Search Results (83)

Radiation therapy, including external-beam radiation therapy (EBRT) and brachytherapy, is curative for localized prostate cancer. Hydrogel spacer (HS) placement between the rectum and prostate is popular for reducing radiation-related complications. Criteria to identify patients who benefit from HS placement would be clinically valuable. In a retrospective analysis of 430 patients with localized prostate cancer treated between November 2010 and March 2023 with ≥2 years of follow-up, we evaluated the incidence of rectal hemorrhage and its association with the median distance at the midpoint between the prostate and the rectum (mDPR) on pretreatment MRI. Rectal hemorrhage occurred in 6% of HS cases and 18% of non-HS cases (p < 0.001). Among 268 patients who received EBRT (±brachytherapy), the incidence was 9% with HS and 30% without HS (p < 0.001). In non-HS cases, the rate in patients with mDPR ≤ 1.62 mm was higher than in those with mDPR > 1.62 mm (24% vs. 12%, respectively; p = 0.04). In patients with EBRT and mDPR ≤ 1.62 mm, HS significantly reduced hemorrhage (9% vs. 39%, respectively; p < 0.001). Multivariate analysis identified mDPR and HS as independent predictors of rectal hemorrhage (both p = 0.02). Thus, HS placement may be safely omitted in non-EBRT cases with mDPR ≥ 1.62 mm. Full article

Introduction: Interventional radiotherapy (brachytherapy, IRT, BT) has evolved with technological advancements, improving dose precision while minimizing exposure to healthy tissues. The integration of 3D-printing technology in IRT has enabled the development of patient-specific devices, optimizing treatment personalization and dosimetric accuracy. Methods: A systematic literature search was conducted in PubMed, Scopus, and Google Scholar to identify studies published between 2020 and 2024 on 3D-printing applications in IRT. The selection process resulted in 74 peer-reviewed articles categorized by radioactive source, brachytherapy technique, endpoint of the 3D-printed product, and study type. Results: The analysis highlights the growing implementation of 3D-printed devices in brachytherapy, particularly in gynecological, prostate, and skin cancers. Most studies focus on technique, including intracavitary, interstitial, and contact applications, with custom applicators and templates emerging as predominant endpoints. The majority of studies involved in vivo clinical applications, followed by in silico computational modeling and in vitro experiments. Conclusions: The upward trend in scientific publications underscores the growing attention on 3D printing for enhancing personalized brachytherapy. The increasing use of 3D-printed templates and applicators highlights their role in optimizing dose delivery and expanding personalized treatment strategies. The current research trend is shifting toward real-world data and in vivo studies to assess clinical applications, ensuring these innovations translate effectively into routine practice. The integration of 3D printing represents a major advancement in radiation oncology, with the potential to enhance treatment efficacy and patient outcomes. Future research should focus on standardizing manufacturing processes and expanding clinical validation to facilitate broader adoption. Full article

Background: Combining external beam radiotherapy (EBRT) with high-dose-rate (HDR) brachytherapy (BT) enables biologically effective dose escalation in prostate cancer. However, comparative evaluation of such regimens using radiobiological modeling remains limited. Methods: Dose regimens based on clinical practice were analyzed using α/β values of 1.5 and 3 Gy for the prostate. Ten patients with available planning CT, pelvic MRI, and ultrasound-guided BT plans were retrospectively evaluated. Physical and biological dose distributions were recalculated for various EBRT and HDR-BT combinations. Biological effective dose (BED) values were determined for the prostate and organs at risk (OARs: anterior rectal wall, bladder base, urethra). Regimens yielding the highest ΔBED between prostate and OARs were considered most favorable. Results: All regimens met clinical dose constraints. The most favorable ΔBED profiles for bladder and rectum were observed with HDR-BT regimens (2 × 15 Gy) combined with either 23 × 2 Gy or 15 × 2.5 Gy EBRT, independent of the assumed α/β value. EBRT-only regimens achieved superior urethral sparing, while higher HDR doses led to increased urethral exposure. Conclusions: This study underscores the value of radiobiological modeling in differentiating and optimizing prostate cancer radiotherapy strategies. While the trade-offs between dose escalation and OAR sparing are clinically known, our biologically driven analysis provides a more quantitative foundation for selecting and tailoring combined EBRT/HDR-BT regimens in practice. Full article

