Purpose High dose-rate brachytherapy (HDR-BT) combined with external beam radiotherapy (EBRT) is a widely accepted treatment for patients with clinically localized prostate cancer. A significant impact on sexual health related quality of life (sHRQoL) is reported in published series. The etiology is probably multifactorial, including baseline factors, trauma and dose to the neurovascular bundles (NVB). Magnetic resonance imaging (MRI) enables the visualization and proper localization of the NVB. Herein we aim to analyze the long-term sHRQoL after MRI-guided whole gland HDR-BT boost for prostate cancer and to assess the impact of the dose to the NVB and other factors on sHRQoL. Materials and Methods Sixty-one patients were treated with a single 15 Gy MRI-guided HDR-BT followed by EBRT as part of a prospective phase II trial approved by the local Research Ethic Board (09-0026-C). For this analysis, patients who received over 12 months of androgen deprivation therapy (ADT) and / or patients with a baseline erectile dysfunction were excluded. The left and right NVB were delineated in retrospect on T2-weighted images. Sexual HRQoL was prospectively collected using the expanded prostate index composite (EPIC) questionnaire at baseline, 1month, 3 months, 6 months, 12 months and Q12 monthly thereafter until 60 months. A minimally important difference (MID) was defined as a deterioration of sHRQoL scores at 3 months ≥ 0.5 standard deviation of baseline score. Linear and logistic regression models were used. Results Twenty-eight patients met the criteria to be included in this analysis. A short course of ADT was given to 15 patients. the mean baseline sexual HRQOL score was 48.1 (SD=27.1): 41.9 (SD=28.5) for sexual function and 63.8 (SD=37.9) for sexual bother (37.9). At 12, 24, 36 and 60 months the mean sexual score was 37.5 (SD=26.3), 47(SD=24.3), 45.1 (SD=20.4) and 36.8 (SD=29.1), p>0.05. A MID was reported by 50% of patients at 60 months. The mean sHRQoL score at 60 months of patients who had a short course of ADT was 44.1 (SD=27.1) versus 32.2 (SD=31.1), p>0.05.The mean delineated volume of the NVB was 0.35 cc ± 0.12 on the right and 0.36 cc ± 0.13 on the left. The median number of needles used was 18 [interquartile range(IQR):17-19]. The median dose max to the left NVB is 20.9 Gy (17.4-22.8) and to the right NVB is 21.1 Gy (19.0-24.0). the median dose to the penile bulb was 5.4 Gy (4.2-7.8).There was no association found between any of the baseline or dosimetric parameters with the deterioration sHRQoL. Conclusions Fifty percent of prostate cancer patients treated with MRI-guided HDR-BT followed by EBRT reported a MID in their sHRQoL at 5 years after . The dose received by the NVB bilaterally was consistently higher than 120% of the prescription dose. A short course of ADT was not associated with a worse sHRQoL score at 5 years. Further studies should focus on using MRI to accurately delineate the NVB and assess the feasibility and impact of limiting the dose to the NVB.

Localized high-risk (HR) prostate cancer (PCa) is a heterogeneous disease whose likelihood of a biochemical recurrence, metastatic progression and cancer-related mortality after initial treatment is higher when compared with patients with low (LR) or intermediate-risk (IR) disease. In the past, neoadjuvant therapy has shown an improvement in postoperative oncological variables but failed to demonstrate any survival advantages. With the promising results from novel treatments in metastatic and non-metastatic castration resistant PCa settings, new evidence has appeared in the literature in the neoadjuvant setting. Background/Objectives: To describe the current evidence for different neoadjuvant treatments before a radical prostatectomy in high-risk prostate cancer. Methods: We performed a comprehensive English literature search for original and review articles through January–August 2024, using Pubmed, Medline and ClinicalTrials.gov databases, as well as a comprehensive review of different international guidelines, searching the following terms: “neoadjuvant ADT prostate cancer”, “neoadjuvant ADT”, “prostate cancer surgery” and “neoadjuvant high-risk prostate cancer”. We included 61 papers for the final review. Results and Discussion: Neoadjuvant therapy is not recommended in daily practice by any international guideline. The National Comprehensive Cancer Network (NCCN) guidelines strongly discourage the use of ADT as a neoadjuvant therapy outside of clinical trials. ADT + ARTAs show promising data in phase-II trials, including favorable pCR, MRD, PSA relapse and salvage therapy rates. Clinical trials on chemotherapy, 177Lu-PSMA, genomic-targeted therapies and markers of response leave room for further evidence acquisition due to their encouraging results. Conclusions: Currently, no phase III data supports systemic neoadjuvant therapy before RP. Phase II studies show promising data for ADT with second-generation agents, including favorable pCR, MRD, PSA relapse and salvage therapy rates.

