO is of the opinion that, in addition to the use of radical hysterectomy to treat patients with invasive cervical cancer which is FIGO stage IA2 - IB1 ≤ 2 cm with an infiltration depth of < 1 cm, simple total hysterectomy may also be considered for primary surgical therapy on a case-by-case basis after suitable explanation of the associated risks. It will be necessary to wait for the data of the full publication before discussing whether this approach should be included in official guidelines and defining it as a new therapy standard.

Value of postoperative radiotherapy and analysis of prognostic factors in early-stage neuroendocrine carcinoma of cervix

Objective: To evaluate the effect of postoperative radiotherapy and high-risk pathological factors on the prognosis of early-stage neuroendocrine carcinoma of cervix (NECC). Methods: A single-center retrospective cohort study of early-stage NECC in Peking Union Medical College Hospital from January 2011 to April 2022 were enrolled. The patients were treated with radical hysterectomy±adjuvant treatment. They were divided into postoperative non-radiation group and postoperative radiation group. The possible postoperative recurrence risk factors identified by univariate analysis were assessed using multivariate logistic regression. The Kaplan-Meier method was used to analyze the progression free survival (PFS), overall survival (OS), recurrence rate, and mortality rate. Results: (1) Sixty-two cases were included in the study, including 33 cases in postoperative non-radiation group and 29 cases in postoperative radiation group. (2) The median follow-up time was 37 months (ranged 12-116 months), with 23 cases (37%) experienced recurrences. There were 7 cases (11%) pelvic recurrences and 20 cases (32%) distant recurrences, in which including 4 cases (6%) both pelvic and distant recurrences. Compared with postoperative non-radiation group, the postoperative radiation group had a lower pelvic recurrence rate (18% vs 3%; P=0.074) but without statistic difference, a slightly elevated distant recurrence rate (24% vs 41%; P=0.150) and overall recurrence rate (33% vs 41%; P=0.513) without statistically significances. Univariate analysis showed that lymph-vascular space invasion and the depth of cervical stromal invasion≥1/2 were risk factors for postoperative recurrence (all P<0.05). Multivariate analysis showed lymph-vascular space invasion was an independent predictor for postoperative recurrence (OR=23.03, 95%CI: 3.55-149.39, P=0.001). (3) During the follow-up period, 18 cases (29%, 18/62) died with tumor, with 10 cases (30%, 10/33) in postoperative non-radiation group and 8 cases (28%, 8/29) in postoperative radiation group, without significant difference (P=0.814). The postoperative 3-year and 5-year survival rate was 79.2%, 60.8%. The depth of cervical stromal invasion≥1/2 was more common in postoperative radiation group (27% vs 64%; P=0.011), and postoperative radiation in such patients showed an extended trend in PFS (32.3 vs 53.9 months) and OS (39.4 vs 73.4 months) but without statistic differences (P=0.704, P=0.371). Compared with postoperative non-radiation group, the postoperative radiation did not improve PFS (54.5 vs 37.3 months; P=0.860) and OS (56.2 vs 62.4 months; P=0.550) in patients with lymph-vascular space invasion. Conclusions: Postoperative radiation in early-stage NECC patients has a trend to reduce pelvic recurrence but not appear to decrease distant recurrence and overall recurrence, and has not improved mortality. For patients with the depth of cervical stromal invasion≥1/2, postoperative radiation has a trend of prolonging OS and PFS but without statistic difference. Lymph-vascular space invasion is an independent predictor for postoperative recurrence, but postoperative radiation in such patients does not seem to have any survival benefits.

An international randomized phase III trial comparing radical hysterectomy and pelvic node dissection (RH) vs simple hysterectomy and pelvic node dissection (SH) in patients with low-risk early-stage cervical cancer (LRESCC): A Gynecologic Cancer Intergroup study led by the Canadian Cancer Trials Group (CCTG CX.5-SHAPE).

