Biochemical recurrence (BCR) after primary treatments for prostate cancer (PC) is an extremely heterogeneous phase and at least a stratification into low- and high-risk cases for early progression in metastatic disease is necessary. At present, PSA-DT represents the best parameter to define low- and high-risk BCR PC, but real precision medicine is strongly suggested to define tailored management for patients with BCR. Before defining management, it is necessary to exclude the presence of low-volume metastasis associated with PSA progression using new-generation imaging, preferably with PSMA PET/CT. Low-risk BCR cases should be actively observed without early systemic therapies. Early treatment of low-risk BCR with continuous androgen deprivation therapy (ADT) can produce disadvantages such as the development of castration resistance before the appearance of metastases (non-metastatic castration-resistant PC). Patients with high-risk BCR benefit from early systemic therapy. Even with overall survival (OS) as the primary treatment endpoint, metastasis-free survival (MFS) should be used as a surrogate endpoint in clinical trials, especially in long survival stages of the disease. The EMBARK study has greatly influenced the management of high-risk BCR, by introducing the concept of anticipation and intensification through the use of androgen receptor signaling inhibitors (ARSIs) and ADT combination therapy. In high-risk (PSA-DT ≤ 9 months) BCR cases, the combination of enzalutamide with leuprolide significantly improves MFS when compared to leuprolide alone, maintaining an unchanged quality of life in the asymptomatic phase of the disease. The possibility of using ARSIs alone in this early disease setting is suggested by the EMBARK study (arm with enzalutamide alone) with less evidence than with the intensification of the combination therapy. Continued use versus discontinuation of enzalutamide plus leuprolide intensified therapy upon reaching undetectable PSA levels needs to be better defined with further analysis. Real-world analysis must verify the significant results obtained in the context of a phase 3 study.

Background: The advantage of a robotic-assisted (RARP) over a laparoscopic (LRP) approach in radical prostatectomy (RP) remains to be demonstrated. Aim: The aim of the study is to use a homogeneous population in real life and single primary surgeon surgery to analyze the oncological and functional results based on the type of surgical approach and pathological features. Methods: This is a prospective trial on non-metastatic prostate cancer (PCa) patients considered after a multidisciplinary decision to conduct a RP, using a RARP or LRP approach. A real-life setting was analyzed at our Urological Departments using homogeneous criteria for the management of PCa cases and a single surgeon experience on 444 cases (284 LRP and 160 RARP). Results: Mean operating time was significantly lower in RARP (153.21 ± 25.1 min) than in LRP (173.33 ± 44.3 min) (p < 0.001). In cases submitted to an extended lymph node dissection (eLND), the mean number of lymph nodes removed was 15.16 ± 7.83 and 19.83 ± 4.78, respectively, in LRP and RARP procedures (p < 0.001), but positive lymph nodes (pN1) were similarly found in 15.8% of LRP patients and 13.6% of RARP patients (p = 0.430). Surgical margins (SM) positivity was not significantly higher in the RARP group (20.0%) when compared to the LRP group (15.9%) (p = 0.145). During the postoperative follow-up, a biochemical recurrence (BCR) was detected in 14.4% and 7.5% of cases in the LRP and RARP group, respectively, (p = 0.014). Better results of PAD tests at 3-month intervals using the RARP approach (mean pad weight 75.57 ± 122 g and 14 ± 42 g, respectively, in LRP and RARP (p < 0.01)) were described. Conclusions: In the comparison between the RARP and LRP approach, a clear advantage of the robotic approach is a significant reduction in operating times, days of hospitalization, and postoperative catheterization compared to laparoscopic surgery. It is not possible to describe any certain oncological advantage both in terms of surgical margins and pathological lymph nodes removed. In RARP cases a reduction to the limit of significance is described in terms of biochemical recurrence. RARP produces a more rapid recovery of urinary continence at 3 months postoperatively without significant advantages in terms of erective potency recovery.

The increasing diffusion of genetic analysis regarding the pathogenetic variants (PVs) of genes involved in DNA Damage Repair (DDR) mechanisms and the development of Poly ADP ribose polymerase (PARP) inhibitors (PARPis) led to the first valid precision medicine option tailored toward metastatic prostate cancer (mPC). The concept of anticipation in the systemic treatment of mPC was initially adopted for androgen receptor signaling inhibitors (ARSIs) to describe the expansion of their indications, from the setting of the late-stage second-line treatment of metastatic castration-resistant prostate cancer (mCRPC) to first-line therapy in selected cases. There is already mounting evidence in favor of the anticipation of PARPis in the first line of mCRPC therapy, and further evidence in favor of mHSPC is emerging. Many studies have demonstrated the synergism between ARSIs and PARP inhibitors. Recent discoveries regarding the crosstalk between the androgen receptor (AR) and DNA repair mechanisms are disconnecting the use of PARPis from genetic analysis. The new message emerging is that the combination of PARPis with ARSIs may work independently of DDR mutational status. As a matter of fact, most of the recent trials analyzing the combination of PARPis with abiraterone or enzalutamide as a first-line therapy enrolled mCRPC patients irrespective of their mutational status. The PROPEL trial concluded that the advantage of the combination was independent of PV status, despite a higher advantage being reported in the BRCA1/2 mutated subgroup. The MAGNITUDE trial, however, showed a significant advantage only in the DDR mutated subgroup, and the DDR non-mutated cohort was closed for further enrollment. The combination of PARPis with ARSIs represents a significant strategy with a view to the anticipation and intensification of care in mPC. However, it should not nullify the advantages of precision medicine linked to the genetic analysis of DDR genes.