Background/Objectives: Focal therapy (FT) and technology are closely connected. Advanced imaging allows for precise identification of the index lesion, enabling the targeted use of various thermal and non-thermal energy sources through different approaches, with specific techniques tailored to lesion location and operator expertise. This personalized approach enhances both safety and effectiveness, facilitating customized treatment planning. Methods: The International Consultation on Urological Diseases formed a committee to review the current literature on FT for prostate cancer (PCa), focusing specifically on the technique. Following in-depth discussions, the committee chose a “by lesion” approach rather than the traditional “by energy” approach to structure the review. A comprehensive PubMed search was conducted to gather relevant articles on the various energy modalities and procedural approaches used in FT for PCa. Results: Lesions in the apex, anterior, and posterior regions of the prostate can be accessed through several FT approaches, each associated with specific energy modalities and techniques. The transrectal approach utilizes high-intensity focused ultrasound (HIFU) and focal laser ablation (FLA), while the transperineal approach is compatible with energy sources such as cryotherapy, irreversible electroporation (IRE), brachytherapy, and FLA. The transurethral approach supports methods such as transurethral ultrasound ablation (TULSA). Each approach offers distinct advantages based on lesion location, treatment area, and energy modality. The choice of technique evaluated the safety and efficacy of each energy source and approach based on specific treatment areas within the prostate, highlighting the need for robust research across lesion locations and modalities, rather than focusing solely on each modality for a specific region. Conclusions: FT is rapidly advancing with new energy sources, technological improvements, and increasing operator expertise. To further optimize FT, research should prioritize evaluating the safety and effectiveness of different energy sources for various lesion locations, focusing on the treatment area rather than the energy modality itself. Full article

While multi-parametric magnetic resonance imaging (mpMRI) is known to be a specific and reliable modality for the diagnosis of non-metastatic prostate cancer (PC), positron emission tomography (PET) using ⁶⁸Ga labeled ligands targeting the prostate-specific membrane antigen (PSMA) is known for its reliable detection of prostate cancer, being the most sensitive modality for the assessment of the extra-prostatic extension of the disease and the establishment of a diagnosis, even before biopsy. Background/Objectives: Here, we compared these modalities in regards to the localization of intraprostatic cancer lesions prior to local HDR brachytherapy. Methods: A cohort of 27 patients received both mpMRI and PSMA-PET/CT. Based on 24 intraprostatic segments, two readers each scored the risk of tumor-like alteration in each imaging modality. The detectability was evaluated using receiver operating characteristic (ROC) analysis. The histopathological findings from biopsy were used as the gold standard in each segment. In addition, we applied a patient-based “congruence” concept to quantify the interobserver and intermodality agreement. Results: For the ROC analysis, we included 447 segments (19 patients), with their respective histological references. The two readers of the MRI reached an AUC of 0.770 and 0.781, respectively, with no significant difference (p = 0.75). The PET/CT readers reached an AUC of 0.684 and 0.608, respectively, with a significant difference (p < 0.001). The segment-wise intermodality comparison showed a significant superiority of MRI (AUC = 0.815) compared to PET/CT (AUC = 0.690) (p = 0.006). Via a patient-based analysis, a superiority of MRI in terms of relative agreement with the biopsy result was observed (n = 19 patients). We found congruence scores of 83% (MRI) and 76% (PET/CT, p = 0.034), respectively. Using an adjusted “near total agreement” score (adjacent segments with positive scores of 4 or 5 counted as congruent), we found an increase in the agreement, with a score of 96.5% for MRI and 92.7% for PET/CT, with significant difference (p = 0.024). Conclusions: This study suggests that in a small collective of low-/intermediate risk prostate cancer, mpMRI is superior for the detection of intraprostatic lesions as compared to PSMA-PET/CT. We also found a higher relative agreement between MRI and biopsy as compared to that for PET/CT. However, further studies including a larger number of patients and readers are necessary to draw solid conclusions. Full article