LBA5511 Background: In the last 2 decades, there has been a trend towards less radical surgery in patients with low-risk cervical cancer. Retrospective data suggested that less radical surgery may be safe and associated with less morbidity. The objective of this non-inferiority phase III prospective randomized trial was to compare RH to SH in women with LRESCC. Methods: Women with LRESCC defined as stage 1A2 or 1B1 with lesion ≤ 2cm were randomized to RH or SH after stratification by cooperative group, intended use of sentinel node mapping, stage, histological type, and tumour grade. The primary endpoint was pelvic recurrence rate at 3 years (PRR3). Non-inferiority of SH to RH is claimed when the 95% upper one-sided confidence limit (95% UCL) for the difference in PRR3 of SH to RH (DPRR3), calculated by the Kaplan-Meier method for pelvic-relapse free survival, is lower than or equal to 4%. Primary intention to treat (ITT) analysis included all patients randomized. Per-protocol (PP) analysis included patients eligible at baseline and without evidence of more advanced disease found at the time of surgery or final pathology, based on treatment received. Secondary endpoints included extrapelvic relapse-free survival (ERFS), overall survival (OS), and quality of life (QoL). Results: 700 women (12 countries, 130 centers) were enrolled from December 2012 to November 2019. Patient characteristics were well balanced: median age was 44 (24-80); 91.7% were stage 1B1 and 61.7% had squamous histology. 50% of the hysterectomies were done laparoscopically (56% SH vs. 44% RH), 25% robotically (24% vs. 25%) and 23% abdominally (17% vs. 29%). 4.4% of patients had lymph node metastasis (4.1% SH and 5.1% RH) and 3.1% had extrauterine extension (2.6% SH and 3.7% RH). A total of 8.8% of women received post-surgical adjuvant therapy (9.2% SH and 8.4% RH). With a median follow-up of 4.5 years, 21 pelvic recurrences were identified (11 SH and 10 RH). The PRR3 was 2.5% with SH and 2.2% with RH (DPRR3 0.35% with 95% UCL 2.32%) in ITT analysis; 2.8% with SH and 2.3% with RH (DPRR3 0.42% with 95% UCL 2.56%) in PP analysis. The 3-year ERFS and OS were respectively 98.1% and 99.1% with SH; 99.7% and 99.4% with RH. RH had significantly higher surgery related incidence of urinary incontinence (11.0% vs. 4.7% with SH; p=0.003) and urinary retention (9.9% vs. 0.6% with SH; p&lt;0.0001) during follow-up. QoL scales with significant difference between the two groups over time were all in favor of SH. Conclusions: The pelvic recurrence rate at 3 years in women with low risk early-stage cervical cancer who underwent a simple hysterectomy is not inferior to those who received a radical hysterectomy. Fewer surgical complications and better quality of life were observed with SH. Clinical trial information: NCT01658930 .

CCTG EN10: A phase II study of tailored adjuvant therapy in POLE-mutated and p53-wildtype/NSMP early-stage endometrial cancer (EC)—RAINBO BLUE and TAPER.

TPS5632 Background: Molecular classification of EC provides an opportunity to personalize treatment for patients with early disease based on prognosis. We hypothesize that de-escalated adjuvant treatment in patients with early-stage POLE-mutated ( POLEmut) or p53wt/NSMP (p53 wildtype/no specific molecular profile) EC is feasible and associated with favourable disease control, QOL and health economics. Methods: EN.10 is a Canadian Cancer Trials Group led phase II trial that enrolls two independent cohorts of patients with early stage EC based on tumour molecular status: POLEmut (substudy A) and p53wt/NSMP (substudy B). The primary objective is to estimate the 3-year rate of pelvic recurrence. Secondary objectives include estimated 3-year isolated vaginal recurrence, para-aortic recurrence, distant metastasis, survival (recurrence-free, EC-specific, overall survival) and to describe the patient decisional conflict and fear of recurrence. Tertiary objectives: QOL, economic evaluation and interrogation/discovery of additional prognostic biomarkers. Statistical Design: Registration to Substudy A or B is based on molecular classification. Treatment will be deescalated in both substudies; to surveillance-only (all early stage POLEmut, and a proportion of NSMP), or vaginal brachytherapy (proportion of NSMP), with NSMP stratification based on histological grade, and lymphovascular invasion. Substudy A can enroll endometrioid, serous, clear cell, un/dedifferentiated and carcinosarcomas whereas Substudy B is confined to endometrioid histotype. Both arms require ECOG 0-2 and hysterectomy+BSO with nodal assessment required for stage II and grade 3 EC. A total of 120 patients with POLEmut (Sub-study A) and 180 with p53wt/NSMP ER+ (Sub-study B) EC will be recruited in 3 years. If the upper 95% confidence limit is less than 5% in either of Substudy A, Cohort A1 and Sub-study B or both, it will be concluded that patients in one or both groups have an acceptable low risk of pelvic recurrence at 3 years with molecularly-tailored de-escalated adjuvant treatment An additional estimated 25 patients with higher risk POLEmut EC will be enrolled for an exploratory analysis. Conduct to Date: Study activation Dec 19 2022. Enrollment January 31, 2023: 36 Supported by Canadian Cancer Society, Canadian Institutes of Health Research, Gynecologic Cancer Initiative, BC Cancer Foundation. Clinical trial information: NCT05640999 .

