Research autopsy programmes in oncology: shared experience from 14 centres across the world
Metastatic disease is the main cause of death from cancer and is currently almost always incurable . The multi‐step progression from early to metastatic cancer has been described for some tumour types (reviewed in ). However, many of the steps in the cascade are still poorly understood from a biological point of view . Additionally, inter‐ and intra‐patient tumour heterogeneity is increasingly being described at the (epi)genomic, transcriptomic, phenotypic, and micro‐environmental levels , and complicates the clinical management of metastatic disease . A better biological understanding of metastatic cancer is key to advancing the clinical management of cancer patients. The goals of research include the discovery of features shared by all metastases that are efficiently targetable, of ways to reduce intra‐tumour heterogeneity, or of mutually exclusive mechanisms that can be targeted through combination strategies. This requires comprehensive studies of multiple samples per patient at multiple points in time. Unfortunately, obtaining a biopsy from a metastatic site is often not possible due to their anatomical localisation and the invasiveness of the procedure. Even when technically feasible, the biopsy may not be representative of the full tumour profile. Liquid biopsies, such as blood samples, can represent an elegant way of sampling a more complete tumour profile, but to what extent different metastases contribute has so far been studied only in small cohorts . Research autopsies, aimed at collecting multiple patient samples within a short timeframe after death for the specific purpose of translational research, constitute an invaluable answer to this problem. Also termed rapid autopsy or postmortem tissue donation programmes, they importantly differ from clinical autopsies not only in their goals but also in their organisation . The concept is not new and has been of great value in areas of research in which access to samples is problematic during life, such as neurological  and chronic (infectious) diseases . More recently, research autopsies have also been used to help to understand organ damage from COVID‐19 . In oncology, multiple excellent autopsy programmes have been developed and have described their structure and logistics of approach . Most publications are, however, single programme reports and do not compare methodologies across locations in a structured way . The research autopsy as a method of enhancing access to tissue samples is also still under‐utilised. This study evaluated 14 research autopsy programmes in oncology worldwide to identify commonalities, important logistical aspects of tissue donation, and ethical considerations. Experience gained in these studies may be informative for increasing transparency, enhancing worldwide interdisciplinary collaborative research, as well as for the initiation of new programmes and expansion of existing programmes.   Ethics approval statement Each programme has its respective ethics approval and patient consent for participation. A questionnaire with over 150 questions on five topics (study design, patient enrolment, study conduct and tissue donation procedure, sample and data management, and challenges and opportunities) was designed for this study (supplementary material, Table ). Research autopsy programmes in oncology were identified based on literature reviews, clinical trial databases, and professional networks. Programmes temporarily on hold were eligible, while programmes for paediatric patients (which generally have distinct inclusion procedures) or pure clinical autopsy programmes were excluded. Programmes were contacted via e‐mail, and follow‐up meetings after questionnaire completion were conducted to clarify uncertainties and to ensure data completeness across the topics. No ethical approval was needed for this study. Information was retrieved between December 2022 and May 2023. The results are presented in a descriptive manner.   Each programme has its respective ethics approval and patient consent for participation. A questionnaire with over 150 questions on five topics (study design, patient enrolment, study conduct and tissue donation procedure, sample and data management, and challenges and opportunities) was designed for this study (supplementary material, Table ). Research autopsy programmes in oncology were identified based on literature reviews, clinical trial databases, and professional networks. Programmes temporarily on hold were eligible, while programmes for paediatric patients (which generally have distinct inclusion procedures) or pure clinical autopsy programmes were excluded. Programmes were contacted via e‐mail, and follow‐up meetings after questionnaire completion were conducted to clarify uncertainties and to ensure data completeness across the topics. No ethical approval was needed for this study. Information was retrieved between December 2022 and May 2023. The results are presented in a descriptive manner.   