Primary lymph-node staging with 68Ga-PSMA PET in high-risk prostate cancer: pathologic correlation with extended pelvic lymphadenectomy specimens.

AIM OF THE STUDY: This study aims to assess the diagnostic efficacy of Gallium-68-prostate-specific membrane antigen positron emission tomography (PET)/computed tomography (CT) (68Ga PSMA PET-CT) in primary nodal staging of high-risk prostate cancer (PCa) when compared to pathologic findings of extended pelvic lymph-node dissection (eLND). MATERIALS AND METHODS: The records of high-risk PCa patients who were preoperatively staged through 68Ga PSMA PET-CT and who underwent robot-assisted radical prostatectomy with eLND either alone or as part of multimodal definitive therapy between August 2016 and November 2019 were retrospectively reviewed. Surgeons were not blinded to the results of the 68Ga PSMA PET-CT scan. Pathologic uptake was defined as any anomalous uptake which was not better explained by another cause and was suggestive of PCa. The reference standard for this study was the pathologic confirmation using a node-based analysis. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for 68Ga PSMA PET-CT were calculated in a per-patient analysis using IBM SPSS Statistics version 25. RESULTS: Seventeen patients met the selection criteria. Mean age was 63 years (range 44-77) and mean and median preoperative serum prostate specific antigen was 19.25 and 9 ng/ml (range 6-131), respectively. The most common pathologic Gleason score was 8 (52.9% of cases). Seven patients (41%) had positive surgical margins and were submitted to adjuvant radiotherapy. Mean number of per patient removed lymph-nodes was 13 (±2.19). 68Ga PSMA PET-CT showed findings compatible with lymph node metastases in 4/17 patients and with locally-confined disease in 13/17 patients. Following pathologic confirmation, the per-patient sensibility of the 68Ga PSMA PET-CT was calculated at 75% (1 false negative) and the specificity at 92.3% (1 false positive) for detection of lymph node metastasis on primary staging of high-risk PCa patients. Positive and negative predictive value were 75% and 92.3%, respectively; accuracy of the test was calculated at 88.2%. All patients were submitted to 68Ga PSMA PET-CT re-evaluation 6 months after surgery and tested negative for local, nodal, or distant recurrence of disease. CONCLUSIONS: 68Ga PSMA PET-CT appears to have a high negative predictive value for local lymph node metastases in high-risk primary PCa when compared to pathologic findings of eLND. Its role in the primary nodal staging of high-risk PCa patients worths further evaluation.

Focal therapy for prostate cancer: current status and future perspectives.

Focal therapy is a relatively new and extremely attractive option of treatment for prostate cancer. It has been described as the "middle approach" between active surveillance and radical treatment, aiming to destroy the tumor itself or the region containing the tumor in order to preserve surrounding non-cancerous tissue. The goal is to maintain disease control at acceptable levels, while preserving erectile, urinary, and rectal function. While a lot of technologies have been described for delivering targeted therapy to the prostate, such as cryoablation, high intensity focused ultrasound, photodynamic therapy, irreversible electroporation and laser, the key point is the patient selection. Recent advances in mpMRI and the introduction of new biopsy techniques that use MR images as a guidance, have significantly improved localization of the tumor lesions and the detection rate, evolving prostate biopsy toward targeted rather than systematic biopsies. The future challenge to clinicians is to precisely risk-stratify patients to differentiate between those who would profit from focal treatment and who would not. Forthcoming research efforts should pursue to identify molecular, genetic, and imaging characteristics that distinguish aggressive prostate tumors from indolent lesions.

Prostate cancer diagnosis through electronic nose in the urine headspace setting: a pilot study.

