Bevacizumab Treatment for Low-Grade Serous Ovarian Cancer: A Systematic Review.

Serous epithelial ovarian cancer, classified as either high-grade (90%) or low-grade (10%), varies in molecular, histological, and clinicopathological presentation. Low-grade serous ovarian cancer (LGSOC) is a rare histologic subtype that lacks disease-specific evidence-based treatment regimens. However, LGSOC is relatively chemo-resistant and has a poor response to traditional treatments. Alternative treatments, including biologic therapies such as bevacizumab, have shown some activity in LGSOC. Thus, the objective of this systematic review is to determine the effect and safety of bevacizumab in the treatment of LGSOC. Following PRISMA guidelines, Medline ALL, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Embase all from the OvidSP platform, ClinicalTrials.gov, International Clinical Trials Registry Platform, International Standard Randomised Controlled Trial Number Registry were searched from inception to February 2022. Articles describing bevacizumab use in patients with LGSOC were included. Article screening, data extraction, and critical appraisal of included studies were completed by two independent reviewers. The effect of bevacizumab on the overall response rate, progression-free survival, overall survival, and adverse effects were summarized. The literature search identified 3064 articles, 6 of which were included in this study. A total of 153 patients were analyzed; the majority had stage IIIC cancer (56.2%). The overall median response rate reported in the studies was 47.5%. Overall, bevacizumab is a promising treatment for LGSOC, with response rates higher than traditional treatment modalities such as conventional chemotherapy, and is often overlooked as a treatment tool. A prospective clinical trial evaluating the use of bevacizumab in LGSOC is necessary to provide greater evidence and support these findings.

Identifying Borderline Ovarian Tumor Recurrence Using Routine Ultrasound Follow-Up.

Borderline ovarian tumors (BOTs) are non-invasive tumors frequently diagnosed in young patients. Surgical removal of the uterus, fallopian tubes, ovaries, and omentum is considered definitive management, however fertility-sparing approach is a recognized option. Surveillance is important due to known recurrence, but there is controversy over the effectiveness of follow-up modalities. The objective is to determine the efficacy of ultrasound screening in identifying tumor recurrence. This retrospective chart review evaluated all patients consulted and/or treated surgically at our institution from January 2015 to June 2020 diagnosed with BOT. Patients were excluded if concurrently diagnosed with another gynecologic malignancy, did not have yearly ultrasound follow-up, or were lost to follow-up. This study included 56 patients, 17 of whom underwent fertility preserving surgery. The overall rate of recurrence was 10.7%; with recurrence rates of 23.5% for the fertility preserving surgery population and 5.1% for the definitive surgery population. Ultrasound first identified 5 of the 6 (83.3%) recurrences. Overall time to recurrence was 51.5 months. In conclusion, recurrences were identified on routine ultrasound screening prior to symptom onset or detection via physical exam in 83.3% of cases. While the best modality of follow-up remains controversial, this review provides evidence supporting the use of routine ultrasound follow-up for early detection of BOT recurrence.

Hormone maintenance therapy for women with low-grade serous ovarian cancer in the front-line setting: A systematic review.

OBJECTIVE: Low-grade serous ovarian cancer (LGSOC) is a rare form of ovarian cancer that accounts for 5-10% of epithelial ovarian cancers. LGSOCs are difficult to treat as they respond poorly to traditional chemotherapy treatments. This systematic review aims to appraise the literature describing the efficacy of hormone maintenance therapy (HMT) in patients with LGSOC given after cytoreductive surgery. METHODS: Medline, EMBASE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews were searched from inception to November 2020. No language restrictions were applied. Publications describing HMT in the primary setting following cytoreductive surgery with or without chemotherapy in women with LGSOC were included. Publications describing HMT in recurrence, non-LGSOC carcinomas, and in-vitro or animal studies were excluded along with case reports, case series, and conference proceedings. We summarized oncologic outcomes, HMT used, and hormone receptor status where reported. Studies were assessed for risk of bias and quality of evidence. RESULTS: The literature search identified 14,799 records. Four cohort studies met eligibility criteria. A total of 558 patients were included, of which 127 were treated with HMT. There was significant heterogeneity between studies demonstrated by differences in HMT regimens used, dosing, and study population, leading to various outcomes following treatment with HMT. CONCLUSIONS: Treatment of LGSOC remains a challenge. One retrospective study demonstrated improved progression-free survival following HMT for LGSOC, while two others failed to show significant improvements. However, there is limited data available in the literature which restricts the generalizability of these results. Therefore, well-designed, prospective, and randomized trials are needed to confirm the benefit of HMT in patients with this rare subgroup of ovarian cancer.