Purpose: To evaluate the learning curve of robotic-assisted simple prostatectomy (RASP) using a transvesical approach and to identify the impact of patient-related factors, such as prostatic volume and Body Mass Index (BMI), on operative efficiency. Materials and methods: A retrospective analysis of 103 consecutive RASP procedures performed by a single surgeon was conducted. A multiple linear regression model was developed to calculate predicted operative times adjusted for prostatic volume and BMI. Risk-adjusted Cumulative Sum (RA-CUSUM) analysis was applied to the residuals to characterize the learning curve. Perioperative outcomes were compared across the identified phases using the χ² test or Fisher’s exact test for categorical variables and one-way ANOVA or the Kruskal-Wallis test for continuous variables. Results: Both prostatic volume ( p < 0.001) and BMI ( p = 0.029) were independent predictors of operative duration. The RA-CUSUM analysis identified a learning phase (cases 1–33), a proficiency phase (34–73), and a consolidation phase (74–103). Significant improvements were observed across phases for median operative time (210 vs. 176 vs. 190 min, p = 0.011) and median length of stay (11 vs. 9 vs. 9 h, p < 0.001). No significant differences were found regarding complications or functional outcomes. Conclusions: Proficiency in robotic transvesical simple prostatectomy is achieved after approximately 33 cases, with technical consolidation occurring after the 75th procedure. The transvesical approach provides direct access that may mitigate the technical challenges associated with high BMI, although prostatic volume remains the primary driver of operative duration.

Background/Objectives: The genitourinary microbiome and metabolome may contribute to prostate cancer (PC) biology, but evidence remains limited. This pilot study characterizes the urinary microbiota and volatilome in men with PC and investigates microbial and viral DNA in prostate tissue, comparing findings with benign prostatic hyperplasia (BPH). Methods: We prospectively enrolled 21 non-metastatic PC patients undergoing radical prostatectomy and 17 BPH controls. Lesional and non-lesional prostate tissues and urine were collected from PC patients, as well as urine samples from BPH participants. DNA samples were tested for sexually transmitted pathogens by multiplex real-time PCR. Urine and prostate tissue were analyzed for human polyomaviruses (JCPyV, BKPyV, MCPyV) by qPCR, bacterial profiles via 16S rRNA gene sequencing, and urinary volatile organic metabolites (VOMs) using HS-SPME/GC-MS. Microbial and metabolic profiles were compared, and taxa–metabolites were assessed. Results: JCPyV and BKPyV were detected in urine and tissue from PC patients; MCPyV was detected only in tissue, at low frequency. In BPH, viral prevalence was lower and MCPyV was absent. JCPyV/BKPyV co-infection was common in cancer. No sexually transmitted pathogen emerged. PC patients showed greater urinary microbial diversity and five enriched genera, along with specific metabolic pathways. 36 urinary VOMs were identified, with 14 differing significantly, with positive correlations between PC-associated genera and metabolites. In contrast, prostate tissue was low-biomass, dominated by Pseudomonas, and showed no significant differences between lesional and non-lesional areas. Conclusions: This preliminary, hypothesis-generating study indicates that urinary, rather than tissue, microbial and volatilome signatures show clearer differences between PC and BPH. These findings suggest possible microbiota–metabolite interactions in PC but require validation in larger cohorts.

Background: Partial nephrectomy (PN) has evolved from an imperative to an elective procedure, now representing the standard of care for localized renal masses. The introduction of robotic surgery has expanded the feasibility and precision of minimally invasive nephron-sparing surgery. The single-port (SP) robotic platform, specifically designed to operate through a single incision, aims to further minimize invasiveness and improve postoperative recovery and cosmetic outcomes. Early experiences with SP robot-assisted PN (SP-RAPN) demonstrated encouraging perioperative, oncological, and functional results comparable to those achieved with the multi-port (MP) approach. The retroperitoneal route, particularly through the lower anterior access (LAA), has shown anesthesiological and surgical advantages, including shorter operative times, reduced pain, and faster discharge. Comparative studies indicate similar safety and cancer-control outcomes between SP and MP-RAPN, with SP offering shorter hospital stays but slightly longer Warm Ischemia Times (WITs). Ongoing technological advancements, artificial intelligence (AI) integration, and refined patient selection tools are expected to further enhance the precision, reproducibility, and accessibility of SP-RAPN. Summary: SP-RAPN offers comparable oncological and functional outcomes to multi-port RAPN (MP-RAPN) while further reducing surgical invasiveness and improving cosmetic results. Careful patient selection remains crucial, with low- to intermediate-complexity tumors being most suitable during the early learning phase. Among the available access routes, retroperitoneal and LAA techniques have gained particular attention for their perioperative and anesthesiological benefits. Although SP-RAPN is associated with slightly longer WITs, it provides advantages in terms of postoperative pain, length of stay, and feasibility in outpatient settings. Ongoing technological innovations, including AI, advanced imaging, and improved robotic articulation, are expected to refine surgical precision and broaden adoption. Key Messages: SP-RAPN is a safe and feasible evolution of nephron-sparing surgery with outcomes comparable to MP-RAPN. The retroperitoneal and LAA approaches offer notable perioperative and anesthesiological advantages. Proper patient selection and structured training programs are key to optimizing outcomes and overcoming technical challenges. Future advances in robotic technology and digital integration will further enhance the role of SP-RAPN in minimally invasive urologic surgery.