Major advances in screening and treatment for lung cancer have occurred through the use of donated tissue from patients undergoing biopsy and associated procedures. Many institutions are now storing these biospecimens in repositories to aid in developing screening measures and discovery of biomarkers in cancer treatment research. These repositories are a promising way to identify the genomic profiles of tumors, including tumor mutation patterns that may be targets for future therapeutic interventions. However, the utility of these samples is often limited due to the small quantity of tissue that can be obtained from living patients undergoing a biopsy, as well as tissue degradation after collection from deceased patients. A lesser-known research mechanism is the use of rapid tissue donation (RTD) which is defined as the procurement of ‘fresh’ tissue within 2–6 h of a donor’s death (Lindell et al. 2006). The fresh tissue yielded from RTD programs provides research opportunities not available from frozen or paraffin embedded specimens. Tumors, metastases, and non-involved organs from the same donor can be obtained with minimal degradation, which provides tremendous research opportunities that can lead to the development novel therapies.

There are several benefits of RTD. First, because no portion of the tissue needs to remain in the body as it does in biopsies, researchers have access to larger quantities of unaltered biospecimens from primary sites, metastases, and normal tissue. Gross total resections are often performed only with tissue from primary sites, and though this yields large amounts of specimen, quick tissue degradation often renders comprehensive analyses difficult. Biospecimen degradation has historically affected research opportunities in lung cancer with only 15–20 % of donations taken after autopsy deemed suitable (Mascia et al. 2010). A second benefit of RTD is the ability to study affected tissue in advanced stages of disease. This allows for molecular studies of disease progression which is responsible for the high morbidity and mortality of many cancers. The third benefit of RTD is that it allows researchers to establish cell lines from primary and metastatic sites to study response and resistance to treatment. Lastly, RTD allows for the study of heterogeneity within tumors, and the formation, response, and resistance to drugs. Researchers can utilize the information obtained from paired samples, i.e. initial biopsy versus post-mortem tissue, to understand the mechanisms involved in the progression of disease and resistance to systemic treatment. This research holds great promise for the development of novel therapies and advanced screening techniques.

Rapid tissue donation programs cannot exist without the willingness and consent of cancer patients to donate their post-mortem tissue and organs, which should not be confused with traditional organ donation. Traditional organ donation is intended for future transplant of that organ into another person. Each state in the US maintains its own laws as to whether a cancer patient may donate his or her organs and tissue for transplantation into a living person. The majority of states, however, prohibit donation if the patient has died from active cancer, with an exception often made for corneas (Buell et al. 2003; Kauffman et al. 2002). In contrast, RTD only uses retrieved organs and tissues for basic science research. Furthermore, traditional post-mortem organ and whole body donation to science, while still holding research value, are less useful due to the rapid degradation of tissue that occurs in the first 24 h (Lindell et al. 2006).

The delicate balance between research for its own purpose and clinical patient care can often be tested, especially when recruiting for tissue banking/RTD. In this article we offer recommendations for examining the cultural and ethical climate of the academic institution or hospital prior to initiating a RTD program and examine the relationship between healthcare professionals and patients, ethical concerns, and strategies for promoting acceptance and buy-in across professionals, patients, and families.

Recruitment for biospecimen donation primarily relies on the altruism of individuals, a term referring to a selfless sacrifice or gesture made to benefit humanity in some way without the expectation of a direct benefit in return. Biospecimen banking programs and traditional organ donation rely on altruism and a patient’s desire to give back to science and society. Altruism has been debated in the literature with some suggesting that genuine altruism does not exist (Batson 1991), meaning that an individual has an expectation to benefit from an altruistic act. However, this has been woven into theories of altruism that can be used to explain an individual’s motivation. Three types of altruism have emerged from the philosophical debate regarding biological donations: (1) Pure altruism/gifting; i.e., do people donate organs, blood, or biopsy material for research solely as a gesture of good will; (2) Reciprocal altruism, i.e., are there elements of expected return for either the donor or family? (McCullough et al. 2008); (3) Empathy-induced altruism/Group Selection Theory, i.e., do individuals agree to biospecimen donations because of a shared group experience and feel they will improve the welfare of this group in the future? (Batson and Ahmad 2009).

