Laparoscopy versus laparotomy for the management of early stage endometrial cancer.

BACKGROUND: This is an update of a previous Cochrane Review published in 2012, Issue 9.Surgery for endometrial cancer (hysterectomy with removal of both fallopian tubes and ovaries) is performed through laparotomy. It has been suggested that the laparoscopic approach is associated with a reduction in operative morbidity. Over the last two decades there has been a steady increase of the use of laparoscopy for endometrial cancer. This review investigated the evidence of benefits and harms of laparoscopic surgery compared with laparotomy for presumed early stage endometrial cancer. OBJECTIVES: To compare overall survival (OS) and disease free survival (DFS) for laparoscopic surgery versus laparotomy in women with presumed early stage endometrial cancer. SEARCH METHODS: For this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 5) in the Cochrane Library, MEDLINE via Ovid (April 2012 to June 2018) and Embase via Ovid (April 2012 to June 2018). We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies. The trial registers included NHMRC Clinical Trials Register, UKCCCR Register of Cancer Trials, Meta-Register and Physician Data Query Protocol. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing laparoscopy and laparotomy for early stage endometrial cancer. DATA COLLECTION AND ANALYSIS: We independently abstracted data and assessed risk of bias. We used hazard ratios (HRs) for OS and recurrence free survival (RFS), risk ratios (RR) for severe adverse events and mean differences (MD) for continuous outcomes in women who received laparoscopy or laparotomy with 9% confidence intervals (CI). These were pooled in random-effects meta-analyses. MAIN RESULTS: We identified one new study in this update of the review. The review contains nine RCTs comparing laparoscopy with laparotomy for the surgical management of early stage endometrial cancer.All nine studies met the inclusion criteria and assessed 4389 women at the end of the studies. Six studies assessing 3993 participants with early stage endometrial cancer found no significant difference in the risk of death between women who underwent laparoscopy and women who underwent laparotomy (HR 1.04, 95% 0.86 to 1.25; moderate-certainty evidence) and five studies assessing 3710 participants found no significant difference in the risk of recurrence between the laparoscopy and laparotomy groups (HR 1.14, 95% CI 0.90 to 1.43; moderate-certainty evidence). There was no significant difference in the rate of perioperative death; women requiring a blood transfusion; and bladder, ureteric, bowel and vascular injury. However, one meta-analysis of three studies found that women in the laparoscopy group lost significantly less blood than women in the laparotomy group (MD -106.82 mL, 95% CI -141.59 to -72.06; low-certainty evidence). A further meta-analysis of two studies, which assessed 3344 women and included one very large trial of over 2500 participants, found that there was no clinical difference in the risk of severe postoperative complications in women in the laparoscopy and laparotomy groups (RR 0.78, 95% CI 0.44 to 1.38). Most studies were at moderate risk of bias. All nine studies reported hospital stay and results showed that on average, laparoscopy was associated with a significantly shorter hospital stay. AUTHORS' CONCLUSIONS: This review found low to moderate-certainty evidence to support the role of laparoscopy for the management of early endometrial cancer. For presumed early stage primary endometrioid adenocarcinoma of the endometrium, laparoscopy is associated with similar OS and DFS. Furthermore, laparoscopy is associated with reduced operative morbidity and hospital stay. There is no significant difference in severe postoperative morbidity between the two modalities.The certainty of evidence for OS and RFS was moderate and was downgraded for unclear risk of bias profiles and imprecision in effect estimates. However, most studies used adequate methods of sequence generation and concealment of allocation so studies were not prone to selection bias. Adverse event outcomes were downgraded for the same reasons and additionally for low event rates and low power thus these outcomes provided low-certainty evidence.

Follow-up strategies after treatment (large loop excision of the transformation zone (LLETZ)) for cervical intraepithelial neoplasia (CIN): Impact of human papillomavirus (HPV) test.

