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The Lancet. Oncology Aug 2022The trade-off between comparative effectiveness and reproductive morbidity of different treatment methods for cervical intraepithelial neoplasia (CIN) remains unclear.... (Meta-Analysis)
Meta-Analysis
Comparative effectiveness and risk of preterm birth of local treatments for cervical intraepithelial neoplasia and stage IA1 cervical cancer: a systematic review and network meta-analysis.
BACKGROUND
The trade-off between comparative effectiveness and reproductive morbidity of different treatment methods for cervical intraepithelial neoplasia (CIN) remains unclear. We aimed to determine the risks of treatment failure and preterm birth associated with various treatment techniques.
METHODS
In this systematic review and network meta-analysis, we searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials database for randomised and non-randomised studies reporting on oncological or reproductive outcomes after CIN treatments from database inception until March 9, 2022, without language restrictions. We included studies of women with CIN, glandular intraepithelial neoplasia, or stage IA1 cervical cancer treated with excision (cold knife conisation [CKC], laser conisation, and large loop excision of the transformation zone [LLETZ]) or ablation (radical diathermy, laser ablation, cold coagulation, and cryotherapy). We excluded women treated with hysterectomy. The primary outcomes were any treatment failure (defined as any abnormal histology or cytology) and preterm birth (<37 weeks of gestation). The network for preterm birth also included women with untreated CIN (untreated colposcopy group). The main reference group was LLETZ for treatment failure and the untreated colposcopy group for preterm birth. For randomised controlled trials, we extracted group-level summary data, and for observational studies, we extracted relative treatment effect estimates adjusted for potential confounders, when available, and we did random-effects network meta-analyses to obtain odds ratios (ORs) with 95% CIs. We assessed within-study and across-study risk of bias using Cochrane tools. This systematic review is registered with PROSPERO, CRD42018115495 and CRD42018115508.
FINDINGS
7880 potential citations were identified for the outcome of treatment failure and 4107 for the outcome of preterm birth. After screening and removal of duplicates, the network for treatment failure included 19 240 participants across 71 studies (25 randomised) and the network for preterm birth included 68 817 participants across 29 studies (two randomised). Compared with LLETZ, risk of treatment failure was reduced for other excisional methods (laser conisation: OR 0·59 [95% CI 0·44-0·79] and CKC: 0·63 [0·50-0·81]) and increased for laser ablation (1·69 [1·27-2·24]) and cryotherapy (1·84 [1·33-2·56]). No differences were found for the comparison of cold coagulation versus LLETZ (1·09 [0·68-1·74]) but direct data were based on two small studies only. Compared with the untreated colposcopy group, risk of preterm birth was increased for all excisional techniques (CKC: 2·27 [1·70-3·02]; laser conisation: 1·77 [1·29-2·43]; and LLETZ: 1·37 [1·16-1·62]), whereas no differences were found for ablative methods (laser ablation: 1·05 [0·78-1·41]; cryotherapy: 1·01 [0·35-2·92]; and cold coagulation: 0·67 [0·02-29·15]). The evidence was based mostly on observational studies with their inherent risks of bias, and the credibility of many comparisons was low.
INTERPRETATION
More radical excisional techniques reduce the risk of treatment failure but increase the risk of subsequent preterm birth. Although there is uncertainty, ablative treatments probably do not increase risk of preterm birth, but are associated with higher failure rates than excisional techniques. Although we found LLETZ to have balanced effectiveness and reproductive morbidity, treatment choice should rely on a woman's age, size and location of lesion, and future family planning.
FUNDING
National Institute for Health and Care Research: Research for Patient Benefit.
Topics: Conization; Female; Humans; Infant, Newborn; Network Meta-Analysis; Premature Birth; Uterine Cervical Neoplasms; Uterine Cervical Dysplasia
PubMed: 35835138
DOI: 10.1016/S1470-2045(22)00334-5 -
Frontiers in Oncology 2022To compare cervical cancer recurrence and patient survival after radical hysterectomy followed by either adjuvant chemotherapy (AC) or adjuvant radiotherapy with or...
