Pathfinder 2022: faster, further and fairer

Target Ovarian Cancer – October 2022

This report shows that although there have been significant improvements over the years for women with ovarian cancer, not enough progress has been made in diagnosis, awareness, treatment and support. It reveals that if diagnosis was faster, further support was available and access to treatment was fairer, there could be potential for more women to survive, live well with ovarian cancer and be supported from diagnosis and throughout treatment. 

Key findings
Awareness
Awareness of ovarian cancer symptoms in the general population has shown some improvement since we first started measuring this in 2009. However, progress has been slow, and we have seen little improvement in the knowledge of
feeling full and urinary symptoms. This is compounded by 40 per cent of women wrongly believing that cervical screening detects ovarian cancer. To tackle this awareness crisis, we need to see widespread government backed
symptoms awareness campaigns.
Diagnosis
The faster ovarian cancer is diagnosed, the greater the chance of receiving treatment and the greater the chance of survival. For the first time, we surveyed GP knowledge of symptoms unpromoted and found good awareness of the
symptoms of bloating and abdominal pain, which is welcome following Target Ovarian Cancer’s investment in GP education programmes. However, similar to the general people population survey, there was less awareness of feeling full and urinary symptoms. We also found delays in both access to diagnostic tests and GPs receiving results, as well as GPs needing more support to interpret test results. It is vital that existing guidelines are updated to provide GPs with the support they need to identify ovarian cancer as quickly as possible.
Treatment
Ovarian cancer treatment has changed significantly since 2016 with widespread access to maintenance treatment and greater access to genomic testing. As genomic testing moves at pace it is vital that the consent process empowers
patients to make the best choice for them. We also found that the pandemic has had an impact on access to surgery and the opportunity to be involved in clinical trials.
We need to see all those who would benefit from surgery able to access it; and clinical trials should be accessible to all, especially those with fewer treatment options.
Support
It is clear that the support for those with ovarian cancer is lacking. We found that the Clinical Nurse Specialist workforce is undervalued and under-resourced which has a knock-on effect on the support available. We found high levels of unmet need including mental health support and support with menopause. There is also a lack of support for those who have finished first line treatment, with those who have a recurrence reporting not having the same level of care as their first line treatment. To tackle this, we need to see greater long-term investment in support services
and the gynaeoncology Clinical Nurse Specialist workforce.

Full Report – Pathfinder 2022: Faster, further, and fairer

New cancer risk test based on routine cervical screening sample can identify breast and ovarian cancer and may help in future cancer risk prediction

Eve Appeal| n.d | New cancer risk test based on routine cervical screening sample can identify breast and ovarian cancer and may help in future cancer risk prediction

Research funded by the charity Eve Appeal, published today in Nature Communications, provides new tools, the Women’s cancer risk identification for breast cancer and ovarian cancer (WID-BC and WID-OC) tests, which can detect these two cancers using only routine cervical screening samples. Importantly, the tests do not detect actual cancer but rather indicate genetic, lifestyle and environment risk factors associated with them and may be able to predict future risk. In this blog, researcher Dr Chiara Herzog goes into detail of how the test works and who it could benefit.

Further details are available in the blog post from the Eve Appeal

Papers are published in Nature Communications

The DNA methylome of cervical cells can predict the presence of ovarian cancer

The WID-BC-index identifies women with primary poor prognostic breast cancer based on DNA methylation in cervical samples

Earlier decisions on breast and ovarian surgery reduce cancer in women at high risk

Marcinkute, R. et al | 2021| Uptake and efficacy of bilateral risk reducing surgery in unaffected female BRCA1 and BRCA2 carriers | Journal of Medical Genetics | Published Online First: 10 February 2021. doi: 10.1136/jmedgenet-2020-107356

This NIHR Alert summarises the recent findings of a longitudinal study that followed more than 800 women who carry the BRCA1 or BRCA2 genes who have an increased risk of developing ovarian and breast cancers (as well as other cancers). After testing positive for these genes, the individuals were followed up twenty years later, where more than half (57.9 per cent) had a risk reducing mastectomy, and 77 per cent had elected for a bilateral salpingo-oophorectomy (RRSO).