Presentation of the included programmes Twenty‐eight programmes were identified, of which 23 were contacted after revision of inclusion criteria (supplementary material, Figure ). Of these, 14 provided us with their data within the set timeframe. Though a majority ( n = 9) were based in the USA (Figure ), others from the United Kingdom, Belgium, Hungary, Australia, and Japan ( n = 1 in each country) were included. The main characteristics of the respective programmes are listed in supplementary material, Table . Of note, none of the 23 identified programmes were in South America or Africa. All principal investigators ( n = 14) had academic positions. The programme set‐up was led by a research team in eight, a clinical team in two, and a combination of both in four programmes. Most programmes followed institutional ethics committee‐approved research protocols as required by their legal and ethical framework for research on deceased patients. Some studies formalised their protocol after conducting sporadic research autopsies at patients’ requests ( n = 6). Others spent a median of 12 months (range 6–48 months) of logistic and administrative preparatory work before any autopsy was performed. The legal framework influenced the establishment and conduct of some of the autopsy programmes. The PEACE (Posthumous Evaluation of Advanced Cancer Environment) programme, for example, experienced autopsy delays due to strict regulations regarding the signature of death certificates. The UPTIDER (UZ/KU Leuven Program for Tissue Donation to Enhance Research), Genitourinary Cancer Biorepository, Legacy Project for Rapid Tissue Donation, and CASCADE (CAncer tiSsue Collection After DEath) programmes operated in regions where assisted dying was or became authorised, enabling pre‐planning of the autopsy if the patient chose euthanasia (which occurred in 25%, <10%, 8%, and 3% of patients in these programmes, respectively). The programmes primarily focused on collecting metastatic and non‐tumour tissues to allow diverse lines of research. Research objectives built on this focused on cancer heterogeneity, tumour evolution, tumour micro‐environment, mechanisms of treatment response/resistance, representability of liquid biopsies, and creation of experimental tumour models. Additionally, some programmes supported research in other diseases or areas, through the sharing of samples or of experience for the creation of other programmes. All programmes adopted a multidisciplinary approach with high involvement of the Departments of Pathology and General Medical Oncology (in n = 14 and n = 13 programmes, respectively). Of note, the number of pathologists involved varies according to the programme: most have a pool of three or four pathologists on rota, while others have dedicated pathologists in the programme or are (co)‐led by pathologists. Many programmes additionally collaborated with other clinical and academic partners, both within their institution and externally. Patient inclusion and follow‐up Six programmes enrolled patients with any primary cancer type (Figure and supplementary material, Table ). Three adopted a focused multi‐cancer approach including only tumour types with established collaborations for maximal sample utilisation. The remaining five programmes allowed up to two primary tumour types: breast in Legacy to Life, Hope for OTHERS (Our Tissue Helping Enhance Research & Science), the UNC Breast Tumour Donation program, and UPTIDER; and prostate and bladder cancer in the Genitourinary Cancer Biorepository. Of note, the multi‐cancer programme CASCADE had a sister project focusing on breast cancer only (BROCADE), which will be discussed separately only if significantly differing from CASCADE. Most programmes ( n = 12) allowed patients dying at home to participate but put restrictions on distance from the programme hospital. Patient referral was allowed in eight programmes, on the condition of registration in one of the enrolling centres. Patients of particular research interest due to clinical features of their cancer, i.e. genetic predisposition or specific treatments, were sometimes targeted for enrolment. However, this was never an official inclusion criterion. Most programmes ( n = 11) did not accept patients with known communicable diseases, either chronically or acutely present at the time of death. In the other programmes, appropriate equipment and measures were used to ensure that autopsies were safely performed in these high‐risk settings . Informed consent was required in all programmes, signed either obligatorily by the patient ( n = 1), by the next‐of‐kin/family ( n = 6), by both ( n = 1), or by either of the two ( n = 6). Treating‐oncologists usually first approached patients and/or their families but sometimes found it difficult to discuss end‐of‐life matters in their role as healthcare providers. In response to this, some programmes have allowed first conversations by psychosocially trained members of the research team. Occasionally, patients touched on the subject themselves, especially in regions where assisted dying was legal. Leaflets in hospital waiting rooms, information on the institution's website, or articles in the general press could enhance self‐referral (ten programmes used this). We have listed tips for best wording to introduce and discuss the topic in Table . Three inclusion strategies emerged from our survey, with corresponding timelines presented in Figure . Firstly, most programmes ( n = 12) included patients in their last line(s) of treatment and/or in best supportive care setting. The median time between enrolment and death in programmes that allowed only this scenario ( n = 2: Legacy to Life and