Bruno Jorge Pereira

Background: Prostate cancer patients with intermediate disease risk [Gleason score (GS)7] can be divided into two groups: GS = 7(3 + 4) (ISUP 2) (favorable disease risk) and GS = 7(4 + 3) (ISUP 3) (unfavorable disease risk). Low-dose-rate brachytherapy (LDR-BT) is an effective treatment for low- and intermediate-disease-risk patients. Objectives: The main goal of this study was to evaluate the effectiveness of LDR-BT monotherapy in prostate cancer patients classified as ISUP 3 when compared with ISUP 2 patients. Methods: This was a retrospective study that evaluated prostate cancer patients classified as ISUP 2 and ISUP 3 followed up at the Center for the Treatment of Urological Diseases, Portugal, who underwent LDR-BT. Overall survival (OS), biochemical recurrence-free survival (BRFS), bone metastasis and complications post-LDR-BT treatment were evaluated. Results: A total of 602 patients classified with GS = 7 (481/602 ISUP 2 and 121/602 ISUP 3) treated with LDR-BT were recruited. High OS rates and a reduced frequency of complications were described in both groups of patients. ISUP 3 patients had a lower BRFS rate, a higher risk of biochemical recurrence, and developed more bone metastasis in a shorter period when compared with ISUP 2 patients. No significant differences were detected in prostate-cancer-specific mortality between groups. Conclusions: LDR-BT monotherapy is a safe and effective treatment for prostate cancer patients with favorable and unfavorable intermediate disease risk, with similar OS rates and reduced complications.

Prostate cancer (PCa) is the second most frequently diagnosed cancer in men worldwide and the fifth leading cause of cancer‐related mortality, presenting urgent unmet clinical needs in diagnosis and treatment. The recognition of the microbiome as a key factor in human health has prompted numerous studies, revealing an exciting new approach to cancer diagnosis and therapy. The bacteriome is the component of the microbiome that is most metabolically active and influenceable by internal and external factors, which is pivotal in the development of cancer. Initial studies exploring the link between the microbiome and PCa focused primarily on the gut bacteriome, which has been implicated in the onset and progression of the disease, as well as in resistance to therapy. Further research has demonstrated that the urologic bacteriome also plays a crucial role in the development of PCa, serving as an important factor for diagnosis and treatment. This review synthesizes current knowledge concerning the significance of the urologic bacteriome in PCa onset, progression, diagnosis/prognosis, and therapy. It also explores the impact of the bacterial metabolome in PCa, emphasizing the importance of this undervalued dimension of the bacteriome. Overall, the review provides a comprehensive analysis of how bacteria and their bioactive metabolites contribute to PCa, highlighting their clinical and therapeutic relevance. It also identifies the existing knowledge gaps, paving the way for the development of new approaches that could enhance PCa diagnosis and treatment.

Background/Objectives: Prostate cancer is one of the most common malignancies diagnosed in men worldwide. Brachytherapy (BT), particularly low-dose rate (LDR)-BT, has been shown to be a successful treatment. The aim of this study was to evaluate the effectiveness of BT treatment in localized prostate cancer patients from a single-center Portuguese cohort. Methods: This was a retrospective study that evaluated prostate cancer patients followed up at the Center for the Treatment of Urological Diseases, Coimbra, Portugal, who underwent LDR-BT between November 2007 and March 2024. Overall survival (OS), biochemical recurrence-free survival (BRFS) and complications post-LDR BT treatment were evaluated during patients’ follow-up time. Results: A total of 1343 patients treated with LDR-BT were recruited. Global OS and BRFS rates were 98.4% and 87.7%, respectively. A reduced frequency of complications such as lower urinary tract symptoms, erectile dysfunction, acute urinary retention, radiation proctitis and stress urinary incontinence were described. High OS (>98%) and BRFS rates were observed particularly in low and intermediate disease risk. Prostate-specific antigen (PSA) serum levels > 20 ng/mL, Gleason score (GS) ≥ 8 and clinical tumor stage (cT) ≥ T2c were identified as the strongest predictors of death and/or biochemical recurrence. Conclusions: BT is an effective treatment in localized prostate cancer patients, with comparable outcomes and consistent with the OS and BRFS rates reported in the current literature for radical prostatectomy and external beam radiotherapy approaches, and with a reduced frequency of complications. PSA serum levels > 20 ng/mL, GS ≥ 8 and cT stage ≥ T2c can be used as strong predictors of death and/or biochemical recurrence during patients’ follow-up.

