Search Results (169)

Background/Objectives: The uniform application of total neoadjuvant therapy (TNT) for locally advanced rectal cancer (LARC) risks overtreatment and surgical complications. We evaluated a novel tailor-made therapy that personalizes radiotherapy and chemotherapy to balance oncological safety with organ preservation. Methods: We retrospectively analyzed 38 patients with cStage II–III LARC treated between 2023 and 2025. Patients were stratified by sphincter preservation feasibility and high systemic risk (cN2, extramural vascular invasion, lateral lymph node enlargement). Group A (sphincter-preserving, n = 20) received induction chemotherapy; long-course chemoradiotherapy (LCCRT) was omitted in favorable responders but added if MRF-positive or to aim for non-operative management (NOM) in exceptional responders. Group B (non-sphincter-preserving, low systemic risk, n = 8) received LCCRT plus consolidation chemotherapy. Group C (non-sphincter-preserving, high systemic risk, n = 10) received short-course radiotherapy plus consolidation chemotherapy. Results: Over a median observation period of 20 months (range, 6–37), NOM was initiated in 7 patients (18% overall; Group A: 10%, Group B: 50%, Group C: 10%), with one local regrowth observed to date, resulting in 6 of 7 patients (85.7%) successfully maintaining NOM. Preoperative radiotherapy was safely omitted in 32% of the total cohort, and notably in 60% of patients in Group A. Surgery was performed in 28 patients (74%), achieving an R0 resection rate of 100% across all groups. Distant metastasis recurrence during preoperative treatment occurred in 5 patients (13%). Risk-stratified, tailor-made therapy for LARC facilitates the highly customized application or omission of radiotherapy. Conclusions: Risk-stratified, tailor-made therapy facilitates the safe omission or targeted application of radiotherapy in LARC. This personalized approach prevents overtreatment, maintains complete surgical curability, and achieves successful organ preservation in appropriately selected patients. Full article

The coexistence of cancer and severe aortic stenosis (AS) is increasing as a result of population aging and substantial improvements in cancer survival. Transcatheter aortic valve implantation (TAVI) has transformed the management of AS; however, patients with active malignancy or a history of cancer remain markedly under-represented in pivotal randomized trials. This under-representation has resulted in persistent uncertainty regarding patient selection, risk stratification, and the expected benefit of TAVI in this growing and clinically heterogeneous population. This review provides a comprehensive and contemporary synthesis of the evidence on TAVI in patients with cancer, integrating cardiovascular (CV), oncologic, and geriatric perspectives. Available data on epidemiological overlap, cancer-specific procedural challenges, and short- and long-term outcomes following TAVI are critically examined, with particular emphasis on distinctions between active cancer and cancer survivorship. Key modifiers of risk and benefit—including prior thoracic radiotherapy, competing thrombotic and bleeding risk, immunosuppression, frailty, sarcopenia, and nutritional status—are discussed in detail. Limitations of conventional surgical risk scores in oncology populations are highlighted, underscoring the need for individualized assessment beyond traditional CV metrics. Across registries and meta-analyses, TAVI is associated with high procedural success and comparable short-term outcomes in patients with and without cancer. Excess mortality observed during mid- and long-term follow-up is driven predominantly by non-CV causes related to malignancy rather than valve-related complications. Importantly, patients with cancer in remission demonstrate outcomes similar to those of non-cancer populations, whereas prognosis in active cancer is strongly influenced by disease stage, biology, and competing risks. Overall, cancer diagnosis alone should not preclude consideration of TAVI. Optimal management requires multidisciplinary, goal-oriented decision-making that integrates oncologic prognosis, functional status, and patients’ priorities. As cancer survivorship continues to expand, prospective studies, integrated risk stratification tools, and closer alignment between cardio-oncology and structural heart programs are essential to guide evidence-based and equitable care. Full article

