Search Results (402)

Head and neck cancer (HNC) encompasses tumors located within the oral cavity, sinonasal cavity, pharynx, and larynx. It is the sixth most common cancer worldwide. Current treatment methods in HNC patients involve radical surgery, radical radiotherapy, and concomitant chemoradiotherapy, along with adjuvant and induction therapies. Accumulating trials examine the role of immunotherapy in patients with HNC. The results of the CheckMate-141 and KEYNOTE-048 trials demonstrated the benefits of using immunotherapy in patients with metastatic or recurrent HNC. Subsequently, numerous other immunotherapy-based protocols have been evaluated. Then, KEYNOTE-689 successfully implemented immunotherapy in patients with locally advanced disease. This review aims to comprehensively present the landscape of immunotherapy opportunities in patients with HNC. It summarizes completed key clinical trials that led to the approval of immunotherapy in HNC and presents currently performed trials with highly expected results. Furthermore, it discusses methods to improve immunotherapy outcomes in the cohort of HNC patients, describes the current role of immunotherapy in HNC, and presents future perspectives of this type of treatment. Full article

Prostate cancer (PCa) is a common malignancy among men worldwide. After radical prostatectomy (RP) and radical radiotherapy (RT), patients may experience biochemical recurrence (BCR) of prostate cancer, indicating disease progression. Therefore, it is meaningful to predict and accurately assess the risk of BCR, and a machine-learning-based-model for BCR prediction in PCa based on fatty-acid metabolism and cancer-cell stemness was developed. A stemness prediction model and ssGSEA (single-sample gene set enrichment analysis) empirical cumulative distribution function algorithm were used to score the stemness scoring (mRNAsi) and fatty-acid metabolism of prostate-cancer samples, respectively, and further analysis showed that the two scores of the samples were positively correlated. Based on WGCNA (weighted correlation network analysis), we discovered modules significantly associated with both stemness and fatty-acid metabolism and obtained the genes within them. Then, based on this gene set, 101 algorithm combinations of 10 machine-learning methods were used for training and prediction BCR of PCa, and the model with the best prediction effect was named fat_stemness_BCR. Compared with 23 published PCa BCR models, the fat_stemness_BCR model performs better in TCGA and CPGEA data. To facilitate the use of the model, the trained model was encapsulated into an R package and an online service tool (PCaMLmodel, Version 1.0) was built. The newly developed fat_stemness_SCR model enriches the prognostic research of biochemical recurrence in PCa and provides a new reference for the study of other diseases. Full article

Background: Prospective trials provide robust evidence for prostate cancer (PCa) treatment but often include highly selective populations, limiting generalizability. Real-world data (RWD) can address these gaps and inform personalized care. Objectives: This study aimed to evaluate treatment-free survival (TFS) and secondary treatment sequences after initial curative therapy for PCa using electronic health record (EHR) data and to analyze associated medication profiles. Methods: We studied 3024 patients treated with radical prostatectomy (RP), brachytherapy (BT), or curative radiotherapy (RT) at Erasmus MC (2009–2023), the Netherlands. Outcomes included TFS, treatment sequences, and medication patterns across treatment lines. Results: Median age at diagnosis was 65 years (IQR 61–69) for RP, 68 (62–73) for BT, and 72 (68–76) for RT. At 10 years, TFS was 89% (95% CI: 84.9–94.1) for BT, 85% (95% CI: 83–87) for RT, and 71% (95% CI: 65.7–75.8) for RP. Most patients remained treatment-free, but up to five treatment lines occurred, mainly in patients with low comorbidity scores. Medication profiles reflected treatment-related morbidity: alpha-blocker use increased after BT and RT, while bladder relaxants were common after RP. Comorbidity-related medication use remained low among patients undergoing multiple sequenced treatments. Conclusions: These findings highlight the real-world application of multiple secondary treatments after different primary curative therapy options for PCa and associated comorbidity and medication use patterns. They confirm the durability and long-term effectiveness of curative treatments in real-world PCa care. By combining treatment trajectories and medication profiles, RWD provides insights for personalized counseling, helping clinicians and patients anticipate long-term treatment needs, and enabling informed decisions aligned with health status and preferences. Full article

