James Nevin

Outcomes following implementation of symptom triggered diagnostic testing for ovarian cancer

OBJECTIVESnUK is the first country to implement symptom triggered testing for suspected ovarian cancer (OC) following guidance from National Institute of Clinical Excellence in 2011. We evaluated its impact on cancer outcomes and implications on clinical practice.nnnSTUDY DESIGNnThis is a cohort study and we analysed data for all new urgent referrals for suspected OC from two large teaching hospitals using a prospectively collected electronic referral database, supplemented with clinical data from electronic records. We evaluated outcomes prior to (2011) and after (2013) implementation of guidance to evaluate stage shift, referrals workload and surgical procedures generated.nnnRESULTSnSecondary care received 2185 new referrals from primary care for women with suspected gynaecological cancer in post guideline cohort. Of these, 217 women were referred for suspected OC. 90% of primary care referrals were not compliant with guidance. Following implementation of guidance, more women with OC were diagnosed through urgent referral (rapid access clinics): Almost double, 21 of the total 67 (31.34%) OCs in 2013 (post guidance) in comparison to only 11 of 69 OCs (15.94%) were diagnosed in 2011 (pre guidance) through urgent referrals, p=0.03. The predictive value of detecting cancer through rapid access clinics increased, from 4.5% to 9.6%, p=0.04; however, no stage shift was noted. Over 25% of patients underwent surgeries for non-malignant conditions in the post-guideline cohort. No increase was seen in workload of cancer clinics.nnnCONCLUSIONnImplementation of Symptom-triggered testing is challenging in clinical practice. Such testing results in more patients with OC accessing expedited care pathways leading to streamlined routes of diagnosis and care. However, current implementation does not lead to stage shift in diagnosis and may not achieve significant mortality benefit.

Meeting the challenge of developing and maintaining radical hysterectomy skills

A radical hysterectomy (RH), in combination with bilateral pelvic lymphadenectomy, is the standard therapy for a woman with stage 1b1 cervical cancer. This complex surgical procedure carries the risk of serious complications and therefore selecting women for and safely undertaking this operation has become the responsibility of subspecialist gynaecological oncologists. The process by which this occurred evolved over the last two decades. The first step was the development of a gynaecological oncology subspecialty training syllabus by the Royal College of Obstetricians and Gynaecologists (RCOG). This was followed by the establishment of a number of training centres throughout the UK. The third step followed national organisational changes that classify hospitals as either cancer units or cancer centres and arrange them in a ‘hub and spoke’ pattern. Cancer units undertake diagnostic and simple surgical procedures whereas complex surgery has become the responsibility of cancer centres. As a result, RH caseloads achieved the critical mass that allowed not only the development of but also the maintenance of the skills and experience necessary to ensure quality care. Informal discussions within the UK gynaecological oncology community suggest a growing level of disquiet about the emergence of a number of new obstacles to the maintenance of this critical mass. First, the number of RH being undertaken is falling because overall rates of cervical cancer are falling, fertility-sparing operations have been introduced, primary chemoradiotherapy has been shown to be a viable non-surgical option, simple hysterectomy for low volume stage 1b1 tumours is acceptable and there have been efforts to limit rates of adjuvant post-RH chemoradiotherapy. Second, subspecialty trainees are entering programmes with less surgical experience – which necessitates more time on the development of basic surgical skills in the early phases of training programmes thereby leaving less time for the development of radical surgical skills and experience. Third, the introduction of laparoscopic techniques has reduced the number of RH undertaken via the open route. As the skills to undertake this complex operation laparoscopically are ideally developed against a background of experience with open operations, trainees are being placed in the unfortunate quandary of having access to too few open operations to develop the skills to undertake these operations laparoscopically. The aim of this study is to provoke formal discussions on this subject by presenting an analysis of the treatments offered to a cohort of women with newly diagnosed stage 1b1 cervical cancer managed in a moderate to large gynaecological cancer centre over a three-year period.