UPTIDER) was 3 and 5 weeks, respectively. Secondly, more than half of the programmes additionally allowed inclusion in early non‐curative ( n = 8) or even curative treatment settings ( n = 3). This answers the documented preference of patients to be active decision makers when the choice is not urgent, as with organ donation . Thirdly, six programmes allowed the enrolment of patients after death, via the next‐of‐kin's consent. This strategy had the advantages of tailoring inclusion based on timing of death (e.g. avoiding weekend autopsies) and alignment with obtaining consent for clinical autopsies. On the other hand, there was little time for patient‐specific autopsy preparation. While many countries allowed after‐death next‐of‐kin consent, this might bring psychological discomfort to the family and researchers. The Michigan Legacy Tissue Program resolved this through after‐death consent via the next‐of‐kin, but only after thorough discussions with the patient during life. Apart from eligibility criteria and timing, there were other reasons not to approach patients. Seven programmes preferentially did not contact patients who were not coping well with their prognosis, were not well supported by their families, had a strained relationship with their clinicians, or had refused to participate in other research/biobanking studies in the past. Seven programmes reported an estimate on the percentage of patients who are eventually approached out of all eligible patients, with the average being 40% (range 5–80%). Of note, some patients were approached carefully but if their initial reaction to the programme was not positive, it was not mentioned thereafter. With these inclusion strategies, enrolment of patients was highly successful. Of those who received the informed consent documents, 75% (average of the percentages in all programmes; range 40–100%) signed up. Many reasons for participation were listed by the patients including contributing to scientific advancements, helping future patients, and being offered an alternative for organ donation. The most common reason for not participating was psychosocial distress. Only one programme reported that patients were sometimes not convinced of the project's scientific value. Almost all programmes ( n = 12) allowed opt‐out from parts of the study, such as certain anatomical regions (e.g. brain) being sampled, and collaboration with non‐academic partners. Patients seldom (<10% of cases in all but one programme) chose these opt‐outs. Importantly, the family played a big role in recruitment and follow‐up in most programmes. Family objections because of psychosocial distress or possible impact on funeral services were reported in ten studies as a reason for not participating. In the interval between enrolment and death, programmes maintained contact with caregivers or passively followed up through medical file checks. Table suggests tips for effective interaction and strategies to handle challenges during follow‐up. At death: logistics and tissue donation procedure Eight programmes performed autopsies 24 h/7 days (Figure ), with associated challenges discussed in Table . Their median postmortem interval (PMI, between death and autopsy start) was 4 h (range of medians 2.5–14) for patients dying outside of the hospital (vast majority). In programmes restricting autopsies to (extended) working hours, the median PMI was 9 h (range of medians 4 h to 4 days). Transportation of patients who passed away outside of the hospital was performed by a company contracted specifically for the study in seven programmes. Upon arrival, the body was ideally refrigerated until the autopsy commenced. Four programmes performed imaging before the autopsy (whole body CT and/or MRI), either as part of the standard forensic procedure or as part of the research protocol. The median number of staff present at each autopsy was 4 (range 2–13). Essential roles included a pathologist and/or a mortuary technician (officially referred to as an anatomical pathology technologist (APT) in the UK and often referred to as a morgue or autopsy technician in many other countries), a coordinator overseeing sample procurement, and research personnel handling sample processing and registration. Autopsies took around 3 h (median of reported medians) to complete [range of medians 1 h (Semmelweis University) to 6.5 h (UPTIDER)] (Figure ). Several factors influenced autopsy times. Research teams performing the autopsies themselves reported longer autopsy durations compared with clinical pathology services. On‐site sample processing prolonged the autopsy; many programmes instead transported samples on ice to a research laboratory. Extensive annotation and electronic registration of sample information added to autopsy times (see ‘Sample and data management’ below). Lastly, three programmes implemented body sterilisation and the use of sterile drapes to reduce infection risk in subsequent tumour models, potentially slightly increasing autopsy durations. Clinical autopsy rooms were usually used and additional equipment was brought in for the procedure. Supplementary material, Figure depicts the room's set‐up in two different programmes. Almost all programmes ( n = 11) collected blood first and all programmes ( n = 14) collected other types of body fluids, such as ascites, bone marrow, pleural fluid, pericardial fluid, cerebrospinal