Tertiary lymphoid structures generate and propagate anti-tumor antibody-producing plasma cells in renal cell cancer.

The presence of intratumoral tertiary lymphoid structures (TLS) is associated with positive clinical outcomes and responses to immunotherapy in cancer. Here, we used spatial transcriptomics to examine the nature of B cell responses within TLS in renal cell carcinoma (RCC). B cells were enriched in TLS, and therein, we could identify all B cell maturation stages toward plasma cell (PC) formation. B cell repertoire analysis revealed clonal diversification, selection, expansion in TLS, and the presence of fully mature clonotypes at distance. In TLS+ tumors, IgG- and IgA-producing PCs disseminated into the tumor beds along fibroblastic tracks. TLS+ tumors exhibited high frequencies of IgG-producing PCs and IgG-stained and apoptotic malignant cells, suggestive of anti-tumor effector activity. Therapeutic responses and progression-free survival correlated with IgG-stained tumor cells in RCC patients treated with immune checkpoint inhibitors. Thus, intratumoral TLS sustains B cell maturation and antibody production that is associated with response to immunotherapy, potentially via direct anti-tumor effects.

A Multicenter, Randomized, Single-blind, 2-Arm Intervention Study Evaluating the Adverse Events and Quality of Life After Irreversible Electroporation for the Ablation of Localized Low-intermediate Risk Prostate Cancer.

PURPOSE: Our goal was to evaluate the effect of focal vs extended irreversible electroporation on side effects, patient-reported quality of life, and early oncologic control for localized low-intermediate risk prostate cancer patients. MATERIALS AND METHODS: Men with localized low-intermediate risk prostate cancer were randomized to receive focal or extended irreversible electroporation ablation. Quality of life was measured by International Index of Erectile Function, Expanded Prostate Cancer Index Composite questionnaire, and International Prostate Symptom Score. RESULTS: A total of 51 and 55 patients underwent focal and extended irreversible electroporation, respectively. The median follow-up time was 30 months. Rates of erectile dysfunction and rates of adverse events were similar between the 2 groups at 3 months. The focal ablation group seemed to have better International Index of Erectile Function scores at 3 months; it also had a better Expanded Prostate Cancer Index Composite-sexual function score than the extended ablation group across time that was close to statistical significance (mean difference 1.4; 95% CI -0.13 to 2.9, P = .073). There were no significant differences between the 2 groups in other quality-of-life measures. Upon prostate biopsy at 6 months, the rate of residual clinically significant prostate cancer (Gleason ≥3 + 4) was 18.8% and 13.2% in the focal and extended irreversible electroporation groups, respectively, without significant differences. CONCLUSIONS: Focal and extended irreversible electroporation ablation had similar safety profile, urinary function, and oncologic outcomes in men with localized low-intermediate risk prostate cancer. In addition, focal ablation demonstrated superior erectile function outcome over extended irreversible electroporation in the first 3-6 months.

What is the ideal combination therapy in de novo, oligometastatic, castration-sensitive prostate cancer?

PURPOSE: To review current evidence regarding the management of de novo, oligometastatic, castration-sensitive prostate cancer (PCa). METHODS: A literature search was conducted on PubMed/Medline and a narrative synthesis of the evidence was performed in August 2022. RESULTS: Oligometastatic disease is an intermediate state between localized and aggressive metastatic PCa defined by ≤ 3-5 metastatic lesions, although this definition remains controversial. Conventional imaging has limited accuracy in detecting metastatic lesions, and the implementation of molecular imaging could pave the way for a more personalized treatment strategy. However, oncological data supporting this strategy are needed. Radiotherapy to the primary tumor should be considered standard treatment for oligometastatic PCa (omPCa). However, it remains to be seen whether local therapy still has an additional survival benefit in patients with de novo omPCa when treated with the most modern systemic therapy combinations. There is insufficient evidence to recommend cytoreductive radical prostatectomy as local therapy; or stereotactic body radiotherapy as metastasis-directed therapy in patients with omPCa. Current data support the use of intensified systemic therapy with androgen deprivation therapy (ADT) and next-generation hormone therapies (NHT) for patients with de novo omPCa. Docetaxel has not demonstrated benefit in low volume disease. There are insufficient data to support the use of triple therapy (i.e., ADT + NHT + Docetaxel) in low volume disease. CONCLUSION: The present review discusses current data in de novo, omPCa regarding its definition, the increasing role of molecular imaging, the place of local and metastasis-directed therapies, and the intensification of systemic therapies.