Cervical Cancer Recurrence and Patient Survival After Radical Hysterectomy Followed by Either Adjuvant Chemotherapy or Adjuvant Radiotherapy With Optional Concurrent Chemotherapy: A Systematic Review and Meta-Analysis.
OBJECTIVE
To compare cervical cancer recurrence and patient survival after radical hysterectomy followed by either adjuvant chemotherapy (AC) or adjuvant radiotherapy with or without concurrent chemotherapy (AR/CCRT).
METHODS
We systematically searched PubMed, EMBASE, the Cochrane Library and clinicaltrials.gov to identify studies reporting recurrence or survival of cervical cancer patients who received AC or AR/CCRT after radical hysterectomy. Data were meta-analyzed using a random-effects model, and heterogeneity was evaluated using the test. Subgroup and sensitivity analyses were performed to identify potential sources of heterogeneity.
RESULTS
The meta-analysis included 14 non-randomized studies and two randomized controlled trials, altogether involving 5,052 cervical cancer patients. AC and AR/CCRT groups did not differ significantly in rates of total or local recurrence or mortality. Nevertheless, AC was associated with significantly lower risk of distant recurrence [odds ratio (OR) 0.67, 95% confidence interval (CI) 0.55-0.81] and higher rates of overall survival [hazard ratio (HR) 0.69, 95%CI 0.54-0.85] and disease-free survival rate (HR 0.77, 95%CI 0.62-0.92).
CONCLUSIONS
AC may be an effective alternative to AR/CCRT for cervical cancer patients after radical hysterectomy, especially younger women who wish to preserve their ovaries and protect them from radiation damage.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier PROSPERO (CRD42021252518).
PubMed: 35311123
DOI: 10.3389/fonc.2022.823064 -
Taiwanese Journal of Obstetrics &... Jan 2022The presence of intermediate risk factors reduces the predictability of radical hysterectomy, demanding the use of adjuvant therapy for treatment of Early stage cervical... (Meta-Analysis)
Meta-Analysis Review
Comparison of adjuvant chemoradiotherapy versus radiotherapy in early-stage cervical cancer patients with intermediate-risk factors: A systematic review and meta-analysis.
The presence of intermediate risk factors reduces the predictability of radical hysterectomy, demanding the use of adjuvant therapy for treatment of Early stage cervical cancer (ESCC) patients. Adjuvant radiotherapy (RT) and chemoradiotherapy (CRT) has been widely used with varied efficacy and safety issues. Therefore, the aim of this systematic review and meta-analysis was to update the available evidence and assess the effect of post-surgical adjuvant RT versus adjuvant CRT on survival rate and complications/toxicities in management of ESCC patients with intermediate risk factors. PubMed, EMBASE and Web of Science (WOS) and CENTRAL were searched using a combination of relevant keywords. All studies comparing outcomes of adjuvant RT versus CRT in ESCC patients with intermediate-risk factors in terms of recurrence free survival (RFS), overall survival (OS) and toxicities/complications were included. Both qualitative and quantitative analysis was carried out. The risk of bias assessment was done using Newcastle-Ottawa scale (NOS) for retrospective cohort studies and Cochrane risk of bias assessment tool was used for randomized clinical trials. Eleven retrospective cohort studies and two randomized clinical trials were included in this review. Adjuvant CRT was found to have better RFS with ESCC patients with multiple intermediate risk factors with OR 3.11 95% CI [1.04, 4.99], p < 0.0001; i2 = 6%. However, similar benefit was observed between both regimens in presence of a single intermediate risk factor OR 1.80 95% CI [0.96, 3.36], p = 0.07; i2 = 0%. Grade 3 or 4 haematological toxicity among patients receiving post-surgical adjuvant RT versus adjuvant CRT showed increased association of toxicity with adjuvant CRT with OR 7.73 95%CI [3.40, 17.59], p < 0.0001; i2 = 62%. Adjuvant CRT shows favourable RFS and OS in ESCC patients with multiple intermediate risk factors. CRT also showed greater incidence of grade 3 or 4 haematological and non-haematiological toxicity, however, the same could be well tolerated when used within the recommended dosage.
