OBJECTIVES:To review the waiting list data and outcomes after liver transplantation (LT) in patients with cystic fibrosis (CF) in Australia and New Zealand. METHODS:The Australia and New Zealand Liver and Intestinal Transplant Registry was utilised to identify patients with CF listed for LT, including as a component of multi-organ transplantation. Outcomes were compared to non-CF patients. RESULTS:Between January 1989 and July 2022, 55 patients with CF underwent LT at a median age of 18.9 (13.5-30.0) years. Twenty-five (45%) were less than 18 years of age at the time of LT. Thirty-seven (67%) underwent isolated LT, and 18 (33%) underwent LT as a component of multi-organ transplantation. In paediatric CF isolated LT recipients, 15-year survival was similar to non-CF recipients (90.9% vs. 83.4%, p = 0.71); however, waiting list mortality was higher (3/21 [14.3%] vs. 33/779 [4.2%], p = 0.03). In adult CF recipients, there was no significant difference in 5- and 10-year survival after isolated LT (CF: 72.7% and 60.6% vs. non-CF: 83.0% and 73.0%, respectively, p = 0.07), and no significant difference in 5- and 10-year survival after multi-organ transplantation (excluding liver-kidney) compared to non-CF recipients (CF: 60.7% and 45.5% vs. non-CF: 66.7% and 66.7%, p = 0.27). In adult CF recipients, waiting time was longer (293 days [IQR 69-534] vs. 82 days [IQR 19-203], p = 0.004), and time to waiting list mortality in those listed for multi-organ transplantation was shorter (129 days [IQR 47-161] vs. 351 days [IQR 166-691], p = 0.049) than non-CF recipients. CONCLUSIONS:Survival after isolated LT in children with CF is equivalent to non-CF patients; however, waiting list mortality is higher. Adults with CF experience longer waiting times and shorter time to waiting list mortality.

BACKGROUND:Skin cancer is one of the most common comorbidities for liver transplant recipients (LTRs). Carcinogenesis is a multifaceted process: immunosuppression and personal risk factors such as smoking status, UV exposure, past history of skin cancer and family history of skin cancer can all play a significant role in determining the extent of skin cancer development. OBJECTIVE:To undertake a large-scale retrospective case matched cohort study examining the effect of personal and transplant related risk factors in cutaneous carcinogenesis. METHODS:A case-control study was performed of 114 LTRs who developed skin cancer who were compared to 288 age, sex, time since transplant and aetiology matched controls (1:2 ratio). Data, including histology, were collected via chart review and phone interviews and analysed using logistic regression to determine odds ratios. RESULTS:A total sample size of 342 was attained. Harmful risk factors that achieved statistical significance were being of Fitzpatrick skin type 1 or 2 (OR = 6.98, p < 0.01), incurring greater than five blistering sun burns (OR = 3.71, p < 0.01), pre-transplant history of skin cancer (OR = 3.36, p < 0.01), smoking status (OR = 3.30, p < 0.01). Immunosuppression protocols that included mTOR inhibitors (OR = 0.30, p < 0.01) were shown to be protective. Most skin cancers were high risk SCCs (63.11%). CONCLUSIONS:Personal and transplant related risk factors significantly modify the risk of cutaneous carcinogenesis in LTRs. Risk stratification of the likelihood of skin cancer development post liver transplant can help to structure an individualised surveillance scheme to facilitate early detection and treatment of skin cancers in LTRs.

BACKGROUND:Colorectal cancer (CRC) can induce stresses on the immune system that can affect both the numbers and function of immune cells. Changes in immune cell functions can also occur during ageing and these may affect both the ability to fight infections and to protect against cancers. As the incidence of CRC is age-related, the aim of this work was to identify changes in immune cell subtypes that are specific to CRC and not merely due to age-related changes. METHODS:Whole blood samples from 49 CRC patients about to undergo surgery and 22 healthy controls were collected. Samples were analysed by immunophenotyping, detection of HLA-DR on T-lymphocytes and monocytes, and senescent-like T-lymphocytes. RESULTS:CD4 staining intensity of monocytes was significantly increased in CRC patients and showed a positive correlation with their HLA-DR staining intensity. In most CRC patients, the numbers of helper T-lymphocytes were lower with the progression of the disease, while cytotoxic T-lymphocytes were higher (an opposite pattern to the immunophenotypes of the healthy ageing cohort). NKbright cells were higher while NKdim cells were lower in patients with large tumours. An increase in the T-lymphocytes to B-lymphocytes ratio correlated with the metastatic status. CONCLUSIONS:Complex changes in the immune phenotypes in CRC, distinct from those that occur during ageing were observed, that imply development of an immuno-suppressive phenotype that may aid tumour evasion of immunity.