The role of postoperative radiation after radical hysterectomy for women with early-stage neuroendocrine carcinoma of the cervix: A meta-analysis

IntroductionNeuroendocrine carcinoma of the cervix (NECC) is an aggressive disease with high rates of nodal disease spread even in seemingly cervix-confined disease. Many providers routinely prescribe postoperative radiation therapy in an effort to reduce recurrences despite a lack of supporting studies. The objective of this study was to determine recurrence and mortality in patients with early-stage NECC who had pelvic radiation after radical hysterectomy compared to those who did not receive radiation. MethodsWe performed a meta-analysis of 13 unique studies that reported recurrence and/or mortality for patients with early-stage NECC who underwent radical hysterectomy with or without adjuvant radiation therapy. ResultsIn 5 studies that reported overall recurrence rates, 63 (52.5%) of 120 patients who received postoperative radiation recurred compared to 70 (37.8%) of 185 patients who did not (RR 1.21, 95% CI: 0.85–1.70, p = 0.29). In 5 studies that reported pelvic recurrence rates, there were 15 pelvic recurrences (12.5%) in the 120 patients who received postoperative radiation compared to 45 pelvic recurrences (24.3%) in the 185 patients who did not (RR 0.60, 95% CI: 0.34–1.08, p = 0.09). In 13 studies that reported mortality rate, there were 138 deaths (34.8%) in 396 patients who received postoperative radiation therapy compared to 223 (35.2%) in 632 patients who did not (RR 1.08, 95% CI: 0.75–1.56, p = 0.66). ConclusionsThe addition of routine postoperative radiation therapy in all patients with early-stage NECC after radical hysterectomy may reduce pelvic recurrences but does not appear to decrease overall recurrence or death. However, there may still be a role for postoperative radiation therapy in patients with additional high-risk pathologic factors.

Effects of colpotomic approaches on prognosis and recurrence sites of stage Ⅰa2-Ⅱa2 cervical cancer after laparoscopic radical hysterectomy

Objective: To investigate the factors affecting the prognosis of stage Ⅰa2-Ⅱa2 cervical cancer after laparoscopic radical hysterectomy (LRH), and to compare the prognosis and recurrence sites of patients with different colpotomy paths. Methods: The clinical data of 965 patients with stage Ⅰa2-Ⅱa2 cervical cancer who underwent LRH in the First Affiliated Hospital of Army Medical University from January 2015 to December 2018 were collected. The median age was 47.0 years of all patients with a median follow-up of 62 months (48-74 months). Cox regression was used to perform the univariate and multivariate analysis of the clinicopathological factors associated with the prognosis that included disease-free survival (DFS) and overall survival (OS). Patients were categorized into LRH through vaginal colpotomy (VC group, n=475) and LRH through intracorporeal colpotomy (IC group, n=490) according to the colpotomic approaches. The prognosis and recurrence sites of patients in each group were compared. Results: (1) During the follow-up period, 137 cases recurred (14.2%, 137/965) and 98 cases died (10.2%, 98/965). The 5-year DFS and OS were 85.8% and 89.9%, respectively. In univariate analysis, positive vaginal margin (PVM) was significantly affected the 5-year OS of patients with cervical cancer (P=0.023), while clinical stage, maximum diameter of tumor, degree of pathological differentiation, lymph node metastasis (LNM), depth of cervical stromal invasion, parametrium involvement, and uterine corpus invasion (UCI) were significantly associated with 5-year DFS and OS in patients with cervical cancer (all P<0.05). In multivariate analysis, clinical stage (HR=1.882, 95%CI: 1.305-2.716), LNM (HR=2.178, 95%CI: 1.483-3.200) and UCI (HR=3.650, 95%CI: 1.906-6.988) were independent risk factors of 5-year DFS (all P<0.001). Clinical stage (HR=2.500, 95%CI: 1.580-3.956), LNM (HR=2.053, 95%CI: 1.309-3.218), UCI (HR=3.984, 95%CI: 1.917-8.280), PVM (HR=3.235, 95%CI: 1.021-10.244) were independent risk factors of 5-year OS (all P<0.05). (2) Different colpotomy paths did not significantly affect the 5-year DFS and OS of patients with stage Ⅰa2-Ⅱa2 cervical cancer. The 5-year DFS in VC group and IC group were 85.9% and 85.6% (P=0.794), and the 5-year OS were 90.8% and 89.3% (P=0.966), respectively. Recurrence patterns consisted of intraperitoneal recurrence, pelvic recurrence, vaginal stump recurrence, and lymph node and distant metastasis. The intraperitoneal recurrence rate of VC group was significantly lower than that of IC group [0.6%(3/468) vs 2.3% (11/485), P=0.037], while the rates of pelvic recurrence, vaginal stump recurrence, lymph node and distant metastasis and overall recurrence were not significantly different between two groups (all P>0.05). Subgroup analysis of patients with different clinical stages, LNM and UCI showed that statistical differences of the intraperitoneal recurrence rates between two groups were only in patients without LNM (0.5% vs 2.3%, P=0.030) or without UCI (0.7% vs 2.3%, P=0.037). Conclusions: Clinical stage, LNM, PVM and UCI are independent risk factors for the prognosis of patients with stage Ⅰa2-Ⅱa2 cervical cancer. For patients without LNM or UCI, LRH through VC could reduce the intraperitoneal recurrence rate, while it is not enough to improve 5-year DFS and OS of patients. Low proportion of intraperitoneal recurrence, intra-operative tumor cells spillage to vagina stump and pelvic cavity might be the explanation.

