Search Results (284)

Prostate cancer (PCa) is the second most frequently diagnosed malignancy in men worldwide. Although traditionally considered a disease of older men, the incidence of early-onset PCa (diagnosis < 55 years) is steadily rising. Advances in screening and therapy have significantly improved survival, creating a growing cohort of younger survivors for whom post-treatment quality of life—notably reproductive function—is paramount. Curative treatments such as radical prostatectomy, pelvic radiotherapy, androgen-deprivation therapy (ADT), and chemotherapy often cause irreversible infertility via multiple mechanisms, including surgical disruption of the ejaculatory tract, endocrine suppression of spermatogenesis, direct gonadotoxic injury to the testes, and oxidative sperm DNA damage. Despite these risks, fertility preservation is frequently overlooked in pre-treatment counseling, leaving many patients unaware of their options. This narrative review synthesizes current evidence on how PCa therapies impact male fertility, elucidates the molecular and physiological mechanisms of iatrogenic infertility, and evaluates both established and emerging strategies for fertility preservation and restoration. Key interventions covered include sperm cryopreservation, microsurgical testicular sperm extraction (TESE), and assisted reproductive technologies (ART). Psychosocial factors influencing decision-making, novel biomarkers predictive of post-treatment spermatogenic recovery, and long-term offspring outcomes are also examined. The review underscores the urgent need for timely, multidisciplinary fertility consultation as a routine component of PCa care. As PCa increasingly affects men in their reproductive years, proactively integrating preservation into standard oncologic practice should become a standard survivorship priority. Full article

Background/Objectives: Androgen deprivation therapy (ADT) is the mainstay of prostate cancer treatment, especially in advanced disease. In particular, the gonadotropin-releasing hormone agonists (aGnRH) reduce the production of gonadotropin and, therefore, of testosterone. In about 10% of patients, the non-pulsatile stimulation of GnRH receptor initially causes a surge in LH and testosterone, defined as the “flare-up phenomenon”, leading to increased bone pain, spinal cord compression, bladder outlet obstruction and cardiovascular issues. To mitigate this effect, combining a first-generation antiandrogen agent (FGA) with aGnRH is recommended. However, second-generation anti-androgens, such as apalutamide, bind selectively and irreversibly to the androgen receptor (AR), exhibiting a more efficient inhibition of the AR pathway. Methods: This is a descriptive retrospective study of 27 patients (pts) with mHSPC, treated at a single center (“Santa Maria delle Grazie” Hospital in Pozzuoli, ASL Napoli 2 Nord, Italy) between June 2022 and April 2024. Patients received apalutamide monotherapy for 14 days followed by continuous combination with aGnRH plus apalutamide. Serum PSA and testosterone levels were measured at baseline, at day 14 (after 13 days of apalutamide monotherapy), at day 28 (after an additional 15 days of apalutamide plus a aGnRH), and at day 60. Results: PSA levels decreased from a mean of 45.2 (±63.1) ng/mL at baseline to a mean of 12.6 (±23.4) ng/mL at day 14 and to 3.3 ng/mL (±6.0) at day 28 of treatment. After 14 days of apalutamide monotherapy, 21 patients (77.8%) achieved a >50% PSA reduction and 4 (14.8%) a >90% PSA reduction. The number of patients with undetectable PSA was one (3.7%) at day 14, two (7.4%) at day 28, and nine (33.3%) at day 60. The mean serum testosterone levels were 6.56 (±4.46) ng/mL at baseline, 6.58 (±4.42) ng/mL at day 14, and 2.40 (± 3.38) ng/mL at day 28. No significant difference in PSA and testosterone level reduction during treatment emerged between subgroups of patients with low- vs. high-volume disease. Conclusions: Apalutamide alone is a viable option for mitigating the flare-up phenomenon, avoiding first generation anti-androgen therapy, and it can achieve rapid and deep biochemical control. Full article