BACKGROUND:There has been an increasing focus on the potential of cancer vaccines as a therapeutic oncological option, aiming to harness the immune system to recognize and eliminate malignant cells. Unlike traditional therapies, vaccines exploit tumour-associated antigens and neoantigens to generate durable, tumour-specific immune responses. METHODS:This review provides a comprehensive overview of current vaccine strategies, their clinical applications, and implications for surgical oncology. RESULTS:Clinical trials highlight promising results in high-mutational burden cancers such as melanoma, lung, and bladder cancer, as well as in traditionally 'cold' tumours like pancreatic cancer. Combination strategies, particularly with checkpoint inhibitors, have shown enhanced efficacy, exemplified by messenger RNA-4157/V940 and autogene cevumeran in adjuvant settings. Off-the-shelf tumour-associated antigen vaccines offer scalability but face challenges of tolerance and limited specificity. Early data suggest vaccines may improve relapse-free survival and induce antigen spreading, broadening immune responses beyond the initial targets. CONCLUSION:Cancer vaccines are poised to complement surgery and systemic therapies, particularly in the perioperative window. Their integration into multimodal treatment strategies may redefine precision oncology, offering durable disease control and improved patient outcomes.

Background: The impact of human leukocyte antigen (HLA) histocompatibility on graft survival is well established in kidney and haematopoietic stem cell transplantation; however, its role in liver transplantation (LT) remains uncertain. Prior studies have reported inconsistent associations between HLA mismatching and LT graft outcomes. Given emerging evidence linking HLA mismatch to post-transplant complications, this relationship warrants reassessment. Objectives: To investigate the effect of HLA Class I (A, B, C) and Class II (DRB1, DQA, DQB) mismatching on LT graft survival in a single-centre retrospective analysis. Design: A retrospective, single-centre cohort study. Methods: 610 patients who underwent their first deceased donor LT between January 2010 and March 2021 were included. The primary outcome was graft failure. Donor and recipient HLA typing was available at HLA-A, HLA-B and HLA-DRB1 loci in 610 patients, HLA-C in 38 patients, HLA-DQA in 63 patients and HLA-DQB in 63 patients. Graft survival was assessed using Kaplan–Meier analysis and predictors identified using Cox regression. Results: HLA-C mismatching was associated with reduced graft survival on Kaplan–Meier analysis ( p = 0.02); however, this was based on a small subgroup ( n = 38), and the univariate Cox estimate was imprecise (HR 9.24, 95% CI 1.01–83.48, p = 0.047). HLA-DRB1 mismatching was associated with improved graft survival ( p = 0.047) and reduced graft failure risk on multivariate Cox regression (aHR 0.34, 95% CI 0.14–0.87, p = 0.02), although limited by the small number of matched transplants ( n = 9). There was no association between mismatches at other loci and graft survival. Hepatic artery thrombosis worsened graft survival (aHR 3.42, 95% CI 2.44–4.80, p < 0.001) but was not associated with HLA mismatch. Conclusion: These results suggest that the effect of HLA histocompatibility in LT may be locus-specific. Associations were observed for differential graft outcomes at the HLA-C and HLA-DRB1 loci; however, given the small sample sizes and imprecision of estimates, these findings should be considered hypothesis-generating and require validation in larger prospective cohorts.

