The habits of European urologists in the field of cryopreservation before the urological cancers treatment.

INTRODUCTION: Treatments against urogenital cancers frequently have fertility side-effects. The strategy to preserve fertility after oncologic treatments is still a matter of debate with a lack of evidence and international guidelines. The aim of this study is to investigate fertility preservation practices before urogenital cancer treatments and to compare national habits. MATERIAL AND METHODS: An online anonymous survey was submitted from January to June 2021 to six European urological societies. The 31-items questionnaire included questions about demography, habits of evaluation, and management of fertility preservation in case of urogenital cancer treatments. RESULTS: Two hundred twenty-eight urologists from six urological societies in five different countries (Belgium, The Netherlands, Luxembourg, France, Finland) filled out the survey. Three quarter (74%; n = 166) usually propose a cryopreservation before orchidectomy. In case of oligo/azoo-spermia, the technique performed for the sperm extraction during orchidectomy varies among the sample: 70.5% (n = 160) of the responders do not perform a Testicular Sperm Extraction (TESE) nor a Percutaneous Epididymal Sperm Aspiration (PESA). The cryopreservation for prostate cancer treatments is never proposed in 48.17% (n = 105) of responders but conversely it is always proposed in 5.05% (n = 11). The cryopreservation before bladder cancer treatments is not commonly proposed (67.5%, n = 154). CONCLUSION: Our study showed variable country specific tendencies in terms of fertility preservation in the period of treatment of urological cancers. These differences seem to be related to national guidelines recommendations. Standardization of international guidelines is urgently needed in the field of fertility for urological cancer patients.

European countries have different rates of sperm cryopreservation before vasectomy and at the time of reversal.

INTRODUCTION: Effective male contraceptive options are condoms and vasectomy. Vasectomy should not be considered a reversible method of contraception even if vasovasostomy can be offered to men to restore fertility after vasectomy. Therefore, there is a real questioning among urologists concerning cryopreservation before vasectomy. We carried out an international survey concerning the practice of cryopreservation before vasectomy and during vasovasostomy. MATERIAL AND METHODS: An online anonymous survey was submitted from January to June 2021 to six European urological societies. The 31-items questionnaire included questions about demography, habits of cryopreservation before vasectomy or during vasectomy reversal, and in case of urogenital cancers. RESULTS: 228 urologists from six urological societies in five different countries (Belgium, Netherlands, Luxembourg, France, Finland) answered the questionnaire. French urologists were more in favor of cryopreservation before vasectomy than other European urologists (p < 0.0001). They also significantly found that not talking about cryopreservation before vasectomy is a medical fault unlike other urologists (p < 0.0001). The specialization in andrology did not influence the choice of cryopreservation before vasectomy (p = 0.9452). The majority of urologists did not perform intraoperative sperm extraction during vasovasostomy (81%; n = 127) with a significant difference between urologists with or without andrology training (p = 0.0146). Success rates after vasovasostomy are significantly better for robot-assisted surgery (p = 0.0159) or with a microscope (p = 0.0456) versus without a microscope. CONCLUSION: Cryopreservation before definitive sterilization significantly varies among European urologists and seems to be mostly dictated by habits than by knowledge. An international consensus is needed to standardize practices and guide patients' choices.

Prospective Longitudinal Health-related Quality of Life Analysis of the Finnish Arm of the PRIAS Active Surveillance Cohort: 11 Years of Follow-up.

BACKGROUND: Living with an untreated cancer may alter quality of life (QoL) in the long term. OBJECTIVE: To prospectively study long-term changes in general, mental, and physical QoL in a contemporary active surveillance (AS) patient cohort with low-risk prostate cancer (PCa). DESIGN, SETTING, AND PARTICIPANTS: The study population consisted of patients enrolled in the PRIAS trial in Helsinki University Hospital (n = 348). The RAND-36 questionnaire was used to assess general QoL at the start of AS and at 1, 3, 5, 7, 9, and 11 years during follow-up. Patients who had undergone robot-assisted laparoscopic prostatectomy (RALP; n = 88) also received the questionnaire after treatment. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Changes over time were analysed using multilevel mixed-effects regression models, and reported as the mean and95% confidence interval. A rule of 0.5 × standard deviation was used to estimate changes of clinical importance. RESULTS AND LIMITATIONS: Median follow-up until the end of AS or last follow-up was 7.2 (range 0.3-12.7) yr. A decrease was observed in six of eight QoL subdomains at 7 yr. However, all scores were above age-stratified reference values. There was no difference between the group who continued AS throughout the study period and the group who discontinued AS and underwent RALP. More than half of the study cohort discontinued AS (n = 198; 57%), 135 men (68%) because of events specified in the protocol and only seven (3.5%) because of anxiety. Metastatic disease developed in six patients (1.7%), and two cases (0.6%) of PCa-related death were recorded among 348 patients in more than 12 yr of overall follow-up. The lack of a randomised control population is a limitation of the study. CONCLUSIONS: Contemporary protocolised AS does not impair general QoL. Men undergoing a treatment change (RALP) did not experience a decrease in QoL before or after their treatment change. PATIENT SUMMARY: Active surveillance is a safe treatment option for men with low-risk prostate cancer. We show that this follow-up strategy does not cause a decline in patients' general quality of life.