Does Radical Hysterectomy for Clinically Apparent Stage II Endometrial Cancer Affect Risk of Local Recurrence?

OBJECTIVE: Compare recurrence-free survival (RFS) and morbidity between radical hysterectomy (RH) and simple hysterectomy (SH) for clinically diagnosed stage II endometrial cancer. METHODS: A multicentre, retrospective study, from 2000 to 2015, involving patients with endometrial cancer with cervical involvement preoperatively and stromal invasion on final pathology. Wilcoxon rank-sum test, Fisher exact test, Kaplan-Meier survival functions, and Cox proportional hazards models were used for analysis. RESULTS: Ninety of 1613 patients had clinical stage II endometrial cancer; 57 underwent RH and 33 underwent SH, with no difference in adjuvant treatment or morbidity. About half of patients (51%) had pathologic stage III-IV disease. Mean follow-up was 3.3 and 3.8 years for SH and RH, respectively. Thirty-three percent of patients with RH and SH experienced a recurrence. Most recurrences were distant: 90% with SH and 79% with RH. There was no difference in RFS between groups (2-year: SH 65% vs. RH 75%; 5-year: SH 54% vs. RH 63%; P = 0.72). Controlling for stage, adjuvant treatment, and margin status, RH was not associated with RFS (HR 0.62; 95% CI 0.28-1.35). Among 44 patients with pathologic stage II disease, 7 had a recurrence (4 SH and 3 RH); 6 of 7 had distant recurrences. CONCLUSIONS: Fifty-one percent of patients with clinical stage II endometrial cancer had advanced disease on final pathology, highlighting the importance of surgical staging. RH was not associated with RFS or reduced morbidity. Most recurrences were distant. Although RH could be performed to achieve negative surgical margins, SH may be sufficient for central, small tumours given the high risk of advanced disease and distant recurrence. Research efforts should further elucidate the ideal management of these patients.

Same-Day Discharge Among Patients With Obesity Undergoing Laparoscopic Gynaecologic Oncology Surgery.

OBJECTIVES: To determine the likelihood of same-day discharge (SDD) among patients with obesity undergoing laparoscopic gynaecologic oncology surgery and identify predictors of SDD. METHODS: We conducted a retrospective cohort study of gynaecologic oncology patients who underwent laparoscopic procedures between January 2012 and June 2016. Patients were categorized as non-obese, obese class I/II and obese class III (BMI <30, 30-39.9, and ≥40 kg/m2, respectively). We used univariate and multivariable logistic regression to identify variables associated with SDD. RESULTS: Of 496 patients, 288 were non-obese, 161 were obese class I/II, and 47 were obese class III. Overall, 182 patients (36.7%) were discharged same day; 44% of these were non-obese, 30% class I/II and 15% class III. On multivariable analysis, we found negative predictors for SDD to be obesity (OR 0.54; P = 0.03), procedure length (OR 0.51; P < 0.01), and higher American Society of Anesthesiologists (ASA) score (OR 0.63; P < 0.01), while we found being pre-booked for SDD (OR 9.16; P <0.01) was a positive predictor of SDD. Among all patients with obesity, only procedure length (OR 0.47; P < 0.01) and being pre-booked for SDD (OR 9.67; P < 0.01) were associated with SDD when we controlled for BMI, ASA score, intraoperative complications, type of surgery, and surgical start time. Patients discharged same day were less likely to present to the emergency department within 30 days of surgery (OR 0.48; P = 0.01). CONCLUSION: Among the study cohort and after controlling for potential confounders, women with class I, II, and III obesity had a much lower likelihood of SDD than non-obese women. The only significant predictors of SDD among patients with obesity were duration of procedure and pre-booking for SDD. Further study is needed to identify strategies to improve SDD rates among patients with obesity.

The rectus abdominus myoperitoneal flap for vaginal reconstruction.