Renal cell carcinoma (RCC) remains a major challenge in modern oncological urology, owing to its high heterogeneity, latent clinical course, and intrinsic resistance to chemotherapy and radiotherapy. In recent decades, the paradigm of carcinogenesis research has shifted from a primary focus on protein-coding genes alone to a broader investigation of the non-coding part of the transcriptome. Within this framework, long non-coding RNAs (lncRNAs) have emerged as fundamental regulators of cellular homeostasis. Accumulating evidence indicates that lncRNAs are not merely ‘transcriptional noise’ but components of intricate regulatory networks governing epigenetic, transcriptional, and post-transcriptional processes. Here, we present a comprehensive systematic review of the current literature addressing the role of lncRNA in the molecular pathogenesis of RCC. We discuss the roles of these molecules in key oncogenic signaling pathways, including PI3K/AKT/mTOR, Wnt/β-catenin, and Notch, and their contributions to tumor metabolic plasticity. The paper summarizes data on the link between lncRNAs and novel forms of regulated cell death—ferroptosis, cuproptosis, and disulphidosis. Particular attention is paid to their role in mediating resistance to tyrosine kinase inhibitors and their potential utility as highly specific biomarkers. Collectively, this review provides an updated perspective on the contribution of lncRNAs to RCC pathogenesis and outlines strategic directions for future research to support the development of more precise approaches in personalized oncology. Full article

Background: In oncologic patients, hypermetabolic neck lesions identified on F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) are often assumed to indicate nodal metastasis, especially in advanced disease. However, benign tumors such as schwannomas can also demonstrate avid F-18 FDG uptake, potentially leading to false-positive nodal staging and unwarranted assumptions of metastatic disease. Case Presentation: An 85-year-old woman with advanced uterine cervical cancer (FIGO stage IIB) underwent F-18 FDG PET/CT for staging purposes. Alongside intense uptake in the primary tumor, a hypermetabolic mass was incidentally identified in the left neck, raising concerns about nodal metastasis. Further imaging, including MRI and high-resolution ultrasonography (US), suggested a non-nodal origin, and US-guided core needle biopsy confirmed the diagnosis of a schwannoma, with histopathologic examination demonstrating characteristic Antoni A and B areas with diffuse S-100 positivity. Because the patient was elderly and repeatedly declined aggressive treatment, management was ultimately limited to symptom-directed palliative radiotherapy. Although tissue confirmation did not directly alter the delivered treatment strategy, it clarified the staging and prevented the neck lesion from being misclassified as metastatic disease. Conclusions: This case underscores that not all hypermetabolic neck lesions detected on F-18 FDG PET/CT in oncologic patients indicate metastatic lymphadenopathy. A multimodal imaging approach combined with minimally invasive tissue sampling can provide critical diagnostic clarification, particularly when PET/CT findings might otherwise lead to unsupported nodal upstaging or misguided assumptions in treatment planning. Full article

Sex differences influence cancer incidence, treatment response, and susceptibility to cardiovascular toxicity. Males exhibit higher rates and poorer outcomes in most non-sex-specific cancers, while females more frequently experience treatment-related adverse events, including cancer therapy-related cardiac dysfunction. Biological factors such as hormonal status, genetic polymorphisms, immune responses, and pharmacokinetics contribute to these disparities. In cardio-oncology, women—particularly premenopausal or with specific genotypes—may be at increased risk for cardiotoxicity after treatment with anthracyclines, immune checkpoint inhibitors or radiotherapy. Clonal hematopoiesis and certain germline genetic variants such as single nucleotide polymorphisms (e.g., RARG rs2229774, HAS3 rs2232228) are emerging as potential sex-informed biomarkers for predicting cardiotoxicity risk. Despite growing evidence, sex remains insufficiently integrated into clinical trials and guideline development in cardio-oncology. This review highlights the importance of sex-specific surveillance, prevention, and multi-omic risk stratification to advance precision cardio-oncology and support better outcomes for patients across the cancer care continuum. Full article

