Which protocol for prostate biopsies in patients with a positive MRI? Interest of systematic biopsies by sectors.

BACKGROUND: Current prostate biopsy (PBx) protocol for prostate cancer (PCa) diagnosis is to perform systematic biopsies (SBx) combined with targeted biopsies (TBx) in case of positive MRI (i.e. PI-RADS ≥ 3). To assess the utility of performing SBx in combination with TBx, we determined the added value of SBx brought to the diagnosis of PCa according to their sextant location and MRI target characteristics. METHODS: In our local prospectively collected database, we conducted a single-center retrospective study including all patients with a suspicion of PCa, who underwent transrectal ultrasound-guided (TRUS) prostate biopsies (PBx) with a prior MRI and a single lesion classified as PI-RADS ≥ 3. We have characterized the SBx according to their location on MRI: same sextant (S-SBx), adjacent sextant (A-SBx), ipsilateral side (I-SBx) and contralateral side (C-SBx). The added value of SBx and TBx was defined as any upgrading to significant PCa (csPCa) (ISUP ≥2). RESULTS: 371 patients were included in the study. The added value of SBx was 10% overall. Regarding the lesion location and the SBx sextant, the added value of SBx was: 5.1% for S-SBx, 5.4% for A-SBx, 4.9% for I-SBx and 1.9% for C-SBx. The overall added value of SBx was 6.8% for PI-RADS 3 lesions, 14% for PI-RADS 4 lesions and 6.7% for PI-RADS 5 lesions (p = 0.063). The added value of SBx for contralateral side was 1.9% (2/103), 3.1% (5/163) and 0% (0/105) for PI-RADS 3, PI-RADS 4 and PI-RADS 5 lesions, respectively (p = 0,4). The added value of SBx was lower when the number of TBx was higher (OR 0.57; CI 95% 0.37-0.85; p = 0.007). CONCLUSIONS: Our results suggest that the utility of performing SBx in the contralateral lobe toward the MRI lesion was very low, supporting that they might be avoided.

Impact of age on the Quadrella index assessing oncological and functional results after prostate brachytherapy: A 6-year analysis.

Purpose: As the oncological results of prostate brachytherapy (BT) are excellent for low-risk (LR) or favorable intermediate-risk (FIR) prostate cancer (PCa), evaluating the side effects has become a major issue, especially for young men. The objective of the study was to compare the oncologic and functional results of BT using Quadrella index for patients aged 60 or less compared with older patients. Material and methods: From June, 2007 to June, 2017, 222 patients, including 70 ≤ 60 years old and 152 > 60 years old, underwent BT for LR-FIR PCa, with good erectile function at baseline according to International Index of Erectile Function-5 (IIEF-5) > 16. Quadrella index was achieved under the following circumstances: 1) Absence of biological recurrence (Phoenix criteria); 2) Absence of erectile dysfunction (ED) (IIEF-5 > 16); 3) No urinary toxicity (international prostate score symptom) IPSS < 15 or IPSS > 15, and ΔIPSS < 5; 4) No rectal toxicity (RT) (Radiation Therapy Oncology Group, RTOG = 0). Patients were treated on demand with phosphodiesterase inhibitors (PDE5i) post-operatively. Results: The Quadrella index was satisfied for about 40-80% of patients ≤ 60 years vs. 33-46% for older patients during 6-year follow-up (significant difference from the second year). At year 5, 100% of evaluable patients aged ≤ 60 and 91.8% > 60 (p = 0.29) reached Phoenix criteria. The criterion of ED (IIEF-5 < 16) largely explained the validity rate of Quadrella alone. There was no ED for 67.2-81.4% of patients ≤ 60 years compared with 40.0-56.1% for patients > 60 (significant difference since year 4 in favor of young men). After two years of follow-up, more than 90% of patients in both the groups showed neither urinary nor rectal toxicities. Conclusions: For young men displaying LR-FIR PCa, BT appears to be a first-class therapeutic option, as the oncological results were at least equivalent to those of older patients with good long-term tolerance.

