Forsaking cures for cancer: why are we discarding the tumour biospecimens of most patients?

Discarding patients’ cancer samples because of problems with consent processes forgoes potential advances in cancer research, ignores public intent and squanders unique bioresources

Cancers are highly variable — between different types of cancer, between different patients’ cancers and even between different cancer cells within an individual patient’s cancer.1 A critical challenge facing cancer research and therapy is to understand and overcome the heterogeneity of each patient’s cancer. Resected tumours and other samples donated by patients with cancer provide invaluable bioresources for the study of cancer heterogeneity. While animal models and in vitro studies generate therapeutic hypotheses, only confirmation in human cancers can ratify targets as relevant to pursue into the clinic.

Biobanking processes ensure the collection, annotation, management, appropriate storage and transfer of donated (cancer and healthy) tissue and other samples, which are often those resected at surgery. Revolutionary cancer treatments such as mutation-targeted therapies and checkpoint immunotherapy antibodies could not have been developed without studying biobanked biospecimens. Conversely, prospectively annotated high-quality cancer biospecimens are key to understanding which patients will benefit from existing drugs (drug individualisation) and which patients might forgo otherwise toxic therapies altogether (treatment de-escalation).

The value of biobanks to medical research, research communities and public health has been widely recognised. Biobanks can be viewed as both the primary facilitators of biomedical research efforts and the conduits between cancer patients, as contributors of bioresources, and researchers, as recipients. The rate of successful biobanking is proposed as a key performance indicator,2 but the proportion of Australian patients donating tissue at the time of surgical treatment for cancer is poorly reported and, although largely unknown, appears to be low even in highly motivated and research-focused academic centres. Rather than being systematic, biobanking is often opportunistic, driven by individual clinician–researchers, tissue bank professionals and pathology staff. Biobanking seems to be relatively uncommon in private practice, even though a significant proportion of all cancer surgery occurs outside the public sector.

This picture is at odds with the intent and spirit of patients with cancer, their advocates and the Australian public. Recent studies show that Australians, including both cancer tissue donors (95%) and the general public as potential donors (85%), are willing to donate samples for future unspecified research that is approved by a human research ethics committee (HREC).3 Consent rates as high as 99% have been reported.3 This willingness is likely to be altruistically driven by a sense of duty as a citizen and by trust, which can, if tested, be easily eroded.

Biobanks in Australia have been supported by philanthropic and public donations and by governments.4 Despite widespread recognition of their contributions to research, the future sustainability of cancer biobanks in Australia is, at best, uncertain. While biobanking was initially supported through National Health and Medical Research Council (NHMRC) Enabling Grants, funding support for established biobank entities, including members of the Australasian Biospecimen Network Association – Oncology Group, remains tenuous. While organisations such as the state-based cancer councils and cancer institutes have provided much needed support, infrastructure and encouragement, essential funding remains intermittent.

The barriers to biobanking participation extend beyond funding. Although we are moving to national strategies for biobanking,4 many policies and processes are often reinvented at local and statewide levels. However, issues of patient consent appear to be a nationally important barrier between high rates of public approval and low rates of biospecimen collection. Broad consent for biobanking would allow researchers timely access to tissue for ethically approved research without the need to obtain retrospective consent for specific projects, which is costly and neither helpful nor feasible, particularly in patient populations with highly morbid diseases such as cancer. Asking patients to reconfirm consent for access to donated specimens for new or extended studies could be distressing and intrusive to the patients and their families. Asking individuals to reconsent to biobanking and questioning their decision may create uncertainty and compromise the timely conduct of research.

