female humans

Ovarian Cancer: A Review

Author/s: 
Giuseppe Caruso, MD, S. John Weroha, MD, PhD, William Cliby, MD

Importance: Ovarian cancer is the eighth most common cause of cancer and cancer death in women worldwide. In 2022, ovarian cancer was diagnosed in approximately 324 398 individuals, and 206 839 died of ovarian cancer worldwide. In 2025, it is estimated that 20 890 US women will be diagnosed with ovarian cancer and 12 730 patients will die of ovarian cancer.

Observations: Approximately 90% of ovarian cancers are epithelial malignancies, of which 70% to 80% are high-grade serous ovarian cancers. Less common epithelial subtypes include endometrioid, clear cell, low-grade serous, mucinous, and carcinosarcoma. The median age at diagnosis of ovarian cancer is 63 years. Risk factors include older age, family history of breast or ovarian cancer, endometriosis, and nulliparity. Hereditary factors are associated with 25% of cases, predominantly linked to BRCA1/2 gene variants. At diagnosis, approximately 95% of patients experience nonspecific symptoms, such as abdominal pain, bloating, and urinary urgency and frequency, and about 80% have advanced-stage disease (stage III-IV), including extrapelvic disease, ascites, and abdominal masses. Diagnostic and staging evaluation includes pelvic ultrasound; computed tomography of the chest, abdomen, and pelvis; and serum tumor markers such as carbohydrate antigen 125, carbohydrate antigen 19-9, and carcinoembryonic antigen. First-line treatment for early-stage ovarian cancer, defined as limited to the ovary or fallopian tube (stage I) or confined to the pelvis (stage II), is surgery (hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and lymphadenectomy), followed by adjuvant chemotherapy (carboplatin and paclitaxel). With treatment, early-stage ovarian cancer has a 5-year overall survival of 70% to 95%. Advanced-stage ovarian cancer may be treated with primary cytoreductive surgery (removal of all visible cancer in the abdominal cavity) and adjuvant chemotherapy (carboplatin and paclitaxel) or with neoadjuvant chemotherapy followed by cytoreductive surgery and adjuvant chemotherapy. Most patients with advanced-stage ovarian cancer receive maintenance therapy with bevacizumab (a monoclonal antibody that blocks angiogenesis) and/or poly–adenosine diphosphate ribose polymerase (PARP) inhibitors. With treatment, the 5-year overall survival rate for advanced-stage ovarian cancer is 10% to 40%. However, individuals with BRCA-related gene variants have a 5-year overall survival rate of approximately 70% with PARP inhibitor treatment. Despite an initial remission rate of 80%, approximately 75% of patients with advanced-stage disease have ovarian cancer relapse within 2 years.

Conclusions and Relevance: Approximately 21 000 women are diagnosed with ovarian cancer annually in the US, and approximately 80% have advanced-stage ovarian cancer at diagnosis. First-line treatment of early-stage ovarian cancer is surgery and adjuvant platinum-based chemotherapy. Treatment of advanced-stage ovarian cancer includes cytoreductive surgery, platinum-based chemotherapy, and targeted maintenance therapies such as bevacizumab and/or PARP inhibitors.

Pelvic floor muscle training versus no treatment, or inactive control treatments, for urinary incontinence in women

Author/s: 
Dumoulin, Chantale E., Hay-Smith, Jean C., Mac Habee-Seguin, Gabrielle

Background

Pelvic floor muscle training (PFMT) is the most commonly used physical therapy treatment for women with stress urinary incontinence (SUI). It is sometimes also recommended for mixed urinary incontinence (MUI) and, less commonly, urgency urinary incontinence (UUI).

This is an update of a Cochrane Review first published in 2001 and last updated in 2014.

Objectives

To assess the effects of PFMT for women with urinary incontinence (UI) in comparison to no treatment, placebo or sham treatments, or other inactive control treatments; and summarise the findings of relevant economic evaluations.

Search methods

We searched the Cochrane Incontinence Specialised Register (searched 12 February 2018), which contains trials identified from CENTRAL, MEDLINE, MEDLINE In‐Process, MEDLINE Epub Ahead of Print, ClinicalTrials.gov, WHO ICTRP, handsearching of journals and conference proceedings, and the reference lists of relevant articles.

Selection criteria

Randomised or quasi‐randomised controlled trials in women with SUI, UUI or MUI (based on symptoms, signs or urodynamics). One arm of the trial included PFMT. Another arm was a no treatment, placebo, sham or other inactive control treatment arm.