Micro-ultrasound-guided biopsies versus systematic biopsies in the detection of prostate cancer: a systematic review and meta-analysis.

PURPOSE: The diagnosis of prostate cancer (PCa) still relies on the performance of both targeted (TB) and systematic biopsies (SB). Micro-ultrasound (mUS)-guided biopsies demonstrated a high sensitivity in detecting clinically significant prostate cancer (csPCa), which could be comparable to that of magnetic resonance imaging (MRI)-TB, but their added value has not been compared to SB yet. METHODS: We conducted a systematic review and meta-analysis, based on Medline, EMBASE, Scopus, and Web of Science, in accordance with PRISMA guidelines, to compare mUS-guided biopsies to SB. RESULTS: Based on the literature search of 2957 articles, 15 met the inclusion criteria (2967 patients). Most patients underwent mUS-guided biopsies, followed by MRI-TB and SB. Respectively 5 (n = 670) and 4 (n = 467) studies, providing raw data on SB, were included in a random-effect meta-analysis of the detection rate of csPCa, i.e. Gleason Grade Group (GGG) ≥ 2 or non-csPCa (GGG = 1). Overall, PCa was detected in 56-71% of men, with 31.3-49% having csPCa and 17-25.4% having non-csPCa. Regarding csPCa, mUS-guided biopsies identified 196 and SB 169 cases (Detection Ratio (DR): 1.18, 95% CI 0.83-1.68, I2 = 69%), favoring mUS-guided biopsies; regarding non-csPCa, mUS-guided biopsies identified 62 and SB 115 cases (DR: 0.55, 95% CI 0.41-0.73, I2 = 0%), also favoring mUS-guided biopsies by decreasing unnecessary diagnosis. CONCLUSION: Micro-ultrasound-guided biopsies compared favorably with SB for the detection of csPCa and detected fewer non-csPCa than SB. Prospective trials are awaited to confirm the interest of adding mUS-guided biopsies to MRI-TB to optimize csPCa detection without increasing overdiagnosis of non-csPCa.

Expanding inclusion criteria for active surveillance in intermediate-risk prostate cancer: a machine learning approach.

PURPOSE: To develop new selection criteria for active surveillance (AS) in intermediate-risk (IR) prostate cancer (PCa) patients. METHODS: Retrospective study including patients from 14 referral centers who underwent pre-biopsy mpMRI, image-guided biopsies and radical prostatectomy. The cohort included biopsy-naive IR PCa patients who met the following inclusion criteria: Gleason Grade Group (GGG) 1-2, PSA < 20 ng/mL, and cT1-cT2 tumors. We relied on a recursive machine learning partitioning algorithm developed to predict adverse pathological features (i.e., ≥ pT3a and/or pN + and/or GGG ≥ 3). RESULTS: A total of 594 patients with IR PCa were included, of whom 220 (37%) had adverse features. PI-RADS score (weight:0.726), PSA density (weight:0.158), and clinical T stage (weight:0.116) were selected as the most informative risk factors to classify patients according to their risk of adverse features, leading to the creation of five risk clusters. The adverse feature rates for cluster #1 (PI-RADS ≤ 3 and PSA density < 0.15), cluster #2 (PI-RADS 4 and PSA density < 0.15), cluster #3 (PI-RADS 1-4 and PSA density ≥ 0.15), cluster #4 (normal DRE and PI-RADS 5), and cluster #5 (abnormal DRE and PI-RADS 5) were 11.8, 27.9, 37.3, 42.7, and 65.1%, respectively. Compared with the current inclusion criteria, extending the AS criteria to clusters #1 + #2 or #1 + #2 + #3 would increase the number of eligible patients (+ 60 and + 253%, respectively) without increasing the risk of adverse pathological features. CONCLUSIONS: The newly developed model has the potential to expand the number of patients eligible for AS without compromising oncologic outcomes. Prospective validation is warranted.

Annual nationwide analysis of costs and post-operative outcomes after radical prostatectomy according to the surgical approach (open, laparoscopic, and robotic).