Given the high levels of willingness to donate and trust in biobanking that have been reported in studies among the Australian general public, we advocate a waiver of consent for biobanking. Although this may be provocative to some,5 consent for biobanking is already embedded in existing routine admission forms of our public hospitals, and promoting awareness of this should be a priority. Consideration should be given to the idea that consent for surgical procedures is sufficient to allow the routine storage of biomaterials (eg, resected tumour tissue and left-over diagnostic samples) for use in ethically and scientifically robust research approved in future by an HREC (ie, conditional donation). Likewise, data linkage to a patient’s medical record and other medical resource usage can be made in a confidential, encrypted and secure manner,6 where results would be reported in aggregate form to protect patients’ identities but could be potentially re-identifiable if clinically relevant incidental findings required reporting to an individual donor.

National regulation of consent processes provided by the NHMRC National statement on ethical conduct in human research (chapter 2.3)7 has for some time offered guidance to researchers and members of HRECs when considering the circumstances in which a waiver for consent can be justified. While recognising that waiving of consent should always be adopted in a measured fashion,8 there is additional scope to waive consent, particularly where the research involves minimal harm to participants.7 To date, reasons for the inconsistent interpretations of the Statement (and hesitancy in its application) by both researchers and HRECs remain unclear and warrant examination.

Applying a routine consent waiver to the hospital admission process could employ a two-step model, wherein (1) collected samples are automatically stored for research, but (2) pending confirmation of patient consent. This may include an opt-out provision that would require authorisation by the patient at some (negotiable) point during his or her admission. This process would also promote greater awareness among patients and health carers of the benefits of biobanking samples by:

• collecting biospecimens from material that has been taken for diagnostic testing, which would be linked to the patient’s medical record and flagged for future unspecified research approved by an HREC;

• respecting patient preferences and consideration of choice in the type of consent to be obtained at the time of initial contact; and

• providing more seamless and fluid consent processes to minimise unnecessary distress to patients and next of kin, as well as to staff who may be in the position of asking difficult questions at difficult times.

Biobanking has also been the subject of sustained scientific and ethico-legal critique, much of which has focused on the means of obtaining consent for long term storage and future use of tissue. Ethical disagreements frequently centre on the tension between individual autonomy and the “common good”. This tension is significant in the context of biobanking research, which often depends on the participation of large numbers of people (including healthy populations), many of whom are unlikely to benefit from the results of the research.

Persistent and emerging issues seek resolution — these include managing an incidentally identified germline heritable mutation, ensuring data linkage security and ensuring that a patient’s genetic makeup does not cause discrimination or economic harm (eg, denial of insurance). International assessments, however, suggest that the general public still overwhelmingly supports the public good of biobanking and is less concerned with privacy and confidentiality.9

In 2003, the Essentially Yours report10 included numerous submissions from key agencies engaged in ethico-legal debates concerning biobanks, highlighting the critical need to deal with the failure of informed consent processes for tissue collections in public tertiary hospitals. Indeed, the Association of Australian Medical Research Institutes (submission G007) acknowledged that discarding samples could be seen as wasteful and that it would be disrespectful to the donors (including deceased donors) if research on sample collections did not take place, or if there was further insistence on gaining consent from relatives.

An economic argument is also pertinent. With over 40 000 surgical procedures for cancer in Australia every year,11 and a cost to cancer researchers of up to hundreds or thousands of dollars per biospecimen (depending on the economic model used),12,13 millions of dollars of invaluable and irreplaceable resources are being squandered in Australia annually. This must be set against the cost of collecting and maintaining biobanked specimens, which is also hard to quantify. Finally, with rapidly increasing cancer drug prices,14 biobanked specimens will drive research to individualise, optimise and de-escalate treatments, which will be essential for improving and economising cancer treatment in an environment of health care expenditure cost containment.

Cancer biobanks are custodians of invaluable, well annotated biospecimen collections. Community engagement has provided empirical evidence about the consent preferences of actual tissue donors, patients with cancer and the general public (as potential donors). Promoting a shift away from the current focus on locally variable, opt-in, physician-driven consent processes is warranted. Acknowledging the shared common good, humanity and responsibility of biobanking could markedly improve our current practices and enable further advancements. Discarding patients’ unique cancer samples forgoes potential advances in cancer research, ignores the public intent, squanders unique resources and is economically wasteful.