BACKGROUND: To evaluate the efficacy of prostate cancer (PCa) detection by the electronic nose (EN) on human urine samples. METHODS: Urine samples were obtained from candidates of prostate biopsy (PB). Exclusion criteria were a history of urothelial carcinoma or other malignant disease, urine infection, fasting for <12 h before PB or ingestion of alcohol or foods that might alter the urine smell in the last 24 h. The initial part of the voided urine and the midstream were collected separately in two sterile containers. Both samples were analyzed by the EN immediately after the collection. All patients underwent a standard transperineal, transrectal-ultrasound-guided PB. The pathological results were compared with the outcomes of the EN. Sensitivity and specificity of EN were assessed. RESULTS: Forty-one men were included in the study. Fourteen out of the 41 patients were positive for PCa. Midstream urine did not correlate significantly neither with a positive nor with a negative PB. Instead, significantly different results on the initial part of the urine stream between positive and negative PBs were obtained. The EN correctly recognized 10 out of the 14 cases (that is, sensitivity 71.4% (confidence interval (CI) 42-92%)) of PCa while four were false negatives. Moreover, the device recognized as negative 25 out of the 27 (that is, specificity 92.6% (CI 76-99%)) samples of negative PBs, with only two false positives. CONCLUSIONS: We believe this is the first demonstration of an olfactory imprinting of the initial part of the urine stream in patients with PCa that was revealed by an EN, with high specificity.

Transperineal versus transrectal prostate biopsy for predicting the final laterality of prostate cancer: are they reliable enough to select patients for focal therapy? Results from a multicenter international study.

OBJECTIVES: To compare the concordance of prostate cancer (PCa) laterality between the extended transperineal (TP) or transrectal (TR) prostate biopsy (BP) and radical prostatectomy (RP) specimens. To identify predictors of laterality agreement between BP and RP. MATERIALS AND METHODS: Data from 533 consecutive patients with PCa (278 TP and 255 TR-diagnosed) treated with RP were analyzed. A 12-core technique was used for both TP and TR biopsies. Additional cores were obtained when necessary. RESULTS: Overall, the percentage of agreement of PCa laterality between BP and RP was 60% (K = 0.27, p < 0.001). However, the RP confirmation of unilaterality at BP was obtained in just 33% of the cases. Considering the concordance on bilaterality as the ″target″ of our analysis, the sensitivity and specificity were 54.3% and 98.2% , respectively, with TP and 47.5% and 92.5%, respectively with TR. Focusing on patients with unilaterality at biopsy, none of the evaluated preoperative variables (biopsy technique, age, total positive biopsy cores, PSA, prostate volume, Gleason score on biopsy) were able to predict RP bilaterality in the multivariate analyses. CONCLUSIONS: Most of the patients with unilateral involvement at BP harbored bilateral PCa after RP. TR and TP biopsy showed no difference in their capacity to predict the concordance of tumor laterality at RP. None of the preoperative evaluated variables can predict the tumor laterality at RP. Using BP unilaterality to include patients in focal therapy (FT) protocols may hinder the oncologic efficacy of FT.

Transperineal versus transrectal prostate biopsy for predicting the final laterality of prostate cancer: are they reliable enough to select patients for focal therapy? Results from a multicenter international study

Objectives: To compare the concordance of prostate cancer (PCa) laterality between the extended transperineal (TP) or transrectal (TR) prostate biopsy (BP) and radical prostatectomy (RP) specimens. To identify predictors of laterality agreement between BP and RP. Materials and Methods: Data from 533 consecutive patients with PCa (278 TP and 255 TR-diagnosed) treated with RP were analyzed. A 12-core technique was used for both TP and TR biopsies. Additional cores were obtained when necessary. Results: Overall, the percentage of agreement of PCa laterality between BP and RP was 60% (K = 0.27, p < 0.001). However, the RP confirmation of unilaterality at BP was obtained in just 33% of the cases. Considering the concordance on bilaterality as the “target” of our analysis, the sensitivity and specificity were 54.3% and 98.2%, respectively, with TP and 47.5% and 92.5%, respectively with TR. Focusing on patients with unilaterality at biopsy, none of the evaluated preoperative variables (biopsy technique, age, total positive biopsy cores, PSA, prostate volume, Gleason score on biopsy) were able to predict RP bilaterality in the multivariate analyses. Conclusions: Most of the patients with unilateral involvement at BP harbored bilateral PCa after RP. TR and TP biopsy showed no difference in their capacity to predict the concordance of tumor laterality at RP. None of the preoperative evaluated variables can predict the tumor laterality at RP. Using BP unilaterality to include patients in focal therapy (FT) protocols may hinder the oncologic efficacy of FT. .