Topics: Carcinoma, Squamous Cell; Chemoradiotherapy; Chemoradiotherapy, Adjuvant; Female; Humans; Hysterectomy; Neoplasm Staging; Radiotherapy, Adjuvant; Survival Rate; Uterine Cervical Neoplasms
PubMed: 35181028
DOI: 10.1016/j.tjog.2021.11.006 -
Frontiers in Oncology 2021Although minimally invasive surgery (MIS) was commonly used to treat patients with early-stage cervical cancer, its efficacy remained controversial.
BACKGROUND
Although minimally invasive surgery (MIS) was commonly used to treat patients with early-stage cervical cancer, its efficacy remained controversial.
METHODS
We systematically searched PubMed, Web of Science, and Cochrane Library databases until March 2021 to compare the prognosis of early-stage cervical cancer patients who underwent MIS (laparoscopic or robot-assisted radical hysterectomy) or ARH. The primary outcomes included rates of 3- and 5-year disease-free survival (DFS) and overall survival (OS). The study protocol was registered in PROSPERO: CRD42021258116.
RESULTS
This meta-analysis included 48 studies involving 23346 patients (11220, MIS group; 12126, ARH group). The MIS group had a poorer medium-term (3-year) DFS (HR=1.08, 95% CI: 1.01-1.16, =0.031) than the ARH group, without significant difference in medium-term OS as well as long-term (5-year) DFS and OS. Subgroup analysis of 3-year prognosis revealed that although patients in Western countries who underwent MIS had shorter DFS than those who underwent ARH (HR=1.10, =0.024), no difference was observed in DFS among those in Asian countries. Moreover, MIS was linked to poorer 3-year DFS in patients with stage I cervical cancer (HR=1.07, =0.020). Notably, subgroup analysis of 5-year prognosis revealed that patients with tumor size ≥2 cm undergoing MIS exhibited a shorter DFS than those who underwent ARH (HR=1.65, =0.041).
CONCLUSION
Patients with early-stage cervical cancer undergoing MIS may have a poorer prognosis than those undergoing ARH. Therefore, applying MIS in early-stage cervical cancer patients should be conducted with caution.
SYSTEMATIC REVIEW REGISTRATION
The study protocol was registered in PROSPERO: CRD42021258116.
PubMed: 35141141
DOI: 10.3389/fonc.2021.762921 -
Frontiers in Surgery 2021To provide updated evidence on comparative efficacy for clinical outcomes of radical trachelectomy and radical hysterectomy in patients with early-stage cervical...
To provide updated evidence on comparative efficacy for clinical outcomes of radical trachelectomy and radical hysterectomy in patients with early-stage cervical cancer. A systematic search was conducted in the PubMed, Scopus, Cochrane Database of Systematic Reviews, and Google scholar databases. Studies were done in patients with early-stage cervical cancer that compared the outcomes between radical trachelectomy (RT) and hysterectomy (RH) were considered for inclusion in the review. The outcomes of interest were operative time, the volume of blood loss, need for blood transfusion, any complications, length of hospital stay, risk of recurrence, and survival. The strength of association was presented in the form of pooled relative risk (RR), hazards risk (HR), and weighted mean difference (WMD). Statistical analysis was done using STATA version 16.0. A total of 12 articles were included in the meta-analysis. The majority were retrospective cohort-based studies. Compared to RH, the operative time (in min) was comparatively higher in RT (WMD 23.43, 95% CI: 5.63, 41.24). Patients undergoing RT had blood loss (in ml) similar to those undergoing RT (WMD -81.34, 95% CI: -170.36, 7.68). There were no significant differences in the risk of intra-operative (RR 1.61, 95% CI: 0.49, 5.28) and post-operative complications (RR 1.13, 95% CI: 0.54, 2.40) between the two groups. Patients in the RT group had lesser duration of post-operative hospital stay (in days) (WMD -1.65, 95% CI: -3.22, -0.09). There was no statistically significant difference in the risk of recurrence (HR 1.21, 95% CI: 0.68, 2.18), 5-year overall survival (HR 1.00, 95% CI: 0.99, 1.02), and recurrence-free survival (HR 0.99, 95% CI: 0.96, 1.01) between the two groups. Among the patients with early-stage cervical cancer, RT is similar to RH in safety and clinical outcomes. Future studies with a randomized design and larger sample sizes are needed to further substantiate these findings.