OBJECTIVE: Annual countrywide data are scarce when comparing surgical approaches in terms of hospital stay outcomes and costs for radical prostatectomy (RP). We aimed to assess the impact of surgical approach on post-operative outcomes and costs after RP by comparing open (ORP), laparoscopic (LRP), and robot-assisted (RARP) RP in the French healthcare system. PATIENTS AND METHODS: Data from all patients undergoing RP in France in 2020 were extracted from the central database of the national healthcare system. Primary endpoints were length of hospital stay (LOS including intensive care unit (ICU) stay if present), complications (estimated by severity index), hospital readmission rates (at 30 and 90 days), and direct costs of initial stay. RESULTS AND LIMITATIONS: A total of 19,018 RPs were performed consisting in ORP in 21.1%, LRP in 27.6%, and RARP in 51.3% of cases. RARP was associated with higher center volume (p < 0.001), lower complication rates (p < 0.001), shorter LOS (p < 0.001), and lower readmission rates (p = 0.004). RARP was associated with reduced direct stay costs (2286 euros) compared with ORP (4298 euros) and LRP (3101 euros). The main cost driver was length of stay. The main limitations were the lack of mid-term data, readmission details, and cost variations due to surgery system. CONCLUSIONS: This nationwide analysis demonstrates the benefits of RARP in terms of post-operative short-term outcomes. Higher costs related to the robotic system appear to be balanced by patient care improvements and reduced direct costs due to shorter LOS.

Heterogeneity of contemporary grade group 4 prostate cancer in radical prostatectomy specimens.

PURPOSE: The aim was to evaluate the prognostic role of sub-categories of ISUP 4 prostate cancer (PCa) on final pathology, and assess the tumor architecture prognostic role for predicting biochemical recurrence (BCR) after radical prostatectomy. METHODS: From a prospectively-maintained database, we included 370 individuals with ISUP 4 on final pathology. The main outcomes were to evaluate the relationship between different ISUP patterns within the group 4 with pathological and oncological outcomes. Binary logistic regression and Kaplan-Meier estimator were used to evaluate the role of the different categories (3 + 5, 4 + 4, 5 + 3) and tumor architecture (intraductal and/or cribriform) on pathological and oncological outcomes. RESULTS: Among the 370 individuals with ISUP considered for the study, 9, 85 and 6% had grade 3 + 5, 4 + 4 and 5 + 3 PCa, respectively. Overall, 74% had extracapsular extension, while lymph node invasion (LNI) was documented in 9%. A total of 144 patients experienced BCR during follow-up. After adjusting for PSA, pT, grade group, LNI and positive surgical margins (PSM), grade 3 + 5 was a protective factor (HR: 0.30, 95% CI: 0.13,0.68, p = 0.004) in predicting BCR relative to grade 4 + 4. Intraductal or cribriform architecture was correlated with BCR (HR: 5.99, 95% CI: 2.68, 13.4, p < 0.001) after adjusting for PSA, pT, grade group, LNI and PSM. CONCLUSIONS: Patients with tumor grade 3 + 5 had better pathological and prognostic outcomes compared to 4 + 4 or 5 + 3. When accounting for tumor architecture, the sub-stratification into subgroups lost its prognostic role and tumor architecture was the sole predictor of poorer prognosis in terms of biochemical recurrence.

Grade group 1 prostate cancer on biopsy: are we still missing aggressive disease in the era of image-directed therapy?

PURPOSE: Recently, Eggener et al. reignited a debate consisting to redefine Gleason Grade Group (GGG) 1 prostate cancer (PCa) as a precancerous lesion to reduce overdiagnosis and overtreatment. However, historical cohorts showed that some GGG1-labeled disease at biopsy may be underestimated by the standard PCa diagnostic workup. The aim was to assess whether the risk of adverse features at radical prostatectomy (RP) in selected GGG1 patients still exists in the era of pre-biopsy mpMRI and image-guided biopsies. METHODS: We retrospectively reviewed our data from a European RP dataset to assess in contemporary patients with GGG1 at mpMRI-targeted biopsy the rate of adverse features at final pathology, defined as ≥ pT3a and/or pN+ and/or GGG ≥ 3. RESULTS: A total of 419 patients with cT1-T2 cN0 GGG1-PCa were included. At final pathology, 143 (34.1%) patients had adverse features. In multivariate analysis, only unfavorable intermediate-risk/high-risk disease (defined on PSA or stage) was predictive of adverse features (OR 2.45, 95% CI 1.11-5.39, p = 0.02). A significant difference was observed in the 3-year biochemical recurrence-free survival between patients with and without adverse features (93.4 vs 87.8%, p = 0.026). In sensitivity analysis restricted low- and favorable intermediate-risk PCa, 122/383 patients (31.8%) had adverse features and no preoperative factors were statistically associated with this risk. CONCLUSION: In this European study, we showed that there is still a risk of underestimating GGG1 disease at biopsy despite the routine use of image-guided biopsies. Future studies are warranted to improve the detection of aggressive disease in GGG1-labeled patients by incorporating the latest tools such as genomic testing or radiomics.