BACKGROUND: Development of cancer of the cervix is a multi-step process as before cervical cancer develops, cervical cells undergo changes and become abnormal. These abnormalities are called cervical intraepithelial neoplasia (CIN) and are associated with increased risk of subsequent invasive cancer of the cervix. Oncogenic high-risk human papillomavirus (hrHPV), the causative agent of cervical cancer and its precursor lesions, is present in up to one-third of women following large loop excision of the transformation zone (LLETZ) treatment and is associated with increased risk of residual disease and disease recurrence. HPV testing may serve as a surveillance tool for identifying women at higher risk of recurrence. High-risk human papillomavirus testing will enable us to identify women at increased risk of residual or recurrent CIN and therefore will allow us to offer closer surveillance and early treatment, when indicated. OBJECTIVES: • To evaluate the effectiveness and safety of hrHPV testing after large loop excision of the transformation zone (LLETZ) treatment• To determine optimal follow-up management strategies following LLETZ treatment according to hrHPV status SEARCH METHODS: We searched the Cochrane Gynacological Cancer Review Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), PubMed and PsycINFO up to August 2013. We searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies, and we contacted experts in the field. SELECTION CRITERIA: We searched for randomised control trials (RCTs) that compared follow-up management strategies following LLETZ treatment for CIN. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed whether potentially relevant studies met the inclusion criteria. No trials were found; therefore no data were analysed. MAIN RESULTS: The search identified 813 references on MEDLINE, 418 on EMBASE, 22 on CINAHL, 666 on PubMed, 291 on PsycINFO and 145 on CENTRAL. When all references were imported into EndNote and duplications were removed, 1348 references remained. Initial screening of titles and abstracts of these references revealed that 42 references were potentially eligible for this review. After reading the full-text versions, we identified no relevant trials comparing hrHPV and cytology testing versus cytology testing alone for detecting residual or recurrent disease during follow-up to LLETZ treatment of adult women with CIN.We found no evidence on the effects of hrHPV and cytology testing on residual or recurrent CIN2 or higher lesions, anxiety and psychosexual morbidity outcomes in women undergoing colposcopy and treatment for CIN. AUTHORS' CONCLUSIONS: We found no evidence from RCTs to inform decisions about the best surveillance strategy for women following treatment for CIN. A prognostic systematic review is needed to investigate the risk of developing recurrent cervical intraepithelial neoplasia 2+ (CIN2+) in women with a positive hrHPV test after large loop excision of the transformation zone (LLETZ) treatment.

Adjuvant chemotherapy for advanced endometrial cancer.

BACKGROUND: Approximately 13% of women diagnosed with endometrial cancer present with advanced stage disease (International Federation of Gynecology and Obstetrics (FIGO) stage III/IV). The standard treatment of advanced endometrial cancer consists of cytoreductive surgery followed by radiation therapy, or chemotherapy, or both. There is currently little agreement about which adjuvant treatment is the safest and most effective. OBJECTIVES: To evaluate the effectiveness and safety of adjuvant chemotherapy compared with radiotherapy or chemoradiation, and to determine which chemotherapy agents are most effective in women presenting with advanced endometrial cancer (FIGO stage III/IV). SEARCH METHODS: We searched the Cochrane Gynaecological Cancer Collaborative Review Group's Trial Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 10 2013), MEDLINE and EMBASE up to November 2013. Also we searched electronic clinical trial registries for ongoing trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) of adjuvant chemotherapy compared with radiotherapy or chemoradiation in women with FIGO stage III and IV endometrial cancer. DATA COLLECTION AND ANALYSIS: Two review authors selected trials, extracted data, and assessed trials for risk of bias. Where necessary, we contacted trial investigators for relevant, unpublished data. We pooled data using the random-effects model in Review Manager (RevMan) software. MAIN RESULTS: We included four multicentre RCTs involving 1269 women with primary FIGO stage III/IV endometrial cancer. We considered the trials to be at low to moderate risk of bias. All participants received primary cytoreductive surgery. Two trials, evaluating 620 women (83% stage III, 17% stage IV), compared adjuvant chemotherapy with adjuvant radiotherapy; one trial evaluating 552 women (88% stage III, 12% stage IV) compared two chemotherapy regimens (cisplatin/doxorubicin/paclitaxel (CDP) versus cisplatin/doxorubicin (CD) treatment) in women who had all undergone adjuvant radiotherapy; and one trial contributed no data.Overall survival (OS) and progression-free survival (PFS) was longer with adjuvant chemotherapy compared with adjuvant radiotherapy (OS: hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.57 to 0.99, I² = 22%; and PFS: HR 0.74, 95% CI 0.59 to 0.92, I² = 0%). Sensitivity analysis using adjusted and unadjusted OS data, gave similar results. In subgroup analyses, the effects on survival in favour of chemotherapy were not different for stage III and IV, or stage IIIA and IIIC (tests for subgroup differences were not significant and I² = 0%). This evidence was of moderate quality. Data from one trial showed that women receiving adjuvant chemotherapy were more likely to experience haematological and neurological adverse events and alopecia, and more likely to discontinue treatment (33/194 versus 6/202; RR 5.73, 95% CI 2.45 to 13.36), than those receiving adjuvant radiotherapy. There was no statistically significant difference in treatment-related deaths between the chemotherapy and radiotherapy treatment arms (8/309 versus 5/311; Risk Ratio (RR) 1.67, 95% CI 0.55 to 5.00).There was no clear difference in PFS between intervention groups in the one trial that compared CDP versus CD (552 women; HR 0.90, 95% CI 0.69 to 1.17). We considered this evidence to be of moderate quality. Mature OS data from this trial were not yet available. Severe haematological and neurological adverse events occurred more frequently with CDP than CD.We found no trials to include of adjuvant chemotherapy versus chemoradiation in advanced endometrial cancer; however we identified one ongoing trial of this comparison. AUTHORS' CONCLUSIONS: There is moderate quality evidence that chemotherapy increases survival time after primary surgery by approximately 25% relative to radiotherapy in stage III and IV endometrial cancer. There is limited evidence that it is associated with more adverse effects. There is some uncertainty as to whether triplet regimens offer similar survival benefits over doublet regimens in the long-term. Further research is needed to determine which chemotherapy regimen(s) are the most effective and least toxic, and whether the addition of radiotherapy further improves outcomes. A large trial evaluating the benefits and risks of adjuvant chemoradiation versus chemotherapy in advanced endometrial cancer is ongoing.