To review the indications, technique and results of the rectus abdominis myoperitoneal (RAMP) flap for vaginal reconstruction from literature and at a single institution. A literature search was conducted of vaginal reconstruction to identify published cases using RAMP flaps. All cases of vaginal reconstruction at Sunnybrook Health Sciences Center (SHSC) from 2007 to 2019 were reviewed. Twenty-one published cases of vaginal reconstruction with RAMP flaps were identified. Eleven had partial longitudinal vaginal defects, 5 had circumferential defects and 5 had unspecified defects. Eight patients with circumferential (N = 3) or unspecified (N = 5) defects developed vaginal stenosis. None of the 11 patients with partial longitudinal defects developed vaginal stenosis and 8 resumed sexual activity. There were 2 cases of donor site hernia and 4 donor site infections, but no flap loss. At SHSC, 5 cases of RAMP flap vaginal reconstruction were identified. Cases 1-3 and 5 had circumferential vaginal defects and Case 4 had a partial longitudinal defect. There were no cases of flap necrosis or donor site hernia. Case 1 died 18 days after pelvic exenteration from bowel ischemia. Case 2 developed a rectovaginal fistula after an anastomotic leak from a low anterior resection. Case 3 had a wound infection and vaginal shortening to 3-4 cm. Cases 4 and 5 had no complications and the vagina appeared normal on exam post-operatively. The literature and our experience support the use of RAMP flaps for reconstruction of partial longitudinal vaginal defects but not circumferential defects where the risk of vaginal stenosis and shortening is high.

Patterns of recurrence and impact on survival in patients with clear cell ovarian carcinoma.

BACKGROUND: Patients with recurrent clear cell ovarian cancer have poor prognosis and limited effective systemic treatment options. OBJECTIVES: To characterize patterns of recurrence and compare overall survival and post-recurrence survival parameters in patients with recurrent ovarian clear cell carcinoma. METHODS: Clinical data on patients with ovarian clear cell carcinoma between June 1995 and August 2014 were collected. Patients with clear cell ovarian cancer recurrence were included in this study. Patients with different histologic sub-type, persistent or progressive disease on completion of the initial treatment were excluded. Descriptive statistics, univariate and multivariable analyses, and Kaplan-Meier survival probability estimates were completed. The log-rank test was used to quantify survival differences on univariable analysis. To search for significant covariates related to the overall survival and post-recurrence survival, a univariable Cox proportional hazard model was performed. RESULTS: A total of 209 patients met inclusion criteria. Of these, 61 (29%) patients who were free of disease at completion of the initial treatment had recurrence. Patterns of recurrence were as follows: 38 (62%) patients had multiple-site recurrence, 12 (20%) had single-site recurrence, and 11 (18%) had nodal recurrence only. The median overall survival was 44.7 months (95% CI 33.4 to 64.2) and was significantly associated with pattern of recurrence (p=0.005). The median post-recurrence survival was 18.4 months (95% CI 12.5 to 26.7): 54.4 months (95% CI 11 to 125.5) in single-site recurrence, 13.7 months (95% CI 6.8 to 16.5) in multiple-site recurrence, and 30.1 (95% CI 7.2 to 89) months in nodal recurrence (p=0.0002). In the multivariable analysis, pattern of recurrence was a predictor of post-recurrence survival.Six patients (9.8%) had a prolonged disease-free interval after recurrence (disease-free for more than 30 months after completion of treatment for recurrence). Prolonged recurrences were noted in 4 (33%) of 12 patients with single-site recurrence, 1 (9%) of 11 patients with nodal recurrence, and in 1 (2.7%) of 38 patients with multiple-site recurrence. Three of the six patients with a prolonged disease-free interval after recurrence were treated surgically at the time of recurrence. CONCLUSION: Ovarian clear cell carcinoma predominantly recurs in multiple sites and it is associated with a high mortality rate and short post-recurrence survival. When recurrences are limited to a single site, or only to lymph nodes, the median post-recurrence survival is longer. Disease-free interval after recurrence is longer in patients with single-site recurrence who are treated surgically at the time of recurrence.

Early Cervical Cancer: Current Dilemmas of Staging and Surgery.