Current evidence for focal laser ablation and vascular-targeted photodynamic therapy for localized prostate cancer: review of literature published in the last 2 years.

PURPOSE OF REVIEW: Currently, a significant number of patients are diagnosed with unilateral and apparently unifocal low or intermediate-risk prostate cancer (PCa). These patients are suitable for focal therapy, thus preventing radical treatment side effects without affecting cancer control. Among focal therapy energy sources, laser-based technologies have shown promising outcomes. We aimed to summarize recent data on focal laser ablation (FLA) and vascular-targeted photodynamic therapy (VTP) for PCa. RECENT FINDINGS: We selected eight studies reporting data on 1155 patients with PCa who underwent laser-based focal therapy. Five studies were on FLA and three on VTP (six prospective and two retrospective series); four reported both oncologic and functional outcomes whereas in three only oncologic and one only functional outcomes were discussed. Follow-up protocols and durations varied widely among the studies. PCa recurrence rates ranged between 20 and 56%. Urinary and erectile function were preserved after treatment, and complications were mild and transient. A lack of high-quality data on long-term oncological outcomes still remains, thus further highlighting the need for prospective controlled studies. SUMMARY: FLA and VTP are well tolerated procedures with excellent functional outcomes. However, both procedures showed a significant rate of PCa recurrence, thus demonstrating a certain grade of oncologic control failure of the procedure and/or nonoptimal patients' selection.

A systematic review and meta-analysis of Histoscanning™ in prostate cancer diagnostics.

CONTEXT: The value of Histoscanning™ (HS) in prostate cancer (PCa) imaging is much debated, although it has been used in clinical practice for more than 10 years now. OBJECTIVE: To summarize the data on HS from various PCa diagnostic perspectives to determine its potential. MATERIALS AND METHODS: We performed a systematic search using 2 databases (Medline and Scopus) on the query "Histoscan*". The primary endpoint was HS accuracy. The secondary endpoints were: correlation of lesion volume by HS and histology, ability of HS to predict extracapsular extension or seminal vesicle invasion. RESULTS: HS improved cancer detection rate "per core", OR = 16.37 (95% CI 13.2; 20.3), p < 0.0001, I2 = 98% and "per patient", OR = 1.83 (95% CI 1.51; 2.21), p < 0.0001, I2 = 95%. The pooled accuracy was markedly low: sensitivity - 0.2 (95% CI 0.19-0.21), specificity - 0.12 (0.11-0.13), AUC 0.12. 8 of 10 studiers showed no additional value for HS. The pooled accuracy with histology after RP was relatively better, yet still very low: sensitivity - 0.56 (95% CI 0.5-0.63), specificity - 0.23 (0.18-0.28), AUC 0.4. 9 of 12 studies did not show any benefit of HS. CONCLUSION: This meta-analysis does not see the incremental value in comparing prostate Histoscanning with conventional TRUS in prostate cancer screening and targeted biopsy. HS proved to be slightly more accurate in predicting extracapsular extension on RP, but the available data does not allow us to draw any conclusions on its effectiveness in practice. Histoscanning is a modification of ultrasound for prostate cancer visualization. The available data suggest its low accuracy in screening and detecting of prostate cancer.

A systematic review of irreversible electroporation in localised prostate cancer treatment.