BACKGROUND:Biliary anastomotic strictures (BAS) after liver transplant (LT) are a significant contributor to post-transplant morbidity. Although surgical technique has been proposed as a risk factor, accurate evaluation of technique has been limited by inherent bias in conventional definitions for BAS. This study aimed to evaluate the incidence of clinically significant BAS (csBAS) with absorbable suture material and variable anastomotic suture technique in patients undergoing LT with duct-to-duct (DD) anastomosis. METHODS:A retrospective medical record review was conducted of adult patients undergoing LT at a single center between January 1st, 2000 and December 31st, 2023. Suture technique included continuous or interrupted alone, or a combined technique (continuous to posterior wall, interrupted anteriorly), while suture material was either absorbable or non-absorbable suture. Primary endpoint was the incidence of csBAS using a previously introduced surrogate marker, extended biliary dilatation programs (EBDP). Secondary endpoints included time to csBAS, incidence of bile leak, intervention rates with csBAS, and graft failure. Univariable and multivariable analyses were performed to identify independent associations with csBAS. Graft survival with csBAS was assessed using a Kaplan-Meier curve. RESULTS:A total of 842 patients underwent 864 LTs with DD anastomosis, of which 123 LTs (14.2%) developed csBAS. The mean age and follow up time were 53.3 ± 11.3 years and 7.0 ± 5.0 years, respectively. Year of transplant (p < 0.01), donor age (p = 0.01), suture material (p = 0.05) and suture technique (p = 0.01) were associated with csBAS on univariable analysis. On multivariable analysis, only donor age (adjusted OR 1.01, 95% CI 1.00-1.03, p = 0.03) was found to be independently associated, while absorbable suture material, suture technique and year of transplant were not associated. No difference was seen in bile leaks or graft failure with absorbable suture material nor anastomotic technique. No significant association was observed with time to csBAS, nor between csBAS and graft failure. CONCLUSION:Variable suture technique and suture material during DD reconstruction are associated with comparable outcomes following LT.

BACKGROUND AND OBJECTIVE:First-line (1L) treatment options for locally advanced or metastatic urothelial carcinoma (la/mUC) include enfortumab vedotin plus pembrolizumab (EV+P), based on EV-302, or platinum-based chemotherapy (PBC) with avelumab maintenance for patients without progression, based on JAVELIN-Bladder 100 (JB-100). Clinicians must choose between EV+P and PBC without knowing whether patients will respond to PBC and qualify for avelumab. In EV-302, avelumab maintenance was approved after trial initiation and therefore, was potentially underutilized among patients without progression. This modeling study facilitated a true 1L comparison of EV+P versus PBC ± avelumab. METHODS:Progression-free survival and overall survival were compared using EV-302 patient-level data and JB-100 study-level data. The JB-100 hazard ratio (HR) for avelumab versus best supportive care was applied to a comparable EV-302 PBC subgroup of patients without progression after a 22-week 1L period. This replaced EV-302 data for patients without progression to reflect outcomes assuming all EV-302 patients without progression received avelumab as observed in JB-100. Using a weighted hazard approach, patients without progression were combined with EV-302 patients with progression to obtain a hybrid PBC ± avelumab arm, which was compared with observed EV+P outcomes. Weighted average HRs with 95% confidence intervals (CIs) were calculated. KEY FINDINGS AND LIMITATIONS:EV+P improved progression-free survival (HR 0.51, 95% CI 0.44-0.59) and overall survival (HR 0.64, 95% CI 0.49-0.86) versus PBC ± avelumab. Results were consistent across sensitivity analyses. Limitations include assuming all patients without progression received avelumab, which may not reflect real-world patterns. CONCLUSIONS AND CLINICAL IMPLICATIONS:EV+P provides progression-free survival and overall survival benefits over PBC ± avelumab, reinforcing its position as the 1L standard of care in patients with la/mUC.

The 7th Bench-to-Bedside Uro-Oncology: GU Cancers Triad Meeting, organized in conjunction with the 45th Annual Congress of the Société Internationale d’Urologie, was held on 31 October 2025, in Edinburgh, Scotland, and transmitted live on the SIU@U Congress app [...]