Metastatic adenocarcinoma of right supraclavicular fossa – delayed presentation of ovarian primary

The management of primary ovarian ectopic gestation is oophorectomy but a more recent conservative approach is laparoscopic ovarian wedge resection (Hage et al. 1994). Local and systemic injections of methotrexate and prostaglandin PGF2a are also used in cases where the patient is haemodynamically stable and diagnosis is established on scan. These latest advances in management are aimed at conserving fertility.

Diaphragm disease in advanced ovarian cancer: Predictability of pre-operative imaging and safety of surgical intervention

OBJECTIVESnTo establish the positive predictive values of pre-operative identification with CT imaging of metastatic diaphragm disease in surgically managed cases of advanced ovarian cancer (AOC). Additionally, we have assessed the post-operative morbidity and survival following diaphragmatic surgical intervention in a large regional cancer centre in the United Kingdom.nnnSTUDY DESIGNnA retrospective review of all cases of AOC with metastatic diaphragm disease surgically treated at the Pan-Birmingham Gynaecological Cancer Centre, UK between 1st August 2007 and 29th February 2016.nnnRESULTSnA total of 536 women underwent surgery for primary AOC. Diaphragm disease was evident intra-operatively in 215/536 (40.1%) and 85/536 women (15.9%) underwent a procedure involving their diaphragm. Of these 85 cases, 38 peritoneal strippings (38/85, 44.7%), 31 partial diaphragmatic resections (31/85, 35.6%) and 16 electro-surgical ablations (16/85, 18.9%) were performed. There were no significant differences in post-operative complications between the three different diaphragmatic surgical groups. Of those patients who underwent peritoneal stripping or partial diaphragm resection, 12% were upstaged to stage 4A by virtue of pleural invasion. The positive predictive value for pre-operative radiological identification of diaphragmatic disease was 78.6%. CT imaging failed to detect diaphragmatic involvement despite obvious diaphragm disease during surgery in 29.4% of cases, giving a low negative predictive value of 64.8%. The sensitivity and specificity for CT imaging in detecting diaphragm disease was 44.3% and 93.8%, respectively.nnnCONCLUSIONSnDiaphragmatic disease is often discovered in AOC. However, pre-operative assessment with CT imaging is not reliable in accurately detecting diaphragm involvement. Therefore, all patients with AOC should be regarded as in potential need for diaphragm surgery and their operation undertaken in cancer centres with adequate expertise in upper abdominal surgery. If there is a suspicion of diaphragm muscle invasion during diaphragmatic peritonectomy, the muscle should be partially resected. This will lead to potential upstaging of disease to stage 4A and therefore, to suitability for targeted therapy. In our Centre, the surgical removal of diaphragmatic disease did not significantly increase surgical morbidity.

Predictive value of the age-adjusted Charlston co-morbidity index on peri-operative complications, adjuvant chemotherapy usage and survival in patients undergoing debulking surgery after neo-adjuvant chemotherapy for advanced epithelial ovarian cancer

