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Regulatory histories of recently withdrawn ovarian cancer treatment indications of 3 PARP inhibitors in the US and Europe: lessons for the accelerated approval pathway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