fluid, urine, vitreous fluid, or aqueous humour (Figure ). Next, a patient‐specific order of organ inspection was followed in eight programmes, while others stuck to the order in standard clinical autopsies. Photographical documentation of lesions was implemented in 12 programmes. The number of malignant lesions sampled per patient depended on disease burden, tissue viability assessment, and extent of exploration of bone and lymph node metastases. The median number of lesions sampled per patient was 15.5 (median of all medians) and even ≥20 in six programmes (Figure ). Many programmes implemented multiregional sampling for large lesions [up to 38 regions for one tumour site (PEACE)]. All but one programme collected both snap‐frozen and formalin‐fixed samples, sometimes alongside other processing methods (fresh, viably frozen, …). One programme froze any remaining tumour material in vacuum bags. Normal tissue from the same organ with metastases was collected in almost all programmes ( n = 13). Other non‐invaded organ samples were additionally collected in 12 programmes, either as part of the autopsy routine or to answer specific research questions (Figure ). The median number of samples collected during each autopsy per patient ranged from 4 (Akita Rapid Autopsy Program) to 250 (UPTIDER), with the median of all medians being 58 (Figure ). Sample and data management The high number of samples retrieved within a short timeframe demanded an efficient sample registration strategy. Half of the programmes ( n = 7) created sample labels before autopsy start. Barcoding helped seven programmes to track samples, though only one programme used it at autopsy for registration of sample‐specific timepoints and storage locations. Information ultimately recorded for each sample often included the organ (based on anatomical nomenclature or using organ codes ) and the exact location of sampling (for correlation with imaging or treatment response ), alongside the processing method and sample‐specific timepoints. While most programmes try to access the tumour samples that were collected during the patient's life, this can be challenging, especially with regard to the primary tumour, which has often been surgically removed in another hospital many years before the autopsy (Table ). Capturing comprehensive clinical patient information was equally challenging due to the complex and diverse disease trajectory of metastatic disease. Eight programmes had set up electronic databases, most commonly in RedCap ( n = 5). Usually, access to the patient's medical file remained available after death for information extraction as research questions evolved. Other logistical considerations Most programmes ( n = 11) purchased equipment specifically for the study including processing equipment, bone drills, logistic equipment, sterilisation equipment, and consumables. Estimating the total price per patient was challenging for five programmes. The Akita Rapid Autopsy Program reported a cost of only USD 20 per patient due to enrolling in‐hospital patients only and covering the pathologist's salary through their clinical position. For seven programmes, the price ranged between USD 1,000 and 5,000 per patient; one programme even reported a price range of USD 3,000–10,000. The price was often highly influenced by personnel costs, with some researcher time covered through grants and other personnel requiring full funding. Two programmes reported an autopsy fee of USD 1,500 being charged per patient. Transport of the body either was done in‐kind or ranged between USD 185 and 1,500 in median price. Postmortem imaging costs ranged between USD 250 and 750 per patient, or was included in the autopsy fee. The biggest financial contributors were research foundations [mentioned in nine programmes, median contribution out of total budget 45% (range 5–100%)]. This was followed by funding through the host university [seven programmes, median contribution 50% (range 10–95%)] and the affiliated hospitals [four programmes, median contribution 70% (range 6–100%)]. Three programmes additionally received support through private donors, accounting for 20%, 50%, and 50% of their total budget. Of interest, two programmes implemented cost recovery structures where end users were charged for the samples received (contribution to total budget: 25% and 30%), incentivising them to include cost recovery in grants. Prices varied based on collaboration type (close academic partners versus non‐affiliated institutes or industry/commercial partners). No programmes reported structural funding from industry or pharmaceutical companies. Research opportunities and achievements Postmortem programmes allow high‐volume sample collection of tumour tissue, non‐tumour tissue, and liquid biopsies, sometimes in combination with longitudinal sampling (the original primary tumour and/or metastases during life) (Figure ). This has already enabled high‐impact research, as highlighted in Figure and Table with examples from the 14 programmes. Genomics, particularly sequencing multiple metastases per patient, has revealed insights into metastatic seeding, driver events, treatment resistance, and disease phylogenetics . Additionally, it has allowed the exploration of the use of liquid biopsies to profile the different metastases . Phenotyping has highlighted heterogeneity in clinically used biomarkers