Abstract

Background Women testing positive for BRCA1/2 pathogenic variants have high lifetime risks of breast cancer (BC) and ovarian cancer. The effectiveness of risk reducing surgery (RRS) has been demonstrated in numerous previous studies. We evaluated long-term uptake, timing and effectiveness of risk reducing mastectomy (RRM) and bilateral salpingo-oophorectomy (RRSO) in healthy BRCA1/2 carriers.

Methods Women were prospectively followed up from positive genetic test (GT) result to censor date. χ² testing compared categorical variables; Cox regression model estimated HRs and 95% CI for BC/ovarian cancer cases associated with RRS, and impact on all-cause mortality; Kaplan-Meier curves estimated cumulative RRS uptake. The annual cancer incidence was estimated by women-years at risk.

Results In total, 887 women were included in this analysis. Mean follow-up was 6.26 years (range equal to 0.01–24.3; total equal to4685.4 women-years). RRS was performed in 512 women, 73 before GT. Overall RRM uptake was 57.9 per cent and RRSO uptake was 78.6 per cent. The median time from GT to RRM was 18.4 months, and from GT to RRSO–10.0 months. Annual BC incidence in the study population was 1.28 per cent. Relative BC risk reduction (RRM versus non-RRM) was 94 per cent. Risk reduction of ovarian cancer (RRSO versus non-RRSO) was 100 per cent.

Conclusion Over a 24-year period, we observed an increasing number of women opting for RRS. We showed that the timing of RRS remains suboptimal, especially in women undergoing RRSO. Both RRM and RRSO showed a significant effect on relevant cancer risk reduction. However, there was no statistically significant RRSO protective effect on BC.

Uptake and efficacy of bilateral risk reducing surgery in unaffected female BRCA1 and BRCA2 carriers [abstract only]

NIHR Alert Earlier decisions on breast and ovarian surgery reduce cancer in women at high risk

Rotherham NHS staff can request this article from their Library

Ovarian cancer population screening and mortality after long-term follow-up in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial

Menon, U. et al | 2021 | Ovarian cancer population screening and mortality after long-term follow-up in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial | The Lancet | DOI:https://doi.org/10.1016/S0140-6736(21)00731-5

This trial recruited more than 500 000 post menopausal UK women aged between 50 and 74 years of age, 202 638 were recruited and randomly assigned, and 202 562 were included in the analysis: 50 625 (25·0%) in the MMS group, 50 623 (25·0%) in the USS group, and 101 314 (50·0%) in the no screening group

They undertook the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) to determine if population screening can reduce deaths due to the disease. We report on ovarian cancer mortality after long-term follow-up in UKCTOCS, and the findings suggest that screening did not significantly reduce ovarian and tubal cancer deaths, general population screening cannot be recommended.

Background

Ovarian cancer continues to have a poor prognosis with the majority of women diagnosed with advanced disease. Therefore, we undertook the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) to determine if population screening can reduce deaths due to the disease. We report on ovarian cancer mortality after long-term follow-up in UKCTOCS.

Methods

In this randomised controlled trial, postmenopausal women aged 50–74 years were recruited from 13 centres in National Health Service trusts in England, Wales, and Northern Ireland. Exclusion criteria were bilateral oophorectomy, previous ovarian or active non-ovarian malignancy, or increased familial ovarian cancer risk. The trial management system confirmed eligibility and randomly allocated participants in blocks of 32 using computer generated random numbers to annual multimodal screening (MMS), annual transvaginal ultrasound screening (USS), or no screening, in a 1:1:2 ratio. Follow-up was through national registries. The primary outcome was death due to ovarian or tubal cancer (WHO 2014 criteria) by June 30, 2020. Analyses were by intention to screen, comparing MMS and USS separately with no screening using the versatile test. Investigators and participants were aware of screening type, whereas the outcomes review committee were masked to randomisation group. This study is registered with ISRCTN, 22488978, and ClinicalTrials.gov, NCT00058032.