Adjuvant radiotherapy and/or chemotherapy after surgery for uterine carcinosarcoma.

BACKGROUND: Uterine carcinosarcomas are uncommon with about 35% not confined to the uterus at diagnosis. The survival of women with advanced uterine carcinosarcoma is poor with a pattern of failure indicating greater likelihood of upper abdominal and distant metastatic recurrence. OBJECTIVES: To evaluate the effectiveness and safety of adjuvant radiotherapy and/or systemic chemotherapy in the management of uterine carcinosarcoma. SEARCH METHODS: We searched the Cochrane Gynaecological Cancer Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), 2012, Issue 10, MEDLINE and EMBASE up to November 2012. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing adjuvant radiotherapy and/or chemotherapy in women with uterine carcinosarcoma. DATA COLLECTION AND ANALYSIS: Two review authors independently abstracted data and assessed risk of bias. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) and risk ratios (RRs) comparing adverse events in women who received radiotherapy and/or chemotherapy were pooled in random-effects meta-analyses. MAIN RESULTS: Three trials met the inclusion criteria and these randomised 579 women, of whom all were assessed at the end of the trials. Two trials assessing 373 participants with stage III to IV persistent or recurrent disease, found that women who received combination therapy had a significantly lower risk of death and disease progression than women who received single agent ifosfamide, after adjustment for performance status (HR = 0.75, 95% confidence interval (CI): 0.60 to 0.94 and HR = 0.72, 95% CI: 0.58 to 0.90 for OS and PFS respectively). There was no statistically significant difference in all reported adverse events, with the exception of nausea and vomiting, where significantly more women experienced these ailments in the combination therapy group than the Ifosamide group (RR = 3.53, 95% CI: 1.33 to 9.37).In one trial there was no statistically significant difference in the risk of death and disease progression in women who received whole body irradiation and chemotherapy, after adjustment for age and FIGO stage (HR = 0.71, 95% CI: 0.48 to 1.05 and HR = 0.79, 95% CI: 0.53 to 1.18 for OS and PFS respectively). There was no statistically significant difference in all reported adverse events, with the exception of haematological and neuropathy morbidities, where significantly less women experienced these morbidities in the whole body irradiation group than the chemotherapy group (RR= 0.02, 95% CI: 0.00 to 0.16) for haematological morbidity and all nine women in the trial experiencing neuropathy morbidity were in the chemotherapy group). AUTHORS' CONCLUSIONS: In advanced stage metastatic uterine carcinosarcoma as well as recurrent disease adjuvant combination, chemotherapy with ifosfamide should be considered. Combination chemotherapy with ifosfamide and paclitaxel is associated with lower risk of death compared with ifosfamide alone. In addition, radiotherapy to the abdomen is not associated with improved survival.

Surgical cytoreduction for recurrent epithelial ovarian cancer.