and the inadequacy of a single biopsy to assess treatment eligibility . Autopsy programmes have comprehensively assessed metastatic organ involvement  and have facilitated the establishment of patient‐derived xenografts (PDXs) and other experimental models with subsequent investigation of treatment sensitivity . Some programmes are additionally exploring new treatment targets, the metastatic tumour micro‐environment, and the correlation between histological and imaging features. Non‐tumour tissue research has so far explored the presence of driver events in non‐cancerous tissue . Other promising avenues on these tissues include assessment of treatment toxicity, paraneoplastic effects, pre‐metastatic niches, and tumour dormancy. Additionally, non‐cancer‐related health research can also be conducted on these tissues; for example, non‐tumour brain samples collected in the UPTIDER programme are used for research on neurodegenerative diseases.   Twenty‐eight programmes were identified, of which 23 were contacted after revision of inclusion criteria (supplementary material, Figure ). Of these, 14 provided us with their data within the set timeframe. Though a majority ( n = 9) were based in the USA (Figure ), others from the United Kingdom, Belgium, Hungary, Australia, and Japan ( n = 1 in each country) were included. The main characteristics of the respective programmes are listed in supplementary material, Table . Of note, none of the 23 identified programmes were in South America or Africa. All principal investigators ( n = 14) had academic positions. The programme set‐up was led by a research team in eight, a clinical team in two, and a combination of both in four programmes. Most programmes followed institutional ethics committee‐approved research protocols as required by their legal and ethical framework for research on deceased patients. Some studies formalised their protocol after conducting sporadic research autopsies at patients’ requests ( n = 6). Others spent a median of 12 months (range 6–48 months) of logistic and administrative preparatory work before any autopsy was performed. The legal framework influenced the establishment and conduct of some of the autopsy programmes. The PEACE (Posthumous Evaluation of Advanced Cancer Environment) programme, for example, experienced autopsy delays due to strict regulations regarding the signature of death certificates. The UPTIDER (UZ/KU Leuven Program for Tissue Donation to Enhance Research), Genitourinary Cancer Biorepository, Legacy Project for Rapid Tissue Donation, and CASCADE (CAncer tiSsue Collection After DEath) programmes operated in regions where assisted dying was or became authorised, enabling pre‐planning of the autopsy if the patient chose euthanasia (which occurred in 25%, <10%, 8%, and 3% of patients in these programmes, respectively). The programmes primarily focused on collecting metastatic and non‐tumour tissues to allow diverse lines of research. Research objectives built on this focused on cancer heterogeneity, tumour evolution, tumour micro‐environment, mechanisms of treatment response/resistance, representability of liquid biopsies, and creation of experimental tumour models. Additionally, some programmes supported research in other diseases or areas, through the sharing of samples or of experience for the creation of other programmes. All programmes adopted a multidisciplinary approach with high involvement of the Departments of Pathology and General Medical Oncology (in n = 14 and n = 13 programmes, respectively). Of note, the number of pathologists involved varies according to the programme: most have a pool of three or four pathologists on rota, while others have dedicated pathologists in the programme or are (co)‐led by pathologists. Many programmes additionally collaborated with other clinical and academic partners, both within their institution and externally.   Six programmes enrolled patients with any primary cancer type (Figure and supplementary material, Table ). Three adopted a focused multi‐cancer approach including only tumour types with established collaborations for maximal sample utilisation. The remaining five programmes allowed up to two primary tumour types: breast in Legacy to Life, Hope for OTHERS (Our Tissue Helping Enhance Research & Science), the UNC Breast Tumour Donation program, and UPTIDER; and prostate and bladder cancer in the Genitourinary Cancer Biorepository. Of note, the multi‐cancer programme CASCADE had a sister project focusing on breast cancer only (BROCADE), which will be discussed separately only if significantly differing from CASCADE. Most programmes ( n = 12) allowed patients dying at home to participate but put restrictions on distance from the programme hospital. Patient referral was allowed in eight programmes, on the condition of registration in one of the enrolling centres. Patients of particular research interest due to clinical features of their cancer, i.e. genetic predisposition or specific treatments, were sometimes targeted for enrolment. However, this was never an official inclusion criterion. Most programmes ( n = 11) did not accept patients with known communicable diseases, either chronically or acutely present at the time of death. In the other programmes, appropriate equipment and measures were used to ensure that autopsies were safely performed in these high‐risk settings . Informed consent was required in all programmes, signed either obligatorily by the patient ( n = 1), by the next‐of‐kin/family ( n = 6), by both ( n = 1), or by either of the two ( n = 6). Treating‐oncologists usually first approached patients and/or their families but sometimes found it difficult to discuss end‐of‐life matters in their role as healthcare providers. In response to this, some programmes have allowed first conversations by psychosocially trained members of the research team. Occasionally, patients touched on the subject themselves, especially in regions where assisted dying was legal. Leaflets in hospital waiting rooms, information on the institution's website, or articles in the general press could enhance self‐referral (ten programmes used this). We have listed tips for best wording to introduce and discuss the topic in Table . Three inclusion strategies emerged from our survey, with corresponding timelines presented in Figure . Firstly, most programmes ( n = 12) included patients in their last line(s) of treatment and/or in best supportive care setting. The median time between enrolment and death in programmes that allowed only this scenario ( n = 2: Legacy to Life and UPTIDER) was 3 and 5 weeks, respectively. Secondly, more than half of the programmes additionally allowed inclusion in early non‐curative ( n = 8) or even curative treatment settings ( n = 3). This answers the documented preference of patients to be active decision makers when the choice is not urgent, as with organ donation . Thirdly, six programmes allowed the enrolment of patients after death, via the next‐of‐kin's consent. This strategy had the advantages of tailoring inclusion based on timing of death (e.g. avoiding weekend autopsies) and alignment with obtaining consent for clinical autopsies. On the other hand, there was little time for patient‐specific autopsy preparation. While many countries allowed after‐death next‐of‐kin consent, this might bring psychological discomfort to the family and researchers. The Michigan Legacy Tissue Program resolved this through after‐death consent via the next‐of‐kin, but only after thorough discussions with the patient during life. Apart from eligibility criteria and timing, there were other reasons not to approach patients. Seven programmes preferentially did not contact patients who were not coping well with their prognosis, were not well supported by their families, had a strained relationship with their clinicians, or had refused to participate in other research/biobanking studies in the past. Seven programmes reported an estimate on the percentage of patients who are eventually approached out of all eligible patients, with the average being 40% (range 5–80%). Of note, some patients were approached carefully but if their initial reaction to the programme was not positive, it was not mentioned thereafter. With these inclusion strategies, enrolment of patients was highly successful. Of those who received the informed consent documents, 75% (average of the percentages in all programmes; range 40–100%) signed up. Many reasons for participation were listed by the patients including contributing to scientific advancements, helping future patients, and being offered an alternative for organ donation. The most common reason for not participating was psychosocial distress. Only one programme reported that patients were sometimes not convinced of the project's scientific value. Almost all programmes ( n = 12) allowed opt‐out from parts of the study, such as certain anatomical regions (e.g. brain) being sampled, and collaboration with non‐academic partners. Patients seldom (<10% of cases in all but one programme) chose these opt‐outs. Importantly, the family played a big role in recruitment and follow‐up in most programmes. Family objections because of psychosocial distress or possible impact on funeral services were reported in ten studies as a reason for not participating. In the interval between enrolment and death, programmes maintained contact with caregivers or passively followed up through medical file checks. Table suggests tips for effective interaction and strategies to handle challenges during follow‐up.   Eight programmes performed autopsies 24 h/7 days (Figure ), with associated challenges discussed in Table . Their median postmortem interval (PMI, between death and autopsy start) was 4 h (range of medians 2.5–14) for patients dying outside of the hospital (vast majority). In programmes restricting autopsies to (extended) working hours, the median PMI was 9 h (range of medians 4 h to 4 days). Transportation of patients who passed away outside of the hospital was performed by a company contracted specifically for the study in seven programmes. Upon arrival, the body was ideally refrigerated until the autopsy commenced. Four programmes performed imaging before the autopsy (whole body CT and/or MRI), either as part of the standard forensic procedure or as part of the research protocol. The median number of staff present at each autopsy was 4 (range 2–13). Essential roles included a pathologist and/or a mortuary technician (officially referred to as an anatomical pathology technologist (APT) in the UK and often referred to as a morgue or autopsy technician in many other countries), a coordinator overseeing sample procurement, and research personnel handling sample processing and