Abstract The aim of this study was to determine whether the age-adjusted Charlston co-morbidity index (ACCI) can predict post-operative complications, adjuvant chemotherapy usage and overall survival (OS) in patients with advanced epithelial ovarian cancer (AOC) treated with neoadjuvant chemotherapy (NACT). A review was performed of all cytoreductive surgeries performed between 16/8/07-3/2/14 for AOC at a UK Cancer Centre. All surgeries were stratified by ACCI into three groups: Low (0–1), Intermediate (2–3) and High (≥4). Of the 293 cases the ACCI distribution was: 74 (25.26%) low, 164 (55.97%) intermediate and 55 (18.77%) high. Patients with a high ACCI were less likely to receive adjuvant chemotherapy (pu2009=u2009.023), more likely to receive fewer adjuvant cycles (pu2009=u2009.0057) but no more likely to experience complications. Median OS for patients with a low, intermediate and high ACCI was 44.58 (95%CI 36.98–52.19), 34.65 (95%CI 29.48–39.82) and 33.37 (95%CI 17.47–49.27) months. ACCI was associated with OS (pu2009<u2009.01) confirmed on multivariate analysis (pu2009=u2009.03). The ACCI is, therefore, a marker of survival in these patients and predicts adjuvant chemotherapy usage. Impact statement The Age-Adjusted Charlston Co-morbidity Index has previously been identified as a predictor of survival in both medical and surgical conditions. Recently it has also been validated in patients undergoing primary cytoreductive surgery for advanced ovarian cancer. This study is the first to validate the Age-Adjusted Charlston Co-morbidity Index in patients undergoing cytoreductive surgery following neoadjuvant chemotherapy. Our findings demonstrate that it can be used to not only predict overall survival in women undergoing debulking surgery after neo-adjuvant chemotherapy but also predicts the uptake and commencement of adjuvant chemotherapy. Such findings are important considerations to enable an informed patient choice regarding interval surgery in the more co-morbid patients. More importantly, although the ACCI can be used as a marker of overall survival, even in the most co-morbid of patients there remains a significant survival advantage following surgery to the extent that it should not be contraindicated in this cohort. The ACCI is being increasingly incorporated into various clinical trials as a standard demographic measure and this study validates its inclusion in patients undergoing interval debulking surgery.

Complete cytoreduction after five or more cycles of neo-adjuvant chemotherapy confers a survival benefit in advanced ovarian cancer.

OBJECTIVESnTo assess the impact of 5 or more cycles of neoadjuvant chemotherapy (NACT) and cytoreductive outcomes on overall survival (OS) in patients undergoing interval debulking surgery (IDS) for advanced ovarian cancer.nnnMETHODSnA retrospective review of patients receiving NACT followed by IDS between 2007 and 2017. Patients were analysed according to number of NACT cycles received: group 1 consisted of patients receiving ≤4 cycles and group 2 consisted of those receiving ≥5 cycles. Outcomes were stratified by cytoreductive outcome, surgical complexity, stage and chemotherapy exposure.nnnRESULTSn231 patients in group 1 and 167 in group 2 were identified. In group 1, the OS for those achieving Complete (R0), Optimal<1xa0cm (R1) and Suboptimal (R2) was 51.1, 36.1, and 34.3 months respectively. Statistically significant differences in survival were seen in patients achieving R0vR2 (pxa0<xa00.019) but not in R0vR1 (pxa0=xa00.125) or R1vR2 (pxa0=xa00.358). In group 2, the OS for those achieving R0, R1 and R2 was 53.0, 24.7, and 22.1 months respectively. Statistically significant differences were seen between R0vR1 and R0vR2 (pxa0<xa00.00001) but not between R1vR2 (pxa0=xa00.917). No difference in OS was seen between groups 1 and 2. In patients achieving R1, there was a trend towards decreasing OS with increasing exposure to NACT from 36.1 (95%CI 32.0-40.2)months with 3 cycles to 24.3 (95%CI 14.4-34.2)months with ≥6 cycles.nnnCONCLUSIONSnSurgery with utilisation of cytoreductive procedures to achieve complete clearance should be offered to all patients even after ≥5 cycles if R0 can be achieved. R1 cytoreduction has questionable value in those receiving ≤4 cycles and no value in those receiving ≥5 cycles.

Is routine adnexal scanning for postmenopausal bleeding of value? Observational study of 2101 women