BACKGROUND: The standard management of primary ovarian cancer is optimal cytoreductive surgery followed by platinum-based chemotherapy. Most women with primary ovarian cancer achieve remission on this combination therapy. For women achieving clinical remission after completion of initial treatment, most (60%) with advanced epithelial ovarian cancer will ultimately develop recurrent disease. However, the standard treatment of women with recurrent ovarian cancer remains poorly defined. Surgery for recurrent ovarian cancer has been suggested to be associated with increased overall survival. OBJECTIVES: To evaluate the effectiveness and safety of optimal secondary cytoreductive surgery for women with recurrent epithelial ovarian cancer. To assess the impact of various residual tumour sizes, over a range between 0 cm and 2 cm, on overall survival. SEARCH METHODS: We searched the Cochrane Gynaecological Cancer Group Trials Register, MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) up to December 2012. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. For databases other than MEDLINE, the search strategy has been adapted accordingly. SELECTION CRITERIA: Retrospective data on residual disease, or data from randomised controlled trials (RCTs) or prospective/retrospective observational studies that included a multivariate analysis of 50 or more adult women with recurrent epithelial ovarian cancer, who underwent secondary cytoreductive surgery with adjuvant chemotherapy. We only included studies that defined optimal cytoreduction as surgery leading to residual tumours with a maximum diameter of any threshold up to 2 cm. DATA COLLECTION AND ANALYSIS: Two review authors (KG, TA) independently abstracted data and assessed risk of bias. Where possible the data were synthesised in a meta-analysis. MAIN RESULTS: There were no RCTs; however, we found nine non-randomised studies that reported on 1194 women with comparison of residual disease after secondary cytoreduction using a multivariate analysis that met our inclusion criteria. These retrospective and prospective studies assessed survival after secondary cytoreductive surgery in women with recurrent epithelial ovarian cancer.Meta- and single-study analyses show the prognostic importance of complete cytoreduction to microscopic disease, since overall survival was significantly prolonged in these groups of women (most studies showed a large statistically significant greater risk of death in all residual disease groups compared to microscopic disease).Recurrence-free survival was not reported in any of the studies. All of the studies included at least 50 women and used statistical adjustment for important prognostic factors. One study compared sub-optimal (> 1 cm) versus optimal (< 1 cm) cytoreduction and demonstrated benefit to achieving cytoreduction to less than 1 cm, if microscopic disease could not be achieved (hazard ratio (HR) 3.51, 95% CI 1.84 to 6.70). Similarly, one study found that women whose tumour had been cytoreduced to less than 0.5 cm had less risk of death compared to those with residual disease greater than 0.5 cm after surgery (HR not reported; P value < 0.001).There is high risk of bias due to the non-randomised nature of these studies, where, despite statistical adjustment for important prognostic factors, selection is based on retrospective achievability of cytoreduction, not an intention to treat, and so a degree of bias is inevitable.Adverse events, quality of life and cost-effectiveness were not reported in any of the studies. AUTHORS' CONCLUSIONS: In women with platinum-sensitive recurrent ovarian cancer, ability to achieve surgery with complete cytoreduction (no visible residual disease) is associated with significant improvement in overall survival. However, in the absence of RCT evidence, it is not clear whether this is solely due to surgical effect or due to tumour biology. Indirect evidence would support surgery to achieve complete cytoreduction in selected women. The risks of major surgery need to be carefully balanced against potential benefits on a case-by-case basis.

Laparoscopy versus laparotomy for the management of early stage endometrial cancer.