Oligometastatic prostate cancer (OMPC) is an intermediate state between localised disease and widespread metastases that includes a spectrum of disease biology and clinical behaviours. This narrative review will cover the current OMPC scenario. We conducted comprehensive English language literature research for original and review articles using the Medline database and grey literature through December 2021. OMPC is a unique clinical state with inherently more indolent tumour biology susceptible to multidisciplinary treatment (MDT). With the development of new imaging techniques, patients with OMPC are likely to be identified at an earlier stage, and the paradigm for treatment is shifting towards a more aggressive approach to treating potentially curable patients. Multimodal management is necessary to improve patient outcomes due to the combination of available therapies, such as local therapy of primary tumour, metastasis directed therapy or systemic therapy, to reduce tumour load and prevent further disease progression. Additional prospective data are needed to select patients most likely to benefit from a given therapeutic approach.

Objectives To assess whether free PSA ratio (FPSAR) at biochemical recurrence (BCR) can predict metastasis, castrate-resistant prostate cancer (CRPC), and cancer-specific survival (CSS), following therapy for localised disease. Patients and Methods A single-centre retrospective cohort study (NCT03927287) including a discovery cohort composed of patients with an FPSAR after radical prostatectomy (RP) or radiotherapy (RT) between 2000 and 2017. For validation, an independent Biobank cohort of patients with BCR after RP was tested. Using a defined FPSAR cut-off, the metastasis-free-survival (MFS), CRPC-free survival, and CSS were compared. Multivariable Cox models determined the association between post-treatment FPSAR, metastases, and CRPC. Results Overall, 822 patients (305 RP- and 363 RT-treated patients and 154 Biobank patients) were analysed. In the RP cohort, a total of 272/305 (89.1%) and 33/305 (10.9%) had a FPSAR test incidentally and reflexively, respectively. In the RT cohort, 155/363 (42.7%) and 208/263 (57.3%) had a FPSAR test incidentally and reflexively, respectively. However, in the prospective Biobank RP cohort, FPSAR testing was done on all samples of patients diagnosed with BCR. A FPSAR cut-off of 0.10 was determined using receiver operating characteristic analyses in both the RP and RT cohorts. A FPSAR of <0.10 resulted in longer median MFS (14.8 vs 9.3 years and 14.8 vs 13 years, respectively), and longer median CRPC-free survival (median not reached vs 9.9 years and 20.7 vs 13.8 years, respectively). Multivariable analyses showed that a FPSAR of >= 0.10 was associated with increased metastasis in the RP cohort (hazard ratio (HR] 1.915, 95% confidence interval (CI) 1.241-2.955) and RT cohort (HR 1.754, 95% CI 1.112-2.769), and increased CRPC in the RP cohort (HR 2.470, 95% CI 1.493-4.088). Findings were validated in the Biobank cohort. Conclusions A post-treatment FPSAR of >0.10 is associated with more aggressive disease, suggesting a potentially novel role for this biomarker.

OBJECTIVES:To report the oncological and functional outcomes of salvage radical prostatectomy (sRP) after focal therapy (FT). PATIENTS AND METHODS:A retrospective review of all patients who underwent sRP after FT was performed. Clinical and pathological outcomes focussed on surgical complications, oncological, and functional outcomes. RESULTS:In all, 34 patients were identified. The median (interquartile range [IQR]) age was 61 (8.25) years. FT modalities included high-intensity focussed ultrasound (19 patients), laser ablation (13), focal brachytherapy (one) and cryotherapy (one). The median (IQR) time from FT to recurrence was 10.9 (17.6) months. There were no rectal or ureteric injuries. Two (5.9%) patients had iatrogenic cystotomies and four (11.8%) developed bladder neck contractures. The mean (sd) hospital stay was 2.5 (2.1) days. The T-stage was pT2 in 14 (41.2%) patients, pT3a in 16 (47.1%), and pT3b in four (11.8%). In all, 13 (38%) patients had positive surgical margins (PSMs). Six (17.6%) patients received adjuvant radiotherapy (RT). At a mean follow-up of 4.3 years, seven (20.6%) patients developed biochemical recurrence (BCR), and of these, six (17.6%) patients required salvage RT. PSMs were associated with worse BCR-free survival (hazard ratio 6.624, 95% confidence interval 2.243-19.563; P < 0.001). The median (IQR) preoperative International Prostate Symptom Score and International Index of Erectile Function score was 7 (4.5-9.5) and 23.5 (15.75-25) respectively, while in the final follow-up the median (IQR) values were 7 (3.5-11) and 6 (5-12.25), respectively (P = 0.088 and P < 0.001). At last follow-up, 31 (91.2%) patients were continent, two (5.9%) had moderate (>1 pad/day) incontinence, and one (2.9%) required an artificial urinary sphincter. CONCLUSIONS:sRP should be considered as an option for patients who have persistent clinically significant prostate cancer or recurrence after FT. PSMs should be recognised as a risk for recurrent disease after sRP.