Background/Objectives: Amplitude-modulated radiofrequency (AMRF) fields have emerged as promising non-temperature-induced strategies in oncology. While conventional hyperthermia (HT) relies on thermal stress, the biological impact of AMRF, particularly in combination with radiotherapy (RT), remains insufficiently characterized. Methods: We assessed RF and AMRF, alone or with RT, using phenotypic analyses of proliferation, apoptosis, and necrosis across four cancer cell lines (HT29, SW620, U343, U138). Transcriptomic profiling with Kyoto Encyclopedia of Genes and Genomes (KEGG), GO:BP, and Reactome enrichment was performed in SW620 and U138 cells, selected for their strong phenotypic responses. Results: Across the panel, AMRF was associated with broader cytotoxic responses than RF or HT in most but not all cell lines. AMRF+RT produced the strongest necrotic responses, with cell-line-specific exceptions identified explicitly in the Results (the absence of a significant AMRF+RT apoptotic effect in SW620 and the absence of a significant AMRF+RT necrotic response in U343). In SW620 cells, AMRF was associated with extensive transcriptional reprogramming involving immune modulation, extracellular matrix remodeling, and cell cycle regulation, whereas RF alone showed narrower and delayed effects. In contrast, U138 cells showed elevated apoptosis and necrosis but limited transcriptional changes—a phenotype–transcriptome divergence that points to mechanisms operating downstream of transcription and warrants functional investigation in dedicated follow-up studies. Conclusions: AMRF and AMRF+RT emerge as promising non-temperature-induced anticancer modalities in the cell-line models profiled here, with the pattern of response varying between cell lines. These findings expand the biological impact of RF-based treatments and set the grounds for further investigation in mechanistic and translational studies. Full article

Background/Objectives: Testicular cancer accounts for approximately 1% of all male malignancies, with an incidence ranging from 1 to 10 per 100,000 men and it predominantly affects young individuals, with nearly 60% of cases diagnosed between 15 and 35 years of age. In recent decades, the incidence of testicular cancer has markedly increased, paralleling a global rise in male infertility rates. Although chemotherapy is known to adversely affect fertility, the extent to which the tumor itself and its different histological subtypes impact semen quality remains incompletely understood. The aim of this study was to evaluate semen parameters in men diagnosed with testicular cancer prior to oncological treatment and to assess the possible association between tumor histology and semen quality. Methods: This retrospective study included data from 284 men diagnosed with testicular cancer who underwent semen cryopreservation prior to surgery, chemotherapy, or radiotherapy. Data were collected between January 2016 and June 2022 at the Maternal and Child Department of the University of Naples Federico II. Histopathological classification was available for 278 patients and revealed the following distribution: 59% (165/278) classic seminoma, 14.7% (41/278) seminomatous mixed germ cell tumors, 13.3% (37/278) non-seminomatous mixed germ cell tumors, and 12.6% (35/278) non-seminomatous germ cell tumors. Results: No significant association was observed between tumor histology and abnormal semen parameters. According to World Health Organization (WHO) reference values, semen parameters in patients with testicular cancer were predominantly distributed between the 5th and 25th percentiles. Microscopic semen analysis revealed significantly lower sperm concentration, total motility, and normal morphology in cancer patients (p < 0.001; p < 0.001; and p < 0.002, respectively). Logistic regression analysis showed a significant association between age and testicular cancer risk (p < 0.001), with a negative coefficient indicating that the likelihood of developing the disease decreases with increasing age. Additionally, patients with seminoma were significantly older than those with non-seminomatous tumors: on average, 4.07 years older than those with pure non-seminoma (p = 0.007) and 5.60 years older than those with mixed non-seminoma (p < 0.001). No statistically significant age differences were observed among non-seminomatous subtypes. Conclusions: These findings underscore the importance of systematic semen evaluation in young men diagnosed with testicular cancer and highlight the critical role of fertility preservation strategies in the comprehensive management of these patients. Full article