Abstract Our objective is to assess the merits of adnexal scanning during the investigation of women with postmenopausal bleeding (PMB) in terms of adnexal cancer diagnosis. This observational study was designed utilising an institutional PMB database in a teaching hospital, analysing a sample of 2101 consecutive women with PMB seen between 16th February 2012 and 12th August 2014 looking at the prevalence of cancer in adnexal masses identified on Trans-vaginal ultrasound scanning (TVS) in these PMB women. This study suggests that routine adnexal scanning in women with PMB may provide no benefit. It could be exposing women to unnecessary surgery or surveillance with the associated risks and cost implications. Most of the women who underwent surgery presented with palpable masses. Those with negative clinical examination had either benign masses which may have remained inconsequential or non-suspicious scan findings. A well-designed randomised controlled trial is needed to confirm the findings. Impact statement Trans-vaginal ultrasound scanning (TVS) is the standard first line investigation for women presenting with postmenopausal bleeding (PMB) primarily to assess the endometrial thickness. This has led to a widespread practice of opportunistic adnexal scanning, which generated a debate amongst gynaecologists about the value of such practice. This observational study, assessing the merits of routine adnexal scanning in these women in terms of adnexal cancer diagnosis, suggests that this practice may provide no benefit to women with isolated self-limiting PMB and unremarkable bimanual examination. It could be exposing women to unnecessary surgery or surveillance with the associated risks and cost implications when insignificant adnexal masses are identified on the scan. A well-designed randomised controlled trial is needed to elucidate if clinical examination in combination with endometrial scanning only is more effective and cost-effective than clinical examination followed by systematic pelvic scanning to detect cases of ovarian cancer in women with PMB.

Patient-Reported Outcomes After Extensive (Ultraradical) Surgery for Ovarian Cancer: Results From a Prospective Longitudinal Feasibility Study.

Background Extensive (ultraradical) surgery may facilitate complete cytoreduction in ovarian cancer with potential survival benefit but with greater morbidity. Currently, patient-reported outcomes (PROs) from such surgery are unknown. We conducted the Surgery in Ovarian Cancer Quality of life Evaluation Research study (SOCQER 1), a prospective study investigating the feasibility of collection of serial PROs in patients who had extensive surgery and standard surgery for ovarian cancer. Methods Ninety-three patients were recruited for 33 months to complete serial PRO assessments using the validated EORTC QLQ-C30 and the ovarian cancer–specific QLQ-OV28 questionnaires preoperatively, at 6 weeks, and at 3, 6, and 9 months postoperatively. Aletti Surgical Complexity Score of 3 or lower was considered standard surgery; a Surgical Complexity Score of 4 or higher was considered extensive surgery. Prospective data collection was obtained from the hospital electronic database, including patient demographics, American Society of Anaesthesiologists grade, preoperative serum CA125 and albumin levels, chemotherapy regimen, and surgical morbidity. Results Three cohorts of patients—32 benign, 32 undergoing standard surgery, and 24 undergoing extensive surgery—completed the questionnaires. Median questionnaire completion rate in this study was 64%, demonstrating the feasibility of longitudinal quality of life (QoL) assessment after surgery. Patient-reported outcomes revealed a falling trend in QoL in the short-term (6 weeks-3 months) after surgery, which gradually returned to baseline at 6 to 9 months; this trend was more marked after extensive surgery. Conclusions This study provides useful insight into the impact of extensive surgery on patients. Further multicenter studies are needed to evaluate the impact of extensive surgery on patient’s QoL and survival.

The NICE classification for ‘Ultra‐radical (extensive) surgery for advanced ovarian cancer’ guidance does not meaningfully predict postoperative complications: a cohort study

To determine which descriptors of cytoreductive surgical extent in advanced ovarian cancer (AOC) best predict postoperative morbidity.

Hysteroscopy under general anaesthesia: Are we meeting the standards?

About 10% of women presenting with post-menopausal bleeding (PMB) may have a malignancy and the majority of these malignancies will be endometrial in origin. Hysteroscopy retains a role in the assessment of a proportion of women with PMB (Chambers and Chambers 1992). Although transvaginal sonography, endometrial sampling and outpatient hysteroscopy have reduced the number of inpatient hysteroscopies performed under general anaesthesia, a significant minority of patients still require this type of assessment. Hysteroscopy performed under general anaesthesia allows several important clinical objectives to be achieved (van Dongen et al. 2007). These include confirmation of neoplasia; assessment of the ectoand endocervix as potential origins of cancer; assessment of the vagina and vulva; assessment of potential resectability of the uterus and the route of resection. Although this procedure is considered to be both minor in terms of intervention and simple in terms of technique, we were concerned that the full potential for recording the above in its totality was often not met. We believed that a quality assurance audit of this relatively common procedure was justified.