The treatment landscape of metastatic hormone-sensitive prostate cancer (mHSPC) has transformed significantly with the advent of triplet therapy involving androgen deprivation therapy (ADT), docetaxel, and androgen receptor signalling inhibitors (ARSIs). While clinical guidelines increasingly support early intensification, real-world practice remains challenged by patient heterogeneity, evolving evidence, and limited consensus on treatment sequencing. This narrative review integrates evidence from landmark trials, clinical guidelines, and expert insights from oncologists managing mHSPC in India. Findings affirm that triplet therapy, particularly with darolutamide, improves survival in high-volume disease and underscores the need for personalized treatment based on disease burden, comorbidities, and genomic profiles. The review also highlights gaps in real-world data, sequencing strategies, and biomarker-driven therapy, reinforcing the need for precision medicine and locally relevant evidence to guide treatment. Ultimately, optimizing mHSPC management requires harmonizing guideline-based approaches with individualized, real-world decision making to improve patient outcomes. Full article

Background: Prostate cancer (PC) is the second leading cause of cancer-related death in men in the United States. A subset of patients develops non-metastatic, castration-resistant PC (nmCRPC), for which management requires a personalized consideration for appropriate treatment. However, there is no consensus regarding when to switch from androgen deprivation therapy (ADT) to more aggressive treatments like abiraterone or enzalutamide. Methods: We analyzed 5037 nmCRPC patients and employed a Weibull Time to Event Recurrent Neural Network to identify patients who would benefit from switching from ADT to abiraterone/enzalutamide. We evaluated this model using differential treatment benefits measured by the Kaplan–Meier estimation and milestone probabilities. Results: The model achieved an area under the curve of 0.738 (standard deviation (SD): 0.057) for patients treated with abiraterone/enzalutamide and 0.693 (SD: 0.02) for patients exclusively treated with ADT at the 2-year milestone. The model recommended 14% of ADT patients switch to abiraterone/enzalutamide. Analysis showed a statistically significant absolute improvement using model-recommended treatments in progression-free survival (PFS) of 0.24 (95% confidence interval (CI): 0.23–0.24) at the 2-year milestone (PFS rate increasing from 0.50 to 0.74) with a hazard ratio of 0.44 (95% CI: 0.39–0.50). Conclusions: Our model successfully identified nmCRPC patients who would benefit from switching to abiraterone/enzalutamide, demonstrating potential outcome improvements. Full article

Background/Objectives: Androgen deprivation therapy (ADT) is widely used to manage prostate cancer (PC), but the emergence of treatment resistance remains a major clinical challenge. Although the GST family has been implicated in drug resistance, the specific role of GSTM5 remains poorly understood. This study investigates whether GSTM5, alone or in combination with clinical variables, can improve patient stratification based on the risk of early treatment resistance. Methods: In silico analyses were performed to examine GSTM5’s role in protein interactions, molecular pathways, and gene expression. The rs3768490 polymorphism was genotyped in 354 patients with PC, classified by ADT response. Descriptive analysis and logistic regression models were applied to evaluate associations between genotype, clinical variables, and ADT response. GSTM5 expression related to the rs3768490 genotype and ADT response was also analyzed in 129 prostate tissue samples. Results: The T/T genotype of rs3768490 was significantly associated with a lower likelihood of early ADT resistance in both individual (p = 0.0359, Odd Ratios (OR) = 0.18) and recessive models (p = 0.0491, OR = 0.21). High-risk classification according to D’Amico was strongly associated with early progression (p < 0.0004; OR > 5.4). Combining genotype and clinical risk improved predictive performance, highlighting their complementary value in stratifying patients by treatment response. Additionally, GSTM5 expression was slightly higher in T/T carriers, suggesting a potential protective role against ADT resistance. Conclusions: The T/T genotype of rs3768490 may protect against ADT resistance by modulating GSTM5 expression in PC. These preliminary findings highlight the potential of integrating genetic biomarkers into clinical models for personalized treatment strategies, although further studies are needed to validate these observations. Full article