Cancer remains a leading cause of premature death worldwide, posing a significant burden due to its high incidence and mortality. Radiotherapy and chemotherapy remain the most well-established and effective modalities in the current oncological therapeutic arsenal. However, their efficacy is often limited by toxicities owing to their non-selective targeting of rapidly dividing cells and consequent damage to healthy tissues. In recent years, advances in nanomedicine and biotechnology have drawn increasing attention to plant-derived extracellular vesicles (PDEVs) as an emerging, promising strategy for cancer therapy. As novel therapeutic vehicles, PDEVs offer key advantages, including high biocompatibility and low immunogenicity. However, their clinical translation has been significantly hampered by inherent limitations, including insufficient targeting specificity, low and uncontrollable drug-loading efficiency, and challenges in large-scale production and standardization. Current research is actively focused on overcoming these drawbacks through engineering strategies, for instance, surface modification with targeting peptides or antibodies to enhance targeting, alongside optimization of production and drug-loading processes. These developments underscore the potential of PDEVs as a promising platform for next-generation targeted cancer therapeutics. This review provides a comprehensive overview of PDEVs, covering their isolation, biogenesis, physicochemical properties, and anticancer applications. While summarizing these fundamental aspects, this review focuses on engineering strategies to enhance their active targeting capacity, offering theoretical insights to support their future role in cancer treatment. Full article

Primary squamous cell carcinoma (SCC) of the prostate is a rare and biologically aggressive malignancy lacking a standardized management strategy. De novo primary SCC arising without prior androgen deprivation therapy or radiotherapy is uncommon and presents significant diagnostic and therapeutic challenges. We present the clinical presentation, diagnostic evaluation, treatment strategy, and early therapeutic response of de novo primary SCC of the prostate in a 56-year-old male with end-stage renal disease on maintenance hemodialysis. The patient presented with gross hematuria and a bulky prostate mass invading the bladder with bilateral pelvic lymphadenopathy despite low prostate-specific antigen (PSA) levels. Histopathological and immunohistochemical analyses confirmed pure SCC, staged as cT4N1M0. Because systemic chemotherapy was contraindicated and surgery was not feasible, definitive whole-pelvis radiotherapy with a simultaneous integrated boost was administered. Marked tumor regression was observed one month after treatment. Subsequent imaging demonstrated extensive tumor necrosis with fistulous communication in the context of locally invasive disease. Because long-term oncologic durability could not be assessed owing to non-oncologic clinical deterioration, these findings suggest that definitive radiotherapy may provide meaningful locoregional tumor control in selected medically inoperable patients with de novo prostatic SCC. Full article

Background: Non-Wilms renal tumours (NWRTs) are rare paediatric malignancies and account for a small but clinically significant proportion of childhood renal cancers. Due to their low incidence and biological heterogeneity, outcome data are limited, and management is largely extrapolated from international collaborative protocols. No national data describing the incidence and outcomes of NWRTs in children in the Republic of Ireland (ROI) have previously been published. Objective: To determine the incidence, treatment strategies, and survival outcomes of NWRTs in children in the ROI. Methods: A retrospective cohort study was conducted of all children under 16 years of age with histologically confirmed renal tumours diagnosed and treated at Children’s Health Ireland (CHI) at Crumlin between January 2005 and December 2025. As CHI Crumlin is the single national paediatric oncology centre in the ROI, this cohort represents national case ascertainment for the study period. A total of 143 paediatric renal tumours were identified; Wilms tumours (n = 118) were excluded, leaving 25 children (17.48%) with NWRTs for analysis. No cases of bilateral renal tumours were identified. Histological subtypes included renal cell carcinoma (RCC), clear cell sarcoma of the kidney (CCSK), congenital mesoblastic nephroma (CMN), malignant rhabdoid tumour of the kidney (MRTK), and anaplastic sarcoma of the kidney. Demographic characteristics, treatment strategies, and survival outcomes were analysed. Results: Twenty-five children with NWRTs were identified: CCSK (n = 9), RCC (n = 7), CMN (n = 6), MRTK (n = 2), and anaplastic sarcoma of the kidney (n = 1). At a median follow-up of 107.9 months (range 4.5–181.3 months), overall survival for the cohort was 76%. Overall survival by histology was 100% for CMN, CCSK and anaplastic sarcoma, 43% for RCC, and 0% for MRTK. Treatment strategies varied by histology, with 68% undergoing upfront surgery, 32% receiving neoadjuvant chemotherapy, 60% receiving adjuvant systemic therapy, and 44% receiving radiotherapy. Tumour recurrence occurred in 4/25 patients (16%), confined to the RCC (3) and CMN (1) subgroups. Seven Event-Free Survival events were observed, comprising three RCC relapses and one RCC progression, one CMN relapse, and two MRTK progression-related deaths. No recurrences occurred in CCSK. Conclusions: NWRTs comprised 17.5% of all paediatric renal tumours diagnosed nationally during the study period and demonstrated marked heterogeneity in outcomes according to histological subtype. CMN showed excellent survival with six out of seven requiring surgery alone, whereas MRTK remained associated with dismal outcomes despite multimodal therapy. These national data support histology-driven, risk-adapted management and highlight the importance of continued international collaboration to improve outcomes in NWRTs. Full article

