The impact of mpMRI-targeted vs systematic biopsy on the risk of prostate cancer downgrading at final pathology.

PURPOSE: Although targeted biopsies (TBx) are associated with improved disease assessment, concerns have been raised regarding the risk of prostate cancer (PCa) overgrading due to more accurate biopsy core deployment in the index lesion. METHODS: We identified 1672 patients treated with radical prostatectomy (RP) with a positive mpMRI and ISUP ≥ 2 PCa detected via systematic biopsy (SBx) plus TBx. We compared downgrading rates at RP (ISUP 4-5, 3, and 2 at biopsy, to a lower ISUP) for PCa detected via SBx only (group 1), via TBx only (group 2), and eventually for PCa detected with the same ISUP 2-5 at both SBx and TBx (group 3), using multivariable logistic regression models (MVA). RESULTS: Overall, 12 vs 14 vs 6% (n = 176 vs 227 vs 96) downgrading rates were recorded in group 1 vs group 2 vs group 3, respectively (p < 0.001). At MVA, group 2 was more likely to be downgraded (OR 1.26, p = 0.04), as compared to group 1. Conversely, group 3 was less likely to be downgraded at RP (OR 0.42, p < 0.001). CONCLUSIONS: Downgrading rates are highest when PCa is present in TBx only and, especially when the highest grade PCa is diagnosed by TBx cores only. Conversely, downgrading rates are lowest when PCa is identified with the same ISUP through both SBx and TBx. The presence of clinically significant disease at SBx + TBx may indicate a more reliable assessment of the disease at the time of biopsy potentially reducing the risk of downgrading at final pathology.

Significant prostate cancer risk after MRI-guided biopsy showing benign findings: Results from a cohort of 381 men.

BACKGROUND: MRI-guided biopsy (MGB) contributes to the diagnosis of clinically significant Prostate Cancer (csPCa). However, there are no clear recommendations for the management of men after a negative MGB. The aim of this study was to assess the risk of csPCa after a first negative MGB. METHODS: Between 2014 and 2020, we selected men with a PI-RADS score ≥ 3 on MRI and a negative MGB (showing benign findings) performed for suspected prostate cancer. MGB (targeted and systematic biopsies) was performed using fully integrated mobile fusion imaging (KOELIS). The primary endpoint was the rate of csPCa (defined as an ISUP grade ≥ 2) diagnosed after a first negative MGB. RESULTS: A total of 381 men with a negative MGB and a median age of 65 (IQR: 59-69, range: 46-85) years were included. During the median follow-up of 31 months, 124 men (32.5%) had a new MRI, and 76 (19.9%) were referred for a new MGB, which revealed csPCa in 16 (4.2%) of them. We found no statistical difference in the characteristics of men diagnosed with csPCa compared with men with no csPCa after the second MGB. CONCLUSION: We observed a risk of significant prostate cancer in 4% of men two years after a negative MRI-guided biopsy. Performing a repeat MRI could improve the selection of men who will benefit from a repeat MRI-guided biopsy, but a clear protocol is needed to follow these patients.

Endoscopic enucleation for prostate larger than 60 mL: comparison between holmium laser enucleation and plasmakinetic enucleation.

PURPOSE: To compare perioperative and functional outcomes of two different energy sources, holmium laser and bipolar current for endoscopic enucleation of prostate larger than 60 mL. METHODS: A prospective, monocentric, comparative, non-randomized study was conducted including all patients treated for prostate larger than 60 mL, measured by transrectal ultrasound. Patients were assigned to each group based on the surgeons' practice. Perioperative data were collected (preoperative characteristics, operating, catheterization and hospitalization times, hemoglobin loss, complications) and functional outcomes (IPSS, IPSS Quality of Life (QoL), PSA) at 3 months and 1 year. RESULTS: 100 patients were included in each group from October 2015 to March 2018. No differences between HoLEP and plasma groups were observed at baseline, except for mean IPSS score, IPSS QoL score and preoperative PVR that were significantly higher in the HoLEP group. Operating time (142.1 vs 122.4 min; p = 0.01), catheterization time (59.6 vs 44.4 h; p = 0.01) and hospitalization time (2.5 vs 1.8 days; p = 0.02) were significantly shorter in the plasma group. Complication and transfusion rate were no significantly different between HoLEP and plasma. No significant differences were observed concerning functional outcomes at 3 months and 1 year. The urinary incontinence rate was higher 21.1% vs 6.4% (p < 0.01) at 3 months in HoLEP group, but no difference was observed at 1 year. CONCLUSION: Holmium and plasma are both safe and effective for endoscopic treatment for prostate larger than 60 mL. Operating, catheterization and hospitalization times were significantly shorter in the plasma group. The complication rate and functional outcomes were not significantly different.