Irreversible electroporation is a treatment option used for focal therapy. In this systematic review, we summarise data on irreversible electroporation outcomes in patients with localised prostate cancer. We performed a literature search in 3 databases and included articles with own data on irreversible electroporation results in patients with localised prostate cancer. Primary outcome was procedure efficacy measured as the absence of cancer in the treatment area on the follow-up biopsy. Secondary outcomes were the absence of prostate cancer recurrence in the treatment area on MRI, out-of-field recurrence, complications and functional outcomes (erectile function and micturition). In-field recurrence rate was 0%-39% and out-field 6.4%-24%. In all studies, PSA level decreased: twice lower than baseline after 4 weeks and by 76% after 2 years. Most of the authors noted sexual and urinary toxicity during the first half year after surgery. However, functional outcomes recovered to baseline after 6 months with mild decrease in sexual function. Complication rates after irreversible electroporation were 0%-1% of Clavien-Dindo III and 5%-20% of Clavien-Dindo I-II. Irreversible electroporation has promise oncological outcomes, rate of post-operative complications and minimal-to-no effects on erectile and urinary function. However, medium and long-term data on cancer-specific and recurrence-free survival are still lacking.

Switch from abiraterone plus prednisone to abiraterone plus dexamethasone at asymptomatic PSA progression in patients with metastatic castration-resistant prostate cancer.

OBJECTIVE: To evaluate the effects of switching from prednisone (P) to dexamethasone (D) at asymptomatic prostate-specific antigen (PSA) progression in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone acetate (AA). MATERIALS AND METHODS: Among 93 patients treated with AA between January 2013 and April 2016 in our institution, 48 consecutive asymptomatic patients with mCRPC, who experienced biochemical progression on treatment with AA+P 10 mg/day, were included. A corticosteroid switch to AA+D 0.5 mg/day at PSA increase was administered until radiological and/or clinical progression. The primary endpoint was progression-free-survival (PFS). A prognostic score based on independent prognostic factors was defined. RESULTS: The median time to PSA progression on AA+P was 8.94 months. The median PFS on AA+D and AA+corticosteroids (P then D) was 10.35 and 20.07 months, respectively. A total of 56.25% of patients showed a decrease or stabilization in PSA levels after the switch. In univariate analysis, three markers of switch efficiency were significantly associated with a longer PFS: long hormone-sensitivity duration (≥5 years; median PFS 16.62 vs 4.17 months, hazard ratio [HR] 0.30, 90% confidence interval [CI] 0.16-0.56); low PSA level at the time of switch (<50 ng/mL; median PFS 15.21 vs 3.86 months, HR 0.33, 90% CI 0.18-0.60); and short time to PSA progression on AA+P (<6 months; median PFS 28.02 vs 6.65 months, HR 0.41 (90% CI 0.21-0.81). In multivariate analysis, hormone sensitivity duration and PSA level were independent prognostic factors. CONCLUSION: A steroid switch from P to D appears to be a safe and non-expensive way of obtaining long-term responses to AA in selected patients with mCRPC. A longer PFS has been observed in patients with previous long hormone sensitivity duration, and/or low PSA level and/or short time to PSA progression on AA+P.

Update on the ICUD-SIU consultation on multi-parametric magnetic resonance imaging in localised prostate cancer.

INTRODUCTION: Prostate cancer (PCa) imaging is a rapidly evolving field. Dramatic improvements in prostate MRI during the last decade will probably change the accuracy of diagnosis. This chapter reviews recent current evidence about MRI diagnostic performance and impact on PCa management. MATERIALS AND METHODS: The International Consultation on Urological Diseases nominated a committee to review the literature on prostate MRI. A search of the PubMed database was conducted to identify articles focussed on MP-MRI detection and staging protocols, reporting and scoring systems, the role of MP-MRI in diagnosing PCa prior to biopsy, in active surveillance, in focal therapy and in detecting local recurrence after treatment. RESULTS: Differences in opinion were reported in the use of the strength of magnets [1.5 Tesla (T) vs. 3T] and coils. More agreement was found regarding the choice of pulse sequences; diffusion-weighted MRI (DW-MRI), dynamic contrast-enhanced MRI (DCE MRI), and/or MR spectroscopy imaging (MRSI) are recommended in addition to conventional T2-weighted anatomical sequences. In 2015, the Prostate Imaging Reporting and Data System (PI-RADS version 2) was described to standardize image acquisition and interpretation. MP-MRI improves detection of clinically significant PCa (csPCa) in the repeat biopsy setting or before the confirmatory biopsy in patients considering active surveillance. It is useful to guide focal treatment and to detect local recurrences after treatment. Its role in biopsy-naive patients or during the course of active surveillance remains debated. CONCLUSION: MP-MRI is increasingly used to improve detection of csPCa and for the selection of a suitable therapeutic approach.

Biochemical recurrence-free conditional probability after radical prostatectomy: A dynamic prognosis.