Background: Globally, the incidence rate of hepatocellular carcinoma (HCC) has increased among elderly patients. Elderly patients often present with multiple comorbidities that affect treatment tolerance and outcomes, and the optimal management strategy for this population has not yet been established. Therefore, we assessed comorbidities in elderly patients and investigated the treatment outcomes of radiotherapy (RT) to liver-confined HCC. Methods: We retrospectively reviewed 40 elderly patients aged ≥70 years with liver-confined HCC, who were treated with RT between 2015 and 2023. Comorbidity was assessed by using the Charlson Comorbidity Index (CCI). Survival outcomes were analyzed using the Kaplan–Meier method. Results: The median age was 75 years (range, 70–87 years). The Barcelona Clinic Liver Cancer stage was 0 in 7 patients, A in 10 patients, B in 9 patients, and C in 14 patients. Most patients (85%) had Child–Pugh class A hepatic function before RT. The CCI scores ranged from 2 to 9 (median, 5). Various RT techniques were applied according to patients’ condition, tumor burden, and treatment aim: three-dimensional conformal radiotherapy in four patients, intensity-modulated radiotherapy in 20 patients; and stereotactic body radiotherapy in 16 patients. RT was delivered with radical intent in 30 patients and with palliative intent in 10 patients. The median biological effective dose calculated with an α/β ratio of 10 was 53.7 Gy₁₀ (range, 39–134.4 Gy₁₀). The median follow-up period after RT was 18 months. The 1-year local progression-free survival and overall survival (OS) rates were 74% and 81%, respectively, and the 3-year rates were 44% and 52%, respectively. Patients with CCI < 5 had more favorable OS than those with CCI ≥ 5, but the difference was not statistically significant. Conclusions: RT for liver-confined HCC appears to be a feasible treatment option for elderly patients with multiple comorbidities. Full article

High-risk and locally advanced prostate cancer represents 20–25% of new diagnoses of prostate cancer and is associated with high rates of recurrence, morbidity, and mortality. The neoadjuvant window provides a unique opportunity for systemic control prior to definitive therapy with radical prostatectomy or radiotherapy (RT). Early trials with first-generation androgen deprivation therapy (ADT) achieved pathological downstaging but no survival benefit. In the 2000s, the advent of chemohormonal regimes using docetaxel provided excitement but mixed results tempered expectations and is now not recommended prior to surgery. Second-generation androgen receptor pathway inhibitors (ARPIs) combined with ADT have demonstrated significant survival benefit in metastatic prostate cancer and are currently being evaluated in large phase III trials in the neoadjuvant setting. RT remains an alternative curative modality, and recent data highlights similar issues to surgery in eradicating micrometastatic disease despite excellent local control. This has driven parallel efforts to evaluate intensified systemic therapy in the pre-RT/neoadjuvant settings. In addition to the excitement surrounding ARPIs, radioligand therapy, such as [¹⁷⁷Lu]Lu-PSMA-617 has shown promise in the neoadjuvant setting and continues to be investigated. Future research aims to incorporate genomic and molecular factors to enable personalised neoadjuvant therapies by identifying damage immunologically responsive subtypes that may derive greater benefit from immune-directed therapies in the peri-operative setting. This narrative review synthesises current evidence for neoadjuvant therapies in high-risk prostate cancer and future directions. Full article