Data collection and analysis

At least two review authors independently assessed trials for eligibility and risk of bias. We extracted and cross‐checked data. A third review author resolved disagreements. We processed data as described in the Cochrane Handbook for Systematic Reviews of Interventions. We subgrouped trials by diagnosis of UI. We undertook formal meta‐analysis when appropriate.

Main results

The review included 31 trials (10 of which were new for this update) involving 1817 women from 14 countries. Overall, trials were of small‐to‐moderate size, with follow‐ups generally less than 12 months and many were at moderate risk of bias. There was considerable variation in the intervention's content and duration, study populations and outcome measures. There was only one study of women with MUI and only one study with UUI alone, with no data on cure, cure or improvement, or number of episodes of UI for these subgroups.

Symptomatic cure of UI at the end of treatment: compared with no treatment or inactive control treatments, women with SUI who were in the PFMT groups were eight times more likely to report cure (56% versus 6%; risk ratio (RR) 8.38, 95% confidence interval (CI) 3.68 to 19.07; 4 trials, 165 women; high‐quality evidence). For women with any type of UI, PFMT groups were five times more likely to report cure (35% versus 6%; RR 5.34, 95% CI 2.78 to 10.26; 3 trials, 290 women; moderate‐quality evidence).

Symptomatic cure or improvement of UI at the end of treatment: compared with no treatment or inactive control treatments, women with SUI who were in the PFMT groups were six times more likely to report cure or improvement (74% versus 11%; RR 6.33, 95% CI 3.88 to 10.33; 3 trials, 242 women; moderate‐quality evidence). For women with any type of UI, PFMT groups were two times more likely to report cure or improvement than women in the control groups (67% versus 29%; RR 2.39, 95% CI 1.64 to 3.47; 2 trials, 166 women; moderate‐quality evidence).

UI‐specific symptoms and quality of life (QoL) at the end of treatment: compared with no treatment or inactive control treatments, women with SUI who were in the PFMT group were more likely to report significant improvement in UI symptoms (7 trials, 376 women; moderate‐quality evidence), and to report significant improvement in UI QoL (6 trials, 348 women; low‐quality evidence). For any type of UI, women in the PFMT group were more likely to report significant improvement in UI symptoms (1 trial, 121 women; moderate‐quality evidence) and to report significant improvement in UI QoL (4 trials, 258 women; moderate‐quality evidence). Finally, for women with mixed UI treated with PFMT, there was one small trial (12 women) reporting better QoL.

Leakage episodes in 24 hours at the end of treatment: PFMT reduced leakage episodes by one in women with SUI (mean difference (MD) 1.23 lower, 95% CI 1.78 lower to 0.68 lower; 7 trials, 432 women; moderate‐quality evidence) and in women with all types of UI (MD 1.00 lower, 95% CI 1.37 lower to 0.64 lower; 4 trials, 349 women; moderate‐quality evidence).

Leakage on short clinic‐based pad tests at the end of treatment: women with SUI in the PFMT groups lost significantly less urine in short (up to one hour) pad tests. The comparison showed considerable heterogeneity but the findings still favoured PFMT when using a random‐effects model (MD 9.71 g lower, 95% CI 18.92 lower to 0.50 lower; 4 trials, 185 women; moderate‐quality evidence). For women with all types of UI, PFMT groups also reported less urine loss on short pad tests than controls (MD 3.72 g lower, 95% CI 5.46 lower to 1.98 lower; 2 trials, 146 women; moderate‐quality evidence).

Women in the PFMT group were also more satisfied with treatment and their sexual outcomes were better. Adverse events were rare and, in the two trials that did report any, they were minor. The findings of the review were largely supported by the 'Summary of findings' tables, but most of the evidence was downgraded to moderate on methodological grounds. The exception was 'participant‐perceived cure' in women with SUI, which was rated as high quality.

Authors' conclusions

Based on the data available, we can be confident that PFMT can cure or improve symptoms of SUI and all other types of UI. It may reduce the number of leakage episodes, the quantity of leakage on the short pad tests in the clinic and symptoms on UI‐specific symptom questionnaires. The authors of the one economic evaluation identified for the Brief Economic Commentary reported that the cost‐effectiveness of PFMT looks promising. The findings of the review suggest that PFMT could be included in first‐line conservative management programmes for women with UI. The long‐term effectiveness and cost‐effectiveness of PFMT needs to be further researched.

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