OBJECTIVE: To estimate the conditional biochemical recurrence-free probability and to develop a predictive model according to the disease-free interval for men with clinically localized prostate cancer treated with minimally invasive radical prostatectomy. METHODS: The study population consisted of 3576 consecutive patients who underwent laparoscopic radical prostatectomy and 2619 men treated with robotic radical prostatectomy in the past 15 years at Institute Mutualiste Montsouris, Paris, France. Biochemical recurrence was defined as serum prostate-specific antigen ≥0.2 ng/dL. Univariable and multivariable survival analyses were carried out to identify the prognostic factors for overall free-of-biochemical recurrence probability and conditional survival with respect to the years from surgery without recurrence. A detailed nomogram for the static and dynamic prognosis of biochemical recurrence was developed and internally validated. RESULTS: The median follow-up period was 8.49 years (interquartile range 4.01-12.97), and 1148 (19%) patients experienced biochemical recurrence. Significant variables associated with biochemical recurrence in the multivariable model included preoperative prostate-specific antigen, positive surgical margins, extracapsular extension, pathological Gleason ≥4 + 3 and laparoscopic surgery (all P < 0.001). Conditional survival probability decreased with increasing time without biochemical recurrence from surgery. When stratified by prognosis factors, the 5- and 10-year conditional survival improved in all cases, especially in men with worse prognosis factors. The concordance index of the nomogram was 0.705. CONCLUSIONS: Conditional survival provides relevant information on how prognosis evolves over time. The risk of recurrence decreases with increasing number of years without disease. An easy-to-use nomogram for conditional survival estimates can be useful for patient counseling and also to optimize postoperative follow-up strategies.

Comparative Analysis of Partial Gland Ablation and Radical Prostatectomy to Treat Low and Intermediate Risk Prostate Cancer: Oncologic and Functional Outcomes.

PURPOSE: We analyzed the oncologic and functional outcomes of partial gland ablation compared with robot-assisted radical prostatectomy in patients with low and intermediate risk prostate cancer. MATERIALS AND METHODS: A total of 1,883 patients underwent robot-assisted radical prostatectomy and 373 underwent partial gland ablation from July 2009 to September 2015. We selected 1,458 of these participants for analysis, including 1,222 and 236 treated with robot-assisted radical prostatectomy and partial gland ablation, respectively. Patients had a Gleason score of 3 + 3 or 3 + 4, clinical stage T2b or less, prostate specific antigen 15 ng/dl or less, unilateral disease and life expectancy greater than 10 years. Propensity score matching analysis (1:2) was applied in the overall robot-assisted radical prostatectomy sample, which selected 472 patients for comparison. For partial gland ablation 188 men underwent high intensity focused ultrasound and 48 underwent cryotherapy. Oncologic outcomes were analyzed in terms of the need for salvage treatment. Partial gland ablation failure was defined as any positive control biopsy after treatment. Functional outcomes were assessed by validated questionnaires. RESULTS: Matching was successful across the 2 groups, although men treated with partial gland ablation were older (p <0.001). Mean followup in the partial gland ablation group was 38.44 months. Partial gland ablation failure was observed in 68 men (28.8%), including 53 (28.1%) treated with high intensity focused ultrasound and 15 (31.2%) treated with cryotherapy. Partial gland ablation was associated with a higher risk of salvage treatment (HR 6.06, p <0.001). Complications were comparable between the groups (p = 0.06). Robot-assisted radical prostatectomy was associated with less continence recovery and a lower potency rate 3, 6 and 12 months after surgery (p <0.001). CONCLUSIONS: In select patients with organ confined prostate cancer partial gland ablation offered good oncologic control with fewer adverse effects that required additional treatments. Potency and continence appeared to be better preserved after partial gland ablation.

Modified York Mason technique for repair of iatrogenic recto-urinary fistula: 20 years of the Montsouris experience.