Theories of altruism

Altruistic motivation and cancer patients’ perceptions of RTD programs have not been reported in the literature, creating difficulties in initiating RTD programs at clinical institutions. However, understanding potential sources for altruistic motivation may help with strategies for successful implementation and recruitment. Patients can be guided into understanding their own natural altruism to ensure the decision is voluntary; this is a personal, subjective, response that enhances the argument suggesting that recruitment should be assessed individually, taking into account the current situation, values, and expectations (Roberts 2002, p. 707).

The gift relationship

Altruistic theories of giving are well described in Titmuss’ The Gift Relationship, which assessed the motivation of blood donors (Titmuss 1970). Titmuss identified that the primary motivation for voluntary blood donation was a selfless desire to help others. This altruistic desire was then carefully infused and used as a marketing tool for blood donations (Titmuss 1970). The community-based philosophy of altruism is reinforced, according to Titmuss, through the anonymous donation of blood without expectations for reward, allowing individuals to cultivate their civic duty of helping others whose lives are threatened, or who are in extreme distress or need. (Valencia Declaration 2002) As such, blood products escaped becoming a commodity or product and became valuable as a ‘gift’ for the most significant purpose: life. Similar to tissue collected for RTD programs, the donor also enters into a gift relationship with research, future patients, the cancer community, and the team of physicians at their treating hospital. When processing the decision to consent for RTD, terminal cancer patients are not likely to consider their tissue donation as a commodity that can be bought and sold by various research entities. Rather, as with blood and organ donation, RTD can be promoted as ‘giving the gift of life.’ Referring to the tissue as a “gift” instead of a donation is likely to influence the donor and cause them to view their decision as morally commendable and altruistic (Healy 2006; Siminoff and Chillag 1999; Sque et al. 2007). Terminal cancer patients may see RTD as an opportunity to endow a variety of beneficiaries simultaneously by providing the gift of enhanced research to their fellow and future cancer sufferers, their descendants, the physicians, and the hospital providing care.

Titmuss’ idea of donation as a gift has been challenged in the literature, citing that the term ‘gift’ may be inappropriate. In today’s consumer culture, gifts are often given with little thought or meaning (Shaw 2010). In addition, for the donor and donor’s family, the discussion of organ donation as ‘gift’ often arises at an extremely painful, confusing time wherein the family of the deceased is asked to come to terms with the loved one’s prior decision and death. The best time to request the gift or donation in RTD has been under debate. Some healthcare professionals have suggested asking at the time of entry into the healthcare system, at the same time other decision based legal documents are completed such as an advanced directive. However, asking the patient this early may have a deleterious effect in the patient hopes for cure. In addition, a recent pilot study among patients and caregivers of a large cancer hospital revealed the majority of patients prefer to be asked by their physician, after they have established a relationship with him or her, and only after initial treatment therapies have been unsuccessful McIntyre et al. (2012). Other authors have suggested the term ‘sacrifice’ be used instead so that the process of discussing RTD does not become over-simplified by the term ‘gift’ (Shaw 2008; Trivers 1971).

Reciprocal altruism

Altruism is typically thought to be void of expectation and obligation, allowing individuals to assume there is a built-in capacity for selfless giving among humans. Reciprocal altruism, a contrasting theory of true or gift-based altruism, speaks to the skepticism of selflessness. An altruistic act is considered a behavior that decreases one person’s comfort, happiness, or values in order to serve another’s comfort, happiness, or values. A central tenant of reciprocal altruism is the idea that the altruistic act will be returned to the giver in some form (Trivers 1971). This theory differs from others with the assumption that persons operating within reciprocal altruism maintain an expectation that a beneficial act will be reciprocated in the future, revealing an underlying principle of mutual obligation. Reciprocal altruism relates to ‘therapeutic misconception;’ for example, a patient participating in clinical research may have an expectation of receiving direct benefits from the drug under investigation or a higher level of care (Zodrow 2003). If not explicitly stated, RTD donors may feel their donation will result in a future benefit for their family.