registration. Autopsies took around 3 h (median of reported medians) to complete [range of medians 1 h (Semmelweis University) to 6.5 h (UPTIDER)] (Figure ). Several factors influenced autopsy times. Research teams performing the autopsies themselves reported longer autopsy durations compared with clinical pathology services. On‐site sample processing prolonged the autopsy; many programmes instead transported samples on ice to a research laboratory. Extensive annotation and electronic registration of sample information added to autopsy times (see ‘Sample and data management’ below). Lastly, three programmes implemented body sterilisation and the use of sterile drapes to reduce infection risk in subsequent tumour models, potentially slightly increasing autopsy durations. Clinical autopsy rooms were usually used and additional equipment was brought in for the procedure. Supplementary material, Figure depicts the room's set‐up in two different programmes. Almost all programmes ( n = 11) collected blood first and all programmes ( n = 14) collected other types of body fluids, such as ascites, bone marrow, pleural fluid, pericardial fluid, cerebrospinal fluid, urine, vitreous fluid, or aqueous humour (Figure ). Next, a patient‐specific order of organ inspection was followed in eight programmes, while others stuck to the order in standard clinical autopsies. Photographical documentation of lesions was implemented in 12 programmes. The number of malignant lesions sampled per patient depended on disease burden, tissue viability assessment, and extent of exploration of bone and lymph node metastases. The median number of lesions sampled per patient was 15.5 (median of all medians) and even ≥20 in six programmes (Figure ). Many programmes implemented multiregional sampling for large lesions [up to 38 regions for one tumour site (PEACE)]. All but one programme collected both snap‐frozen and formalin‐fixed samples, sometimes alongside other processing methods (fresh, viably frozen, …). One programme froze any remaining tumour material in vacuum bags. Normal tissue from the same organ with metastases was collected in almost all programmes ( n = 13). Other non‐invaded organ samples were additionally collected in 12 programmes, either as part of the autopsy routine or to answer specific research questions (Figure ). The median number of samples collected during each autopsy per patient ranged from 4 (Akita Rapid Autopsy Program) to 250 (UPTIDER), with the median of all medians being 58 (Figure ).   The high number of samples retrieved within a short timeframe demanded an efficient sample registration strategy. Half of the programmes ( n = 7) created sample labels before autopsy start. Barcoding helped seven programmes to track samples, though only one programme used it at autopsy for registration of sample‐specific timepoints and storage locations. Information ultimately recorded for each sample often included the organ (based on anatomical nomenclature or using organ codes ) and the exact location of sampling (for correlation with imaging or treatment response ), alongside the processing method and sample‐specific timepoints. While most programmes try to access the tumour samples that were collected during the patient's life, this can be challenging, especially with regard to the primary tumour, which has often been surgically removed in another hospital many years before the autopsy (Table ). Capturing comprehensive clinical patient information was equally challenging due to the complex and diverse disease trajectory of metastatic disease. Eight programmes had set up electronic databases, most commonly in RedCap ( n = 5). Usually, access to the patient's medical file remained available after death for information extraction as research questions evolved.   Most programmes ( n = 11) purchased equipment specifically for the study including processing equipment, bone drills, logistic equipment, sterilisation equipment, and consumables. Estimating the total price per patient was challenging for five programmes. The Akita Rapid Autopsy Program reported a cost of only USD 20 per patient due to enrolling in‐hospital patients only and covering the pathologist's salary through their clinical position. For seven programmes, the price ranged between USD 1,000 and 5,000 per patient; one programme even reported a price range of USD 3,000–10,000. The price was often highly influenced by personnel costs, with some researcher time covered through grants and other personnel requiring full funding. Two programmes reported an autopsy fee of USD 1,500 being charged per patient. Transport of the body either was done in‐kind or ranged between USD 185 and 1,500 in median price. Postmortem imaging costs ranged between USD 250 and 750 per patient, or was included in the autopsy fee. The biggest financial contributors were research foundations [mentioned in nine programmes, median contribution out of total budget 45% (range 5–100%)]. This was followed by funding through the host university [seven programmes, median contribution 50% (range 10–95%)] and the affiliated hospitals [four programmes, median contribution 70% (range 6–100%)]. Three programmes additionally received support through private donors, accounting for 20%, 50%, and 50% of their total budget. Of interest, two programmes implemented cost recovery structures where end users were charged for the samples received (contribution to total budget: 25% and 30%), incentivising them to include cost recovery in grants. Prices varied based on collaboration type (close academic partners versus non‐affiliated institutes or industry/commercial partners). No programmes reported structural funding from industry or pharmaceutical companies.   