Lymph-vascular Space Involvement and/or p53 Overexpression Correlated With the Clinical Outcome of Early-stage Endometrial Cancer Patients Treated With Adjuvant Vaginal Brachytherapy.

The majority of patients with endometrial cancer (EC) are diagnosed at an early stage and undergo primary surgery, followed by observation or adjuvant therapy according to risk factors on surgical samples. The objective of this study was to assess the correlation between a risk profile represented by the presence of substantial lymph-vascular space involvement (LVSI) and/or p53 overexpression and the clinical outcome of patients with early-stage endometrial cancer (EC) who received adjuvant vaginal brachytherapy (BT). This investigation assessed 79 patients who underwent hysterectomy, bilateral salpingo-oophorectomy, and pelvic and/o aortic lymphadenectomy or sentinel lymph node biopsy followed by hypofractionated (HDR)-vaginal BT, using 192Ir source, for stage I-II endometrioid (n=70) or non-endometrioid (n=9) EC. Thirty-four patients (43.0%) were considered to have an unfavorable risk profile defined by the presence of substantial LVSI and /or p53 overexpression. Five-year disease-free survival (DFS) and five-year overall survival (OS) were 93.7% and 95%, respectively. There was a significant correlation between unfavorable risk-profile and pelvic recurrence rate (p=0.002) and distant recurrence rate (p=0.017). Patients with abnormal p53 had a higher risk of local relapse (p=0.041). Substantial LVSI was strongly associated with pelvic recurrence (p=0.001) and distant metastasis (p<0.001). The presence of substantial LVSI and/or p53 overexpression strictly correlated with poor outcome of patients with early-stage EC and should be taken into consideration for better planning adjuvant treatment in this clinical setting.

Evaluation of vaginal brachytherapy for treating early-stage endometrial cancer according to the European Society of Medical Oncology 2020 risk stratification.

The aim was to evaluate vaginal brachytherapy (VB) after surgery in early-stage endometrial cancer. The patients with Stage I-II endometrial adeno-cancer operated between 1998 and 2018 and whose adjuvant therapies had been arranged were evaluated retrospectively. A total of 618 patients were enrolled. In 409 patients in the low-risk group, the vaginal, pelvic recurrence, and distant metastasis rates were found to be higher in the VB group. When the results of 112 patients in the intermediate-risk group were evaluated, there was no statistically significant difference between the vaginal, pelvic recurrence, and distance metastasis rates. In 89 patients in the intermediate-high risk group, vaginal recurrence rates were 0%, 4.8%, 0%, and 25% for VB, external beam radiotherapy, combination radiotherapy, and the follow-up groups, respectively (p=0.010), and pelvic recurrence rates were found to be 18.2%, 0%, 1.9% and 0% (p=0.036). Distant metastasis rates were 0%, 0%, 9.6% and 0% (p=0.229). When the overall survival in all groups was examined, no significant difference was found between the groups. In conclusion, no adjuvant treatment is a proper approach for low-risk patients. Brachytherapy can be considered a suitable option for the intermediate risk group. Combined treatments instead of VB in the high-intermediate risk group would be preferred in terms of local control.