Introduction: Digital rectal examination (DRE) is part of the clinical evaluation of men on active surveillance (AS). The purpose of the present study is to analyze the value of DRE as a predictor of upgrading in a population of men with prostate cancer (PCa) treated with AS. Methods: We used the prostate biopsy (PBx) database from an academic center, including PBx from 2006-2018, and identified 2029 confirmatory biopsies (CxPBx) of men treated with AS, of which 726 men had both diagnostic (initial) and CxPBx information available. We did a descriptive analysis and evaluated sensitivity, specificity, and predictive values of DRE for the detection of clinically significant PCa (csPCa). Multivariable regression analysis was done to identify predictors of csPCa. The primary outcome was to evaluate DRE as a predictor of the presence of csPCa at CxPBx. Results: Among the 2029 patients with a CxPBx, 75% had PCa, and of these, 30.3% had upgrading to International Society of Urologic Pathologists (ISUP) grade >= 2. Thirteen percent of men had a suspicious DRE (done by their treating physician). Sensitivity, specificity, negative and positive predictive values of DRE to detect csPCa were best with a prostate-specific antigen (PSA) <4 ng/ml (27%, 88%, 31%, and 87%, respectively). A suspicious DRE at CxPBx, particularly if the DRE at diagnosis was negative, was a predictor of csPCa (odds ratio [OR] 2.3.4, p = 0.038). The main limitation of our study is the retrospective design and the lack of magnetic resonance imaging. Conclusions: We believe DRE should still be used as part of AS and can predict the presence of csPCa, even with low PSA values. A suspicious nodule on DRE represents a higher risk of upgrading and should prompt further assessment.

Introduction: Digital rectal examination (DRE) is part of the clinical evaluation of men on active surveillance (AS). The purpose of the present study is to analyze the value of DRE as a predictor of upgrading in a population of men with prostate cancer (PC) treated with AS. Methods: We used the prostate biopsy (PBx) database from an academic center, including PBx from 2006–2018, and identified 2029 confirmatory biopsies (CxPBx) of men treated with AS, of which 726 men had both diagnostic (initial) and CxPBx information available. We did a descriptive analysis and evaluated sensitivity, specificity, and predictive values of DRE for the detection of clinically significant PC (csPC). Multivariable regression analysis was done to identify predictors of csPC. The primary outcome was to evaluate DRE as a predictor of the presence of csPC at CxPBx. Results: Among the 2029 patients with a CxPBx, 75% had PC, and of these, 30.3% had upgrading to ISUP Grade ≥2. Thirteen percent of men had a suspicious DRE (done by their treating physician). Sensitivity, specificity, negative and positive predictive values of DRE to detect csPC were best with a PSA <4 ng/ml (27%, 88%, 31%, and 87%, respectively). A suspicious DRE at CxPBx, particularly if the DRE at diagnosis was negative, was a CUAJ – Original Research Herrera-Caceres et al Utility of DRE for men on active surveillance 2 © 2020 Canadian Urological Association predictor of csPC (odds ratio [OR] 2.34; p=0.038). The main limitation of our study is the retrospective design and the lack of magnetic resonance imaging. Conclusions: We believe DRE should still be used as part of AS and can predict the presence of csPC even with low PSA values. A suspicious nodule on DRE represents a higher risk of upgrading and should prompt further assessment. Introduction Active surveillance (AS) has become the standard of care for men with low risk prostate cancer (PC).1,2 One of the criteria used for including patients in AS protocols is the digital rectal examination (DRE). Most guidelines allow for cT2 patients to be offered AS, as long as the rest of the low risk criteria are fulfilled.3,4 AS follow up protocols vary between institutions.4-7 The follow up usually includes periodical prostate specific antigen (PSA) measurements, DRE and prostate biopsies (PBx).4 Most centers mandate a confirmatory PBx within 6-18 months from the initial diagnostic PBx, as the initial PBx can miss clinically significant prostate cancers (csPC) 5 Large AS series have reported a consistent rate of pathological progression (upgrading and/or upstaging) at the confirmatory PBx of 19.9-28.1%.5 Accurate and timely detection of patients with csPC who require treatment is crucial, although we also struggle to determine who may safely avoid or delay a confirmatory PBx. Risk factors for upstaging/upgrading include high volume ISUP Grade 1, suspicious lesions on magnetic resonance imaging (MRI), PSA density, race, and age.8-12 DRE is widely considered a component of clinical evaluation in men with prostate cancer diagnosis, although in AS the value of DRE is uncertain. Nonetheless, DRE involves mild discomfort and may require an additional patient visit. The objective of the present study was to analyse the value of DRE as a predictor of upgrading in a population