Postmortem programmes allow high‐volume sample collection of tumour tissue, non‐tumour tissue, and liquid biopsies, sometimes in combination with longitudinal sampling (the original primary tumour and/or metastases during life) (Figure ). This has already enabled high‐impact research, as highlighted in Figure and Table with examples from the 14 programmes. Genomics, particularly sequencing multiple metastases per patient, has revealed insights into metastatic seeding, driver events, treatment resistance, and disease phylogenetics . Additionally, it has allowed the exploration of the use of liquid biopsies to profile the different metastases . Phenotyping has highlighted heterogeneity in clinically used biomarkers and the inadequacy of a single biopsy to assess treatment eligibility . Autopsy programmes have comprehensively assessed metastatic organ involvement  and have facilitated the establishment of patient‐derived xenografts (PDXs) and other experimental models with subsequent investigation of treatment sensitivity . Some programmes are additionally exploring new treatment targets, the metastatic tumour micro‐environment, and the correlation between histological and imaging features. Non‐tumour tissue research has so far explored the presence of driver events in non‐cancerous tissue . Other promising avenues on these tissues include assessment of treatment toxicity, paraneoplastic effects, pre‐metastatic niches, and tumour dormancy. Additionally, non‐cancer‐related health research can also be conducted on these tissues; for example, non‐tumour brain samples collected in the UPTIDER programme are used for research on neurodegenerative diseases.   We present here the shared experience and accomplishments of 14 research autopsy programmes that were created to advance metastatic cancer research around the world. At the geographical level, most programmes are in the United States and we could not identify any programme in South America or Africa. This means that, currently, these programmes might not be capturing the full spectrum of the disease. The programmes ranged from slight modification of clinical autopsy procedures to extensive postmortem tissue sampling performed by research personnel. Autopsies performed 24 h/7 days had a median PMI of only 4 h, enabling the qualitative collection of fragile molecules and viable cells. This structure, however, came at a psychological and logistical cost. All programmes have successfully collected highly valuable liquid and tissue samples, with a median of 58 samples stored per patient across all programmes, including from organs otherwise unethical/impossible to sample. The rapid nature of the procedures (often completed within 12 h after death) and implementation of cooling mitigated postmortem effects on molecules/RNA degradation. Genomic analyses were possible in every programme, leading to major discoveries in metastatic tumour progression and biology. Sample prioritisation, sterile procurement, and reduced transport times have facilitated the creation of unique tumour models shaping future drug discoveries and testing. In the era of precision medicine, autopsy programmes can be an invaluable link in the research chain towards better patient outcomes. Through this work, we hope to foster collaborations (contact details are provided in supplementary material, Table for all programmes) and to encourage the creation of new programmes. A society of research autopsy programmes will help to achieve this goal and is currently being created, including non‐oncological and paediatric programmes. Importantly, we also plan on further exploring how the role of patients in the design and support of the programmes can be increased in the future, as they are the cornerstone of and the sole reason for the research we do.   TG was responsible for conceptualisation, methodology, validation, formal analysis, investigation, resources, data curation, writing the original draft, review and editing of the manuscript, visualisation and project administration. MM was responsible for conceptualisation, methodology, review and editing of the manuscript and project administration. JEH was responsible for resources, review and editing of the manuscript and supervision. SO, AVL, WVDB and GF were responsible for methodology, resources, and review and editing of the manuscript. LM, JMA, MR, SP, HT, LD, DB, ERB, KI, MS, LR, ALW, LG, RMu, PC, AK, CN‐L, HB, CS, MJ‐H, LK, CM, MC, AMC, AW, RMe, ZR, LAC, EK, DM, AG, JK, MS, BS and A‐MT helped with resources and writing the manuscript (review and editing). CD was involved in conceptualisation, methodology, review and editing of the manuscript and supervision.   Figure S1. Flow diagram of the number of rapid autopsy programmes identified, contacted, and finally included in the survey Figure S2. Examples of the set‐up of the autopsy room in two different programmes Table S1. Blank version of the five fact sheets containing all questions in the survey Table S2. Main characteristics of the respective programmes   