An overview on mixed action drugs for the treatment of overactive bladder and detrusor overactivity.

OBJECTIVES: To provide an overview on the efficacy, tolerability, safety and health-related quality of life (HRQoL) of drugs with a mixed action used in the treatment of overactive bladder (OAB). EVIDENCE ACQUISITION: MEDLINE database and abstract books of the major conferences were searched for relevant publications from 1966 to 2011 and using the key words 'overactive bladder', 'detrusor overactivity', 'oxybutynin', 'propiverine', and 'flavoxate'. Two independent reviewers considered publications for inclusion and extracted relevant data, without performing a meta-analysis. EVIDENCE SYNTHESIS: Old and conflicting data do not support the use of flavoxate, while both propiverine and oxybutynin were found to be more effective than placebo in the treatment of OAB. Propiverine was at least as effective as oxybutynin but with a better tolerability profile even in the pediatric setting. Overall, no serious adverse event for any product was statistically significant compared to placebo. Improvements were seen in HRQoL with treatment by the oxybutynin transdermal delivery system and propiverine extended release. CONCLUSIONS: While there is no evidence to suggest the use of flavoxate in the treatment of OAB, both oxybutynin and propiverine appear efficacious and safe. Propiverine shows a better tolerability profile than oxybutynin. Both drugs improve HRQoL of patients affected by OAB. Profiles of each drug and dosage differ and should be considered in making treatment choices.

Insight into new potential targets for the treatment of overactive bladder and detrusor overactivity.

Although overactive bladder (OAB) and detrusor overactivity (DO) are not synonyms, they share therapeutic options and partially underlying physiopathological mechanisms. The aim of this overview is to give insight into new potential targets for the treatment of OAB and DO. A narrative review was done in order to reach this goal. Ageing, pelvic floor disorders, hypersensitivity disorders, morphologic bladder changes, neurological diseases, local inflammations, infections, tumors and bladder outlet obstruction may alter the normal voluntary control of micturition, leading to OAB and DO. The main aim of pharmacotherapy is to restore normal control of micturition, inhibiting the emerging pathological involuntary reflex mechanism. Therapeutic targets can be found at the levels of the urothelium, detrusor muscles, autonomic and afferent pathways, spinal cord and brain. Increased expression and/or sensitivity of urothelial-sensory molecules that lead to afferent sensitization have been documented as a possible pathogenesis of OAB. Targeting afferent pathways and/or bladder smooth muscles by modulating activity of ligand receptors and ion channels could be effective to suppress OAB.

[High-intensity focused ultrasound and prostate cancer: technology, state of the art and future].

BACKGROUND. The potential applications of the high-intensity focused ultrasound (HIFU) as a minimally invasive therapy of the localized prostate cancer explain the growing interest of the urologic community towards this technique. HIFU has been assessed for its role in the treatment of localized prostate cancer in patients who otherwise would not have benefited from surgery, and in local recurrences after radiation failure. Methods. Relevant information on HIFU treatment was identified through a literature search of published studies. RESULTS. High biochemical efficacy, excellent tumor local control and favorable mid- and long-term oncological data with a low morbidity rate have been shown in many series of patients. CONCLUSIONS. Although HIFU is a recent and emerging technology, it has been well studied and developed to a point that HIFU will undoubtedly be an effective alternative to radiation therapy.