5 year oncological outcomes of the HIGHLOW randomized clinical trial

IntroductionThe oncological outcomes of low ligation (LL) compared to high ligation (HL) of the inferior mesenteric artery (IMA) during low-anterior rectal resection (LAR) with total mesorectal excision are still debated. The aim of this study is to report the 5 year oncologic outcomes of patients undergoing laparoscopic LAR with either HL vs. LL of the IMA Materials and methodsBetween June 2014 and December 2016, patients who underwent elective laparoscopic LAR + TME in 6 Italian non-academic hospitals were randomized to HL or LL of IMA after meeting the inclusion criteria (HighLow trial; ClinicalTrials.gov Identifier NCT02153801). We analyzed the rate of local recurrence, distant metastasis, overall survival, disease-specific survival, and disease-free survival at 5 years of patients previously enrolled. ResultsFive-year follow up data were available for 196 patients. Recurrence happened in 42 (21.4%) of patients. There was no statistically significant difference in the distant recurrence rate (15.8% HL vs. 18.9% LL; P = 0.970) and pelvic recurrence rate (4,9% HL vs 3,2% LL; P = 0.843). No statistically significant difference was found in 5-year OS (p = 0.545), DSS (p = 0.732) or DFS (p = 0.985) between HL and LL. Low vs medium and upper rectum site of tumor, conversion rate, Clavien-Dindo post-operative grade ≥3 complications and tumor stage were found statistically significantly associated to poor oncological outcomes in univariate analysis; in multivariate analysis, however, only conversion rate and stage 3 cancer were found to be independent risk factors for poor DFS at 5 years. ConclusionWe confirmed the results found in the previous 3-year survival analysis, the level of inferior mesenteric artery ligation does not affect OS, DSS and DFS at 5-year follow-up.

Cancer de l’endomètre de stade localisé : la perspective d’une désescalade thérapeutique guidée par la classification moléculaire

In Europe, endometrial cancer is the fourth most common cancer among women. The majority of patients are diagnosed at a localized stage. For these patients, the standard of care is based on an hysterectomy with salpingo oophorectomy±lymph node staging. Through the assessment of histopathologic features, risk groups are determined: low, intermediate, high-intermediate, and high risk. Adjuvant strategies are guided by these risk groups. While the prognosis of low-risk and high-risk is well known, that of intermediate and high-intermediate risk is more heterogeneous, and the therapeutic index of adjuvant treatments is more questionable. Several trials (PORTEC [Post Operative Radiation Therapy in Endometrial Carcinoma] I, GOG [Gynecologic Oncology Group] 99, ASTEC [A Study in the Treatment of Endometrial Cancer] EN.5, PORTEC II, Sorbe et al trial) have assessed observation, vaginal cuff brachytherapy and/or pelvic external beam radiotherapy in this population. Vaginal cuff brachytherapy reduces the local recurrence rate, and pelvic external beam radiotherapy the pelvic recurrence rate. However, no benefit in terms of overall survival or occurrence of distant metastases is highlighted. Compared to observation, brachytherapy and above all external beam radiotherapy are associated with an increased morbidity, and with a decreased quality of life. In order to improve the therapeutic ratio and to optimize medico-economic decisions, therapeutic de-escalation strategies, based on the molecular profiles, are emerging in clinical trials, and in the recommendations for the management of intermediate and high-intermediate risk endometrial cancers. The four main molecular profiles highlighted by the genomic analyzes of The Cancer Genome Atlas (TCGA) – POLE (polymerase epsilon) mutation, non-specific molecular profile, MMR (MisMatch repair) deficiency, and p53 mutation – but also the quantification of lymphovascular space invasion (absent, focal or substantial), and the assessment of L1CAM (L1 cell adhesion molecule) overexpression represent growing concerns. Thus, the use of molecular-integrated risk profile to determine the best adjuvant treatment represent a major way to personalize adjuvant treatment of endometrial cancers, with therapeutic de-escalation opportunity for around half of the high-intermediate risks. However, in the absence of prospective data, inclusion in clinical trials assessing molecular profile-based treatment remains the best therapeutic opportunity.

The effect of adjuvant radiotherapy on oncological outcomes in patients with early-stage cervical carcinoma with only intermediate-risk factors: a propensity score matching analysis