4583 Background: The DISCUS trial compared 3 versus 6 cycles (3C versus 6C) of chemotherapy followed by avelumab in 267 patients receiving first-line treatment for metastatic urothelial cancer. It showed 3 cycles of chemotherapy followed by maintenance avelumab was associated with better QoL than six cycles (NCT06892860). Efficacy outcomes of the two arms appeared similar. Here we compare the cisplatin (cis) or carboplatin (carbo) chemotherapy subsets in the 3C and 6C arms. Methods: Patients were randomized to receive either 3 or 6 cycles of chemotherapy. Cisplatin or carboplatin was allocated by physician choice. Progression free survival (PFS), Overall survival (OS), response rates, patient-reported outcomes (PROs) and treatment related adverse events were collected (TRAEs) were collected. The analysis was exploratory and p values nominal. Results: 267 were included of whom 55 received 3C/cis, 55 6C/cis, 78 3C/carbo and 79 6C/carbo. Patients receiving carboplatin had poor performance status (ECOG >=1 in 17% cis vs 35% carbo). Table 1 showed similar efficacy outcomes with potentially marginally superior OS with cisplatin. The comparison of efficacy and QOL endpoints for 3 vs 6 cycles of carboplatin showed many similarities. Six cycles of cisplatin-based chemotherapy was associated with a major drop in QOL compared to 3 cycles without showing any clear benefits in efficacy endpoints. Conclusions: The QoL benefits of shorter chemotherapy appear to be more marked in patients receiving cisplatin than carboplatin. The efficacy results for 3 cycles of cisplatin were impressive. This study was not powered for non-inferiority. Clinical trial information: NCT06892860 . Outcomes by treatment arm. 3C/cis (n=56) 3C/carbo (n=77) 6C/cis (n=54) 6C/carbo(n=80) CR (%) 16% 10% 14% 12% PFS (months), median(95% CI) 8.8(6.5-12.8) 8.0(5.8-12.0) 8.7(6.4-18.9) 9.0(6.6-13.1) OS (months), median(95% CI) Not reached(12.8-.) 18.5(12.6-.) 21.9(10.5-.) 15.0(9.8-.) G3 and above TRAE (n) 32 40 49 79 PRO (change from baseline to C7D1) 2.96 -2.51 -13.44 -4.86

OBJECTIVES:To establish a UK consensus vision of a standardised genomic testing pathway in unresectable/metastatic urothelial cancer (mUC) with clear roles and responsibilities for multidisciplinary team (MDT) members and molecular pathology laboratory teams, and to agree how the pathway must evolve to accommodate emerging innovations. SUBJECTS AND METHODS:A modified Delphi method was used. Six healthcare professionals (HCPs) with expertise in UC formed the Steering Committee (SC), which met in May 2025. Seven key consensus topics were developed covering the steps of the pre-testing and genomic testing pathways, the current and future state of precision medicine, and approaches to overcome barriers and ensure readiness for the future. Within these topics, statements were developed and distributed to clinical scientists and HCPs via an on-line 4-point Likert scale survey. Respondents could opt out of responding to statements outside their area of expertise. Consensus was pre-defined as ≥75% agreement. RESULTS:Overall, 50 responses were received; consensus was reached on 41/42 statements. The statement that did not achieve consensus was part of a paired set. A proposed pathway for pre-testing and genomic testing in unresectable or mUC was developed based on survey results and discussions at SC meetings. Key priorities for the pathway include: timely fibroblast growth factor receptor 3 testing, ideally at the commencement of first-line systemic therapies; selection of specimens based on volume of tissue and recency; immediate access to the genomic testing report for all MDT members; and secure data environments with federated access to genomic results. Since the stopping criteria were met, no further survey rounds were required. CONCLUSION:Adopting the genomic testing pathway derived from this Delphi consensus will provide greater clarity around MDT and molecular laboratory responsibilities, reduce regional inequities in access, and optimise patient outcomes through timely delivery of genomic testing and subsequent treatment.

5001 Background: The STAMPEDE trials showed that adding abiraterone acetate + prednisolone (AAP) ± enzalutamide (ENZ) to standard of care androgen deprivation therapy (SOC) improves metastasis-free survival (MFS) in high-risk non-metastatic (M0) prostate cancer (PCa) patients (pts). However, variable responses & adverse events underscore the need for prognostic & predictive biomarkers. We evaluated performance of a validated MMAI algorithm (ArteraAI Prostate Test v1.2) to identify pts who benefit most from the addition of AAP ± ENZ (ARPI). Methods: High-risk M0 STAMPEDE pts treated with SOC+ARPI (N=555) or SOC (N=781) with sufficient quality H&E biopsy images & clinical data (T stage, age, PSA) were included. MMAI score association with PCa specific mortality (PCSM, primary outcome measure) & distant metastasis (DM) was analyzed using Fine-Gray regression & cumulative incidence curves, with other cause mortality treated as competing risks. MFS was assessed using Cox regression & Kaplan-Meier curves. An optimal cut-point was identified via grid search to maximize ARPI benefit separation across biomarker positive (pos, MMAI in top quartile) & negative (neg) subgroups. Hazard ratios [95% CI] & p values are reported. Results: PCSM median follow-up was 6.0 years (N=1336). Continuous MMAI scores were statistically significantly associated with poorer PCSM (1.65 [1.43-1.90], p<0.001), MFS (1.42 [1.29-1.56], p<0.001) & DM (1.54 [1.36-1.74], p<0.001). Using clinically-established prognostic cut-offs, 89% of pts were MMAI high-risk. The optimal ARPI MMAI cut-point identified 334 biomarker-pos pts who had significantly higher PCSM than biomarker-neg pts. A statistically significant biomarker-treatment interaction for PCSM (p-int=0.04) revealed that biomarker-pos pts treated with ARPI had improved PCSM (0.42 [0.24-0.74], p=0.003), while biomarker-neg pts did not derive a treatment benefit (0.85 [0.56-1.29], p=0.45). Estimated 5-year PCSM was 9% for biomarker-pos pts receiving ARPI vs. 17% with SOC, compared to 4% & 7% for biomarker-neg pts, respectively, with similar results observed in M0N0 pts (Table 1). Conclusions: For the first time, we demonstrate that a validated MMAI algorithm can identify high-risk non-metastatic PCa pts most likely to benefit from the addition of ARPI. Notably we identify a positive biomarker-treatment interaction in the highest MMAI score quartile, which in cases of clinical equipoise could inform clinical decision-making. We highlight MMAI’s potential to optimize treatment decisions & spare biomarker-neg pts from unnecessary therapy & toxicities. Clinical trial information: NCT00268476 . Estimated 5-yr absolute risk reduction from ARPI vs SOC-treated patients by biomarker groups in M0 (M0N0) pts. Biomarker-neg Biomarker-pos PCSM 3% (1%) 8% (9%) MFS 2% (-1%) 17% (16%) DM 5% (3%) 12% (15%)