PURPOSE OF REVIEW: Advances in cervical cancer screening and treatment have resulted in high cure rates in developed countries for early-stage disease. Current research focuses on minimizing morbidity and maximizing quality of life. RECENT FINDINGS: Imaging has been disappointing in identifying small volume metastases. Sentinel lymph node biopsy represents a significant advantage with high sensitivity, low false negative rates, reduced morbidity, and equivalent survival in recent studies compared to pelvic lymphadenectomy. Non-radical surgical options are currently being investigated for early cervical cancer in a number of large prospective studies in patients at low risk for metastases. Evidence suggests that sentinel lymph node biopsy and non-radical surgery are safe approaches for the staging and management of early cervical cancer in appropriately selected patients with the potential to significantly reduce treatment-related morbidity.

Can sentinel lymph node biopsy replace pelvic lymphadenectomy for early cervical cancer?

OBJECTIVE: Evaluate recurrence-free survival (RFS) and short-term morbidity in patients with early cervical cancer who undergo bilateral pelvic lymphadenectomy (BPLND) versus bilateral sentinel lymph node biopsy only (BSLNB) at primary surgery. METHODS: All patients with pathologically confirmed node negative stage IA/IB cervical cancer managed with BPLND or BSLNB were identified in the University of Toronto's prospective cervical cancer database from May 1984-June 2015. Groups were compared with Wilcoxon rank-sum, Chi-square, and Fisher's exact tests. Predictors of RFS were identified with Cox proportional hazard models. Kaplan-Meier survival curves were compared. Statistical significance was p<0.05. RESULTS: 1188 node negative patients were identified, BPLND-1078; BSLNB-110. There was no difference between BPLND and BSLNB in 2 and 5year RFS (95% vs 97% and 92% vs 93% respectively), tumor size, histology, invasion depth, intra-operative complications or short-term morbidity. BPLND was associated with increased surgical time (2.8 vs 2.0h, p<0.001), blood loss (500mL vs 100mL, p<0.001), transfusion (23% vs 0%, p<0.001) and post-operative infection (11% vs 0%, p=0.001). Age, surgery date, stage, LVSI, and radicality of surgery differed between groups. Controlling for age, stage, LVSI, invasion depth and histology, there was no significant difference in RFS between groups. Only invasion depth, LVSI and histology were predictors of RFS. CONCLUSION: A negative BSLNB is not associated with a difference in RFS compared to a negative BPLND. Short-term morbidity may be reduced, however due to the long study period, changes in demographics and surgery may contribute to differences noted.

Fertility-sparing management in cervical cancer: balancing oncologic outcomes with reproductive success.

BACKGROUND: Cervical cancer is the fourth most common cancer among women worldwide, many of who are still within their reproductive lifespan. Advances in screening and treatment have increased the 5-year survival for early stage disease to over 90 % in developed countries. The focus is now shifting to reducing morbidity and improving fertility outcomes for cervical cancer patients. Radical trachelectomy with lymph node assessment became the standard of care for selected women with lesions <2 cm who desire fertility preservation. However, several questions still remain regarding the degree of surgical radicality required for tumors <2 cm, and fertility-sparing options for women with early-stage disesase ≥2 cm, and those with more advanced disease. Here, we compile a narrative review of the evidence for oncologic and pregnancy outcomes following radical trachelectomy, non-radical fertility-sparing surgery, and the use of neoadjuvant chemotherapy prior to surgery for larger lesions. We also review the literature for assisted reproductive technologies in women with more advanced disease. FINDINGS: Available literature suggests that the crude recurrence and mortality rates after radical trachelectomy are <5 and <2 %, respectively (approx. 11 and 4 % for tumors ≥ 2 cm). Among 1238 patients who underwent fertility-sparing surgery for early cervical cancer there were 469 pregnancies with a 67 % live birth rate. Among 134 cases with lesions ≥ 2 cm, there were ten conceptions with a live birth rate of 70 %. Outcomes after non-radical surgery (simple trachelectomy or cervical conization) are similar, although only applicable among a highly selected patient population. For patients ineligible for fertility-preserving surgery or who require adjuvant radiation therapy, current options include ovarian transposition and cryopreservation of oocytes or embryos but other techniques are under investigation. CONCLUSION: Today, many cervical cancer survivors have successful pregnancies. For those with early-stage disease, minimally invasive and fertility sparing techniques have resulted in improved obstetrical outcomes without compromising oncologic safety. Results from three ongoing trials on non-radical surgery for low-risk tumors <2 cm will further inform the need for radical surgery in such patients. For those in whom natural childbearing is unachievable, advances in assisted reproductive technologies provide reproductive options. Despite our advances, the effects of cervical cancer survivorship on quality of life are not fully elucidated.

