Earlier is better

Timing of Palliative Care, End-of-Life Quality Indicators, and Health Resource Utilization

https://tinyurl.com/yc2bf5p3

For most ovarian cancer patients and their carers there comes a time for acceptance and a need for support and compassion. This is best provided through Palliative Care (PC). This study looks at the benefits to the individual and community which result from earlier referral to PC.

Retrospective analysis of the outcomes of more than 8000 women with ovarian cancer showed survival of about 3 years with death around the age of Seventy. 98% of these women received PC. One third of the women did not start PC before the last 3 months of life

There was a significant difference in the amount of aggressive end-of-life care, with fewer admissions to ICU, consultations with specialists, and less late stage chemotherapy for those women who began PC early. Also significant was the lower rate of death in Hospital which was about two-thirds less likely.

Avoiding aggressive end-of-life care has previously been shown to greatly improve the individual’s quality of life. The authors also stress the savings to the community which results from decreased use of high-cost clinical services. Education of care providers and cancer patients towards early PC will benefit all.

Why the FDA withdrew support for PARPi

Regulatory histories of recently withdrawn ovarian cancer treatment indications of 3 PARP inhibitors in the US and Europe: lessons for the accelerated approval pathway

https://tinyurl.com/3mrm6z4r

The recent decision by the FDA to withdraw access to PARP inhibitors for patients with recurrent ovarian cancer has raised issues about the approval process and questions about the efficacy of these drugs

Personalised therapy with enzyme inhibitors such as PARPi has revolutionised the treatment of ovarian cancer. The success, in terms of increased survival, led to pressure for the use of such drugs to be expanded beyond the initial target group to more women.

Real-world experience often causes reappraisal of the benefits and it is now clear that use of PARPi for treatment of recurrent ovarian cancer increases the likelihood of major adverse effects such as marrow suppression. A decrease in survival compared to standard therapy was also seen and long-term use of PARPi reduces the effectiveness of standard platinum-based chemo.

All of these drugs benefited from accelerated approval processes. Recent decisions by the FDA to approve some expensive drugs with contentious experimental evidence, such as aducanumab for dementia, have caused criticism of the accelerated process. The withdrawal of these PARPi drugs will increase the scrutiny and may result in unavoidable delays to important changes in cancer treatment.

Most times it’s not cancer

Ovarian cancer risk among older patients with stable adnexal masses

https://tinyurl.com/5fytnf57

Benign ovarian masses are common. About 30% of women with a normal menstrual cycle will develop an ovarian mass. For women with irregular menstruation this figure increases to 50%.

It is important to recognise this and avoid invasive surgery. This study looks at older women of over 50 years in age and demonstrates that, for stable tumours smaller than 10 cm in size, there is a low likelihood of cancer.

Almost 5000 women in this age group, presented to one community health organisation with ovarian masses, during the period 2016-2020. Of whom, more than 4000 had a stable appearance at repeat ultrasound examination 6 weeks later. Those women, with stable appearances, did not have surgery. 

During the almost 4 years of follow up, the incidence of ovarian cancer was very low, with only 11 cancers being detected (0.27%). The authors suggest that, with a stable appearance at the 6 weeks ultrasound, older women with a small ovarian mass do not need active follow up.

An impossible dream?

Reducing ovarian cancer mortality through screening: an impossible dream?

https://tinyurl.com/4524jh8f

The history of screening tests for ovarian cancer is not good. Two huge trials; the UKCTOCS with more than 200,000 recruits over 20 years and the PLCO trial with more than 3 million pathology samples showed no benefit in terms of survival from ovarian cancer.

This article addresses the stages of ovarian cancer using an alternative approach called the clinical continuum, which divides cancer into 3 phases, no disease, pre-clinical (detectable disease), and clinical (overt cancer).

Obviously for a screening test to be effective, cancer needs to be detected before the clinical phase. However, ovarian cancer is unlike other cancer in that the precursor occurs in the fallopian tube and there is an argument to say that, by the time ovarian cancer has occurred, it is always advanced and metastatic. This time interval between initial and advanced disease has been called, “the sojourn”. A short sojourn implies that screening tests are unlikely to be helpful.

Any ovarian screening test would have to demonstrate cost-effectiveness. Because of the short sojourn, screening would need to be at less than yearly intervals. Also, the authors note the continual decline in the incidence of ovarian cancer, over the last 100 years. These factors make the allocation of scarce resources to ovarian cancer screening unlikely.

Why Old?

The Gut Microbiome in Ageing and Ovarian Cancer

https://tinyurl.com/yk8nt6w6

Ovarian cancer is mostly a disease of the seventh decade. The reasons for this are unclear. One suggestion is that changes in the Gut bacterial flora or microbiome may be associated.

This review looks at which bacteria become more common with age and which decrease. Using data from previously published material, it is clear that bacteria which increase inflammatory change become more common, and that bacteria which assist oestrogen metabolism decrease.

The overall complexity of the microbiome changes with age, with some loss of diversity. However, no correlation of ovarian risk to bacterial diversity has been shown.