PURPOSE: Iatrogenic recto-urinary fistulas are a disastrous complication of therapeutic interventions on the prostate. Many surgical approaches have been described to repair recto-urinary fistulas and no consensus has been reached regarding the better approach. The objective of this study is to present the results of our updated 20-year experience in the surgical management of recto-urinary fistula using a modified York Mason procedure. METHODS: We proceed to a retrospective single-institution review of surgically treated patients for iatrogenic recto-urinary fistulas between 1998 and 2017 by the modified York Mason technique. Descriptive analysis of our population was performed. Continuous and categorical variables were compared using Mann-Whitney and Fischer tests, respectively. All tests were two-sided with a significance level set at p value < 0.05. RESULTS: We included 30 consecutive patients treated for iatrogenic recto-urinary fistula. The median follow-up was 76 months (2-195). The median size of the fistula was 5 mm (2-20). Successful healing of the recto-urinary fistula was observed in 80, 97, and 100% of patients after 1, 2, or 3 York Mason procedure. During the study period, no one single case of acquired urinary incontinence or durable fecal incontinence has been observed. CONCLUSIONS: Our modified York Mason technique is a reliable and effective procedure with a 100% success rate for the repair of small iatrogenic recto-urinary fistulas in non-irradiated patients. It has a very low morbidity rate, and no case of postoperative urine or fecal incontinence has been observed.

Multiparametric MRI for Suspected Recurrent Prostate Cancer after HIFU:Is DCE still needed?

PURPOSE: To assess the added value of the dynamic contrast-enhanced sequence (DCE) to combination T2-weighted imaging (T2w) + diffusion-weighted imaging (DWI) in detecting prostate cancer (PCa) recurrence after HIFU (high-intensity focused ultrasound). METHODS: Forty-five males with clinical and biological suspected PCa recurrence were retrospectively selected. All underwent multi-parametric MRI (mpMRI) before biopsies. Two readers independently assigned a Likert score of cancer likelihood on T2w + DWI + DCE and T2w + DWI images. Prostatic biopsies were taken as the gold standard. RESULTS: Recurrent PCa was identified at biopsy for 37 patients (82%). Areas under the receiver-operating curve of T2w + DWI and T2w + DWI + DCE imaging were not significantly different for both readers. Using a Likert score ≥ 3 for the PCa diagnosis threshold, sensitivity at the lobe level for the (1) senior and (2) junior reader for T2w +DWI +DCE sensitivity was (1) 0.97 and (2) 0.94 vs. (1) 0.94 and (2) 0.97 for T2w + DWI. CONCLUSION: Accuracy of mpMRI was not significantly improved by adding DCE to T2w + DWI. Sensitivity was high for T2w + DWI + DCE and T2w + DWI with no significant difference for either the junior or senior reader. KEY POINTS: • MpMRI has the capability to detect PCa recurrence in post-HIFU monitoring. • The sensitivity of T2w and DWI for detecting PCa recurrence was not improved by DCE. • Readers with different degrees of experience did not improve their performance with DCE.

Biochemical recurrence after radical prostatectomy: what does it mean?

BACKGROUND: Radical prostatectomy (RP) has been used as the main primary treatment for prostate cancer (PCa) for many years with excellent oncologic results. However, approximately 20-40% of those patients has failed to RP and presented biochemical recurrence (BCR). Prostatic specific antigen (PSA) has been the pivotal tool for recurrence diagnosis, but there is no consensus about the best PSA threshold to define BCR until this moment. The natural history of BCR after surgical procedure is highly variable, but it is important to distinguish biochemical and clinical recurrence and to find the correct timing to start multimodal treatment strategy. Also, it is important to understand the role of each clinical and pathological feature of prostate cancer in BCR, progression to metastatic disease and cancer specific mortality (CSM). Review design: A simple review was made in Medline for articles written in English language about biochemical recurrence after radical prostatectomy. OBJECTIVE: To provide an updated assessment of BCR definition, its meaning, PCa natural history after BCR and the weight of each clinical/pathological feature and risk group classifications in BCR, metastatic disease and CSM.

Padeliporfin vascular-targeted photodynamic therapy versus active surveillance in men with low-risk prostate cancer (CLIN1001 PCM301): an open-label, phase 3, randomised controlled trial.