Background: Periprostatic adipose tissue (PPAT) has been shown to play a significant role in prostate cancer (PCa) development and progression. This relationship is further exacerbated by obesity, as PPAT-secreted factors increase PCa aggressiveness and have also been implicated in chemotherapy resistance. Therefore, identifying the molecular mediators of PPAT–prostate interorgan communication and the factors that disrupt this crosstalk is pivotal for better disease management. Obesogens, i.e., endocrine-disrupting chemicals that dysregulate adipose tissue towards an “obese” phenotype, have recently been implicated in disrupting this crosstalk, with an impact on prostate cell fate. Objectives: This study aimed to investigate whether obesogenic dysregulation of human PPAT secretory activity affects PCa cell viability and their response to docetaxel and cabazitaxel. Methods/Results: Through ex vivo culture of human PPAT and conditioned medium assays, we demonstrated that exposure to the model obesogen tributyltin (TBT) induced an “obese” phenotype in human PPAT, characterised by adipocyte enlargement and increased secretion of leptin and C-C motif chemokine ligand 7. The TBT-treated PPAT secretome enhanced cell viability and decreased the sensitivity of PCa cells to taxanes. Conclusions: This study provides preliminary evidence that lays the groundwork for future investigations, dissecting the molecular pathways underpinning prostate carcinogenesis and resistance to chemotherapy induced by obesogen-dysregulated PPAT.

Introduction: Hyperthermic intravesical chemotherapy (HIVeC) with mitomycin C (MMC) is an emerging strategy in the management of intermediate-risk non-muscle-invasive bladder cancer (Ir-NMIBC). By combining chemotherapy with controlled hyperthermia (43°C), this approach aims to enhance drug absorption, increase cytotoxicity, and stimulate immune activation, potentially improving efficacy compared to standard MMC. The aim of this study was to compare oncologic efficacy, adverse effects, and safety between HIVeC and standard normothermic MMC in patients with Ir-NMIBC.Patients and methods: we conducted a retrospective cohort study including 76 patients with Ir-NMIBC treated between January 2020 and december 2023. Patients received HIVeC (n=36) or standard MMC (n=40) following complete transurethral resection of bladder tumor (TUrBT). The instillation schedule consisted of four weekly induction instillations followed by three monthly maintenance instillations. The primary endpoint was recurrence-free survival (rFs); secondary endpoints included progression-free survival (PFs), adverse events (Aes), and treatment compliance.Results: A total of 76 patients were included: 36 received HIVeC and 40 received standard MMC. Baseline characteristics were balanced across groups, with a median age of 68 years and 86.8% male. Most tumors were unifocal (85.5%), stage pTa (88.2%), and low-grade (61.8%). At a median follow-up of 36 months (IQr 24-36), recurrence occurred in 38.9% of HIVeC patients vs 30.0% in the MMC group. Median time to recurrence was longer with HIVeC (15.0 vs 10.5 months). The 24-months recurrence-free survival was 62.2% for HIVeC and 69.4% for MMC (p=0.365). Progression to muscle-invasive disease occurred in one MMC patient (2.5%); none progressed in the HIVeC arm (PFs at 24 months: 100% vs 97.5%, p=0.343). Compliance was high in both arms (HIVeC 88.9%, MMC 87.5%). Adverse events were mild (grade 1-2) and evenly distributed; no grade ≥3 events were observed. Treatment discontinuation due to toxicity occurred in 13% of HIVeC and 7% of MMC patients (p=0.47).Conclusions: HIVeC with MMC demonstrated comparable oncologic outcomes to normothermic MMC in Ir-NMIBC, with a longer time to recurrence and similar tolerability. These findings suggest its potential use in selected patients, but should be interpreted with caution due to the retrospective design and limited sample size.

