Biochemical recurrence (BCR) after primary treatments for prostate cancer (PC) is an extremely heterogeneous phase and at least a stratification in low and high-risk cases for early progression in metastatic disease is necessary. At now PSA-DT represents the best parameter to define low and high risk BCR PC, but a real precision medicine is strongly suggested to define a tailored management of 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 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. The primary end point must be metastasis-free survival (MFS), even with the same overall survival (OS). The EMBARK study is able to impact on the management of high risk BCR, by introducing the concept of anticipation and intensification through the use of androgen receptor signaling inhibitors (ARSI) 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 the quality of life unchanged in an asymptomatic phase of the disease. The possibility of using ARSI alone in this early disease setting is suggested by the EMBARK study (arm with enzalutamide alone) with less evidence than the intensification of the combination therapy. Continued use versus discontinuation upon reaching undetectable PSA levels of enzalutamide plus leuprolide intensified therapy 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.

The possibility of treating more patients for a longer time, has exploded the concept of anticipation in the systemic treatment of metastatic prostate cancer (mPC). The genetic analysis of Damage DNA Repair (DDR) mutations in pathogenetic variants (PV) and the development of poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors led to the first valid precision medicine option tailored for mPC. PARP inhibitors are repeating the same evolutionary path experienced for androgen receptor signaling inhibitors (ARSI), starting from the late stage of second line mCRPC in a limited population and time frame. Inevitably also PARP inhibitors will be absorbed by the concept of anticipation and intensification of care. The anticipation of PARP inhibitors in the first line mCRPC therapy is already underway and further one in mHSPC will soon be verified. According to the crosstalk between androgen receptors (AR) and DNA repair, the new message that is emerging is that the combination of PARP inhibitors with ARSI, disconnects PARP from the genetic analysis. Most of the recent trials analyzing PARP inhibitors plus abiraterone or enzalutamide, enrolled first line mCRPC irrespectively to gene PV. The conclusion of the PROPEL trial was that the advantage was independent to PV status, however the highest advantage was reported in BRCA1/2 mutated subgroup. The conclusion of the MAGNITUDE trial was different, with a significant advantage only in the DDR mutated subgroup and the DDR non-mutated was closed for further enrollment. The combination of PARP inhibitors with ARSI represents a significant strategy in the concept of anticipation and intensification of care in mPC. However, it should not nullify the advantages of precision medicine linked to the genetic analysis of DDR.

The National Cancer Institute (NCI) recognizes the potential of technologies based on the use of nanoparticles (NPs) in revolutionizing clinical approaches in the diagnosis and prognosis of cancer. Recent research suggests that once NPs come into contact with a biological fluid of cancer patients, they are covered by proteins, forming a "protein corona", composed of hundreds of plasma proteins. The concept of a personalized, disease-specific protein corona, demonstrating substantial differences in NP corona profiles between cancer and non-cancer patients has been introduced. We developed the design of an experimental prospective single center study with patients allocated in a 1:1:1 ratio of one of three arms: untreated patients with benign prostatic hyperplasia (BPH); untreated patients with non-metastatic prostate cancer (PCa); metastatic prostate cancer patients starting systemic therapies with new androgen-targeted agents or taxanes.. The protocol will aim to develop and implement sensitive nanotools with two distinct objectives. First, by designing NPs capable of selectively binding and detecting biomarkers in order to build a predictive diagnostic model to effectively discriminate between patient sera affected by BPH and PCa. Secondly, within the population with PCa, in case of initial advanced metastatic diagnosis, the objective will be to find biomarkers capable of predicting the response to systemic treatments to improve the precision and efficiency of monitoring treatment outcomes. For protein and metabolite corona experiments, we developed a cross-reactive sensor array platform with cancer detection capacity made of three liposomal formulations with different surface charges. For proteomics-NPs studies, proteins will be identified and quantified by nano-high-performance LC (nanoHPLC) coupled to MS/MS (nanoHPLC−MS/MS). Metabolites will be instead analyzed by an untargeted metabolomic approach.

Backgound: Exosomes are extracellular nanovesicles, carriers of different biomolecules such as lipids, proteins, nucleic acids. Their composition and the fact that their release dramatically increases in case of tumorigenesis, opens different scenarios on the possible application in the research for new biomarkers.Methods: The most widely applied methodologies include ultracentrifugation techniques, size-based techniques, immunoaffinity capture-based techniques (mainly ELISA) and precipitation. To optimize the acquisition of exosomes from the reference sample, more techniques can be applied in sequence for a single extraction, determining an increase in labor time and costs. Results: The analysis of PSA-expressing exosomes provides an incredibly accurate way to discriminate between healthy patients and those with prostate disease. Specifically, IC-ELISA alone method achieved 98.57% sensitivity and 80.28% specificity in discriminating prostate cancer (PC) from benign prostatic hyperplasia (BPH).An immunocapture-based ELISA assay was performed to quantify and characterize carbonic anhydrase (CA) IX expression in exosomes. The results revealed that CA IX positive exosomes were 25-fold higher in plasma samples from PC patients than in those from healthy control. Conclusions: The analysis of PC-linked exosomes represents a promising diagnostic model that can effectively distinguish patients with PC from those with non-malignant prostatic disease, However, the use of exosome analysis in clinical practice is currently limited by several issues, including a lack of standardization in the analytical process and high costs, which are still too high for a large-scale use.

Background: The advantage of a robotic assisted (RARP) over a laparoscopic (LRP) approach in radical prostatectomy (RP) remains to be demonstrated. Aim of the study is to use a homogeneous population in real life and single surgeon surgery, to analyze the oncological and functional results based on the type of the surgical approach. Methods: This is a prospective trial on non-metastatic prostate cancers (PC) patients considered after multidisciplinary decision to RP, using RARP or LRP. A real-life setting was analyzed at our Urological Departments, using homogeneous criteria for the management of PC cases and a one surgeon experience on 444 cases (284 LRP and 160 RARP) .Results: Mean operative time was significantly lower in RARP (173.33±44.3 min) than in LRP (153.21±25.1 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 RARP group (20.0%) when compared to 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 test at 3-month interval using RARP approach (mean pad weight 75.57±122 grams and 14±42 grams respectively in LRP and RARP (p<0.01)) were described. Conclusions: In the comparison between 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.