In the case of RTD, it is not known if families of the patient expect researchers to find a cure or enhanced treatment specifically due to the donation by their family member, and if they expect their act of altruism to be repaid (Lidz et al. 2004). Patients may feel obligated to participate in RTD programs as a form of payment after receiving care from their treating hospital, which may also provide psychosocial and financial support. Additionally, if the patient’s cancer did not respond to treatment or if therapy was ongoing for a number of years, patients may feel obligated to participate in RTD programs due to the efforts of the medical team and the resources they used. Consenting for a RTD program may then prompt a web of mutual obligations such as the patient assuming researchers receiving this tissue are obligated to find a cure for the particular cancer, or reciprocate the act of altruism with a higher level of care to the surviving family. It is also unknown if the patient who participates in an RTD program is motivated to do so based on the hope that future terminal patients will also contribute through RTD as an act of reciprocation for those who have donated before them.

The central tenets behind reciprocal altruism can serve as barriers not just against consenting patients for RTD but also in sustaining the program. Is it acceptable for a HCP (health care provider) to recruit patients utilizing a reciprocal altruism approach? Perhaps this may be acceptable if patients feel their ‘return’ is internal satisfaction, i.e., ‘I do good, so I feel good.’ However, the ability to assess the motivation of a terminal cancer patient and family is vital to the consenting process, and not understanding these motivations can lead to unfulfilled expectations and perpetuate the family’s grief. It is important to provide education and identify whether the family believes the institution is obligated to reciprocate the altruistic gesture in order to avoid a loss of expectations, unfulfilled assumed promises, and negative publicity for the program. It may also be ethically challenging for a HCP to recruit for RTD without also promoting the expectations of reciprocal altruism among patients and families.

Group selection theory

Individuals frequently consider themselves as a member of a larger group: their family, their community, their religion, their country, etc. In this group context, individuals hold tacit responsibility for the welfare of their group in varying degrees. According to Group Selection Theory (GST), altruism is an individual trait that has been cultivated due to the benefits of being part of a group that also shares those traits (Caporael 2001). GST assumes a person will voluntarily act in the best interest of the group, even if it requires personal sacrifice. Research has shown that individuals diagnosed with a similar illness (thus, their ‘group’) exhibit this altruistic desire with donations of blood, tissue, or whole organs (Amir and Haskell 1997; Barr 2006; Sanner 2006). GST also assumes others in the illness group possess the same altruistic values, perpetuating the evolutionary biology theory that these traits developed to ensure survival and prosperity.

Cancer patients often seek information at the time of diagnosis and continue to do so as a survivor, which can uncover multiple support opportunities. Online or in-person support groups offer a sense of community, as well as giving the patient confidence they will be accepted unconditionally in this group due to the shared illness (Ussher et al. 2006; Ziebland et al. 2004). These behaviors are the beginning of GST, wherein the patient builds relationships and trust within his or her group, laying the groundwork for future altruism.

A natural grieving course emerges after a cancer diagnosis. The patient and family are faced with managing the loss of health and accepting the road of treatment that lies ahead. However, this is a complex and non-linear process. While a patient may have accepted his or her own illness, it is a unique and separate process to accept one’s mortality. Hinton found that hospice patients were more anxious if their death was considered to be a possibility instead of an imminent prognosis (Hinton 1999)—i.e., patients with an uncertain prognosis have more difficulty coping than patients with a definitive one. The HCP must first assess the patient’s coping strategy and perceptions of their future in order to overcome this potential barrier. Patients who have not accepted their diagnosis may not have a strong loyalty to their cancer group, thus recruiting for RTD utilizing a GST approach may not be successful. If the patient and family are exhibiting appropriate coping techniques and have expressed acceptance of the future, the patient is more likely to possess a desire to voluntarily give back to the cancer group, which can be used as a springboard to discuss RTD. Considerable research is needed to determine how a HCP can assess acceptance and altruistic desires.

Assessing altruism

The theories presented here should be investigated in clinical settings to identify best practice guidelines for RTD recruitment. We consider tapping into altruistic behaviors of terminal patients ethical for several reasons. Humans have an innate desire to perform actions that benefit the greater good of mankind, even if these actions will not be realized until after their death (Erikson 1959; Chochinov et al. 2002; Schwartz et al. 2003). This altruistic tendency is an opportunity to gain a donor, but assessing the cultural and ethical climate among health care professionals for RTD participation is as important as assessing patient and family desire for donation.