We aimed to evaluate whether adjuvant radiotherapy had a survival benefit for patients with early-stage cervical carcinoma with intermediate-risk factors. This study included patients who underwent radical hysterectomy and lymphadenectomy according to Wertheim–Okabayashi for stage IB1-IIA2 cervical carcinoma. Each patient had at least one intermediate-risk factor including tumour diameter ≥4 cm, deep stromal invasion, and positive lymphovascular space invasion (LVSI). Patients with lymph node metastasis, parametrial invasion, and positive surgical margins according to the final paraffin section were excluded. In total, 183 patients were included. Seventy-three (39.9%) patients had one, 85 (46.4%) had two, and 25 (13.7%) had three intermediate risk factors. Sixty-seven (36.6%) patients received adjuvant radiotherapy. There was a statistically significant difference in terms of stage, LVSI, and endometrial/uterine invasion between the groups that did and did not receive adjuvant radiotherapy (p = .024, p = .018, and p = .001, respectively). These two groups were homogenised by performing propensity score matching (PSM) analysis. In the new matched cohort (n = 134), 5-year disease-free survival (DFS) was 89.5% in the group that received adjuvant radiotherapy and 82% in the group that did not (HR: 0.484, 95% CI: [0.171–1.369]; p = .171). Also, receiving adjuvant radiotherapy was not associated with an improvement in oncologic outcomes in patients with one, two, or more intermediate risk factors. In univariate analysis, none of the risk factors was associated with DFS. In conclusion, adjuvant radiotherapy had no favourable effect on survival outcomes in patients with early-stage cervical carcinoma with only intermediate risk factors. IMPACT STATEMENT What is already known on this subject? Radiotherapy after radical hysterectomy in cervical carcinoma is accepted as the standard of care when high-risk factors – positive surgical margins, lymph node metastasis, and parametrial involvement – are found in the surgical specimen. However, the necessity of adjuvant radiotherapy in patients with intermediate-risk factors – deep stromal invasion, positive LVSI, tumour diameter ≥4 cm – is controversial. What do the results of this study add? We compared patients who received adjuvant radiotherapy and those who did not. No significant difference was found between the two groups in terms of oncologic outcomes. There was no difference between the two groups in terms of pelvic and extrapelvic recurrence rates. The number of positive intermediate-risk factors did not affect survival. Moreover, age, tumour type, stage, number of removed lymph nodes, grade, bilateral salpingo-oophorectomy, and endometrial/uterine invasion were not associated with DFS among patients with stage IB–IIA cervical carcinoma with only intermediate-risk factors. What are the implications of these findings for clinical practice and/or further research? Debate remains over the prognostic factors and the adjuvant treatment options in patients with early-stage cervical carcinoma who possess intermediate-risk factors. Adjuvant radiotherapy can be ignored if initial adequate surgery has been performed in this patient group.

Estro-Progestins and Pain Relief in Endometriosis

Endometriosis is a benign, hormone-responsive chronic disease that affects women of reproductive age; long-term treatment to balance satisfactory tolerability with clinical efficacy is necessary for these patients. The first-line therapy for endometriosis is predominantly medical treatment, in order to improve symptoms or prevent post-surgical disease recurrence. Multiple factors including age and women preference, pain severity, and endometriosis stage must be considered in the choice of the most suitable therapy. Estrogen-progestogins are generally used as first-line hormone therapies among different medical options currently effective for endometriosis management. Several studies have shown that they are able to improve pain symptoms in most patients, are well tolerated, and are inexpensive. Combined hormonal contraception treatment, administered cyclically or continuously, with different types of hormones and route of administration, results in clinically noticeable decrease in dysmenorrhea, noncyclic pelvic pain, dyspareunia, and recurrence rate after surgery, and also in quality of life improvement.

Effect of tumor morcellation in patients with early uterine sarcoma: a multicenter study in Germany

Objective:The use of power morcellation at laparoscopy may worsen survival rates for patients with malignancy. The aim of the present study was to report the outcome of patients with early-stage uterine sarcoma after morcellation or total en-bloc resection, and evaluate potential signs of sarcoma preoperatively.Material and Methods:This multicenter retrospective study consisted of patients, who underwent surgery for FIGO-stage-1 uterine sarcoma. Twenty-four patients were divided into a non-morcellation group and a morcellation group. Clinical records and the outcomes of patients, including one-, three- and five-year survival rates were reviewed. Preoperative characteristics of patients with sarcoma were compared to those of a control group with uterine myoma (1:4 ratio), matched by age and type of operation.Results:Obesity was an independent risk factor for uterine myoma. Tumor growth, solitary growth, largest-diameter lesion >8.0 cm, and anechoic areas suggesting necrosis and increased vascularization were significantly more common in the sarcoma group. A large tumor diameter was significantly associated with mortality. Patients in the non-morcellation group had a slightly lower disease-free survival, but poorer overall survival (OS) rates compared to patients in the morcellation group, but neither difference was statistically significant. Patients in the non-morcellation group, who had undergone a re-exploration experienced late recurrence, but no upstaging was evident after the operation.Conclusion:Preoperative ultrasound characteristics could be useful to distinguish sarcoma from leiomyoma of uterus. Morcellation of a sarcoma may increase abdominal and pelvic recurrence rates, but may not be associated with OS in patients with FIGO-stage-1 disease.

Laparoscopic versus open lateral pelvic lymph node dissection in locally advanced rectal cancer: multicentre retrospective cohort study.