Introduction: Hemorrhagic cystitis is defined by the presence of hematuria, lower urinary tract symptoms and cystoscopy findings indicative of underlying urothelial damage. It is common in patients with prior radiotherapy for pelvic malignancies. The severity of the bleeding can vary from mild to severe hematuria refractory to conservative therapy and with a continuous need for transfusions. Treatment can be challenging not only by the lack of clear guidelines but also the multiple comorbidities of these patients. Urinary diversion with or without cystectomy should be reserved for those who have failed all the previously available therapy, because of the morbidity/mortality associated with this type of procedure. Supratrigonal cystectomy can be an option in patients with intense fibrosis of the pelvic region. The purpose of this article is to present the results of our institution with supratrigonal cystectomy with urinary diversion as a last line treatment for radiation-induced hemorrhagic cystitis. Materials and methods: We retrospectively analyzed 17 patients who underwent supratrigonal cystectomy and bladder mucosa fulguration with urinary diversion for refractory radiation-induced hemorrhagic cystitis in our institution from January 2010 to December 2020. Results and discussion: Median patient age at time of cystectomy was 69 years and 64.7% (11) were females. The most common etiology was prior radiation therapy for gynecologic malignancies (11-64.7%). All the patients had prior therapy with bladder irrigation and fulguration. Besides that, 29.4% (n=5) received intravesical therapy with formalin, 11.8% (n=2) hyperbaric oxygen therapy and 5.9% (n=1) prior urinary diversion. Median time between radiation therapy and cystectomy was 65 months. Median ASA score of 3, median preoperative hemoglobin was 9,6mg/dl and 10.5 mg/dl at time of discharge after surgery. Ileal conduit was used in 52.9% (9), cutaneous ureterostomy in 41.2% (7) and ureterosigmoidostomy in 5.9% (1). Majority of patients (10-58.8%) did not require any blood transfusion during surgery or during their stay. Clavien-Dindo complications grade III or higher occurred in 29,4% (5). Median hospital stay postoperative was 12 days. No mortality was reported in the 30 days after surgery. Median follow-up after cystectomy was 28 months, with a 1-year survival of 93.3% (14 of 15) and 3-year survival of 83.3% (10 of 13). There was no difference in the presence of postoperative complications or overall survival between the types of urinary diversion. Conclusions: This represents one of the largest series on cystectomy in hemorrhagic cystitis, that we found to this date. Supratrigonal cystectomy is a valid option as a last line treatment for radiation-induced hemorrhagic cystitis, reducing the risks associated with simple cystectomy in patients with prior pelvic radiation.

Endocrine-disrupting chemicals (EDCs) are natural or synthetic compounds that are ubiquitous in the environment and in daily-usage products and interfere with the normal function of the endocrine system leading to adverse health effects in humans. Exposure to these chemicals might elevate the risk of metabolic disorders, developmental and reproductive defects, and endocrine-related cancers. Prostate cancer is the most common hormone-dependent cancer in men, and the fifth leading cause of cancer-related mortality, partly owing to a lack of knowledge about the mechanisms that lead to aggressive castration-resistant forms. In addition to the dependence of early-stage prostate cancer on androgen actions, the prostate is a target of oestrogenic regulation. This hormone dependence, along with the fact that exogenous influences are major risk factors for prostate cancer, make the prostate a likely target of harmful actions from EDCs. Various sources of EDCs and their different modes of action might explain their role in prostate carcinogenesis.

Background: Most men diagnosed with prostate cancer will be candidates for active treatment and 20 to 50% of patients treated with organ preserving strategies recur within the prostate. Optimal treatment of recurrence is controversial. Prostate cryosurgery has been increasingly used as primary, recurrence and focal treatment for prostate cancer. Methods: We analysed 55 patients submitted to cryotherapy as salvage treatment after recurrence. Results: Study population presented with a mean age of 70.9 ± 6.2 years, mean initial PSA of 7.6 ng/ml and average prostate volume by ultrasound of 43.2 ± 14.7 grams. Mean follow-up was of 18.0 months. Biochemical free survival at one year of follow-up was of 85%. Conclusions: Cryotherapy can be an effective and safe treatment for recurrence after primary curative treatment failure.