Prognostic significance of PI-RADS 5 lesions in patients treated by radical prostatectomy.

PURPOSE: To analyse the pathological features and survival of patients with a PI-RADS 5 lesion on pre-biopsy MRI. METHODS: We extracted from a European multicentre prospectively gathered database the data of patients with a PI-RADS 5 lesion on pre-biopsy MRI, diagnosed using both systematic and targeted biopsies and subsequently treated by radical prostatectomy. The Kaplan-Meier model was used to assess the biochemical-free survival of the whole cohort and univariable and multivariable Cox models were set up to study factors associated with survival. RESULTS: Between 2013 and 2019, 539 consecutive patients with a PI-RADS 5 lesion on pre-biopsy MRI were treated by radical prostatectomy and included in the analysis. Follow-up data were available for 448 patients. Radical prostatectomy and lymph node dissection specimens showed non-organ confined disease in 297/539 (55%), (including 2 patients with a locally staged pT2 lesion and lymph node involvement (LNI)). With a median follow-up of 25 months (12-39), the median biochemical recurrence-free survival was 54% at 2 years (95% CI 45-61) and 28% at 5 years (95% CI 18-39). Among the factors studied, MRI T stage [T3a vs T2 HR 3.57 (95%CI 1.78-7.16); T3b vs T2 HR 6.17 (95% CI 2.99-12.72)] and PSA density (HR 4.47 95% CI 1.55-12.89) were significantly associated with a higher risk of biochemical recurrence in multivariable analysis. CONCLUSION: Patients with a PI-RADS 5 lesion on pre-biopsy MRI have a high risk of early biochemical recurrence after radical prostatectomy. MRI T stage and PSA density can be used to improve patient selection and counselling.

An automated landmark method to describe geometric changes in the human mandible during growth.

OBJECTIVE: The principal aim of this study was to assess an automatic landmarking approach to human mandibles based on the atlas method. The secondary aim was to identify the areas of greatest variation in the mandibles of middle-aged to older adults. DESIGN: Our sample consisted of 160 mandibles from computed tomography scans of 80 men and 80 women aged between 40 and 79 years. Eleven anatomical landmarks were placed manually on mandibles. The automated landmarking through point cloud alignment and correspondence (ALPACA) method implemented in 3D Slicer was used to automatically place landmarks to all meshes. Euclidean distances, normalized centroid size, and Procrustes ANOVA were calculated for both methods. A pseudo-landmarks approach was followed using ALPACA to identify areas of changes among our sample. RESULTS: The ALPACA method showed significant differences in Euclidean distances for all landmarks compared to the manual method. A mean Euclidean distance of 1.7 mm was found for the ALPACA method and 0.99 mm for the manual method. Both methods found that sex, age, and size had a significant effect on mandibular shape. The greatest variations were observed in the condyle, ramus, and symphysis regions. CONCLUSION: The results obtained using the ALPACA method are acceptable and promising. This approach can automatically place landmarks with an average accuracy of less than 2 mm, which may be sufficient in most anthropometric analyses. In the light of our results, however, odontological application such as occlusal analysis is not recommended.

Direct comparison between Grade Group assessed on systematic and MRI/ultrasound fusion targeted biopsies correlated to the radical prostatectomy specimens in patients with prostate cancer.

OBJECTIVES: To compare the correlation of Gleason score (GS) and ISUP grade determined by prostate biopsies (PBx) and radical prostatectomy (RP) specimens according to the biopsy technique: ultrasound randomised (RBx) vs. MRI/ultrasound fusion targeted (TBx). MATERIALS AND METHODS: Between March 2013 and June 2018, we retrospectively included patients who underwent RP for prostate cancer (PCa) histopathologically proven by RBx and/or TBx. All patients had a prebiopsy MRI by a single radiologist (using PI-RADS score), then transrectal RBx (12cores, blinded to MRI lesions) and TBx (2-4 cores/target) with elastic MRI/ultrasound fusion (UroStation™, Koelis, Grenoble, France). Histological findings were compared: PBx vs. RP. RESULTS: One hundred and four patients underwent RP after RBx and/or TBx. ISUP concordance rate was better with the association RBx+TBx 49% (51/104) vs. 43.3% with TBx (P=0.07) and 43.3% with RBx (P=0.13). With RBx, 50% of the patients were downgraded (52/104) against 42.3% (44/104) with TBx (P=0.088). The association RBx+TBx significantly decreased the rate of downgrading of the ISUP score compared to the ISUP score of RP 35.6% (37/104) vs. RBx (50%, P=0.0001) and vs. TBx (42.3%, P=0.016). CONCLUSION: In half of cases, the ISUP score was underestimated in RBx compared to RP specimens. Adding TBx to RBx significantly reduced downgrading. The combination of both biopsy techniques appeared to be the best protocol to get closer to ISUP score and GS of the RP specimens. LEVEL OF EVIDENCE: C.