BackgroundLateral pelvic lymph node dissection (LPLND) is an option in the treatment of rectal cancer and may reduce local recurrence/improve disease-free survival. Advancements in minimally invasive technology have improved the ability to identify anatomy and neurovascular structures that may help in LPLND. The aim of this retrospective study was to evaluate the technical feasibility and oncological safety of laparoscopic LPLND compared with the open LPLND.MethodBetween July 2010 and July 2019, patients from three tertiary referral hospitals who underwent LPLND with total mesorectal excision for primary rectal cancer were included. Baseline patient characteristics, perioperative outcomes, pathologic results, recurrence, and survival were compared between the laparoscopic and open groups.ResultsThere were 126 and 70 patients in the laparoscopic and open groups respectively. The laparoscopic group had less estimated blood loss (100 ml versus 300 ml, P < 0.001) and lower transfusion rate (0.8 per cent versus 10.0 per cent; P = 0.003) but longer operating times (318 min versus 270 min, P = 0.004). The laparoscopic group had fewer wound infections (1.6 per cent versus 10.0 per cent, P = 0.011) and neuropathy (0 per cent versus 4.3 per cent, P = 0.044). Lateral pelvic recurrence rate was 7.6 per cent in the laparoscopic group and 19.6 per cent in the open group (P = 0.053). Recurrence-free survival (72.2 per cent versus 63.5 per cent; P = 0.190) and overall survival (93.3 per cent versus 85.0 per cent; P = 0.118) were not significantly different.ConclusionLaparoscopic LPLND was associated with improved perioperative outcomes and non-inferior oncological outcomes.

Meta-analysis of Elective Pelvic Nodal Irradiation Using Moderate Hypofractionation for High-Risk Prostate Cancer

Despite several advances in planning and delivery of radiation therapy (RT) for prostate cancer, the role of elective pelvic nodal irradiation (EPNI) remains controversial for high-risk disease. We performed a meta-analysis to evaluate the outcomes of patients treated with moderate hypofractionated RT (MHF-RT) with EPNI using modern RT techniques. Eligible studies were identified on MEDLINE, Embase, the Cochrane Library, and proceedings of annual meetings through October 2021. We followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) and MOOSE (Meta-analyses of Observational Studies in Epidemiology) guidelines. A metaregression analysis was performed to assess a possible correlation between selected variables and outcomes. A P value <.05 was considered significant. Eighteen studies with a total of 1745 patients (median follow-up, 61 months) treated with EPNI using MHF-RT were included. The biochemical relapse-free survival at 5, 7, and 10 years was 90% (95% confidence interval [CI], 88%-94%), 83% (95% CI, 78%-91%), and 78% (95% CI, 68%-88%). The 5-year prostate cancer-specific survival, disease-free survival, distant metastases-free survival, and overall survival were 98% (95% CI, 97%-99%), 88.7% (95% CI, 85%-93%), 91.2% (95% CI, 88%-92%), and 93% (95% CI, 90%-96%), respectively. The rates of local, pelvic, and distant recurrence were 0.38% (95% CI, 0%-2%), 0.13% (95% CI, 0%-1.5%), and 7.35% (95% CI, 2%-12%), respectively. The rate of late grade ≥2 gastrointestinal and genitourinary toxic effects were 6.7% (95% CI, 4%-9%) and 11.3% (95% CI, 7.6%-15%), with heterogeneity, but with rare cases of grade 3 to 5 toxic effects. EPNI with concomitant MHF-RT provides satisfactory biochemical relapse-free survival in long-term follow-up, with low rates of genitourinary and gastrointestinal severe toxic effects and minimal pelvic and local failure.

Uterine papillary serous and clear cell carcinomas: Comparison of characteristics and clinical outcomes.

To assess the rate of disease control and survival after adjuvant treatment in patients with uterine papillary serous (PSC) and clear cell carcinoma (CCC) and compare the results between these two subtypes. The medical charts of 199 patients with de novo uterine PSC or CCC who underwent radiotherapy (RT) following surgery between 2001 and 2019 in three radiation oncology departments were retrospectively evaluated. Adjuvant treatment was decided by a multidisciplinary tumor board. All patients were planned to undergo adjuvant 4-6 cycles of chemotherapy with external beam RT (EBRT) and/or vaginal brachytherapy (VBT). Median age was 63 years for all, 64 years for PSC, and 59 years for CCC, respectively. Complete surgical staging was applied in 98% of patients. Histopathologic subtype was PSC in 142 (71%) and pure CCC in 57 (29%) patients, respectively. FIGO stage was I in 107 (54%), II in 35 (18%), and III in 57 (28%) patients, respectively. Lympho-vascular space invasion and positive peritoneal cytology (PPC) were present in 42% and 10% of patients, respectively. All patients but 23 (12%) underwent adjuvant chemotherapy. Median follow-up was 49.5months for all patients, 43.9months for patients with PSC, and 90.4months for patients with CCC, respectively. During follow-up, 20 (10%) patients developed pelvic recurrence (PR) and 37 (19%) developed distant metastasis (DM). PSC subtype increased the PR and DM rates, although the latter not statistically significant. The 5-year overall survival and disease-free survival rate was 73% and 69% for all patients, 71% and 66% for patients with PSC, and 77% and 75% for patients with CCC, respectively. The difference was more prominent in patients with stage ≥ IB disease. In multivariate analysis, advanced age and PPC significantly decreased all survival rates. PSC has a worse prognosis than CCC with regard to pelvic and distant recurrence with a trend for decreased survival rates. Therefore, a more aggressive therapy is needed for patients with uterine PSC, particularly in patients with stage ≥ IB disease.