Background/Objectives: In men with biochemical recurrence (BCR) after a radical prostatectomy (RP), salvage radiotherapy (SRT) is commonly recommended when imaging shows no metastases. The optimal management for patients with negative prostate-specific membrane antigen (PSMA) PET/CT findings at BCR remains uncertain. This study evaluated outcomes of patients with BCR and negative PSMA PET/CT to identify who may be safely observed and who may benefit from early SRT. Methods: This retrospective multicentre cohort study included 89 patients with BCR and negative PSMA PET/CT findings after a RP (2015–2022) who were managed with observation. The exclusion criteria were PSA levels ≥ 0.8 ng/mL at baseline, prior SRT, or prior or ongoing hormonal therapy. Minimum follow-up was 3 years. Biochemical progression (PSA rise > 0.2 ng/mL above baseline or initiation of additional treatment) and radiological progression (local or metastatic disease on follow-up PSMA PET/CT) were assessed. Patients were stratified by EAU BCR-risk classification. Multivariable Cox regression included age, biochemical persistence (BCP) after a RP, pathological tumour stage (pT), pathological ISUP grade group (pISUP), node status (pN), margin status (R), and PSA doubling time (PSAdt). Results: The median age was 66 years (IQR 60–69) and the median PSA measurement at BCR was 0.2 ng/mL (IQR 0.2–0.3). A total of 27/89 (30%) patients were EAU BCR low-risk and 62/89 (70%) were high-risk. At three years, biochemical progression occurred in 14/27 (52%) low-risk vs. 51/62 (83%) high-risk patients, with time to progression being 21 vs. 12 months (p = 0.01). A pISUP grade group ≥ 4 (HR 2.04 [95%-CI 1.11–3.74]; p = 0.022) and a PSAdt < 20 months (HR 5.72 [95%-CI 2.41–13,56]; p < 0.01) independently predicted biochemical progression. Radiological progression occurred in 43/68 (66%) rescanned patients, with 32/43 (74%) showing disease outside the prostatic fossa. Conclusions: Nearly half of patients with BCR and negative PSMA PET/CT findings who were classified as EAU BCR low-risk remained progression-free at three years. These results support a risk-adapted approach, indicating that SRT may be deferred in selected low-risk patients. Full article

Bladder cancer is the 5th most common cancer in Canada and a quarter of diagnosed patients have muscle-invasive bladder cancer (MIBC). Standard treatment options, systemic therapy and radical cystectomy (RC) are associated with high rates of adverse outcomes. Recently, trimodal treatment (TMT), a bladder preservation strategy defined as maximal transurethral resection of bladder tumor (TURBT) and chemoradiation, has been considered an alternative per guidelines for select patients who prefer bladder preservation or those with comorbidities. Nevertheless, the uptake of bladder preservation strategies in Canada remains low. We conducted a retrospective evaluation in British Columbia (BC) to assess the real-world outcomes of bladder-sparing radiotherapy. Cohort treated with combined chemoradiotherapy (concurrent and/or adjuvant, neoadjuvant chemotherapy) showed numerical improvements across all evaluated endpoints, including disease-specific survival and progression-free survival, compared with radiation therapy alone, which is generally considered an inferior strategy. However, these differences did not reach statistical significance, contrasting with the literature. Despite the limitations posed by the small sample size and the study’s retrospective design, the findings highlight the pivotal role of appropriate patient selection in achieving meaningful therapeutic outcomes. Future studies integrating biomarker-driven strategies are needed to enhance outcomes through individualized treatment selection, particularly for older patients with multiple comorbidities. Full article

Cervical cancer is one of the most common gynecological tumors globally. When diagnosed, treatment decisions should be based on a risk–benefit analysis of each treatment modality to obtain a cure with minimum complications. The optimal approach for management should consider clinical factors such as age, menopausal status, medical comorbidities, histological type, tumor size, and the extent of disease. Radiotherapy is the cornerstone for successful management in almost all clinical stages of this disease. Options for primary treatment in patients with early cervical cancer may include radical hysterectomy, fertility-sparing surgery, and postoperative radiotherapy with or without platinum-based chemotherapy (CT) according to pathology specimen findings. For locally advanced cervical cancer, chemoradiotherapy has been the standard of care based on the results of clinical trials that showed an overall survival (OS) advantage when adding cisplatin to radiotherapy. After chemoradiotherapy, a cervical boost is mandatory for increased local control and better survival. For metastatic or recurrent cervical cancer, the treatment approach is tailored according to symptoms and performance status. As many techniques and new technologies are available to decrease toxicity while improving the therapeutic ratio, it becomes necessary to collate the current evidence that most effectively enables clinicians to make informed decisions in the management of cervical cancer patients. Full article