Background: Androgen deprivation therapy (ADT) is a primary treatment for prostate cancer (PCa) that effectively reduces androgen levels to suppress tumor progression. However, growing evidence suggests potential cognitive side effects, raising concerns about the long-term neurological consequences of this treatment. Objective: This scoping review aims to synthesize the existing evidence linking ADT to cognitive changes in men with PCa, identifying the key cognitive domains affected and outlining gaps in the existing literature. Methods: A systematic literature search was conducted according to the PRISMA-ScR guidelines in CINAHL, PubMed, Scopus, and Web of Science. Studies investigating cognitive function in ADT-treated PCa patients were included, covering randomized controlled trials (RCTs) and cohort, case–control, and cross-sectional studies. The extracted data included the study design, evaluated cognitive characteristics, measurement tools, and overall findings. Results: A total of 22 studies met the inclusion and exclusion criteria. Cognitive assessments varied across studies. While some studies reported cognitive impairments in ADT-treated patients—particularly in working, verbal, and visual memory and executive function—others found no significant effects. The variability in prostate cancer staging, epidemiological study designs, and treatment regimens; the exclusion of comorbid conditions; and the differences in assessment tools, sample sizes, and study durations hinder definitive conclusions about the cognitive effects of ADT. Conclusions: This scoping review highlights the heterogeneous and often contradictory evidence regarding ADT-associated cognitive dysfunction. While certain cognitive domains may be affected, methodological inconsistencies limit robust conclusions. Standardized cognitive assessments and longer longitudinal studies are required to clarify ADT’s role in cognitive decline. As the PCa survival rate increases with extended ADT use, integrating routine cognitive monitoring into clinical practice should be considered for PCa patients. Full article

At diagnosis, metastatic prostate cancer (PC) is sensitive to androgen deprivation therapy (ADT), and patients are usually referred to as having castration-sensitive prostate cancer (mCSPC). The combination of ADT and androgen receptor pathway inhibitors (ARPI) is the current standard of care for mCSPC. This study aimed to review the literature on economic evaluations and health economic models related to mCSPC. A literature search was performed covering Medline, Embase, and Scopus with additional grey literature sources. Studies with data on health economic evaluations focusing on Europe or North America were relevant. 18 peer-reviewed articles and 10 grey literature documents were included. The majority (n = 23) had a deterministic Markov structure and applied either Markov cohort or partitioned survival models. Evaluations investigated various types of ADT-based combinations, comparing the addition of ARPI, chemotherapy agents, or radiation therapy to ADT alone. We concluded that economic evaluations in the field of PC are widely published, and there are a large number of publications even in the specific subgroup of mCSPC. Regardless of the investigated interventions, most studies applied similar methodologies and simulated patients from the mCSPC state until the development of mCRPC or death. Full article

Current guidelines recommend either radical prostatectomy (RP) or radiation with androgen deprivation therapy (ADT) for unfavorable intermediate- or high-risk prostate cancer. There has been emerging interest in the potential benefits of neoadjuvant ADT prior to RP for this population. Past trials indicate neoadjuvant ADT may be associated with reduced surgical complexity, pathologic downstaging, decreased positive margins, and decreased rates of nodal positivity, although they have not shown benefits for cancer progression and survival. Accordingly, neoadjuvant ADT is currently not recommended for surgical patients. Conversely, ADT is a mainstay of treatment in metastatic disease, and interest remains in expanding its use towards patients with clinically localized disease. There are several ongoing trials of second-generation androgen blockers such as enzalutamide, darolutamide, radiopharmaceuticals, and poly (ADP-ribose) polymerase (PARP) inhibitors to explore long-term cancer-specific survival benefits with neoadjuvant use. In this narrative review, we provide a comprehensive overview of the recent literature and ongoing efforts to incorporate neoadjuvant therapy for clinically localized prostate cancer patients who are at high-risk of recurrence after prostatectomy. Full article

Prostate cancer (PCa) is a highly heterogeneous disease, with castration-resistant prostate cancer (CRPC) and neuroendocrine prostate cancer (NEPC) representing its most aggressive and therapy-resistant forms. Emerging evidence indicates that lineage plasticity—driven by key transcription factors such as Octamer Binding Factor 4 (OCT4)—plays a crucial role in therapeutic resistance and disease progression. OCT4, in coordination with SOX2 and NANOG, acts as a master regulator of stemness and is frequently upregulated in prostate cancer stem cells (PCSCs). This upregulation contributes to tumor initiation, metastasis, and resistance to both androgen deprivation therapy (ADT) and chemotherapy. In this review, we explore the role of OCT4 in mediating lineage plasticity in prostate cancer, with particular emphasis on its involvement in treatment resistance and neuroendocrine differentiation. We also examine therapeutic strategies aimed at targeting OCT4 directly, such as microRNA-mediated suppression, small-molecule inhibitors, and suicide gene therapy, as well as indirect approaches that modulate OCT4 expression via FGFR and NF-κB signaling pathways. While these strategies offer promising avenues, challenges such as adaptive resistance and the intricate signaling networks within PCSCs remain significant hurdles. A deeper understanding of the molecular mechanisms underlying OCT4-driven plasticity may pave the way for novel therapeutic approaches and improved outcomes in advanced prostate cancer. Full article