Contamination in control group led to no effect of PSA-based screening on prostate cancer mortality at 9 years follow-up: Results of the French section of European Randomized Study of Screening for Prostate Cancer (ERSPC).

INTRODUCTION: European Randomized Study of Screening for Prostate Cancer (ERSPC) mortality results were reported for 7 European countries (excluding France) and showed a significant reduction in Prostate cancer (PCa) mortality. As those results have not been part of the global ERSPC results, it is of interest to report PCa mortality at a median follow-up of 9 years for French section of ERSPC. MATERIAL AND METHODS: Two administrative departments were involved in the study. Only men after randomization in the screening group were invited by mail to be screened by PSA testing with two rounds at 4-6 year intervals. Biopsy was recommended if PSA>=3.0 ng/mL. No information other that the French Association of Urology recommandations on the use of PSA was offered to the control group (own decision of physicians and patients). Follow up was based on cancer registry database. Contamination defined as the receipt of PSA testing in control arm was measured. Poisson regression models were used to estimate the Rate Ratio (RR) of PCa mortality and incidence in the screening vs. control arm. RESULTS: Starting from 2003, 80,696 men aged 55-69 years were included. The percentage of men in the screening arm with at least one PSA test (compliance) was 31%. Compared to the control arm, PCa incidence increased by 10% in the screening arm (RR=1.10; 95% CI=[1.04-1.16], P=0.001), but PCa mortality did not differ (0.222 and 0.215 deaths/1000 person-years; RR=1.03[0.75-1.42], P=0.9). DISCUSSION: Limitations include low participation rate. PSA testing in the control arm was observed in 32% of men (contamination). CONCLUSIONS: Contamination in control group led to no effect of PSA-based screening on prostate cancer mortality at 9 years follow-up. LEVEL OF EVIDENCE: 3.

Can We Predict Morbidity and Mortality of Patients Aged 75 Years and Older Undergoing Cystectomy?

Radical cystectomy is associated with a high postoperative mortality and morbidity in older patients. We aimed to define the predictive value of comorbidity scores and determine the prognostic factors of postoperative complications. Preoperative associated morbidities were collected and graded according to the American Society of Anesthesiologists (ASA) score system, the Adult Comorbidity Evaluation (ACE) scale and the Charlson comorbidity index. Surgical complications were graded according to Clavien classification. Early and late complications were recorded. Data are from 49 consecutive patients aged ≥ 75 years who had an open surgery for bladder cancer. The most commonly associated conditions were smoking, renal insufficiency, and arterial hypertension. Incidence of early and late complications was 49% and 16%, respectively. Four and 25 death events occurred during the early and late follow-up, respectively. The incidence of morbidity and mortality were not related to ASA, ACE or Charlson scores. Preoperative malnutrition, renal insufficiency, higher need of perioperative blood transfusions, and prolonged ileus were identified as risk factors of postoperative morbidity. Late complications seemed related to low weight.

MRI evaluation following partial HIFU therapy for localized prostate cancer: A single-center study.

OBJECTIVE: To evaluate the value of MRI for surveillance of primary hemi-HIFU therapy for localized PCa in a single-center. PATIENTS AND METHODS: Patients with localized prostate cancer were treated with hemi-HIFU from October 2009 to March 2014. All patients performed MRI before focal therapy, the reader was blinded to the treatment. Oncological failure was defined as positive biopsy or biochemical recurrence (Phoenix). RESULTS: Twenty-five patients were treated with hemi-HIFU in one center. The median nadir PSA was 1.45±1.4ng/mL. Prostate volume decreased from 45 cc to 25 cc on MRI findings. At 20 months, none of the patients had histological recurrence. Biochemical-free survival rate was 88%. MRI evaluation had a negative predictive value of 100% on the treated area and 81% on the untreated area. PSAd≥0.1ng/mL(2) was a predictive factor for cancer on untreated area (P=0.042). CONCLUSION: MRI control at 6 months is a potentially effective evaluation of treated area after hemi-HIFU and may replace randomized biopsies if PSAd<0.1ng/mL(2) during follow-up. LEVEL OF EVIDENCE: 4.

Essential role for SphK1/S1P signaling to regulate hypoxia-inducible factor 2α expression and activity in cancer.