The protective effect of physical activity on breast cancer recurrence may be mediated changes in by sex hormone levels. In this study, we examined the association between habitual physical activity and estrogen and androgen plasma levels in postmenopausal women with localised breast cancer. We conducted a cross-sectional study among 47 postmenopausal women who were breast cancer survivors with estrogen receptor-positive tumours (enrolled at the Medical Oncology Department of University Hospital Dr. Peset, Valencia, Spain). Habitual physical activity was assessed using the International Physical Activity Questionnaire (IPAQ), and a weighted estimate of total physical activity per week (MET∙min∙wk⁻¹) was calculated. Total plasma levels of estrone, 17β-estradiol, progesterone, androstenedione, testosterone, and dehydroepiandrosterone-sulphate (DHEA-sulphate) were measured. Bivariate analyses by the Spearman correlation test were done between physical activity and each hormone concentration. Multivariate analyses (linear regression) using concentration of each hormone as the dependent variable and physical activity, age, marital status, BMI, Charlson Comorbidity Index, tumour stage, previous radiotherapy, or previous chemotherapy as predictor variables. Estrone concentration was positively and significantly correlated with BMI (ρ = 0.332, p = 0.022), but no other correlations were found between BMI and the other hormone concentrations, nor were concentrations of any hormone associated with age or Charlson Comorbidity Index (p > 0.05 in all cases). Physical activity was significantly and inversely correlated with estrone concentration (ρ = −0.308; p = 0.035). Linear regression analysis confirmed a statistically significant association between estrone concentration and BMI and physical activity, after adjusting for all potential confounders (for BMI: standardised β coefficient = 0.407; non-standardised β coefficient = 1.054; t = 2.898; p = 0.006; 95% CI for non-standardised beta: 0.318- to 1.790; for physical activity: standardised β coefficient = −0.300; non-standardised β coefficient = −0.005; t = −2.135; p = 0.039; 95% CI for non-standardised beta: −0.010- to 0.000). The relationship between estrone concentration and physical activity may be further explored as a biomarker for evaluating the protective effect of physical activity against breast cancer recurrence in women receiving anti-estrogen therapies. Full article

