Cell-free DNA (cfDNA) has recently emerged as a real-time biomarker for diagnosis, monitoring and prediction of therapy response in tumoral disease. Here, we evaluated cfDNA as a prognostic biomarker for monitoring muscle-invasive bladder cancer (MIBC) patients at different follow-up time points. Blood samples from 37 MIBC patients who underwent radical cystectomy (RC) were collected at cystectomy and 1, 4, 12 and 24 months later. Plasma cfDNA amount and fragmentation patterns were determined. Four mutations were analyzed in cfDNA to detect circulating tumor DNA (ctDNA) during patient follow-up. During a median follow-up of 36 months, 46% of patients progressed; median time to progression was 10 months. cfDNA levels and ctDNA status four months after RC were identified as independent prognostic biomarkers of tumor progression (HR 5.290; p = 0.033) and cancer-specific survival (HR 4.199; p = 0.038), respectively. Furthermore, ctDNA clearance four months after RC was significantly associated with patients’ clinical outcomes. In conclusion, cfDNA levels and ctDNA status four months after RC have prognostic implications in MIBC patients. In addition, cfDNA monitoring is useful to predict patient outcomes after RC. cfDNA analysis in the clinical setting could greatly improve MIBC patient management.

Background: The integration of Artificial Intelligence (AI) technology in cancer care has gained unprecedented global attention over the past few decades. This has impacted the way that cancer care is practiced and delivered across settings. The purpose of this study was to explore the perspectives and experiences of healthcare professionals (HCPs) on cancer treatment and the need for AI. This study is a part of the INCISIVE European Union H2020 project's development of user requirements, which aims to fully explore the potential of AI-based cancer imaging technologies. Methods: A mixed-methods research design was employed. HCPs participating in cancer care in the UK, Greece, Italy, Spain, Cyprus, and Serbia were first surveyed anonymously online. Twenty-seven HCPs then participated in semi-structured interviews. Appropriate statistical method was adopted to report the survey results by using SPSS. The interviews were audio recorded, verbatim transcribed, and then thematically analysed supported by NVIVO. Results: The survey drew responses from 95 HCPs. The occurrence of diagnostic delay was reported by 56% (n = 28/50) for breast cancer, 64% (n = 27/42) for lung cancer, 76% (n = 34/45) for colorectal cancer and 42% (n = 16/38) for prostate cancer. A proportion of participants reported the occurrence of false positives in the accuracy of the current imaging techniques used: 64% (n = 32/50) reported this for breast cancer, 60% (n = 25/42) for lung cancer, 51% (n = 23/45) for colorectal cancer and 45% (n = 17/38) for prostate cancer. All participants agreed that the use of technology would enhance the care pathway for cancer patients. Despite the positive perspectives toward AI, certain limitations were also recorded. The majority (73%) of respondents (n = 69/95) reported they had never utilised technology in the care pathway which necessitates the need for education and training in the qualitative finding; compared to 27% (n = 26/95) who had and were still using it. Most, 89% of respondents (n = 85/95) said they would be opened to providing AI-based services in the future to improve medical imaging for cancer care. Interviews with HCPs revealed lack of widespread preparedness for AI in oncology, several barriers to introducing AI, and a need for education and training. Provision of AI training, increasing public awareness of AI, using evidence-based technology, and developing AI based interventions that will not replace HCPs were some of the recommendations. Conclusion: HCPs reported favourable opinions of AI-based cancer imaging technologies and noted a number of care pathway concerns where AI can be useful. For the future design and execution of the INCISIVE project and other comparable AI-based projects, the characteristics and recommendations offered in the current research can serve as a reference.

Penile squamous cell carcinoma (PSCC) is a rare but aggressive neoplasm with dual pathogenesis (human papillomavirus (HPV)-associated and HPV-independent). The development of targeted treatment is hindered by poor knowledge of the molecular landscape of PSCC. We performed a thorough review of genetic alterations of PSCC focused on somatic mutations and/or copy number alterations. A total of seven articles have been identified which, overall, include 268 PSCC. However, the series are heterogeneous regarding methodologies employed for DNA sequencing and HPV detection together with HPV prevalence, and include, in general, a limited number of cases, which results in markedly different findings. Reported top-ranked mutations involve TP53, CDKN2A, FAT1, NOTCH-1 and PIK3CA. Numerical alterations involve gains in MYC and EGFR, as well as amplifications in HPV integration loci. A few genes including TP53, CDKN2A, PIK3CA and CCND1 harbor both somatic mutations and copy number alterations. Notch, RTK-RAS and Hippo pathways are frequently deregulated. Nevertheless, the relevance of the identified alterations, their role in signaling pathways or their association with HPV status remain elusive. Combined targeting of different pathways might represent a valid therapeutic approach in PSCC. This work calls for large-scale sequencing studies with robust HPV testing to improve the genomic understanding of PSCC.