Purpose: To evaluate the long-term oncological outcomes and toxicity profile based on 24 years of follow-up in patients with localized very high-risk prostate cancer (VHR PCa) treated with a combination of high-dose-rate brachytherapy (HDR-BT) and pelvic external beam radiation therapy (EBRT). Methods: A retrospective analysis was conducted on 87 patients with VHR PCa, classified according to National Comprehensive Cancer Network (NCCN) criteria, who received HDR-BT and EBRT. Androgen deprivation therapy (ADT) was administered to 72 patients (82.8%). The primary endpoints were biochemical control and cancer-specific survival (CSS), while the secondary endpoints included local control rates, tumor-free survival (TFS), overall survival (OS), and treatment-related toxicity. Results: The 24-year biochemical control rate was 68% (standard deviation [SD]: ±4%), while CSS and TFS at 24 years were 82% (SD ±4%) and 78% (SD ±4%), respectively. Local control rates remained at 98% at 24 years. Furthermore, the OS rate at 24 years was 30%. Multivariate Cox regression analysis identified the T category in the TNM classification as the only factor significantly associated with biochemical control, with 24-year rates of 69%, 71%, and 50% for patients with T-classifications of ≤T2c, T3a, and T3b-T4, respectively (p = 0.024). Notably, no grade ≥3 late toxicities were observed during the follow-up period. Conclusions: The 24-year outcomes support the viability and therapeutic efficacy of EBRT combined with a conformal HDR-BT boost for patients with VHR PCa. Full article

Prostate cancer, a slow-growing tumor, develops through the over-proliferation of malignant cells in the prostate and is one of the most common types of cancer. Active surveillance, radical prostatectomy, external beam radiation, brachytherapy, cryotherapy, stereotactic body radiation therapy, hormone therapy, and chemotherapy are common treatment strategies for prostate cancer. However, resistance to treatment in advanced prostate cancer is a concerning issue in the use of these therapies. Immune checkpoint inhibitor (ICI) therapy for prostate cancer is an emerging strategy for the treatment of advanced prostate cancers but the resistance and limited efficacy to ICIs observed in metastatic castration-resistant prostate cancer (mCRPC) raises concerns. The ongoing clinical trials for combination therapies for mCRPC have provided some hope. This review concisely discusses the molecular and cellular mechanisms, immunotherapy, the limitations of ICIs, combination therapies, and the prospects of developing novel therapeutics for prostate cancer. Full article

Background/Objectives: Clinical studies have shown a marked reduction in tumor control in prostate cancer treated with radically hypofractionated high-dose-rate brachytherapy (HDR-BT). The purpose of this study was to analyze the dose–response of prostate cancer treated with HDR-BT, specifically aiming at investigating the potential failure of the linear–quadratic (LQ) model to describe the response at large doses-per-fraction. Methods: We collated a dataset of dose–response to HDR-BT (3239 patients). The analysis was conducted separately for low and intermediate risk, resulting in 21 schedules (1633 patients) and 23 schedules (1606 patients), respectively. Data were fitted to tumor control probability models based on the LQ model, the linear–quadratic–linear (LQL), and a modification of the LQ model to include the effect of reoxygenation during treatment. Results: The LQ cannot fit the data unless the $\alpha /\beta$ is allowed to be high (∼[20, >100] Gy, 95% confidence interval). If the $\alpha /\beta$ is constrained to be low (≤8 Gy), the LQ model cannot reproduce the clinical results, and the LQL model, which includes a moderation of radiation damage with increasing dose, significantly improves the fitting. On the other hand, the reoxygenation model does not match the results obtained with the LQL. The clinically observed reduction in tumor control in prostate cancer treated with radical HDR-BT is better described by the LQL model. Using the best-fitting parameters, the BED for a 20 Gy × 1 treatment (128 ${\mathrm{Gy}}_{\alpha /\beta }$) is far less than that of a conventional 2 Gy × 37 fractionation (196 ${\mathrm{Gy}}_{\alpha /\beta }$). Conclusions: Our analysis showed that the substantial loss of tumor control observed in extremely hypofractionated HDR-BT trials can only be explained by the LQ model if the $\alpha /\beta$ is very large (≥100 Gy), in clear disagreement with the limits set in the analysis of external radiotherapy data. It seems more reasonable that there is a moderation of the LQ-predicted effect with increasing dose per fraction. These results may assist in the design of radical HDR-BT treatments. Full article