Because RTD is a relatively new procedure, there is a critical need to understand the perceptions and reservations toward RTD programs of physicians, researchers, surgeons, nurses, and psychosocial workers. Developing and maintaining RTD programs requires researchers and clinicians to examine the scope of their roles. Treating physicians must consider their own motivations for requesting a donation from the patient, who may be balancing his or her innate sense of altruism while struggling to accept that treatments have failed and death may be imminent. Despite the scientific knowledge and potential treatments that may be developed from RTD, there are several ethical concerns that may prevent HCP from getting involved in these programs. Although there is limited published research investigating HCP knowledge and perceptions of RTD programs research from our institution suggests there may be resistance on the part of the HCP primarily due to lack of knowledge (Boyette et al. 2012).

Anecdotal evidence from physicians at our institution, a National Cancer Institute designated Cancer Center, suggests terminally ill lung cancer patients often seek information about whole body donation to research as a gesture of altruism and a desire to show appreciation for the clinical care they received. This is particularly true of patients who are ineligible to participate in clinical trials and are likely to support RTD as a way of giving back. Patients with limited financial resources also inquire about whole body donation as a way to give back to the institution providing care with the belief that this donation will decrease burial costs (Gunderman 2008).

Because there are very few RTD programs in existence, it is unknown what communication strategies are used to initiate discussions about RTD, especially during a time of crisis for the patient and their family. Patients must perceive that the HCP giving direct clinical care has the goal of providing the best and most aggressive treatment possible, and not that the HCP has lost interest in the patient’s survival or quality of life. In addition, the short time frame needed for post-mortem tissue retrieval may affect family members’ willingness to honor the donation. Families are likely focused on coping with their loss and making funeral arrangements for a loved one; discussing RTD at this time could lead the family to believe that the donor’s body would not be returned for pertinent religious and cultural practices, such as kissing, praying over, and touching the body (Ngata 2005).

Professional and ethical challenges

There are several professional and ethical standards HCPs must maintain when utilizing altruism to establish and recruit for an RTD program. The likelihood of increased scientific knowledge gained through donated organs and tissues is motivating to the research community (Teno et al. 2004) but may not be an incentive for a terminal patient who, in addition to contemplating death, may have concerns that agreeing to be a donor in the RTD program will result in reduced end-of life care. Further, there are cases reported in the literature of patients who mistakenly believed agreeing to participate in end of life research would provide them with better healthcare or reduced costs for their care (Back et al. 2008).

Patients

We suggest it is ethical for a HCP to present the opportunity for a terminal cancer patient to participate in a procedure that will enhance research and provide a mechanism for the patient to give back, based on the premise of GST, gifting, or reciprocal altruism. While RTD allows terminal cancer patients to fulfill a desire of altruism especially when financial gifting is not an option, there can be an ethical challenge in describing the purpose of RTD so that it is attractive to the patient while avoiding coercive tactics such as allowing the patient to believe the HCP will be disappointed, or that his or her treatment will be compromised if refused. If the HCP realizes the patient fears the consequences of not participating in RTD, it would be unethical and coercive behavior to not address this fear. Such recommendations also hold for clinical research trials (McMillan 1995). Additionally, adding this complex, unique responsibility of recruitment to the already over-worked members of the treatment team may influence HCPs to avoid becoming involved in an RTD program.

Assessing the type of altruistic motivation from a patient is no easy task. This directly relates to how voluntary the decision is to participate in RTD. The HCP has a duty to assess the authenticity of a patient’s consent out of altruism and ensure the decision is void of fear and coercion. A conveyed desire to ‘gift’ may be driven by fear of disappointing the physician, yet is still considered to be a voluntary consent (Roberts 2002). In a study examining the motivations of individuals participating in an experimental court-ordered drug program, over half of the respondents agreed that their primary reason for participating was a hope that the judge would look favorably on their pending court case (Dugosh et al. 2010). While this may not seem out of the ordinary, there may have been additional motivations of the individuals in this study that were not expressed at the time of recruitment, such as an altruistic desire to give back to the community in exchange for their crime. Such feelings are not mutually exclusive. There will be situations an HCP faces wherein a patient is struggling between natural altruistic desires and the dissociation from their cancer group, sacrifice of religious values, or expectations of reciprocity. The treatment team must accept the responsibility of using the patient’s natural altruism to help process these conflicts, ultimately allowing clear decision-making to flourish.