PubMed: 34859038
DOI: 10.3389/fsurg.2021.735944 -
Gynecologic Oncology Feb 2022After the LACC trial, the SUCCOR study, and other studies, we know that patients who have undergone minimally invasive surgery for cervical cancer have worse outcomes,... (Meta-Analysis)
Meta-Analysis
Pattern of relapse in patients with stage IB1 cervical cancer after radical hysterectomy as primary treatment. Minimally invasive surgery vs. open approach. Systematic review and meta-analysis.
BACKGROUND
After the LACC trial, the SUCCOR study, and other studies, we know that patients who have undergone minimally invasive surgery for cervical cancer have worse outcomes, but today, we do not know if the surgical approach can be a reason to change the pattern of relapses on these patients. We evaluated the relapse pattern in patients with stage IB1 cervical cancer (FIGO, 2009) who underwent radical hysterectomy with different surgical approaches.
METHODS
A systematic review of literature was performed in PubMed, Cochrane Library, Clinicaltrials.gov, and Web of science. Inclusion criteria were prospective or retrospective comparative studies of different surgical approaches that described patterns or locations of relapse in patients with stage IB1 cervical cancer. Heterogeneity was assessed by calculating I2.
RESULTS
The research resulted in 782 eligible citations from January 2010 to October 2020. After filtering, nine articles that met all inclusion criteria were analyzed, comprising data from 1663 patients who underwent radical hysterectomy for IB1 cervical cancer, and the incidence of relapse was 10.6%. When we compared the pattern of relapse (local, distant, and both) of each group (open surgery and minimally invasive surgery), we did not see statistically significant differences, (OR 0.963; 95% CI, 0.602-1.541; p = 0.898), (OR 0.788; 95% CI, 0.467-1.330; p = 0.542), and (OR 0.683; 95% CI, 0.331-1.407; p = 0.630), respectively.
CONCLUSION
There are no differences in patterns of relapse across surgical approaches in patients with stage IB1 cervical cancer undergoing radical hysterectomy as primary treatment.
Topics: Female; Humans; Hysterectomy; Laparoscopy; Laparotomy; Minimally Invasive Surgical Procedures; Neoplasm Recurrence, Local; Neoplasm Staging; Uterine Cervical Neoplasms
PubMed: 34848071
DOI: 10.1016/j.ygyno.2021.11.018 -
Deutsches Arzteblatt International Nov 2021Approximately 4380 cases of cervical carcinoma were diagnosed in Germany in 2016. In women who had not participated in early detection programs, cervical carcinoma was...
BACKGROUND
Approximately 4380 cases of cervical carcinoma were diagnosed in Germany in 2016. In women who had not participated in early detection programs, cervical carcinoma was usually already in an advanced stage at the time of diagnosis. Certified structures for care in conformity with the existing guidelines are available.
METHODS
The new German clinical practice guideline was revised with the participation of 50 medical societies under the expert guidance of the Guideline Program in Oncology, which includes the German Association of the Scientific Medical Societies (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF). A systematic literature review was conducted. Systematic reviews, meta-analyses, and randomized controlled trials (RCTs) were considered.
RESULTS
The histologic tumor stage and lymph-node stage are essential determinants of the treatment strategy. The main innovation regarding surgical treatment is the revival of open hysterectomy (overall survival [minimally invasive vs open hysterectomy]: 94.04% vs 99.4%; hazard ratio [HR]: 6.00; 95% confidence interval [1.77; 20.30]). In addition, for tumors measuring 2 cm or less, sentinel node biopsy is recommended rather than radical pelvic lymphadenectomy. MRI-guided brachytherapy is an oblig atory component of radiochemotherapy (overall survival [radiochemotherapy with vs without brachytherapy]: 58.2% vs 46.2%, p<0.001). The standard palliative treatment consists of bevacizumab combined with a platinum-containing agent (overall survival: HR: 0.77 [0.62; 0.95]; p = 0.007).