Background/Objectives: Prostate cancer (PCa) cells may acquire radioresistance during radiation therapy (RT), resulting in PCa recurrence. This study was aimed at investigating the radiosensitizing effect of 5-aminolevulinic acid (5-ALA) on radioresistant PCa cells. Methods: Radioresistant PCa cells were developed through successive irradiation of two human PCa cell lines (PC-3 and DU 145) and a murine PCa cell line (Myc-CaP). The radiosensitivity of these PCa cells and the radiosensitizing effect of 5-ALA were evaluated using clonogenic assays. Mitochondrial accumulation of protoporphyrin IX (PpIX) and mitochondrial reactive oxygen species (ROS) were evaluated. A syngeneic mouse model with radioresistant PCa was established, and the immunohistochemistry of cell specimens from PCa patients with local recurrence after primary RT was examined. Results: Radioresistant PCa cells showed lower radiosensitivity compared to parental PCa cells. In radioresistant PCa cells with 5-ALA administration, compared to the group administered irradiation alone, the survival rate after irradiation was significantly reduced by promoting mitochondria-mediated apoptosis caused by increased PpIX accumulation and mitochondrial ROS generation. Similar results were observed in vivo. However, compared with parental PCa cells, radioresistant PCa cells were less affected by the radiosensitizing effect of 5-ALA, owing to decreased PpIX accumulation and mitochondrial ROS production caused by upregulated expression of the drug transporter ABCG2. ABCG2 expression was upregulated in human PCa specimens with post-RT recurrence. Conclusions: 5-ALA enhanced the antitumor effects of RT in radioresistant PCa cells; however, ABCG2 upregulation decreased PpIX accumulation, resulting in a reduced radiosensitizing effect of 5-ALA on radioresistant PCa cells compared with that on parental PCa cells. ABCG2 could be a potential therapeutic target for overcoming radioresistance. Full article

Prostate cancer (PCa) remains the most prevalent cancer among men and the second leading cause of cancer-related deaths worldwide. Early diagnosis is crucial as it opens up various treatment options with curative intent. Recent advancements confirm that radiotherapy (RT), particularly through modern techniques like stereotactic body RT (SBRT) and single-dose RT (SDRT), is a safe and effective treatment for both localized and advanced PCa. This manuscript reviews the evolution and current state of primary prostate SDRT, focusing on its benefits and limitations. SDRT offers advantages such as reduced treatment time and enhanced patient convenience, showing promising efficacy and safety, especially for low- and intermediate-risk PCa. Challenges include controlling intrafraction variability and organ motion, as well as minimizing urethral toxicity. Next-generation imaging and MR-guided RT are improving treatment accuracy. While SDRT shows potential for cost-effective PCa treatment, further research is needed to address its limitations and refine its clinical application. Full article

Background/Objectives: The number of older adults requiring a kidney transplant (KT) is increasing; hence, postoperative sarcopenia prevention is necessary. KT recipients require permanent oral immunosuppressants (ISs), and the gut microbiota (GM) plays a role in various systemic diseases. However, few studies have evaluated post-kidney transplantation frailty and the associations among ISs, GM, and muscle mass alterations. Therefore, we investigated the effects of ISs on GM and skeletal muscle mass in mice and human KT recipients. Methods: Mice were treated with six different ISs, and their skeletal muscle mass, GM diversity, and colonic mucosal function were assessed. Human KT recipients and donors were monitored before and after surgery for 1 year, and GM diversity was evaluated before and 1 month after surgery. Results: The abundance of Akkermansia, crypt depth, and mucin 2 expression were lower in tacrolimus- and prednisolone-treated mice. The psoas muscle volume changes at 1 month and 1 year after surgery were lower in KT recipients than in donors. Furthermore, the beta diversity was significantly different between the operative groups (p = 0.001), and the KT group showed the lowest Shannon index. Conclusions: The findings of this study indicate potential links among ISs, GM, and muscle mass decline. Further investigation is required to improve therapeutic strategies and patient outcomes. Full article

Focal therapy offers a promising approach for treating localized prostate cancer (PC) with minimal invasiveness and potential cost benefits. High-intensity focused ultrasound (HIFU) and brachytherapy (BT) are among these options but lack long-term efficacy data. Patient follow-ups typically use biopsies and multiparametric MRI (mpMRI), which often miss recurrences. PET/CT with PSMA has emerged as a promising tool for detecting residual disease or recurrence post-treatment, offering higher sensitivity and specificity than traditional imaging. We retrospectively reviewed patients who underwent [⁶⁸Ga]Ga-PSMA-11 PET/CT for biochemical recurrence (BCR) after HIFU or brachytherapy from 2016 to 2024. Out of 22 patients, 32% had HIFU and 68% had brachytherapy. The median time from treatment to PET scan was 77 months, with a median PSA level of 3 ng/mL. [⁶⁸Ga]Ga-PSMA-11 PET/CT identified PC recurrence in 63.6% of cases. Of these, 50% showed prostate recurrence, 14% had lymph node involvement, and 28% had metastatic disease. Focal therapies like HIFU and brachytherapy are effective and minimally invasive options for localized PC. [⁶⁸Ga]Ga-PSMA-11 PET/CT is valuable for detecting recurrence or residual disease, enhancing post-treatment surveillance. Full article