Background: This study aimed to develop a predictive model for acute gastrointestinal (GI) and genitourinary (GU) toxicity in prostate cancer patients treated with salvage radiotherapy (SRT) post-prostatectomy, using machine learning techniques to identify key prognostic factors. Methods: A multicenter retrospective study analyzed 454 patients treated with SRT from three Italian radiotherapy centers. Acute toxicity was assessed using Radiation Therapy Oncology Group criteria. Predictors of grade ≥ 2 toxicity were identified through Least Absolute Shrinkage and Selection Operator (LASSO) regression and Classification and Regression Tree (CART) modeling. The analyzed variables included surgical technique, clinical target volume (CTV) to planning target volume (PTV) margins, extent of lymphadenectomy, radiotherapy technique, and androgen-deprivation therapy (ADT). Results: No patients experienced grade ≥ 4 toxicity, and grade 3 toxicity was below 1% for both GI and GU events. The primary determinant of acute toxicity was the surgical technique. Open prostatectomy was associated with significantly higher grade ≥ 2 GI (41.8%) and GU (35.9%) toxicity compared to laparoscopic/robotic approaches (18.9% and 12.2%, respectively). A CTV-to-PTV margin ≥ 10 mm further increased toxicity, particularly when combined with extensive lymphadenectomy. SRT technique and ADT were additional predictors in some subgroups. Conclusions: SRT demonstrated excellent tolerability. Surgical technique, CTV-to-PTV margin, and treatment parameters were key predictors of toxicity. These findings emphasize the need for personalized treatment strategies integrating surgical and radiotherapy factors to minimize toxicity and optimize outcomes in prostate cancer patients. Full article

Background/Objectives: Prognostic information for nonmetastatic prostate cancer (nmPC) patients with prevalent vertebral fractures (PVFs) is very limited. Vertebral fractures can impair physical function, limit activities of daily living, and decrease quality of life. Prevention of vertebral fractures may be important to improve patient prognosis. This study aims to investigate the impact of the presence and severity of PVFs on overall survival in patients with nmPC undergoing androgen deprivation therapy (ADT). Methods: A total of 275 men (median age: 73 years) with nmPC who underwent ADT were studied retrospectively. The median observation period was 55 months. Variables included age, body mass index, T classification, N classification, Gleason score, and pretreatment serum prostate-specific antigen levels. PVF was diagnosed from the sagittal computed tomography images of Th1 to L5 before initiating ADT, and the severity was determined by the number of PVFs and the Semiquantitative (SQ) method. Hazard ratios and 95% confidence intervals for overall survival were calculated using the Cox proportional hazards model. Results: During the observation period, 30 patients died from all causes. Multivariate Cox regression analysis identified multiple PVFs and high-grade PVFs, as determined by the SQ method, as significant predictors of overall survival. The analysis utilized two adjustment models: one adjusted for age only and the other adjusted for age, Gleason score, and clinical T stage. Conclusions: Multiple PVFs and high-grade PVF determined by the SQ method prior to ADT initiation were associated with higher all-cause mortality in nmPC patients treated with ADT. Full article