Background: The aim of this study was to estimate the economic burden of radiotherapy (RT) from the perspectives of payers, the healthcare system, patients, and society, and to assess associated quality-of-life (QoL) outcomes. The analysis examined direct medical and non-medical costs, as well as QoL, before, during, and up to six months after RT. Given the inclusion of multiple cancer types, the study reflects a heterogeneous real-world population. An exploratory comparison across RT techniques was also conducted to provide contextual economic insight. Methods: This analysis included data from 301 cancer patients undergoing RT using various techniques, including two-dimensional radiotherapy (2D), 3D conformal radiotherapy (3D-CRT), volumetric-modulated arc therapy (VMAT), and intensity-modulated radiotherapy (IMRT), at the University General Hospital of Heraklion, Crete, Greece. Clinical and cost data were collected retrospectively, while QoL data were collected prospectively using validated instruments at baseline, end of treatment, and six months post-treatment. Quality-adjusted life years (QALYs) were estimated. The primary analysis compared RT with a hypothetical “no RT” comparator derived from published evidence, while comparisons across RT techniques were conducted as exploratory analyses. Costs and QALYs were evaluated over a 6-month time horizon; therefore, discounting was not applied. Incremental cost-effectiveness ratios (ICERs) were calculated, and probabilistic sensitivity analysis was performed to account for parameter uncertainty. Results: The cost per QALY gained with RT compared with the hypothetical “no RT” comparator varied substantially across techniques and cancer types. In the primary analysis, 2D radiotherapy yielded the lowest ICER (€13,043.27/QALY), while VMAT demonstrated an ICER of €29,945.12/QALY. In contrast, IMRT was associated with a substantially higher ICER (€135,529.51/QALY), suggesting limited cost-effectiveness under commonly accepted willingness-to-pay thresholds, whereas 3D-CRT was found to be dominant. Subgroup analyses revealed marked heterogeneity, with ICERs ranging from €3234.45 to €30,232.50 per QALY gained across cancer types. In certain subgroups, RT was either cost-saving or dominant, particularly in breast cancer (cost-saving with similar QALYs) and in skin cancer and sarcoma (dominant strategies). Sensitivity analyses highlighted considerable uncertainty, especially for 2D radiotherapy, primarily driven by small sample sizes and variability in QALY estimates. Conclusions: This study provides short-term, real-world evidence on the cost-effectiveness and quality-of-life outcomes of radiotherapy in a Greek healthcare setting. While simpler techniques such as 2D radiotherapy may appear economically favorable, their limited effectiveness and substantial uncertainty may reduce their overall value. In contrast, advanced techniques—particularly VMAT—demonstrate a more consistent balance between cost and clinical outcomes, supporting their role within value-based, patient-centered oncology care. However, the findings should be interpreted with caution due to population heterogeneity, small subgroup sizes, the short (6-month) time horizon, and the use of a hypothetical comparator. Further research with longer follow-up and disease-specific analyses is warranted. Full article

Background/Objectives: Total neoadjuvant therapy (TNT), integrating systemic chemotherapy and radiotherapy before surgery or surveillance, has become a standard approach for locally advanced rectal cancer (LARC). However, optimal sequencing strategies and long-term outcomes of watch-and-wait (W&W) following sandwich TNT remain insufficiently characterized. We evaluated oncologic outcomes and treatment response in patients treated with an institutional sandwich TNT protocol. Methods: We conducted a retrospective cohort study of consecutive patients with LARC treated with sandwich TNT (induction chemotherapy followed by hypofractionated intensity-modulated radiotherapy with simultaneous integrated boost [IMRT-SIB] chemoradiotherapy and consolidation chemotherapy) at the Institute of Oncology Ljubljana between 2016 and 2023. The primary endpoint was an overall complete response (CR; pathological [pCR] and clinical [cCR]). Secondary endpoints included tumor regression grade (TRG), major pathological response (MPR), R0 resection rate, organ preservation, overall survival (OS), and disease-free survival (DFS). Results: Among 205 patients (median age 61 years), overall CR was 29.5% (pCR 19.3% and cCR 10.2%). Major pathological response (TRG 3–4) occurred in 37.6%. R0 resection was achieved in 94.5%. In the W&W cohort (n = 21), local regrowth occurred in 33.3% (95% CI, 14.6–57.0%) over a median follow-up of 4.96 years. Total mesorectal excision (TME)-free survival at 5 years was 73.1% (95% CI, 55.0–97.2%). Estimated 5-year OS was 81.1% (95% CI, 75.5–87.2%) and 5-year DFS was 75.2% (95% CI, 69.0–82.0). In multivariable analysis, non-R0 resection (HR 6.06, 95% CI, 1.99–18.42), MRI circumferential resection margin positivity (HR 3.11, 95% CI, 1.53–6.33), and MRI extramural vascular invasion positivity (HR 1.97, 95% CI, 1.05–3.91) remained independent predictors of DFS. Conclusions: Institutional sandwich TNT yields meaningful tumor response and durable survival in MRI-defined high-risk LARC. Structured W&W offers organ preservation with acceptable oncologic control under intensive surveillance. Full article