CONCLUSION
Despite the introduction of new treatments, the outcome of patients with advanced cervical carcinoma has not much improved. In the surgical treatment of cervical carcinoma, the open approach is now favored. The sentinel node biopsy technique has become well established for the surgical staging of small tumors. Controlled trials are needed so that the outcome of women with cervical carcinoma, particularly in its advanced and metastatic stages, can be improved.
Topics: Aftercare; Carcinoma; Female; Humans; Hysterectomy; Lymph Node Excision; Neoplasm Staging; Uterine Cervical Neoplasms
PubMed: 34755595
DOI: 10.3238/arztebl.m2021.0352 -
Archives of Gynecology and Obstetrics Aug 2022Radical hysterectomy and pelvic lymphadenectomy is the standard treatment for early cervical cancer. Studies have shown superior oncological outcome for open versus... (Meta-Analysis)
Meta-Analysis Review
Perioperative morbidity of different operative approaches in early cervical carcinoma: a systematic review and meta-analysis comparing minimally invasive versus open radical hysterectomy.
PURPOSE
Radical hysterectomy and pelvic lymphadenectomy is the standard treatment for early cervical cancer. Studies have shown superior oncological outcome for open versus minimal invasive surgery, but peri- and postoperative complication rates were shown vice versa. This meta-analysis evaluates the peri- and postoperative morbidities and complications of robotic and laparoscopic radical hysterectomy compared to open surgery.
METHODS
Embase and Ovid-Medline databases were systematically searched in June 2020 for studies comparing robotic, laparoscopic and open radical hysterectomy. There was no limitation in publication year. Inclusion criteria were set analogue to the LACC trial. Subgroup analyses were performed regarding the operative technique, the study design and the date of publication for the endpoints intra- and postoperative morbidity, estimated blood loss, hospital stay and operation time.
RESULTS
27 studies fulfilled the inclusion criteria. Five prospective, randomized-control trials were included. Meta-analysis showed no significant difference between robotic radical hysterectomy (RH) and laparoscopic hysterectomy (LH) concerning intra- and perioperative complications. Operation time was longer in both RH (mean difference 44.79 min [95% CI 38.16; 51.42]), and LH (mean difference 20.96 min; [95% CI - 1.30; 43.22]) than in open hysterectomy (AH) but did not lead to a rise of intra- and postoperative complications. Intraoperative morbidity was lower in LH than in AH (RR 0.90 [0.80; 1.02]) as well as in RH compared to AH (0.54 [0.33; 0.88]). Intraoperative morbidity showed no difference between LH and RH (RR 1.29 [0.23; 7.29]). Postoperative morbidity was not different in any approach. Estimated blood loss was lower in both LH (mean difference - 114.34 [- 122.97; - 105.71]) and RH (mean difference - 287.14 [- 392.99; - 181.28]) compared to AH, respectively. Duration of hospital stay was shorter for LH (mean difference - 3.06 [- 3.28; - 2.83]) and RH (mean difference - 3.77 [- 5.10; - 2.44]) compared to AH.
CONCLUSION
Minimally invasive radical hysterectomy appears to be associated with reduced intraoperative morbidity and blood loss and improved reconvalescence after surgery. Besides oncological and surgical factors these results should be considered when counseling patients for radical hysterectomy and underscore the need for new randomized trials.
Topics: Female; Humans; Hysterectomy; Laparoscopy; Morbidity; Postoperative Complications; Prospective Studies; Robotic Surgical Procedures; Uterine Cervical Neoplasms
PubMed: 34625835
DOI: 10.1007/s00404-021-06248-8 -
PloS One 2021This meta-analysis comprehensively compared intraoperative and postoperative complications between minimally invasive surgery (MIS) and laparotomy in the management of... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
This meta-analysis comprehensively compared intraoperative and postoperative complications between minimally invasive surgery (MIS) and laparotomy in the management of cervical cancer. Even though the advantages of laparotomy over MIS in disease-free survival and overall survival for management of gynecological diseases have been cited in the literature, there is a lack of substantial evidence of the advantage of one surgical modality over another, and it is uncertain whether MIS is justifiable in terms of safety and efficacy.