[Practice of French urologists concerning the checklist of the operating room]. / Les pratiques professionnelles des chirurgiens urologues en France concernant la check-list au bloc opératoire.

INTRODUCTION: In 2018, the French High Authority of Health (HAS) included a "time-out" phase in the latest version of the checklist for the operating room in order to improve the safety of operated patients. The aim of this study is to evaluate the practice of French urologists concerning the check list (CL) of the operating room. MATERIAL AND METHODS: A survey of 30 items was developed by the committee of accreditation of the French Association of Urology (AFU) and other contributors. It was centered on the characteristics of the urologists, the details of application of the CL, and the evaluation of the current version. After validation, the questionnaire was emailed as an online form in July 2021 for all the members of the AFU and AFUF. RESULTS: Overall, 369 form the 1700 contacted urologists responded to the survey. The majority were more than 40 years old (70.11%) and less than 20 year of experience (54.49%). The engagement in individual or team accreditation was observed in 222 (60.7%) and 145 (39.84%) urologists, respectively. Almost half of them were present at the beginning of the CL (47.18%), and prescribed postoperative medication with the anesthesiologist (55.56%). The CL has modified the practice in 47.54%, however, with greater administrative burden, and 80% preferred that the AFU adapts the CL to the urology field. CONCLUSION: The practice of CL between urologists is variable. On multivariate analysis, the engagement in team accreditation was the only variable to influence the practice of time out.

[Morbidity of extended pelvic lymphadenectomy during robot-assisted laparoscopic prostatectomy for localized cancer prostate]. / Morbidité du curage ganglionnaire pelvien étendu au cours de la prostatectomie totale laparoscopique robot assistée.

OBJECTIVES: To assess the morbidity specific of extended pelvic lymphadenectomy during robot-assisted laparoscopic radical prostatectomy in a 8 year retrospective study. MATERIAL: We carried out a single-center, single-surgeon retrospective study on 342 consecutive patients who underwent a robot-assisted laparoscopic radical prostatectomy and extended pelvic lymphadenectomy, from July 2010 to March 2018. Postoperative complications were recorded up to 3 months after the operation. RESULTS: Thirty (8.8%) patients had at least one complication related to lymphadenectomy including 1 vascular injury (0.3%), 7 injuries of the obturator nerve (2%), 5 venous thromboembolic complications (1.5%) including 4 pulmonary embolisms, 10 symptomatic lymphoceles (2.9%) and 8 lymphoedemas (2.3%). Of these complications, 13 were classified Clavien 1 (43.3%), 8 Clavien 2 (26.7%), 7 Clavien 3a (23.3%) and 2 Clavien 3b (6.7%). In univariate analysis a high age (P=0.04), high BMI (P<0.01) and pT stage (P=0.02) were significantly associated with complication whereas in multivariate analysis, only age (P=0.02) and BMI (P<0.01) lived were. In univariate analysis high BMI (P=0.04) and lymph node involvement (P=0.04) were associated with lymphatic complication. We did not find any other specific risk factor for the other complications. CONCLUSION: With 8.8% of overall complications related to lymphadenectomy and 5% of complication classified Clavien grade 2 or higher, extended pelvic lymphadenectomy was not very morbid. Age and BMI were risk factors for a overall complication. BMI and lymph node involvement were risk factors for lymphatic complications. LEVEL OF PROOF: 4.