Background/Objectives: The standard recommendation for patients with non-muscle invasive bladder cancer is 5-aminolevulinic acid-mediated photodynamic diagnosis. The intensity of the fluorescence caused by the intracellular accumulation of protoporphyrin IX (PPIX) varies among tumors and patients. This study investigated the circadian rhythm of intracellular PPIX accumulation in bladder urothelial cancer cells exposed to 5-aminolevulinic acid. Methods: The expression of two clock genes, PER2 and BMAL1, and their impact on intracellular PPIX accumulation were evaluated in two bladder cancer cell lines, UM-UC-3 and J82, and mouse xenograft models. We evaluated the enzymes involved in the heme synthesis pathway that potentially affect the circadian rhythm of intracellular PPIX accumulation. The red fluorescence intensity of the images captured during photodynamic diagnosis-assisted transurethral resection of bladder tumors was quantified and compared among the four groups according to surgery start time: 9 a.m.–11 a.m., 11 a.m.–1 p.m., 1–3 p.m., and 3–5 p.m. Results: We observed the circadian rhythm of intracellular PPIX accumulation, which was potentially regulated by the clock genes PER2 and BMAL1. Two enzymes involved in the heme synthesis pathway, coproporphyrinogen oxidase and ferrochelatase, exhibit a circadian rhythm. The fluorescence intensity started gradually increasing at 12 p.m., and the highest level was observed in patients who underwent surgery between 3 and 5 p.m. Conclusions: Our findings suggest that it may be possible to optimize the timing of the photodynamic diagnosis in photodynamic diagnosis-assisted transurethral resection of bladder cancer based on the circadian rhythm to improve tumor detection and treatment outcomes. Full article

Low-dose-rate (LDR) brachytherapy with I-125 seeds is one of the most common primary tumor treatments for low-risk and low-intermediate-risk prostate cancer. This report aimed to present an analysis of single-institution long-term results. We analyzed the treatment outcomes of 119 patients with low- and intermediate-risk prostate cancer treated with LDR brachytherapy at our institution between 2014 and 2020. The analysis focused on biochemical recurrence rates (BRFS), overall survival (OS), cumulative local recurrence rate (CLRR), and the incidence of acute and late toxicities. Patient-reported quality of life measures were also evaluated to provide a holistic view on the treatment’s impact. The median follow-up period was 46 months. CLRR was 3.3% (4/119), five-year BRFS was 87%, and the five-year OS rate was 95%. Dysuria was the most common acute urinary toxicity, reported in 26.0% of patients as grade 1 and 13.4% as grade 2. As a late side effect, 12.6% of patients experienced mild dysuria. Sexual dysfunction persisted in 6.7% of patients as grade 1, 7.5% as grade 2, and 10.0% as grade 3. LDR brachytherapy in patients with prostate cancer is an effective treatment, with favorable clinical outcomes and manageable toxicity. The low CLRR and high OS rates, as well as low incidence of severe side effects, support the continued use of LDR brachytherapy as a primary treatment modality for localized prostate cancer. Full article

Background/Objectives: The most important prognostic factors in curatively treated prostate cancer are T and N stage, histology, grade group and initial PSA. A recent study found that men with blood calcium levels at the high end of the normal range are over two-and-a-half times more likely to develop fatal prostate cancer than those with lower calcium levels. However, there is limited evidence regarding the prognostic value of calcium levels at the time of prostate cancer diagnosis. We aimed to determine whether a calcium level in the upper range of normal values has any prognostic value in curatively treated prostate cancer. Methods: We conducted a retrospective analysis of 84 consecutive patients with prostate cancer who underwent curative-intent radiotherapy—either as primary treatment or adjuvant therapy—using external beam radiotherapy with or without brachytherapy. We analyzed all pertinent prognostic factors that could potentially impact disease-free survival. Results: The study revealed that calcium levels at diagnosis significantly predict disease-free survival, whereas the initial PSA level did not hold prognostic significance—likely due to interference from benign prostatic hyperplasia. Conclusions: If our findings are validated, calcium levels at the time of prostate cancer diagnosis could be incorporated into future predictive and prognostic models. Full article