METHODS
In this meta-analysis, the studies were abstracted that the outcomes of complications to compare MIS (laparoscopic or robot-assisted) and open radical hysterectomy in patients with early-stage (International Federation of Gynecology and Obstetrics classification stage IA1-IIB) cervical cancer. The primary outcomes were intraoperative overall complications, as well as postoperative aggregate complications. Secondary outcomes included the individual complications. Two investigators independently performed the screening and data extraction. All articles that met the eligibility criteria were included in this meta-analysis.
RESULTS
The meta-analysis finally included 39 non-randomized studies and 1 randomized controlled trial (8 studies were conducted on robotic radical hysterectomy (RRH) vs open radical hysterectomy (ORH), 27 studies were conducted on laparoscopic radical hysterectomy (LRH) vs ORH, and 5 studies were conducted on all three approaches). Pooled analyses showed that MIS was associated with higher risk of intraoperative overall complications (OR = 1.41, 95% CI = 1.07-1.86, P<0.05) in comparison with ORH. However, compared to ORH, MIS was associated with significantly lower risk of postoperative aggregate complications (OR = 0.40, 95% CI = 0.34-0.48, P = 0.0143). In terms of individual complications, MIS appeared to have a positive effect in decreasing the complications of transfusion, wound infection, pelvic infection and abscess, lymphedema, intestinal obstruction, pulmonary embolism, deep vein thrombosis, and urinary tract infection. Furthermore, MIS had a negative effect in increasing the complications of cystotomy, bowel injury, subcutaneous emphysema, and fistula.
CONCLUSIONS
Our meta-analysis demonstrates that MIS is superior to laparotomy, with fewer postoperative overall complications (wound infection, pelvic infection and abscess, lymphedema, intestinal obstruction, pulmonary embolism, and urinary tract infection). However, MIS is associated with a higher risk of intraoperative aggregate complications (cystotomy, bowel injury, and subcutaneous emphysema) and postoperative fistula complications.
Topics: Disease-Free Survival; Female; Humans; Hysterectomy; Intraoperative Complications; Laparotomy; Minimally Invasive Surgical Procedures; Postoperative Complications; Robotic Surgical Procedures; Uterine Cervical Neoplasms
PubMed: 34197466
DOI: 10.1371/journal.pone.0253143 -
Archives of Gynecology and Obstetrics Aug 2021Villoglandular adenocarcinoma (VGA) of the uterine cervix has been classified as a rare subtype of cervical adenocarcinoma with good prognosis. A conservative surgical... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Villoglandular adenocarcinoma (VGA) of the uterine cervix has been classified as a rare subtype of cervical adenocarcinoma with good prognosis. A conservative surgical approach is considered feasible. The main risk factor is the presence of other histologic types of cancer. In this largest systematic review to date, we assess oncological outcomes associated with conservative therapy compared to those associated with invasive management in the treatment of stage Ia and Ib VGA.
METHODS
Case series and case reports identified by searching the PubMed database were eligible for inclusion in this review (stage Ia-Ib).
RESULTS
A total of 271 patients were included in our literature review. 54 (20%) patients were treated by "conservative management" (conization, simple hysterectomy, and trachelectomy) and 217 (80%) by "invasive management" (radical hysterectomy ± radiation, hysterectomy, and radiation). Recurrences of disease (RODs) were found in the conservative group in two (4%) cases and in the invasive group in nine (4%) cases. There was no significant difference in disease-free survival (DFS) according to conservative or invasive treatment (p = 0.75). The histology of VGA may be complex with underlying usual adenocarcinoma (UAC) combined with VGA.
CONCLUSION
The excellent prognosis of pure VGA and the young age of the patients may justify the management of this tumor using a less radical procedure. The histological diagnosis of VGA is a challenge, and pretreatment should not be based solely on a simple punch biopsy but rather a conization with wide tumor-free margins.
Topics: Adenocarcinoma; Conservative Treatment; Female; Humans; Hysterectomy; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Pregnancy; Uterine Cervical Neoplasms
PubMed: 34036437
DOI: 10.1007/s00404-021-06077-9