[De novo or secondary metastatic prostate cancer management in France: Observational study from "sentinel multidisciplinary meeting" of the French Association of Urology]. / Prise en charge des cancers de la prostate métastatiques synchrones et métachrones en France : étude observationnelle à partir des « RCP sentinelles ¼ de l'AFU.

INTRODUCTION: Metastatic prostate cancer (mPCa) is an heterogeneous disease. Metachronous mPCa (MM) seems to have a better prognosis than synchronous mPCa (SM). However, it is difficult to analyze their specificities from national registries. Data from the so-called "sentinel multidisciplinary meeting" (SMDM) would represent a "real life" data collection. The objective of this national pilot study was to evaluate the concept of SMDM through the description and comparison of the diagnosis, management and follow-up of patients with synchronous or metachronous mPCa in 2018. METHODS: A survey covering clinical, biological, radiological data as well as treatment initiated and follow-up at 3 and 6 months was sent to the SMDM. All patients diagnosed with metastatic disease (SM or MM) between 01/01/2018 and 11/30/2018 were included. RESULTS: In total, 780 patients from 39 centers were included, 408 SM and 372 MM. SM were more symptomatic and had a higher metastatic burden than MM. PET were mostly performed in MM without a prior standard staging. SM patients received more chemotherapy than MM patients whereas new generation androgen deprivation therapy was mostly given to MM patients. At 6 months, there were no more significant difference in clinical presentation between the two groups. CONCLUSION: Specificities of SM and MM patients in terms of clinical presentation, metastatic burden and management were described, validating the concept of SMDM as a source of reliable informations.

Root and canal morphology of the permanent teeth in medieval and current French population.

OBJECTIVE: This work describes and compares the root and root canal morphology of a medieval population dating from the 8th to 10th century from the southwest of France, and a current French population. DESIGN: The root morphology of 579 teeth from 70 medieval individuals was analyzed using cone beam computed tomography, and compared with 690 teeth from a current French population of 329 individuals. The Vertucci classification was used to describe the root canal configuration. RESULTS: In the medieval population, the maxillary first premolar usually had one root. In contrast, in the current population this tooth predominantly had two roots, and the three-root form had appeared. Mandibular canine with two roots was observed in 5.7% of cases, and in the current population this form was found in 1.6% but the difference was not significative. The greatest variability between the two populations in terms of root canal configuration was in one-rooted maxillary first and second premolars, the mandibular canines, and the distal roots of the mandibular first molars. Differences in root numbers and canal configurations of the maxillary molars investigated among the two populations were not significant. CONCLUSIONS: This study indicated that the upper first premolar of the current population tended to have more than one root, while this tooth type of the medieval group mostly appeared with only one. For the root canal configuration, studies in the upper premolars, lower canines and first molars of the current population apparently revealed a significant simplification compared with the ancient group.

The Archean origin of oxygenic photosynthesis and extant cyanobacterial lineages.

The record of the coevolution of oxygenic phototrophs and the environment is preserved in three forms: genomes of modern organisms, diverse geochemical signals of surface oxidation and diagnostic Proterozoic microfossils. When calibrated by fossils, genomic data form the basis of molecular clock analyses. However, different interpretations of the geochemical record, fossil calibrations and evolutionary models produce a wide range of age estimates that are often conflicting. Here, we show that multiple interpretations of the cyanobacterial fossil record are consistent with an Archean origin of crown-group Cyanobacteria. We further show that incorporating relative dating information from horizontal gene transfers greatly improves the precision of these age estimates, by both providing a novel empirical criterion for selecting evolutionary models, and increasing the stringency of sampling of posterior age estimates. Independent of any geochemical evidence or hypotheses, these results support oxygenic photosynthesis evolving at least several hundred million years before the Great Oxygenation Event (GOE), a rapid diversification of major cyanobacterial lineages around the time of the GOE, and a post-Cryogenian origin of extant marine picocyanobacterial diversity.