BACKGROUND: Traditionally, surgery for endometrial cancer (hysterectomy with removal of both fallopian tubes and ovaries) is performed through laparotomy. It has been suggested that the laparoscopic approach is associated with a reduction in operative morbidity. Over the last 10 to 15 years there has been a steady increase of laparoscopy for endometrial cancer. This review investigates the evidence of benefits and harms of laparoscopic surgery compared with laparotomy for presumed early stage endometrial cancer. OBJECTIVES: To compare the overall survival (OS) and disease-free survival (DFS) for laparoscopic surgery versus laparotomy in women with presumed early stage endometrial cancer. SEARCH METHODS: We searched the Cochrane Gynaecological Cancer Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) Issue 3, 2012, MEDLINE, EMBASE and CINAHL up to April 2012. We also searched registers of clinical trials, abstracts of scientific meetings, and reference lists of included studies. Trial registers we searched included NHMRC Clinical Trials Register, UKCCCR Register of Cancer Trials, Meta-Register and Physician Data Query Protocol, as well as abstracts of scientific meetings. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing laparoscopy and laparotomy for early stage endometrial cancer. DATA COLLECTION AND ANALYSIS: We independently abstracted data and assessed risk of bias. Hazard ratios (HRs) were used for OS and recurrence-free survival (RFS), risk ratios (RR) for severe adverse events and the mean difference (MD) method was used for continuous outcomes in women who received laparoscopy or laparotomy and these were then pooled in random-effects meta-analyses. MAIN RESULTS: Eight RCTs comparing laparoscopy with laparotomy for the surgical management of early stage endometrial cancer were identified.All eight trials met the inclusion criteria, 3644 women were assessed at the end of the trials. Three trials assessing 359 participants with early stage endometrial cancer, found no statistically significant difference in the risk of death and disease or recurrence between women who underwent laparoscopy and those who underwent laparotomy (HR = 1.14, 95% confidence interval (CI): 0.62 to 2.10) and HR = 1.13, 95% CI: 0.90 to 1.42 for OS and RFS respectively). There was no statistically significant difference in the rate of peri-operative death, women requiring a blood transfusion, and bladder, ureteric, bowel and vascular injury. However, a meta-analysis of two trials found that women in the laparoscopy group lost significantly less blood than those in the laparotomy group (MD = -106.82 mL, 95% CI: -141.59 to -72.06). A further meta-analysis of two trials, which assessed 2923 women and included one very large trial of over 2500 participants, found that the rate of severe post-operative adverse events was significantly lower in the laparoscopy group compared with the laparotomy group (RR = 0.58, 95% CI: 0.37 to 0.91). The large trial did not give a breakdown of these severe post-operative adverse events into different adverse event categories. Most trials were at moderate risk of bias. Hospital stay was reported in all of the trials and results show that on average, laparoscopy was associated with a significantly shorter hospital stay. AUTHORS' CONCLUSIONS: This review has found evidence to support the role of laparoscopy for the management of early endometrial cancer.For presumed early stage primary endometrioid adenocarcinoma of the endometrium, laparoscopy is associated with similar overall and disease-free survival. Laparoscopy is associated with reduced operative morbidity and hospital stay. There is no significant difference in severe post-operative morbidity between the two modalities.

Interventions for reducing anxiety in women undergoing colposcopy.

BACKGROUND: Prior to the development of cervical cancer abnormal cervical cells can be detected on a cervical smear. The usual practice following an abnormal cervical smear is to perform colposcopy. Colposcopy is the visualisation of the cervix using a binocular microscope. Women experience high levels of anxiety and negative emotional responses at all stages of cervical screening. High levels of anxiety before and during colposcopy can have adverse consequences, including pain and discomfort during the procedure and high loss to follow-up rates. This review evaluates interventions designed to reduce anxiety levels during colposcopic examination. OBJECTIVES: To compare the efficacy of various interventions aimed at reducing anxiety during colposcopic examination in women. SEARCH METHODS: We searched the Cochrane Gynaecological Cancer Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), Issue 3, 2010, MEDLINE and EMBASE up to July 2010. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. SELECTION CRITERIA: Randomised controlled trials (RCTs) of interventions to reduce anxiety during colposcopic examination. DATA COLLECTION AND ANALYSIS: Two review authors independently abstracted data and assessed risk of bias. Mean differences for anxiety levels, knowledge scores, pain, patient satisfaction and psychosexual dysfunction in women who underwent colposcopy were pooled in a random effects meta-analyses. MAIN RESULTS: We found six trials that met our inclusion criteria. These trials assessed the effectiveness of different interventions for reducing anxiety in women undergoing colposcopy for the first time.All comparisons were restricted to single trial analyses or meta analysis of just two trials. There was evidence from a reasonably large trial (n = 220) that was at low risk of bias to suggest that music during colposcopy significantly reduced anxiety levels (MD = -4.80, 95% CI: -7.86 to -1.74) and pain experienced during the procedure (MD = -1.71, 95% CI: -2.37 to -1.05) compared to not listening to music. There was no statistically significant difference between anxiety levels prior to colposcopy in women receiving information leaflets versus no leaflets and information leaflets, video and counselling versus information leaflets and video with no counselling. However, knowledge scores were significantly higher and psychosexual dysfunction scores were significantly lower in women who received leaflets compared to those who did not so there was some sort of benefit to giving patients information leaflets. There is evidence for video colposcopy from a quasi randomised trial which assessed 81 women showing significant anxiety reduction. AUTHORS' CONCLUSIONS: Anxiety appears to be reduced by playing music during colposcopy. Although information leaflets did not reduce anxiety levels, they did increase knowledge levels and are therefore useful in obtaining clinical consent to the colposcopic procedure. Leaflets also contributed to improved patient quality of life by reducing psychosexual dysfunction.