Findings

Between April 17, 2001, and Sept 29, 2005, of 1 243 282 women invited, 202 638 were recruited and randomly assigned, and 202 562 were included in the analysis: 50 625 (25·0%) in the MMS group, 50 623 (25·0%) in the USS group, and 101 314 (50·0%) in the no screening group. At a median follow-up of 16·3 years (IQR 15·1–17·3), 2055 women were diagnosed with tubal or ovarian cancer: 522 (1·0%) of 50 625 in the MMS group, 517 (1·0%) of 50 623 in the USS group, and 1016 (1·0%) of 101 314 in the no screening group. Compared with no screening, there was a 47·2% (95% CI 19·7 to 81·1) increase in stage I and 24·5% (−41·8 to –2·0) decrease in stage IV disease incidence in the MMS group. Overall the incidence of stage I or II disease was 39·2% (95% CI 16·1 to 66·9) higher in the MMS group than in the no screening group, whereas the incidence of stage III or IV disease was 10·2% (−21·3 to 2·4) lower. 1206 women died of the disease: 296 (0·6%) of 50 625 in the MMS group, 291 (0·6%) of 50 623 in the USS group, and 619 (0·6%) of 101 314 in the no screening group. No significant reduction in ovarian and tubal cancer deaths was observed in the MMS (p=0·58) or USS (p=0·36) groups compared with the no screening group.

Interpretation

The reduction in stage III or IV disease incidence in the MMS group was not sufficient to translate into lives saved, illustrating the importance of specifying cancer mortality as the primary outcome in screening trials. Given that screening did not significantly reduce ovarian and tubal cancer deaths, general population screening cannot be recommended.

Ovarian cancer population screening and mortality after long-term follow-up in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial

NICE: Niraparib for maintenance treatment of advanced ovarian, fallopian tube and peritoneal cancer after response to first-line platinum-based chemotherapy

NICE | January 2021 | Niraparib for maintenance treatment of advanced ovarian, fallopian tube and peritoneal cancer after response to first-line platinum-based chemotherapy | [ID1680] | In development [GID-TA10551]Expected publication date: 10 February 2021

NICE has published its final draft of Niraparib for maintenance treatment of advanced ovarian, fallopian tube and peritoneal cancer after response to first-line platinum-based chemotherapy

Niraparib for maintenance treatment of advanced ovarian, fallopian tube and peritoneal cancer after response to first-line platinum-based chemotherapy [ID1680]

NIHR: First-line chemotherapy for ovarian cancer given once every three weeks may preserve quality of life

NIHR | November 2020| First-line chemotherapy for ovarian cancer given once every three weeks may preserve quality of life

NIHR’s latest evidence feature focuses on research that studied the chemotherapy treatment women with a new diagnosis of ovarian cancer receive, this type of cancer is usually treated every three weeks with chemotherapy containing the medicines carboplatin and paclitaxel. Although a recent Japanese studied reported better outcomes without reducing quality of life for weekly chemotherapy, the researchers behind this study found that patients who received weekly paclitaxel had poorer quality of life during treatment. They were also more likely to have nerve damage that lasted up to 18 months.

Taken together with the lack of progression-free survival benefit, their findings do not support routine use of weekly paclitaxel-containing regimens in the management of newly diagnosed ovarian cancer.

What’s new?

1438 women with ovarian cancer were asked about their quality of life at regular intervals for up to five years after starting treatment. They completed written questionnaires on factors such as emotional well-being, fatigue and nerve pain.

Nine months after patients entered the trial, the researchers found:

• Patient well-being fell during chemotherapy but then improved over the following months regardless of which treatment was given
• When researchers looked at well-being scores during and after treatment, those on weekly treatment experienced lower quality of life compared to those receiving treatment every three weeks
• Nerve damage caused by paclitaxel was worse in the weekly treatment arms and persisted for longer. It started later than in women receiving chemotherapy every three weeks
• Patients having weekly treatment reported slightly increased levels of fatigue compared to those treated every three weeks but this was not significant.

Although survival was similar for patients on all treatment plans, well-being data shows a different story. The study suggested weekly schedules were harder for patients to tolerate and caused long-lasting toxicity compared to less frequent chemotherapy.

The researchers believe that three-weekly chemotherapy should remain the standard of care for most newly-diagnosed ovarian cancer patients.