Prognostic factors after adrenalectomy for adrenal metastasis.

PURPOSE: Very few studies have sought prognostic factors after adrenalectomy for metastasis. The aim of this study was to assess prognostic factors for oncological outcomes after adrenalectomy for adrenal metastasis. METHODS: All adrenalectomies for metastases performed in seven centers between 2006 and 2016 were included in a retrospective study. Recurrence-free survival (RFS) and cancer-specific survival (CSS) were estimated using the Kaplan-Meier method. Prognostic factors for CSS and RFS were sought by Cox regression analyses. RESULTS: 106 patients were included. The primary tumors were mostly renal (47.7%) and pulmonary (32.3%). RFS and CSS estimated rates at 5 years were 20.7% and 63.7%, respectively. In univariate analysis, tumor size (HR 3.83; p = 0.04) and the metastasis timing (synchronous vs. metachronous; HR 0.47; p = 0.02) were associated with RFS. In multivariate analysis, tumor size (HR 8.28; p = 0.01) and metastasis timing (HR 18.60; p = 0.002) were significant factors for RFS. In univariate analysis, the renal origin of the primary tumor (HR 0.1; p < 0.001) and the disease-free interval (DFI; HR 0.12; p = 0.02) were associated with better CSS, positive surgical margins with poorer CSS (HR 3.4; p = 0.01). In multivariate analysis, the renal origin of the primary tumor vs. pulmonary (HR 0.13; p = 0.03) and vs. other origins (HR 0.10; p = 00.4) and the DFI (HR 0.01; p = 0.009) were prognostic factors for CSS. CONCLUSION: In this study, tumor size and synchronous occurrence of the adrenal metastasis were associated with poorer RFS. Renal origin of the primary tumor and longer DFI were associated with better CSS. These prognostic factors might help for treatment decision in the management of adrenal metastasis.

[Recommendations CCAFU on the management of cancers of the urogenital system during an epidemic with Coronavirus COVID-19]. / Recommandations CCAFU sur la prise en charge des cancers de l'appareil urogénital en période d'épidémie au Coronavirus COVID-19.

AIM: The French population is facing the COVID-19 pandemic and the health system have been reoriented in emergency for the care of patients with coronavirus. The management of cancers of the urinary and male genital tracts must be adapted to this context. MATERIAL AND METHOD: An expert opinion documented by a literature review was formulated by the Cancerology Committee of the French Association of Urology (CCAFU). RESULTS: The medical and surgical management of patients with any cancers of the urinary and male genital tracts must be adapted by modifying the consultation methods, by prioritizing interventions according to the intrinsic prognosis of cancers, taking into account the patient's comorbidities. The protection of urologists from COVID-19 must be considered. CONCLUSION: The CCAFU issues an expert opinion on the measure to be taken to adapt the management of cancers of the male urinary and genital tract to the context of pandemic by COVID-19.

Three-dimensional analysis of bitemarks: A validation study using an intraoral scanner.

Conservation of the three-dimensional aspect of bitemarks optimizes their analysis. Although bitemarks could be recorded with a surface scanner, in clinical dentistry, intraoral scanners are used as an alternative to conventional dental impressions. Here we assess the reproducibility and the reliability of a three-dimensional bitemark analysis protocol using an intraoral scanner. Twenty-seven volunteers bit on different materials: dental wax, hard cheese, chocolate and apple. Then, bitemarks and dentitions were scanned with the PlanMeca® Emerald intraoral scanner and the scans obtained were exported into the mesh comparison software, CloudCompare®, which can generate overlays automatically. For this purpose, dentitions were aligned and compared with the indentations. The meshing and non-meshing areas were visualized using a colorimetric scale. First, the same blinded observer compared the bitten materials by analyzing 256 meshing areas for each. Secondly, comparisons of bitemarks from wax were analyzed in a randomized blinded study involving four observers (dentist, dental student, forensic scientist and police officer) and predictive values were calculated. The wax support obtained the best result and apple the worst. The rate of correct classifications was high and misclassification was rare. For the all observers, negative predictive values were near 100%. Positive predictive values were more variable. Moreover, the work clearly highlighted the importance of experience in odontology.