BACKGROUND:Postoperative pancreatic fistula (POPF) is the primary cause of morbidity after distal pancreatectomy (DP). This trial investigated the application of a combined polyethylene glycol (PEG) and recombinant human albumin sealant gel to the stapled, transected pancreatic margin to reduce clinically significant POPF. METHODS:A multicenter randomised controlled trial in patient candidates for DP with stapled transection was conducted. Participants were randomised to receive DP with or without PEG sealant applied to the stapled margin. The primary outcome was clinically significant POPF. Secondary outcomes included other complications, length of hospital stay and 90-day mortality. RESULTS:Seventy-eight patients with completed DP were included, 38 of whom underwent stapled DP combined with the use of PEG sealant (PEG group). No significant differences between the two groups were observed with respect to pathology type, operative approach or operative time. The PEG group exhibited significantly fewer complications (18% vs. 50% in the control group; p = 0.003), and a lower rate of POPF (11% vs. 28%; p = 0.08, respectively). Multivariate analysis revealed a significant association between spleen preservation and the rate of clinically significant fistula (OR 4.4; 95% CI 1.1-18.0; p = 0.038). The rate of POPF was lower in the PEG group but did not reach statistical significance (OR 0.3; 95% CI 0.1-1.2; p = 0.091). CONCLUSION:Stapled DP combined with PEG application was associated with reduced complications. There was a lower rate of POPF in the PEG sealant group that did not reach statistical significance. AUSTRALIAN NEW ZEALAND CLINICAL TRIALS REGISTRY:ACTRN12620001336976p.

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BACKGROUND:We aim to compare the incidence and risk factors for biliary anastomotic stricture (BAS) in patients undergoing orthotopic liver transplant (OLT) with and without transcystic externalised trans-anastomotic biliary stenting. METHODS:A retrospective analysis was performed of a prospective database focused on 836 cadaveric OLT. Primary outcome measures were the incidence of BAS and risk factors related to its development. RESULTS:Duct-to-duct anastomosis was the most commonly performed biliary reconstruction (90.5%). Transcystic externalised trans-anastomotic biliary stenting was performed in 420 patients (62.0%), being mostly used in patients having a duct-to-duct anastomosis (63.6%). BAS was seen in 222 (32.8%) patients, with a median time to diagnosis of 145.5 days (IQR 50.3-370.5). BAS was higher in patients with a duct-to-duct reconstruction when compared to those having a bilio-enteric reconstruction (34.3% vs. 18.7%, p = 0.02). The prevalence of BAS was not significantly different between patients who were stented and those who were not (34.5% vs. 30.0% respectively, p = 0.25). Multivariable analysis showed that older donor age, transplants performed earlier in the study period, higher MELD score, and type of biliary reconstruction (duct-to-duct) were independently associated with a higher risk of BAS. CONCLUSION:Transcystic externalised biliary anastomotic stenting is not associated with a reduced biliary stricture incidence in OLT.