The sphingosine kinase-1/sphingosine 1-phosphate (SphK1/S1P) signaling pathway has been reported to modulate the expression of the canonical transcription factor hypoxia-inducible HIF-1α in multiple cell lineages. HIF-2α is also frequently overexpressed in solid tumors but its role has been mostly studied in clear cell renal cell carcinoma (ccRCC), the most common form of kidney cancer, where HIF-2α has been established as a driver of a more aggressive disease. In this study, the role of SphK1/S1P signaling with regard to HIF-2α was investigated in various cancer cell models including ccRCC cells. Under hypoxic conditions or in ccRCC lacking a functional von Hippel-Lindau (VHL) gene and expressing high levels of HIF-2α, SphK1 activity controls HIF-2α expression and transcriptional activity through a phospholipase D (PLD)-driven mechanism. SphK1 silencing promotes a VHL-independent HIF-2α loss of expression and activity and reduces cell proliferation in ccRCC. Importantly, downregulation of SphK1 is associated with impaired Akt and mTOR signaling in ccRCC. Taking advantage of a monoclonal antibody neutralizing extracellular S1P, we show that inhibition of S1P extracellular signaling blocks HIF-2α accumulation in ccRCC cell lines, an effect mimicked when the S1P transporter Spns2 or the S1P receptor 1 (S1P1) is silenced. Here, we report the first evidence that the SphK1/S1P signaling pathway regulates the transcription factor hypoxia-inducible HIF-2α in diverse cancer cell lineages notably ccRCC, where HIF-2α has been established as a driver of a more aggressive disease. These findings demonstrate that SphK1/S1P signaling may act as a canonical regulator of HIF-2α expression in ccRCC, giving support to its inhibition as a therapeutic strategy that could contribute to reduce HIF-2 activity in ccRCC.

[Mechanisms of castration resistance: Intratumoral hypoxia stimulates the androgen receptor expression]. / Mécanismes de résistance à la castration : l'hypoxie intratumorale stimule l'expression du récepteur aux androgènes.

PURPOSE: Tumor hypoxia and its biological consequence lead to microenvironment adaptation of tumor initiation, promotion and progression. The aim of the study was to observe the influence of hypoxia on the expression of the androgen receptor (AR), using an original model of multicellular spheroids obtained from castration-resistant prostate tumor cells. MATERIAL: Two human castration-resistant prostate cancer cell lines have been used to generate multicellular tumor spheroids (MTS). The conditions and duration of incubation modulated the final size of the MTS and the intrinsic hypoxia gradient. The expression of AR was studied by immunohistochemistry (IHC) and secretion of PSA measured in the culture medium. RESULTS: The IHC expression of AR was characterized by a decreasing gradient from the periphery to the center of MTS (less intense in central hypoxic zone), corresponding to a nuclear translocation of activated AR. This result was proportionally correlated with the duration of hypoxic incubation period. Hypoxia caused significant increase in AR expression at 6h of oxygen deprivation. This activation of AR was correlated with transcriptional activity increase of target genes, including increased secretion of PSA. CONCLUSION: This demonstration of activation, increased expression and increased transcriptional activity of AR by hypoxia is the first to have been made with an original model of hypoxia, closer to reality than previous models, i.e. close to tissue hypoxia observed in primary prostate cancer. LEVEL OF EVIDENCE: 4.

[Treatment of small renal masses: Effectiveness and cost-comparison analysis]. / Le traitement des petites tumeurs du rein: efficacité et comparaison des coûts.

OBJECTIVE: The stage of discovery and treatment of kidney cancer have changed. Partial nephrectomy is the standard treatment for small renal masses (SRM). Also are recommended the thermal ablative techniques. The cost of these treatments for the establishment and society is often unclear. The purpose of this study was to calculate the cost of treatment of SRM in order to assess the profitability for a health institution that invests in innovation. MATERIALS AND METHODS: A retrospective single-center study was conducted with 124 patients treated for SMR (T1a) by open partial nephrectomy (OPN), laparoscopic partial nephrectomy (LPN) and robot-assisted partial nephrectomy (LRPN), radio frequency (RF) and cryotherapy (CT) between 2009 and 2011. We calculated the price of stay of each patient, searched the amount billed to health insurance and calculated the profitability of treatment for the establishment. RESULTS: The OPN cost on average 7884±1201€ and reported 451±1861€, the LPN cost on average 6973±3503€ and reported 2271±3370€, the cost of the LRPN was on average 9600±4595€ and resulted in a deficit of 838±3007€. The radiofrequency cost on average 2724±813€ and caused a deficit of 954±684€, cryotherapy cost on average 6702±857€ and resulted in a deficit of 4723±941€. CONCLUSION: According to current repayment terms, the LPN was the treatment of SRM that offered the best profitability.