Overexpression of certain transient receptor potential and Orai channels in prostate cancer is associated with decreased risk of systemic recurrence after radical prostatectomy.

BACKGROUND: Several studies had suggested the potential role of calcium signaling in prostate cancer (PCa) prognosis and agressiveness. We aimed to investigate selected proteins contributing to calcium (Ca2+ ) signaling, (Orai, stromal interaction molecule (STIM), and transient receptor potential (TRP) channels) and involved in cancer hallmarks, as independent predictors of systemic recurrence after radical prostatectomy (RP). METHODS: A case-control study including 112 patients with clinically localized PCa treated by RP between 2002 and 2009 and with at least 6-years' follow-up. Patients were divided into two groups according to the absence or presence of systemic recurrence. Expression levels of 10 proteins involved in Ca2+ signaling (TRPC1, TRPC4, TRPV5, TRPV6, TRPM8, STIM1, STIM2, Orai1, Orai2, and Orai3), were assessed by immunohistochemistry using tissue microarrays (TMAs) constructed from paraffin-embedded PCa specimens. The level of expression of the various transcripts in PCa was assessed using quantitative polymerase chain reaction (qPCR) analysis. RNA samples for qPCR were obtained from fresh frozen tissue samples of PCa after laser capture microdissection on RP specimens. Relative gene expression was analyzed using the 2-▵▵Ct method. RESULTS: Multivariate analysis showed that increased expression of TRPC1, TRPC4, TRPV5, TRPV6, TRPM8, and Orai2 was significantly associated with a lower risk of systemic recurrence after RP, independently of the prostate-specific antigen (PSA) level, percentage of positive biopsies, and surgical margin (SM) status (P = .007, P = .01, P < .001, P = .0065, P = .007, and P = .01, respectively). For TRPC4, TRPV5, and TRPV6, this association was also independent of Gleason score and pT stage. Moreover, overexpression of TRPV6 and Orai2 was significantly associated with longer time to recurrence after RP (P = .048 and .023, respectively). Overexpression of TRPC4, TRPV5, TRPV6, and Orai2 transcripts was observed in group R- (3.71-, 5.7-, 1.14-, and 2.65-fold increase, respectively). CONCLUSIONS: This is the first study to suggest the independent prognostic value of certain proteins involved in Ca2+ influx in systemic recurrence after RP: overexpression of TRPC1, TRPC4, TRPV5, TRPV6, TRPM8, and Orai2 is associated with a lower risk of systemic recurrence. TRPC4, TRPV5, and TRPV6 appear to be particularly interesting, as they are independent of the five commonly used predictive factors, that is, PSA, percentage of positive biopsies, SM status, Gleason score, and pT stage.

[Robotic-assisted laparoscopic implantation of artificial urinary sphincter AMS 800® in woman: Single center experience]. / Implantation du sphincter artificiel AMS 800® chez la femme par cœlioscopie robot-assistée : expérience monocentrique.

INTRODUCTION: Artificial urinary sphincter (AUS) is the treatment of last resort of stress urinary incontinence (UI) due to intrinsic sphincter deficiency (IS). The implantation procedure has been described by open surgery and laparoscopy with a significative rate of complication by Lucas et al. (2012) and Costa et al. (2001). We report our experience of implantation of SUA by robotic-assisted laparoscopy (R-SUA) in 17 patients among 3 revisions. MATERIAL AND METHODS: Between 2012 and 2017, 17 patients have been consecutively included. The surgical technique was described by Fournier et al. The continence was defined by the absence of urine leakage. RESULTS: The median age at implantation was 66,8±7 years, in the primo-implantation (PI) group, one patient had a neurological acontractile bladder, and bladder was open in 11 patients (78,6%) to ensure the bladder neck dissection. In the revision group (R) 3 patients had a complete replacement of SUA for mechanical failure. One vaginal bound was reported, but did not compromise the implantation, and the survival of SUA. Duration of intervention, size of cuff, postoperative catheterization and hospitalization time were respectively 205±34 and 112±8min; 7,7±0.9 and 5.2±0.8cm; 5.9±2.1 and 4.3±4 days; 6.6±1.5 and 7±3.6 days for PI and R groups. At the end of a mean follow-up of 24.6±18.4 and 59±5 months, continence was respectively 86% and 100%, for the PI and R groups. CONCLUSION: The implantation of R-SUA was feasible and safe with encouraging results. Other studies must evaluate the place of R-SUA among the different enabled surgical techniques. LEVEL OF EVIDENCE: 4.