Purpose/Objectives: Salvage radiotherapy (SRT) after a radical prostatectomy is a curative approach for patients with biochemical recurrence (BR). However, outcomes are often less favorable when imaging reveals macroscopic local recurrence. In such cases, dose escalation through stereotactic salvage radiotherapy (SSRT) may offer improved disease control. The STARR trial (NCT05455736) is a prospective, multicenter study evaluating the efficacy and safety of SSRT in patients with macroscopic prostate bed recurrence. This interim analysis reports early findings from the initial patient cohort. Materials and Methods: Patients with BR (PSA > 0.2 ng/mL) post-prostatectomy and PET-confirmed macroscopic recurrence (PSMA or Choline PET, confirmed by MRI) were eligible. Treatment involved CyberKnife^®-based SSRT delivering 35 Gy in five fractions to the visible lesion. Androgen deprivation therapy (ADT) was not permitted. Complete biochemical response (CBR) was defined as PSA < 0.2 ng/mL, and biochemical response (BR) as a ≥50% PSA reduction. Additional outcomes included biochemical, radiological, and ADT-free survival (bPFS, rPFS, aPFS). Results: As of analysis, 51 patients were enrolled, with a median follow-up of 16 months (95% CI: 16–22). CBR and BR were achieved in 45.1% and 80.4% of patients, respectively. Events affecting bPFS, rPFS, and aPFS occurred in 12, 5, and 6 patients, with median values not yet reached. Toxicity was minimal, with two cases each of acute grade 2 GI and GU events, and one late grade 2 GI event. No grade ≥ 3 toxicities were reported. Conclusion: Early data support SSRT as a safe and a promising option for macroscopic local recurrence, with encouraging response rates and minimal toxicity. Full article

The treatment of choice for prostate cancer is androgen deprivation (ADT) and novel hormonal agents such as Abiraterone, Enzalutamide, or Apalutamide. Initially, this therapy is highly effective, but a significant challenge arises as most patients eventually develop resistance, resulting in castration-resistant prostate cancer (CRPC). Furthermore, the sequential use of these drugs can lead to cross-resistance, diminishing their efficacy. Tumor heterogeneity plays a pivotal role in the development of resistance to different treatments. This study utilized cellular models of CRPC to assess the response to Apalutamide when it was administered as a second- or third-line treatment. Functional and genetic analyses were conducted in various CRPC cell models exposed to Apalutamide. These analyses included real-time cell monitoring assays, flow cytometry, clonogenicity assays, and RT-qPCR. CRPC cell models were capable of continued proliferation, maintained cell cycle profiles similar to those of untreated cells, and retained their clonogenic potential. Cross-resistance to Apalutamide in models of ADT, ADT plus Enzalutamide, or Abiraterone resistance did not correlate with the expression levels of AR-V7 and AR-V9 variants. Gene expression analysis of resistant prostate cancer cell lines revealed that treatment with Apalutamide induced the emergence of more aggressive phenotypes, including cancer stem cells or neuroendocrine differentiation profiles. Most CRPC cell models developed cross-resistance to Apalutamide and were able to proliferate and retain their clonogenic capability. Apalutamide resistance was not linked to the expression of AR-V7 or AR-V9 variants but was instead associated to bypass of AR signaling pathway and the emergence of more aggressive expression profiles. Full article

Background/Objectives: The management of localized prostate cancer with regional lymph node involvement (N1M0) presents significant clinical challenges. While once considered indicative of systemic disease, improved imaging and evolving treatment paradigms have redefined node-positive disease as potentially curable. This systematic review aims to assess current evidence regarding treatment modalities and outcomes for patients with localized N1M0 prostate cancer. Methods: A systematic review was conducted to identify studies evaluating therapeutic strategies for N1M0 prostate cancer. Eligible studies included randomized controlled trials, retrospective analyses, and consensus guidelines. Treatment approaches reviewed included radical prostatectomy (RP) with pelvic lymph node dissection (PLND), whole pelvic radiotherapy (WPRT), prostate-only radiotherapy (PORT), androgen deprivation therapy (ADT), and metastasis-directed therapy (MDT), including stereotactic body radiotherapy (SBRT). Key outcomes included overall survival (OS), biochemical recurrence-free survival (bRFS), disease-free survival (DFS), and treatment-related toxicity. Results: Multimodal approaches—particularly the combination of ADT with WPRT or adjuvant radiotherapy following RP—were associated with improved survival outcomes. Patients with limited nodal burden and undetectable postoperative prostate-specific antigen (PSA) levels derived the most benefit. The use of prostate-specific antigen membrane positron-emission tomography/computed tomography (PSMA PET/CT) enhanced detection and guided MDT in oligorecurrent disease. SBRT, simultaneous integrated boost (SIB), and hypofractionated regimens demonstrated promising efficacy with acceptable toxicity profiles. Conclusions: Node-positive localized prostate cancer is optimally managed with individualized, multidisciplinary strategies. Combining systemic and locoregional treatments improves outcomes in selected patients. Ongoing prospective studies are warranted to refine patient selection, optimize treatment sequencing, and integrate novel imaging and systemic agents. 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