Families

It is important for future research efforts to examine familial perceptions of RTD and the best ways to approach this discussion. Since no research currently exists on this topic, HCPs can make use of the knowledge gained from traditional organ donation programs and autopsy research when strategizing how to approach families. Similar ethical issues with organ donation and autopsies should act as a historical guidebook.

General autopsies have been on the decline for over 10 years, and the majority of clinicians attribute this decline to the difficulty of obtaining consent from relatives due to perceptions of disfigurement (Loughrey et al. 2000). Other reasons given by families include lack of knowledge about the autopsy procedure and fear of not receiving the results of the autopsy (McPhee et al. 1986). This shows the high informational needs of families, and that families should be educated to avoid confusing RTD with traditional autopsies.

Families who are approached for RTD should not feel hurried to make a decision as the HCP may inadvertently exhibit anxiety and pressure due to the narrow window of tissue collection time required. For families who object to organ donation, discussing facts and structured information that is understandable and in their own language has been shown to ameliorate the fears driving their refusal (Sanner 1994). It is likely that families who are unsure of RTD would also benefit from early education that assures the use of tissue for basic research only and other uses outlined in the informed consent.

Another issue with RTD programs could be the family’s refusal to allow tissue collection shortly after the patient’s death, despite the patient consenting for RTD. Approximately 38 % of organ donors have not been successful after death due to family refusal (Organización Nacional de Trasplantes 2010). The 2006 Uniform Anatomical Gift Act posits that an individual’s donor card or driver’s license indicating organ donation acts similarly to a will and serves as legal consent despite the family’s wishes (Revised Uniform Anatomical Gift Act 2006). However, next-of-kin (NOK) largely influence the outcome of post-mortem organ collection. Hospital policies should coincide with state policy, and currently in the US all 50 states have adopted legislation on the Uniform Gift Act. NOK may find ways to prevent the donation if the hospital does not include the exact same language in the operating policy and procedures as was in the original consent form. Though the desires of NOK do not legally override the patient’s organ donor documents, “a strong objection by the next-of-kin donation will stop procurement to avoid causing a major negative impact on the next-of-kin” (Rosenblum et al. 2012). Hospitals and HCP participating in RTD programs should prepare for this objection and halt the tissue or organ retrieval if the family changes their minds.

An objection from the family could dishonor the patient’s wishes, which may be troubling for HCPs treating individuals with cancer as they often provide care over a number of years and form strong relationships. The desire to honor the patients request over family objections could be strong. Overcoming family refusal in RTD requires continuous research about communication strategies and appropriate pre-education about the process. Despite the best intentions of institutional policy, the consent process, patient wishes, and pre-education, family members may react negatively and with strong emotion at the time of death. An examination of factors impacting organ donation between donor and non-donor families suggests families who have had less time to process the death were less likely to agree to donation (Exley et al. 2002). Strategies used in end-of-life consenting issues can be employed for RTD such as minimizing objectifying medical terminology, i.e., ‘harvest’ and ‘cadaver’ instead of ‘retrieve’ and ‘donor’ (Sharp 1995).

Personal and professional

Physicians are expected to uphold the ideals outlined in the 2001 Declaration of Professional Responsibilities, which includes nine items specifying roles as clinicians (items 3–5), researchers (item 6), educators (items 7 and 9), and members of a civil society (items 1, 2, and 8) (American Medical Association 2001). Though a physician’s duty as a clinician is first and foremost, recruiting for an RTD program may conflict with the dual duty as a researcher.

Research suggests personal views and experiences of HCP impact how and if families are approached to give consent for an autopsy (Cahill and Ettar 2008). Roberts et al. reported that over 60 % of medical examiners encountered an ethical dilemma during their career regarding tissue use obtained from an autopsy (Roberts et al. 2000). Other physician concerns include the need to assess which family member would be receptive to the idea, and which family member would be distressed if approached with this question (Kamal et al. 1997; Snowdon et al. 2004).

The opportunity to approach patients and family members regarding RTD spans across clinical boundaries with no standardized role for physicians, researchers, and other HCPs. Two schools of thought, however, have emerged regarding the clinician type who should make the offer for sensitive issues like autopsy, organ donation, and participation in post-mortem research. One practice recommendation suggests the clinician providing direct care for the terminal patient not be the one to approach the patient about RTD, ensuring that his or her role is to care for the patient only (Kamal et al. 1997; Pentz et al. 2005). Another strategy suggests clinicians who have formed a strong bond with a terminal patient and have already discussed end of life issues may be in the best position to inquire if a patient is interested in donating, as seen in Siminoff’s 1995 study regarding organ donation (Siminoff et al. 1995). More research is required to determine the best ways to assess these preferences from patients and families perspectives as they relate to RTD.