Factors predictive of parametrial boost in patients with cervical cancer treated with definitive chemoradiation

ObjectiveThe aim of this study is to identify demographic, clinical, and treatment-related characteristics associated with the prescription of parametrial boost (PMB) in cervical cancer patients undergoing definitive chemoradiation. Materials/MethodsA retrospective chart review of 132 non-metastatic cervical cancer patients treated with definitive chemoradiation from May 2017 to December 2019 was performed. Demographic, clinical, and treatment characteristics were obtained and compared between those who received PMB and those who did not. Clinical outcomes (pelvic recurrence, tumor persistence, distant metastases, and median survival time) were also gathered and compared. Statistical software was used for analysis, with a p < 0.05 considered statistically significant. ResultsOf the 132 patients included in the analysis, 74 (56%) received PMB of 10 Gy in five daily fractions and 58 (44%) did not. Patients who received PMB were more likely to have pelvic sidewall invasion at the time of diagnosis (OR 4.053, 95% CI 1.163–14.13, p < 0.05) and received more cycles of concurrent chemotherapy during whole pelvis irradiation (OR 2.149, 95% CI 1.370–3.371, p < 0.05). At a median follow-up of 24 months, there was no statistically significant difference in the crude rates of pelvic recurrence, tumor persistence, distant metastasis, and median survival between the two groups. ConclusionPresence of pelvic sidewall invasion at diagnosis and increased number of chemotherapy cycles were predictive of administering PMB after whole pelvis irradiation. There was no significant difference in treatment outcomes for those with and without PMB.

Efficacy evaluation of vaginal-assisted laparoscopic radical hysterectomy and laparoscopic radical hysterectomy for cervical cancer: a single-center retrospective case series study.

BackgroundTo investigate the survival outcomes of abdominal radical hysterectomy (ARH), laparoscopic radical hysterectomy (LRH), and vaginal-assisted laparoscopic radical hysterectomy (VALRH) in the treatment of cervical cancer patients.MethodsThis was a retrospective study. We collected the clinical data of 654 patients with cervical cancer (406 ARH, 172 LRH, and 76 VALRH), then compared the effects of different surgical methods on recurrence and survival.ResultsTotal overall survival (OS) were no significant differences in three groups (P>0.05). Total disease-free survival (DFS) was significantly higher in ARH group than in LRH group [hazard ratio (HR) =2.8, 95% confidence interval (CI): 1.199–3.607, P=0.004]; however, there were no significant differences between the VALRH (94.7%) and ARH (93.3%) groups. Subgroup stratification analysis showed that the overall recurrence rate in LRH group was significantly higher than that of the ARH groups for patients with a tumor size from ≥2 to <4 cm, negative postoperative lymph nodes, and no postoperative adjuvant therapy (all P<0.05). However, in the subgroup with tumor sizes of ≥2, <4, and ≥4 cm, no matter whether the lymph nodes were positive or not, and those with no postoperative supplementary adjuvant therapy, LRH was associated with a significantly higher local pelvic recurrence rate than ARH (all P<0.05). No significant differences between VALRH and ARH in any of the subgroup analyses (all P>0.05). A Cox analysis indicated that LRH increased the risk of overall and local pelvic recurrence after surgery compared with ARH (HR =2.338, 95% CI: 1.186–4.661, P=0.014; HR =10.313, 95% CI: 2.839–37.460, P<0.001); however, no significant difference between VALRH and ARH (all P>0.05). Sensitivity analysis of surgeons did not change the conclusions.ConclusionsOur analyses showed that the local pelvic recurrence rates and overall recurrence rates of LRH were significantly higher than ARH. VALRH could avoid tumor intraperitoneal exposure and achieve the same tumor prognosis as open surgery. By improving the standardization of minimally invasive surgery for early cervical cancer and paying close attention to the tumor-free concept, minimally invasive radical hysterectomy may achieve the same tumor outcome as open surgery.