Comprehensive molecular classification of localized prostate adenocarcinoma reveals a tumour subtype predictive of non-aggressive disease.

Background: Management of localized prostate cancer (PCa) is a major clinical challenge since most of these cancers would not evolve but a majority of patients will still undergo a life-changing radical surgery. Molecular studies have shown that PCa can be classified according to their genomic alterations but none of the published PCa molecular classifications could identify a subtype corresponding to non-evolutive tumours. Materials and methods: Multi-omics molecular profiling was carried out on post-radical prostatectomy material from a cohort of 130 patients with localized PCa. We used unsupervised classification techniques to build a comprehensive classification of prostate tumours based on three molecular levels: DNA copy number, DNA methylation, and mRNA expression. Merged data from our cohort and The Cancer Genome Atlas cohort were used to characterize the resulting tumour subtypes. We measured subtype-associated risks of biochemical relapse using Cox regression models and survival data from five cohorts including the two aforementioned. Results: We describe three PCa molecular subtypes associated with specific molecular characteristics and different clinical outcomes. Particularly, one subtype was strongly associated with the absence of biochemical recurrence. We validated this finding on 746 samples from 5 distinct cohorts (P = 3.41 × 10-8, N = 746 tumour samples), and showed that our subtyping approach outperformed the most popular prognostic molecular signatures to accurately identify a subset of patients with a non-evolutive disease. We provide a set of 36 transcriptomic biomarkers to robustly identify this subtype of non-evolutive cases whose prevalence was estimated to 22% of all localized PCa tumours. Conclusion: At least 20% of patients with localized PCa can be accurately predicted to have a non-evolutive disease on the basis of their molecular subtype. Those patients should not undergo immediate surgery and rather be placed under active surveillance.

Dating phototrophic microbial lineages with reticulate gene histories.

Phototrophic bacteria are among the most biogeochemically significant organisms on Earth and are physiologically related through the use of reaction centers to collect photons for energy metabolism. However, the major phototrophic lineages are not closely related to one another in bacterial phylogeny, and the origins of their respective photosynthetic machinery remain obscured by time and low sequence similarity. To better understand the co-evolution of Cyanobacteria and other ancient anoxygenic phototrophic lineages with respect to geologic time, we designed and implemented a variety of molecular clocks that use horizontal gene transfer (HGT) as additional, relative constraints. These HGT constraints improve the precision of phototroph divergence date estimates and indicate that stem green non-sulfur bacteria are likely the oldest phototrophic lineage. Concurrently, crown Cyanobacteria age estimates ranged from 2.2 Ga to 2.7 Ga, with stem Cyanobacteria diverging ~2.8 Ga. These estimates provide a several hundred Ma window for oxygenic photosynthesis to evolve prior to the Great Oxidation Event (GOE) ~2.3 Ga. In all models, crown green sulfur bacteria diversify after the loss of the banded iron formations from the sedimentary record (~1.8 Ga) and may indicate the expansion of the lineage into a new ecological niche following the GOE. Our date estimates also provide a timeline to investigate the temporal feasibility of different photosystem HGT events between phototrophic lineages. Using this approach, we infer that stem Cyanobacteria are unlikely to be the recipient of an HGT of photosystem I proteins from green sulfur bacteria but could still have been either the HGT donor or the recipient of photosystem II proteins with green non-sulfur bacteria, prior to the GOE. Together, these results indicate that HGT-constrained molecular clocks are useful tools for the evaluation of various geological and evolutionary hypotheses, using the evolutionary histories of both genes and organismal lineages.