Background/Objectives: Thymic neuroendocrine neoplasms (t-NENs) are rare, biologically aggressive malignancies of the anterior mediastinum. Due to their low incidence, clinical evidence remains limited, and treatment recommendations are primarily based on expert opinion and extrapolation from other neuroendocrine tumors. This study aimed to analyze the clinicopathological features, treatment patterns, and survival outcomes of patients with t-NENs treated at a single comprehensive cancer center over 25 years. Methods: A retrospective review was performed on 19 adult patients diagnosed with t-NENs between 2000 and 2024. Data on demographics, histology, treatment intent, modalities used, and outcomes were collected. Survival analyses—of overall survival (OS), disease-free survival (DFS) and progression-free survival (PFS)—were conducted using the Kaplan–Meier method. Results: The median age was 52 years; 63% of patients were male. Atypical carcinoid was the most common histologic subtype (52.6%), followed by large cell neuroendocrine carcinoma (31.6%). Paraneoplastic syndromes, including Cushing’s syndrome, were observed in 26.3% of cases. Radical surgery was performed for 8 patients, but R0 resection was achieved in only 25% of them. Postoperative radiotherapy and chemotherapy were used for 36.8% and 15.8% of patients, respectively. Disease recurrence occurred in 44.4% of curatively treated patients. The median OS for the entire cohort was 127 months; patients treated with curative intent had a significantly longer OS (170 months) compared to those after palliative treatment (33 months). Median PFS in the palliative group was 11 months. Conclusions: t-NENs are aggressive tumors with high risk of recurrence and limited systemic treatment efficacy. Complete surgical resection remains the cornerstone of curative therapy. However, the overall prognosis remains poor, emphasizing the need for novel therapeutic strategies and prospective multicenter studies. Full article

Introduction. This study aims to conduct a cost-effectiveness analysis comparing two primary treatment approaches: radical prostatectomy versus radiotherapy plus androgen deprivation therapy (ADT) in patients with Prostate Imaging Reporting and Data System (PI-RADS) 5 lesions. Patients and Methods. Data were extracted from two published retrospective cohort studies. Using survival data from two retrospective studies, we reconstructed Kaplan–Meier curves, overlaid them for comparative metasurvival analysis, and developed a cost-function model to assess economic implications alongside clinical outcomes. The primary outcomes included biochemical recurrence-free survival (FFBF) at 2 and 5 years; the area under the survival curve; total cost per treatment strategy; and cost per recurrence-free patient at 5 years. Results. At 5 years, the estimated FFBF was 83% for radiotherapy vs. 28% for prostatectomy. Radiotherapy yielded an AUC of 80.7, while prostatectomy showed 41.9. Radiotherapy yielded a cost of 21,211 € per FFBF patient compared to 113,730 € for prostatectomy. Conclusion. Our study demonstrates that radiotherapy combined with ADT, when selected based on mpMRI stratification, may represent a cost-efficient alternative, pending prospective validation. To radical prostatectomy in patients with PI-RADS 5 prostate cancer, with a favourable cost–benefit profile. Full article

Background/Objectives: Pelvic exenteration is a complex surgery considered for locally advanced or recurrent pelvic malignancies, entailing a radical en-block resection of multiple adjacent pelvic organs, followed by reconstructive surgery. Achieving R0 resection (complete removal of macroscopic and microscopic disease) is critical for improving survival outcomes. This study aimed to define patient, tumour, and surgical predictors of R0 resection in an irradiated field, thereby optimising patient selection and establishing a surgical roadmap for pelvic exenterations. Methods: Our retrospective observational cohort study includes consecutive patients undergoing exenteration post-radiotherapy for non-ovarian gynaecological malignancies at Oxford University Hospitals between 1 January 2011 and 31 December 2024. The primary outcome was margin status. Secondary outcomes were intraoperative and postoperative complications. Results: Twenty-seven patients were identified, with a median age of 63 years (range 41–81) and median BMI of 27 (range 17–45). Primary tumour sites included the vulva (11.1%), vagina (14.8%), cervix (40.7%), and uterus (33.3%). R0 was achieved in 77.8% (n = 21) of cases. Intraoperative complications occurred in 29.6%, and significant postoperative complications (Clavien-Dindo IIIA/IIIB) in 22.2% of patients. R0 resection was significantly associated with younger age (median 61 vs. 70 years, p = 0.035) and primary cervical tumours (p = 0.036). On univariable logistic regression, tumour size on imaging (p = 0.038, OR 2.9) and on histology (p = 0.020, OR 2.01), and estimated blood loss (p = 0.048, OR 1.002) were significant predictors of R0 resection. None of these variables retained significance in multivariable logistic regression. Conclusions: Tumour size, primary tumour site, and patient age should be considered when selecting patients for pelvic exenteration following radiotherapy, and blood loss should be kept minimal in order to maximise the chances of achieving R0 resection. Full article