Effectiveness of the risk of malignancy index and the risk of ovarian malignancy algorithm in a cohort of women with ovarian cancer: does histotype and stage matter?

OBJECTIVE: To examine the performance of the Risk of Malignancy Index (RMI) and Risk of Ovarian Malignancy Algorithm (ROMA) by histologic subtype and stage of disease in a cohort of women with ovarian cancer. METHODS: All patients with confirmed ovarian cancer at the Princess Margaret Hospital between February 2011 and January 2013 were eligible for study inclusion. Preoperative cancer antigen 125, human epididymis protein 4, and ultrasound findings were reviewed, and the sensitivity and false-negative rates of the RMI and ROMA were determined by stage of disease and tumor histology. RESULTS: A total of 131 patients with ovarian cancer were identified. High-grade serous (HGS) histology was most frequently associated with stage III/IV disease (n = 46 [72% of stage III/IV]) vs stage I (n = 5 [11% of stage I]; P < 0.0001). Clear cell (CC) and endometrioid (EC) histology presented most commonly with stage I disease (n = 9 [20%] and n = 13 [29% of stage I cases], respectively). Median cancer antigen 125 and human epididymis protein 4 values were significantly higher for HGS than for EC or CC histology. Risk of Malignancy Index II demonstrated the highest sensitivity of the 3 RMI algorithms. All RMIs and ROMA were significantly more sensitive in predicting malignancy in patients with HGS than EC or CC histology. Risk of Malignancy Index II (n = 38) and ROMA (n = 35) exhibited sensitivities of 68% and 54% and false-negative rates of 32% and 46%, respectively, for patients with stage I disease vs sensitivities of 94% and 93% and false-negative rates of 6% and 7% for patients with stage III/IV disease. CONCLUSION: Both RMI and ROMA performed well for the detection of advanced ovarian cancer and HGS histology. These triaging algorithms do not perform well in patients with stage I disease where EC and CC histologies predominate. Clinicians should be cautious using RMI or ROMA scoring tools to triage isolated adnexal masses because many patients with stage I malignancies would be missed.

Minimally invasive surgical management of a second trimester pregnancy in a rudimentary uterine horn.

BACKGROUND: Pregnancy in a rudimentary uterine horn is a rare form of ectopic pregnancy with a high risk of rupture. Management usually involves excision of the rudimentary horn. If diagnosed after the first trimester, it has been managed in the past by laparotomy. CASE: A primigravid woman was found on routine ultrasound to have a rudimentary horn pregnancy. The diagnosis was confirmed on MRI, and a thin uterine wall was demonstrated. Management comprised fetal injection of potassium chloride followed by complete laparoscopic excision of the rudimentary horn at 16 weeks' gestation. CONCLUSION: Laparoscopic management of a mid-trimester rudimentary horn pregnancy is feasible, but expert radiological characterization is required for optimal surgical planning.

Contexte : La grossesse dans une corne utérine rudimentaire constitue une forme rare de grossesse ectopique qui compte un risque élevé de rupture. Sa prise en charge met habituellement en jeu l'excision de la corne rudimentaire. Par le passé, lorsqu'une telle grossesse était diagnostiquée après le premier trimestre, elle faisait l'objet d'une prise en charge par laparotomie. Cas : Nous avons constaté, à la suite d'une échographie régulière, qu'une primigravide présentait une grossesse dans une corne utérine rudimentaire. Le diagnostic a été confirmé par IRM et la présence d'une mince paroi utérine a été démontrée. La prise en charge a pris la forme d'une injection fœtale de chlorure de potassium, suivie d'une excision laparoscopique complète de la corne rudimentaire à 16 semaines de gestation. Conclusion : Bien que la prise en charge laparoscopique d'une grossesse dans une corne utérine rudimentaire au deuxième trimestre soit faisable, l'obtention d'une caractérisation radiologique spécialisée s'avère requise pour assurer une planification chirurgicale optimale.