The dilemmas do not end with identifying the most ethical way to approach a potential patient donor for RTD. The consenting process alone has been scrutinized for ethical loopholes. Some argue that using ‘blanket consent,’ or a consent that does not itemize uses of the tissue, is unethical (Australian Law Reform Commission 2003; National Health and Medical Research Council 1999; Hansson et al. 2006; Hofmann 2009) and patients and families may not understand the scope of the future research to be conducted with their biospecimen. Further, dilemmas of ownership of the tissue and future benefits and profits from discoveries related to the biospecimen could be a deterrent for a HCP to engage in recruitment. The current legislation and regulations regarding intellectual property and rights to benefits are presently under debate in the mainstream media and courts (Andanda 2008; Greenberg v Miami Children’s Hospital 2003; Gupta 2004; Moore v Regents of the University of California 1990). Venezuela and other countries offer a unique right to tissue donation in that donors may prohibit access to their specimen if they suspect further research will impact their biodiversity and cultural uniqueness (Gupta 2004).

Call to action

We have discussed the natural tendency for individuals to behave altruistically in order to benefit their group, which can be those with the same cancer diagnosis as in GST and the Gift Relationship, or family members as in Reciprocal Altruism. More behavioral and communication research is needed to determine how to assess and channel this altruism to effectively consent for RTD. Some HCPs may not be aware of the scientific advantages of RTD over whole body donation, as this procedure is not currently discussed most in medical schools (Boyette et al. 2012). Currently, the Licensing Committee on Medical Education does not provide any specific accreditation standards for medical schools curriculum addressing organ and body procurement or donation (Liaison Committee on Medical Education 2008).

Although there have been recent publications regarding the process of establishing an institutional RTD program, there are no evidence-based guidelines for recruiting patients. The consent process is a crucial step to enrolling patients, and there may be difficulties formulating standardized language; human research subjects are defined as living, thus Intuitional Review Board purview does not extend to human research with the deceased (Pentz et al. 2005). A recent article provides two approaches for addressing ethical issues in recruiting for biobanking, which can also be applied to establishing an RTD: a ‘top-down’ approach that elicits policy and procedure guidelines from major stakeholders, and a ‘bottom-up’ approach that seeks information from the affected community and inductively develops policy and procedure (Meslin 2010). The ‘bottom-up’ approach by all accounts would ensure that an RTD program is infused with the concerns, preferences, and altruistic desires of the affected group in order to benefit others afflicted by cancer, which will surely vary by cancer type.

It is necessary to investigate the numerous components that may influence the success of an institution’s RTD, and provide guidelines that overcome these professional and ethical challenges. Revolutionary algorithms have pioneered the successful establishment of RTD programs at research institutions (Rubin et al. 2000; Ghorpade et al. 2005; Lindell et al. 2006), however it is still unknown what makes an institution ready for an RTD program. The lack of focus on RTD in medical education and media calls first for an assessment of the climate that would allow the implementation of a program. This would be in the context of formative research to develop effective strategies to cultivate ‘buy-in’ from patients, families, and HCPs. In order to operationalize buy-in, it will be necessary to explore the knowledge, perceptions, and potential barriers of RTD programs from patients as well as HCPs stratified by specialty (e.g., oncologists vs. palliative care teams). This can be accomplished most effectively through focus groups or anonymous surveys. Once a baseline perception is established, appropriate interventions can be tailored. For example, if there is a lack of knowledge but positive perception of RTD indicated by physician surveys, a grand rounds symposium for continuing medical education credits may be warranted. Additionally, if patients who participate in focus groups express a high altruistic motivation yet exhibit heterogeneity among altruistic types, demographic characteristics can be ascertained to establish guidelines that assist HCP in utilizing effective recruitment strategies that also help the patient potentially fulfill altruistic legacies. The clear need for formative research should be compiled into effective provider training initiatives that are infused with data from stakeholders. This will foster an institutional environment ripe for the establishment of an ethically-sound RTD program that will contribute to the future of quality cancer care.