Background/Objectives: Extramammary Paget’s disease (EMPD) is a rare cutaneous malignancy arising in areas rich in apocrine glands that poses diagnostic and therapeutic difficulties. Although surgery remains the standard of care, achieving clear margins is challenging and recurrence rates are high. This review explores the contribution of non-invasive imaging for diagnosis and monitoring, and evaluates conservative, non-surgical therapies as alternatives to radical surgery. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), a systematic review was conducted: eligible studies included interventional and observational research, as well as case series and reports, assessing non-invasive diagnostic methods or non-surgical treatments for EMPD. Data extraction and risk-of-bias evaluation were performed independently by multiple reviewers, and a narrative synthesis summarized therapeutic outcomes and diagnostic performance. Results: Of 808 identified records, 82 met the inclusion criteria: 66 focused on non-surgical therapies, 15 on diagnostic techniques, and one on both. Reflectance confocal microscopy (RCM) and photodynamic diagnosis (PDD) showed high concordance with histopathology, aiding both diagnosis and margin delineation. Among therapies, topical imiquimod and photodynamic therapy (PDT) demonstrated encouraging response rates, while radiotherapy, laser ablation, and systemic chemotherapy were less consistently reported. Evidence quality was limited by small cohorts, heterogeneous regimens, and variable follow-up. Conclusions: Non-invasive imaging enhances diagnostic accuracy and surgical planning, while non-surgical treatments—particularly imiquimod and PDT—offer viable alternatives in selected cases. Larger prospective studies are needed to establish standardized protocols and clarify long-term outcomes. Full article

In recent years, several randomized controlled trials have been published regarding cervical cancer therapy and significantly changed the treatment landscape. Recent advances have improved the treatment options and allow personalized treatment concepts with escalation of treatment in high-risk disease and de-escalation with reduction in morbidity in selected low-risk patients. This review aims to provide a comprehensive analysis of the latest landmark studies that are poised to significantly influence clinical practice. Personalized treatment concepts with careful patient selection allow de-escalation in the surgical treatment of cervical cancer. In low-risk cervical cancer patients (lesions of ≤2 cm with limited stromal invasion), simple hysterectomy (SH) was non-inferior to radical hysterectomy in terms of 3-year incidence of pelvic recurrence and was associated with a lower risk of urinary incontinence or retention and improved sexual health and quality of life. Furthermore, sentinel lymphadenectomy is constantly replacing systematic pelvic lymphadenectomy in patients with low-risk cervical cancer. In addition, further studies are necessary to clarify the role of postoperative therapy for patients with intermediate-risk cervical cancer. Starting in 2008, the EMBRACE studies assess the role of Image guided adaptive brachytherapy (IGABT) in LACC in addition to modern external beam radiotherapy concurrent to chemotherapy. The publication of the results of the EMBRACE I prospective study established MRI guided IGABT as state-of-the-art brachytherapy for LACC. EMBRACE II and additional prospective studies emerging from this consortium will address important questions in modern radiotherapy for LACC. Immune checkpoint inhibitors (CPIs) have been evaluated across various clinical settings and are expected to be utilized in numerous scenarios due to several positive randomized trials. Particularly, the combination of platinum-based chemotherapy and pembrolizumab, with or without bevacizumab, has been established as the new standard treatment for primary metastatic or recurrent PD-L1 positive high-risk cervical cancer. In locally advanced cervical cancer, two new treatment escalation regimens—neoadjuvant chemotherapy and adjuvant CPI therapy—have been evaluated in addition to chemoradiation. Furthermore, antibody-drug conjugates, such as tisotumab-vedotin, represent a promising future therapeutic option for recurrent cervical cancer. Full article