Background: Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related mortality with poor survival outcomes. Resection is the sole definitive management; however, most PDACs are diagnosed with unresectable disease including metastatic, locally advanced (LAPC) or borderline resectable (BRPC). Recently, neoadjuvant therapy has demonstrated potential in downstaging these tumours for resection. This literature review explores current and novel approaches in the management of BRPC and LAPC. Methods: A systematic search of Medline, Embase, Cochrane Central and Emcare databases was conducted on 7 April 2025. Inclusion criteria were primary articles that explored current and novel therapies that led to downstaging of BRPC and LAPC to resection, as well as resection outcomes and oncological outcomes associated with this. Articles that explored other pancreatic cancer subtypes or either resectable or metastatic disease were excluded. All meta-analyses were performed using a random-effects model based on the inverse variance method. Results: A total of 88 studies involving 8585 patients were included in the review, predominately from retrospective studies (57%, n = 50). Neoadjuvant regimens incorporating chemotherapy or radiotherapy, whether sequential or concurrent, demonstrated the highest proportions of R0 resections with N0 status. Overall, most modalities showed evidence of survival benefit following resection compared to non-operative management, with pooled differences demonstrated for chemotherapy alone (HR 0.33, 95% CI 0.25–0.44) and sequential chemotherapy and radiotherapy (HR 0.49, 95% CI 0.25–0.95). However, no significant differences between these modalities were demonstrated. Other modality-specific conclusions regarding survival benefit could not be elucidated. Conclusions: The rising incidence and global mortality from PDAC underscore the significance of identifying approaches to optimise the management of BRPC and LAPC. This review emphasises the importance of neoadjuvant therapy, both current and novel with surgical resection, which may warrant further investigation in future clinical trials. However, it is important to acknowledge the clinical heterogeneity of current data, which may introduce bias. Nevertheless, these findings can help to inform guidelines on the management of BRPC and LAPC. Full article

Background: Radiotherapy (RT) combined with androgen deprivation therapy (ADT) is a standard treatment for non-metastatic high-risk (HR) prostate cancer (PC). However, the benefit of elective nodal irradiation (ENI) in clinically node-negative (cN0) patients, although suggested, remains controversial, particularly in the elderly. We report the outcomes of elderly HR PC patients treated with prostate-only RT (PORT) and ADT in a “real-word” setting. Methods: Between 2016 and 2022, 43 consecutive elderly patients (median age 76 years) with HR- or very HR-PC according to NCCN criteria version 1.2026 (cN0, cT3-cT4 and/or ISUP Grade Group 4–5 and/or PSA serum levels at diagnosis ≥ 20 ng/mL) were treated at our institution. All patients were staged with abdominal MRI or CT and bone scan; nineteen patients (44.2%) also underwent 68Ga-PSMA-11 or 18F-fluorocholine PET/CT. All patients received PORT (predominantly moderate hypofractionation, 67.5–70 Gy in 25–28 fractions) and ADT (median duration 24 months). To ensure consistency, all oncological endpoints—Biochemical Failure-Free Survival (BFFS; Phoenix criteria), Disease-Free Survival (DFS), Metastasis-Free Survival (MFS), Prostate Cancer-Specific Survival (PCSS), and Overall Survival (OS)—were calculated from a unified time-zero (initiation of first oncological treatment). DFS was defined as a composite endpoint including biochemical failure, radiological recurrence, or initiation of salvage therapy. Results: at a median follow-up of 60 months, no patient reached the Phoenix threshold, resulting in a 100% 5- and 7-year BFFS. However, 4 patients (9.3%) experienced radiological recurrence detected via PET/CT before reaching the nadir + 2 threshold, yielding an estimated 5-year and 7-year DFS of 94.7% and 71.8%, respectively. The 5- and 7-year MFS was of 97.6% and 88.7%, respectively. Seven deaths occurred, all non-PC related, resulting in a 5-year OS of 86.7% and a Prostate Cancer-Specific Survival of 100%. Gastrointestinal toxicity was notably low (no acute or late G3-G4 events). Conclusions: Our findings suggest that PORT, when combined with long-term ADT and modern staging, provides excellent disease control and a favorable safety profile in elderly HR PC patients. Given the high rate of competing mortality in this population, treatment de-escalation via PORT appears to be a clinically reasonable strategy. These results are hypothesis-generating and warrant validation in prospective randomized trials. Full article