P53 immunohistochemistry (IHC) has been proposed as a surrogate for TP53 mutations in penile squamous cell carcinomas (PSCC). We aimed to evaluate the performance of a pattern-based evaluation of p53 IHC in PSCC. Human papilloma virus (HPV) DNA testing, p16 and p53 IHC, and whole exome sequencing were performed in a series of 40 PSCC. p53 IHC was evaluated following a pattern-based framework and conventional p53 IHC evaluation. Out of 40 PSCC, 12 (30.0%) were HPV-associated, and 28 (70.0%) were HPV-independent. The agreement between the p53 IHC pattern-based evaluation and TP53 mutational status was almost perfect (k = 0.85). The sensitivity and accuracy of the pattern-based framework for identifying TP53 mutations were 95.5% and 92.5%, respectively, which were higher than the values of conventional p53 IHC interpretation (54.5% and 70.0%, respectively), whereas the specificity was the same (88.9%). In conclusions, the pattern-based framework improves the accuracy of detecting TP53 mutations in PSCC compared to the classical p53 IHC evaluation.

Penile squamous cell carcinoma (PSCC) is classified into 2 prognostically distinct types: human papillomavirus (HPV)–associated and HPV-independent. However, the impact of p53 status on prognosis remains controversial. We correlated HPV and p53 status with the prognosis of a large series of patients with PSCC. p53 was analyzed according to a recently described immunohistochemical (IHC) pattern-based framework that includes 2 normal and 4 abnormal patterns and closely correlates with TP53 mutational status. A total of 122 patients with surgically treated PSCC in 3 hospitals were included. Based on HPV in situ hybridization and p16 and p53 IHC, the tumors were classified into 3 subtypes: HPV-associated, HPV-independent/p53 normal, and HPV-independent/p53 abnormal. All patients were followed up for at least 22 months (median: 56.9 months). Thirty-six tumors (29%) were HPV-associated, 35 (29%) were HPV-independent/p53 normal, and 51 (42%) were HPV-independent/p53 abnormal. Disease-related deaths were observed in 3/36 (8%), 0/35 (0%) and 14/51 (27%) of the patients, respectively (P < 0.001). A total of 7/14 deaths in the latter group were patients with tumors showing p53 abnormal patterns not recognized in the classic p53 IHC interpretation (basal, null, and cytoplasmic). According to our multivariate analysis, HPV-independent/p53 abnormal tumors and advanced stage were associated with impaired disease-specific survival (hazard ratio = 23.4, 95% CI = 2.7-3095.3; P = 0.001 and 16.3, 95% CI = 1.8-2151.5; P = 0.008, respectively). In conclusion, compared with patients with HPV-associated and HPV-independent/p53-normal PSCC, patients with HPV-independent/p53 abnormal PSCC have worse clinical outcomes. p53 IHC results define 2 prognostic categories in HPV-independent PSCC: HPV-independent/p53-normal tumors as low-risk tumors, whereas HPV-independent/p53-abnormal tumors as aggressive neoplasms.

Introduction. Nowadays, minimally invasive surgery in kidney transplantation is a reality thanks to robotic assistance. In this paper, we describe our experience, how we developed the robotic assisted Kidney transplantation (RAKT) technique, and analyze our results. Material and Methods. This is a retrospective study of all RAKTs performed at our center between July 2015 and March 2020. We describe the donor selection, surgical technique, and analyze the surgical results and complications. A comparison between the first 20 cases and the following ones is performed. Results. During the aforementioned period, 82 living donor RAKTs were performed. The mean age was 47.4 ± 13.4 and 50 (61%) were male. Mean body mass index was 25 ± 4.7 and preemptive in 63.7% of cases. Right kidneys and multiple arteries were seen in 14.6% and 12.2%, respectively. Mean operative and rewarming time was 197 ± 42 and 47 ± 9.6 minutes, respectively. Five cases required conversion to open surgery because of abnormal kidney vascularization. Two patients required embolization for subcapsular and hypogastric artery bleeding without repercussion. Three kidneys were lost, two of them due to acute rejection and one because venous thrombosis. Late complications requiring surgery included one kidney artery stenosis, one ureteral stenosis, two lymphoceles, and three hernia repairs. We noticed a significant reduction in time between the first 20 cases and the following ones from 248.25 ± 38.1 to 189.75 ± 25.3 (p < 0.05). With a mean follow‐up time of 1.8 years (SD 1.3), the mean creatinine was 1.52 (SD 0.7) and RAKT graft survival was 98%. Conclusions. The robotic approach is an attractive, minimally invasive method for kidney transplantation, yielding good results. Further studies are needed to consider it a standard approach.