Most women with ovarian cancer receive antibiotic therapy during chemo, this has been shown in mice to change the microbiome and decrease survival from ovarian cancer.

No definite association between ovarian cancer and the aged microbiome is known but the inflammatory changes and altered oestrogen metabolism may prove to be important factors in the late presentation.

Prevention better than cure

FIGO position statement on opportunistic salpingectomy as an ovarian cancer prevention strategy

https://tinyurl.com/4db8sj3y

The importance of pre-cancerous change in the fallopian tubes as a precursor to ovarian cancer has led to suggest that removal of the fallopian tubes at the time of other abdominal surgery is a significant protective measure.

Now FIGO, (The International Federation of Obstetrics and Gynaecology) have issued a position statement saying they firmly support this.

Evidence for this position is linked to pilot studies in Canada which showed significant reduction in subsequent ovarian cancer rates when the tubes were removed at the time of hysterectomy, (this is not usual practice). 

In addition, an Austrian study showed good acceptance of additional surgery. When women facing gallbladder removal were offered tube resection, 60% accepted. The average increase in operating time was 13 minutes and there was no extra post-operative complication.

One less cause to worry

The impact of inter-cycle treatment delays on overall survival in patients with advanced-stage ovarian cancer

https://tinyurl.com/mrxpksk9

Many patients with ovarian cancer have interruption of their chemo. This may occur because of adverse side effects of treatment, or external factors such as other priorities and logistic issues.

This interruption may cause anxiety which can be expressed as concern that the chemo is less effective.

This retrospective study looked at more than 1500 women with advanced ovarian cancer first diagnosed during the period 2015-2019. The two-year survival for women who had an uninterrupted chemo course was compared to those whose chemo was unavoidably disrupted. Disruption is common with 37% having breaks of at least 7 days. No difference in survival was seen in the two groups.

Knowledge that chemo is just as effective despite interruption means that factors which affect the patient's quality of life can be addressed without fear of harm.

The real financial cost

Study Finds Nearly $70 Billion in Socioeconomic Losses Across 11 Countries Attributable to Ovarian Cancer

https://tinyurl.com/4spw37yz

Ovarian cancer is extremely costly to the individual, the state and the family of each patient. This study uses a true cost of illness approach to assess the annual economic burden of each case of ovarian cancer in high-, middle-, and low-income countries.

Factors included in this determination include cost of treatment, the opportunity cost of loss of productivity for the individual and the carers and the often-forgotten cost of unpaid carer time.

The sums are mind-boggling with an estimate of almost $70 Billion total annual expenditure and individual costs of up to 120 times the usual health expenditure per capita for low-income countries.

Obviously, there is concern about whether this is sustainable and shows the urgent need to reduce the incidence of ovarian cancer.

Alternative therapy ineffectual

Impact of metformin, statins, and beta blockers on survival in patients with primary ovarian cancer: combined analysis of four prospective trials of AGO-OVAR and ENGOT/GCIG collaborators

https://tinyurl.com/597m54hb

Anecdotal experience has previously suggested that off-label use of some commonplace drugs may improve survival for patients with ovarian cancer. This meta-analysis of 4 prospective randomised trials looks at the effect of some of these.

Data was obtained from the trials which recorded use of the additional drug treatment. The prime purpose of the trials having been assessment of efficacy of the enzyme inhibitor, Pazopanib. From the data, patients could be subdivided into two groups; those who had received additional drug therapy and those who had not.

Finding from the results show that use of off-label drugs was associated with greater co-morbidity. Neither metformin or statin therapy had any effect on survival. Use of betablockers had a negative effect, those patients had worse survival outcomes.

Serendipity

Incidental Findings of Borderline Ovarian Tumour or Ovarian Cancer -Real-World Data on Surgical and Oncological Outcome

https://tinyurl.com/5n8284dj

Sometimes ovarian cancer is found by chance during surgical procedures performed for other reasons. The standard of care for such cases is to undergo a repeat surgical procedure at a specialised surgical oncology centre. This study looks at real-world cases and seeks to determine whether this course of action results in worse outcomes. 

This retrospective survey of 390 patients at Bern Hospital during a 10-year period from 2010 showed 228 cases of either borderline ovarian tumour or ovarian cancer. The outcomes for these women were compared to those for women who were known to have ovarian cancer prior to single stage surgery at the same centre.

Apart from a small delay in starting chemo for those women who has a second operation, no difference in outcomes which include morbidity, mortality, and recurrence intervals was noted. 

Comorbidity, poisoned soil

Charlson’s comorbidity and remission outcomes in women diagnosed with epithelial ovarian cancer.

https://tinyurl.com/2hmnmvp9

Any surgery carries risk. Complex surgery such as that required for total clearance of ovarian cancer has a mortality of 4%. For some women this risk is increased by pre-existing medical conditions known as comorbidity.