It is not known why paclitaxel causes nerve damage. The researchers in this study believe long-lasting nerve damage and numbness are likely because the total amount of paclitaxel given is higher for people taking weekly treatment (Source: NIHR)

Primary paper:

Blagden, S.P. (2020) et al. Weekly platinum-based chemotherapy versus 3-weekly platinum-based chemotherapy for newly diagnosed ovarian cancer (ICON8): quality-of-life results of a phase 3, randomised, controlled trial| The Lancet Oncology|21|P. 969-977

Ovarian cancer disease profile

Disease profile in England: Incidence, mortality, stage and survival for ovary, fallopian tube and primary peritoneal carcinomas |  Public Health England

This report provides a detailed insight into the status of ovarian cancer in England.  It is the first report from the Cancer Audit Feasibility Pilot project which runs for two years and includes details of disease incidence, mortality and survival.

Rucaparib for maintenance treatment of relapsed platinum-sensitive ovarian, fallopian tube or peritoneal cancer [ID1485]

NICE |  October 2019 | Rucaparib for maintenance treatment of relapsed platinum-sensitive ovarian, fallopian tube or peritoneal cancer [ID1485]

NICE has announced it has approved the medication for ovarian cancer- rucaparib-  can now be offered to women with relapsed ovarian, fallopian tube or peritoneal cancer, that has responded to platinum-based chemotherapy. Taken as a tablet, twice daily, it slows the progression of cancer by preventing cancer cells repairing so slowing down the tumour’s growth.

Around 1,350 people in England could benefit from this new treatment which will be available immediately through the CDF.

This approval is a change from the committee’s initial decision, where uncertainties in the evidence, and the price of rucaparib, meant it could not be recommended for routine use on the NHS.

Clinical trial evidence shows that rucaparib prevents cancer progression for twice as long as the placebo treatment (median of 10.8 months in the rucaparib group compared with 5.4 months in the placebo group). However, it is not known how this will translate into overall extended life expectancy due to incomplete trial data.

The drug company has since proposed an alternative price for rucaparib. If this revised commercial arrangement is supported with long-term overall survival data, rucaparib has the potential to be a cost-effective use of NHS resources. The committee therefore decided to include rucaparib in the CDF to allow this long-term data to be collected (Source: NICE).

The guidance is expected to be published on 13 November 2019.

Read the press release here

NICE Another treatment option for ovarian cancer approved for the Cancer Drugs Fund

In the news:

OnMedica Watchdog approves ovarian cancer treatment

Olaparib for maintenance treatment of BRCA mutation-positive advanced ovarian, fallopian tube or peritoneal cancer after response to first-line platinum-based chemotherapy

NICE |  August 2019 | Olaparib for maintenance treatment of BRCA mutation-positive advanced ovarian, fallopian tube or peritoneal cancer after response to first-line platinum-based chemotherapy

Olaparib (Lynparza) is available through the Cancer Drugs Fund. It is a possible treatment for advanced ovarian, fallopian tube or peritoneal cancer in adults, if:

• they have a BRCA mutation and
• the cancer has been treated with 1 course of platinum-based chemotherapy.

More evidence on olaparib is being collected, until September 2023. After this, NICE will decide whether or not to recommend it for use on the NHS and update the guidance. It will be available through the Cancer Drugs Fund until then.

Full details from NICE

Excess weight and cancer risk

New figures from Cancer Research UK show that people who are obese now outnumber people who smoke two to one in the UK, and excess weight causes more cases of certain cancers than smoking.

Almost a third of UK adults are obese and, while smoking is still the nation’s biggest preventable cause of cancer and carries a much higher risk of the disease than obesity, Cancer Research UK’s analysis revealed that being overweight or obese trumps smoking as the leading cause of four different types of cancer.

Excess weight causes around 1,900 more cases of bowel cancer than smoking in the UK each year. The same worrying pattern is true of cancer in the kidneys (1,400 more cases caused by excess weight than by smoking each year in the UK), ovaries (460) and liver (180).

The charity wants the Government to act on its ambition to halve childhood obesity rates by 2030 and introduce a 9pm watershed for junk food adverts on TV and online, alongside other measures such as restricting promotional offers on unhealthy food and drinks.

Full story: Obese people outnumber smokers two to one| Cancer Research UK

See also: Obesity ’causes more cases of some cancers than smoking’ | BBC News