Background/Objectives: Bulkamid^® (Axonics, Irvine, CA, USA) is a non-particulate polyacrylamide hydrogel used in the treatment of urinary incontinence. While its effectiveness is well-documented in female stress urinary incontinence (SUI), there is limited data on its role in male stress urinary incontinence, particularly post-prostatectomy incontinence (PPI). This study evaluates the efficacy of Bulkamid as a primary or adjunctive treatment for male PPI. Methods: A retrospective chart review was conducted on male patients who developed PPI and underwent Bulkamid injections between 2016 and 2021. Data collected included pre- and post-procedure pad usage, the volume of Bulkamid injected, prior and subsequent incontinence treatments, and patient-reported satisfaction. Bulkamid was injected transurethrally in four quadrants near the vesicourethral anastomosis using a rigid cystoscope. Results: Twenty-one men with a history of radical prostatectomy (six open and fifteen robotic), including four who received adjuvant radiotherapy, were included. Fifteen underwent Bulkamid injection as a primary treatment, with five (33%) requiring repeat injections due to initial improvement. Eight (54%) subsequently underwent an AdVance XP^® sling placement, while two (13%) required no further treatment. Six patients received Bulkamid as an adjunct to prior incontinence surgery, with 80% of post-sling patients reporting improved continence. Bulkamid was less effective in men with detrusor overactivity or prior radiation. Conclusions: Bulkamid demonstrated a higher success rate as an adjunct to the AdVance XP sling, with 80% of men experiencing improved continence. As a primary treatment for PPI, success was modest, with only 33% achieving improvement, often requiring repeat injections or conversion to a sling. Bulkamid presents a low-risk option for select male PPI patients, particularly those with prior sling placement, but durability and long-term effectiveness remain concerns. Full article

Introduction and Objectives: Local recurrence (LR) in patients treated with surgery for renal cell carcinoma (RCC) remains a significant clinical challenge that requires thorough investigation. Our study aimed to identify the relative risk factors and explore the optimal clinical management of LR. Materials and Methods: We conducted a non-randomized, observational, retrospective multicentric registry involving multiple Italian urological centers. We included patients treated with surgery (either nephron-sparing or radical nephrectomy) who later developed LR, defined as recurrence in the ipsilateral kidney or renal fossa. Patients with hereditary syndromes or metastatic disease at the time of LR diagnosis were excluded. Results: We reported 135 cases of LR with the following characteristics: most primary lesions were monofocal (85.7%), with a median size of 42 mm (23–53), the median R.E.N.A.L. score was 7 (6–8), and the median Padua score was 7 (6–9). Patients were treated with robot-assisted techniques in 59% of cases, laparoscopic surgery in 32.4%, and open surgery in 8.6%. Nephron-sparing surgery was performed in 75.2% of cases. Ischemia occurred in 61% of the cases, with a median ischemia time of 21 min (15.5–24). Intraoperative complications occurred in 3.8% of cases, while postoperative complications were reported in 13.8%, all of which were grade ≤3 according to the Clavien–Dindo classification. The primary tumors were pT1a in 43.5% of cases, pT1b in 26.3%, pT2 in 14.7% and pT3 in 15.5%. Histologically, 84% of cases were clear cell, 11.3% papillary type 1 or 2, and 3.7% chromophobe. Sarcomatoid/rhabdoid variants were present in 10.5% of cases. The median rate of LR was 1.3% (range 0.2–3.6), while the median time to LR was 18 months (12–39). LR occurred in the ipsilateral kidney in 70.5% of cases and in the ipsilateral renal fossa in 29.5%. The median rate of PSM in LR cases at initial surgery was 2.4% (range 0–4.3), while the median rate of negative surgical margin (NSM) in LR cases at initial surgery was 0.1 (0–0.3). Following LR diagnosis, most patients (49.2%) underwent surgery, 29.1% received cryoablation or radiotherapy, 17.1% received systemic treatment alone, and 4.6% followed a watchful waiting/active surveillance approach. At a median follow-up of 62 months, the highest oncological control in terms of 5-year cancer-specific survival and overall survival rates was achieved in surgically treated patients. The PSM, the histological variant, and their combination were found to be independent variables correlated with the occurrence of LR, with relative risks of 3.62, 2.71, and 8.12, respectively. Conclusions: LR after nephron-sparing or radical nephrectomy represents a significant clinical dilemma. Known risk factors are not always sufficient to predict recurrence, emphasizing the necessity of consistent radiological follow-up per guideline recommendations. Early detection of recurrence and a multidisciplinary approach involving expert centers are crucial for optimizing patient outcomes. Full article