This retrospective cohort study seeks to measure the risk increase in the presence of comorbidity. Using the Charlson comorbidity index, which shows associated significant pre-existing disease as a risk factor, even the lowest measure at more than 1 significantly decreased the prospect of complete remission and survival from ovarian cancer.

This means that patients who have one or more other major health issues are less likely to benefit from intensive primary treatment and that maybe alternative therapy, such as maintenance with personalised care should be considered?

AI, the way forward

LITERARY REVIEW OF ARTIFICIAL INTELLIGENCE IN OVARIAN CANCER: TRANSFORMING DIAGNOSIS, TREATMENT, AND FUTURE ADVANCEMENTS

https://tinyurl.com/yc85bx44

Artificial intelligence (AI) has the potential to change the management and improve survival for women with ovarian cancer. This review looks at what is possible now and what may be possible soon in the use of AI for this difficult disease.

Increasingly women with ovarian cancer are receiving personalised therapy base on the genetic, metabolic, and systemic nature of their cancer. More and more information cause problems with the understanding of the relevance and interconnection of the data. The great strength of AI is the ability to quickly correlate information and suggest appropriate measures to address the correct therapy path.

Using AI for the diagnosis of ovarian cancer will increase the sensitivity and avoid unnecessary intervention in some cases. Increasingly AI is being used for drug research, currently existing chemical compounds can be quickly scanned to determine likely effectiveness against ovarian cancer. Any relevant research can be processed and may provide alternative therapy suggestions. 

It seems likely that because of the complexity of ovarian cancer and the increasing amount of information being collected it will soon be essential to use AI as a standard of care. Caution is needed when using AI. There is increasing awareness of potential bias due to inequitable clinical trials and pre-conceived algorithms and constraints.

Suspicions confirmed

Differences in cancer rates among adults born between 1920 and 1990 in the USA: an analysis of population-based cancer registry data

https://tinyurl.com/wzaxy5w5

Anecdotal experience has suggested that cancer is becoming more common for younger patients. This suggests that lifestyle changes and environmental effects are causing more cancer. Using data from population-based cancer registry this study looks at the increase in cancer risk for younger cohorts.

Information is available from this huge study with data from more than 23 million patients, of whom more than 7 million developed cancers. Comparing cancer rates from 5-year birth cohorts showed that for 9 of the 34 different cancers included in the study there was an increase for patients born in the 1990 cohort compared to the 1955 cohort. The mortality has decreased, with better treatment options.

Some cancers notably smoking affected cancers such as lung cancer, show a decrease due to changed lifestyle. Ovarian cancer also is less, probably due to medical intervention with hormonal contraception.

Understanding of these changes suggest a need for modification of lifestyle and environmental factors with more research into underlying causes.

Liquid Biopsy beats CA125

The Impact of Liquid Biopsy in Advanced Ovarian Cancer Care

https://tinyurl.com/5dy6escn

For some time, the presence of circulating tumour DNA (ctDNA) has been shown as a useful marker for many cancers including breast and colon. Testing for ctDNA is readily available by a polymerase chain reaction (PCR), the use of which became commonplace during the Covid pandemic.

Previous studies have shown ctDNA to be present in ovarian cancer. This study looks at whether using ctDNA liquid biopsy improves the management of the cancer, by confirming adequate surgery and earlier detection of recurrence.

Currently the standard marker of active disease is the cancer antigen CA125. There are problems with this in that there is a significant time lag, with persisting elevation of test scores for CA125 after treatment, and delay in a rise to mark recurrence.

ctDNA does clear rapidly from the circulation after complete clearance of cancer, making it a good indicator of adequate surgery, which remains the most significant factor for long survival. Also, in this small group of women (22), ctDNA increase after recurrence was detected several months earlier than CA125 elevation or changes in imaging.

There is a logistic issue due to cost and access, but the use of ctDNA liquid biopsy does offer some promise of improved management for ovarian cancer.

Is there a “gut feeling” for OC?

Ovarian cancer symptoms in pre-clinical invasive epithelial ovarian cancer – An exploratory analysis nested within the UK Collaborative Trial of Ovarian Cancer Screening 

https://tinyurl.com/2nj7cv48

Ovarian cancer is hard to diagnose, no screening test has so far been shown to be effective. Because of this difficulty women are advised to look out for subtle changes thought to be predictors of later disease. These include bowel symptoms such as bloating, dyspepsia and altered bowel habit.

It seems that this advice is intuitive rather than objective, this study aims to use the mass of data from the UKCTOCS trial to determine the importance of such advice.

UKCTOCS was a huge trial over 15 years involving more than 200000 women which ultimately failed to show any increase in survival from ovarian cancer when an array of screening tests was used. As part of the information sought at commencement the women were asked about bowel symptoms. 

Of the 202 women who were actively screened and developed ovarian cancer, 35% had previously described bowel symptoms. For the non-screened 874 women who developed ovarian cancer, only 9% had previously described bowel symptoms.

It seems that once again there is no accurate discriminator for ovarian cancer outside the known high-risk groups. Some caution when interpreting these results should be exercised,as this is use of data for a purpose other than originally intended.