BACKGROUND: Vascular-targeted photodynamic therapy, a novel tissue-preserving treatment for low-risk prostate cancer, has shown favourable safety and efficacy results in single-arm phase 1 and 2 studies. We compared this treatment with the standard of care, active surveillance, in men with low-risk prostate cancer in a phase 3 trial. METHODS: This randomised controlled trial was done in 47 European university centres and community hospitals. Men with low-risk, localised prostate cancer (Gleason pattern 3) who had received no previous treatment were randomly assigned (1:1) to vascular-targeted photodynamic therapy (4 mg/kg padeliporfin intravenously over 10 min and optical fibres inserted into the prostate to cover the desired treatment zone and subsequent activation by laser light 753 nm with a fixed power of 150 mW/cm for 22 min 15 s) or active surveillance. Randomisation was done by a web-based allocation system stratified by centre with balanced blocks of two or four patients. Best practice for active surveillance at the time of study design was followed (ie, biopsy at 12-month intervals and prostate-specific antigen measurement and digital rectal examination at 3-month intervals). The co-primary endpoints were treatment failure (histological progression of cancer from low to moderate or high risk or death during 24 months' follow-up) and absence of definite cancer (absence of any histology result definitely positive for cancer at month 24). Analysis was by intention to treat. Treatment was open-label, but investigators assessing primary efficacy outcomes were masked to treatment allocation. This trial is registered with ClinicalTrials.gov, number NCT01310894. FINDINGS: Between March 8, 2011, and April 30, 2013, we randomly assigned 206 patients to vascular-targeted photodynamic therapy and 207 patients to active surveillance. Median follow-up was 24 months (IQR 24-25). The proportion of participants who had disease progression at month 24 was 58 (28%) of 206 in the vascular-targeted photodynamic therapy group compared with 120 (58%) of 207 in the active surveillance group (adjusted hazard ratio 0·34, 95% CI 0·24-0·46; p<0·0001). 101 (49%) men in the vascular-targeted photodynamic therapy group had a negative prostate biopsy result at 24 months post treatment compared with 28 (14%) men in the active surveillance group (adjusted risk ratio 3·67, 95% CI 2·53-5·33; p<0·0001). Vascular-targeted photodynamic therapy was well tolerated. The most common grade 3-4 adverse events were prostatitis (three [2%] in the vascular-targeted photodynamic therapy group vs one [<1%] in the active surveillance group), acute urinary retention (three [2%] vs one [<1%]) and erectile dysfunction (two [1%] vs three [1%]). The most common serious adverse event in the vascular-targeted photodynamic therapy group was retention of urine (15 patients; severe in three); this event resolved within 2 months in all patients. The most common serious adverse event in the active surveillance group was myocardial infarction (three patients). INTERPRETATION: Padeliporfin vascular-targeted photodynamic therapy is a safe, effective treatment for low-risk, localised prostate cancer. This treatment might allow more men to consider a tissue-preserving approach and defer or avoid radical therapy. FUNDING: Steba Biotech.

Effect of Prior Focal Therapy on Perioperative, Oncologic and Functional Outcomes of Salvage Robotic Assisted Radical Prostatectomy.

PURPOSE: We assessed the impact of focal therapy on perioperative, oncologic and functional outcomes in men who underwent salvage robotic assisted radical prostatectomy compared to primary robotic assisted radical prostatectomy. MATERIALS AND METHODS: Focal therapy was performed in patients presenting with Gleason score 3 + 3 or 3 + 4, clinical stage cT2a or less, serum prostate specific antigen 15 ng/ml or less, unilateral positive biopsy, maximum length of any positive core less than 10 mm and life expectancy greater than 10 years. Focal therapy was defined as target ablation of the index lesion plus a 1 cm safety margin in the normal ipsilateral prostatic parenchyma. The salvage group included 22 men who underwent salvage prostatectomy after focal therapy failure. The primary group was defined using matched pair 1:2 selection of 44 of 2,750 patients treated with primary prostatectomy. The primary and secondary end points were the between group differences in functional and oncologic outcomes, respectively. RESULTS: Complication rates were comparable (p >0.05). Pad-free probability was comparable between the groups at 1 and 2 years (p = 0.8). Recovery of erectile function was significantly lower after salvage robotic assisted radical prostatectomy (p = 0.008), which also showed a significantly lower probability of cumulative biochemical recurrence-free survival compared to primary robotic assisted radical prostatectomy (56.3% vs 92.4% at 2 years, p = 0.001). Salvage prostatectomy demonstrated a significantly increased risk of biochemical recurrence (HR 4.8, 95% CI 1.67-13.76, p = 0.004). Study limitations included the retrospective nature, the lack of randomization and the short followup. CONCLUSIONS: Salvage robotic assisted radical prostatectomy after focal therapy failure is feasible with acceptable complication rates. However, patients assigned to primary focal therapy should be advised about a poorer prognosis in terms of oncologic control and lower erectile recovery rates in case of a future salvage surgery.