PTEN and ERG expression in MRI-ultrasound guided fusion biopsy correlated with radical prostatectomy findings in men with prostate cancer.

BACKGROUND: Conventional systematic prostate biopsies (SBx) have multiple limitations, and magnetic resonance imaging (MRI)-ultrasound fusion targeting is increasingly applied (fusion biopsies [FBx]). In our previous studies, we have shown that loss of the tumor suppressor gene phosphatase and tensin homolog (PTEN) in radical prostatectomy (RP) specimens predicts poor disease-specific survival, and in active surveillance (AS), PTEN loss in SBx predicts an adverse AS outcome, although SBx PTEN status does not correlate well with the corresponding RP status. Here, we have hypothesized that PTEN and erythroblast transformation-specific related gene (ERG) status in FBx correlate better with RP than they would in SBx. METHODS: A total of 106 men, who had undergone FBx and subsequent RP in a single center between June 2015 and May 2017 were included. Fifty-three of the men had concomitant or previous SBx's. All biopsy and RP specimens were collected, and tissue microarrays (TMA) were constructed from RP specimens. Immunohistochemical stainings for PTEN and ERG expression were conducted on biopsies and RP TMAs and results were compared by using Fisher's exact test. RESULTS: The immunohistochemical predictive power of FBx, determined by the concordance of biopsy PTEN and ERG status with RP, is superior to SBx (77.6% vs 66.7% in PTEN, 92.4% vs 66.6% in ERG). FBx was superior to SBx in correlation with RP Gleason Grade Groups and MRI prostate imaging reporting and data system scores. CONCLUSION: FBx grading correlates with RP histology and MRI findings and predicts the biomarker status in the RP specimens more accurately than SBx. A longer follow-up is needed to evaluate if this translates to better prediction of disease outcomes, especially in AS and radiation therapy where prostatectomy specimens are not available for prognostication.

Rectal E. coli above ciprofloxacin ECOFF associate with infectious complications following prostate biopsy.

Transrectal prostate biopsies carry the risk of infection. By using non-selective culture plates, instead of commonly used ciprofloxacin (CIP)-containing plates, we analyzed the association between Escherichia coli CIP minimal inhibitory concentration (MIC) and post-biopsy infectious complications. A pre-biopsy rectal swab was taken from 207 consecutive men, scheduled for transrectal 12-core prostate biopsy with CIP 750 mg as the mostly used prophylaxis. CIP MIC of rectal Gram-negative bacilli was determined from a chromogenic agar. Rectal E. coli were categorized to resistant (R) and intermediate (I) isolates together (R + I, MIC > 0.25 mg/l) and to sensitive (S, MIC ≤ 0.25 mg/l) using EUCAST clinical breakpoints. In addition, epidemiological cutoff (ECOFF R, MIC > 0.064 mg/l) was used for categorization. Eighteen (8.7%) men showed CIP R + I E. coli by the EUCAST breakpoints and 41 (19.8%) using the ECOFF R criteria. During follow-up, 15 (7.2%) men had infectious symptoms, of which 9 (4.3%) were culture-confirmed infections. Only 4 (26.7%) of these 15 patients showed R + I E. coli in the rectal swab according to EUCAST, but 10 (66.7%) using the ECOFF cutoff. Rectal E. coli CIP R + I by the EUCAST clinical breakpoints associated with infectious complications with OR 5.7 (95% CI 1.5-21.8, P = 0.005) and ECOFF R E. coli by OR 10.7 (95% CI 3.0-37.6, P < 0.001). Men carrying rectal E. coli with moderately lowered CIP susceptibility (MIC > ECOFF 0.064 mg/l) were identified and, interestingly, they showed a high risk of developing infectious symptoms after the biopsy. This explains why some men develop infectious complications despite appropriate antibiotics before prostatic biopsies. TRIAL REGISTRATION: NCT02140502.

Patient Experience of Systematic Versus Fusion Prostate Biopsies.

BACKGROUND: The magnetic resonance imaging/ultrasound fusion-guided biopsy (FBx) technique has gained popularity in prostate cancer (PCa) diagnostics, but little is known about its effect on patient experience. OBJECTIVE: To evaluate pain, discomfort and other non-infectious complications in PCa patients undergoing either systematic 12-core transrectal ultrasound-guided biopsy (SBx) or FBx and patient willingness to undergo rebiopsy. DESIGN, SETTING, AND PARTICIPANTS: A prospective trial of 262 male patients, 203 of whom underwent transrectal SBx and 59 FBx at Helsinki University Hospital in 2015-2016. Patients completed two questionnaires immediately after and at 30 d after biopsy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES: Patients reported pain and discomfort on a numeric rating scale (NRS; 0-10) immediately after biopsy. At 30 d, discomfort was measured on a scale ranging from 1 (no inconvenience) to 4 (maximal inconvenience). Other symptoms were reported dichotomously (yes/no) in both questionnaires. Mann-Whitney U, Pearson's χ2, and logistic regression tests were used. RESULTS AND LIMITATIONS: For the SBx and FBx groups the median number of cores per patient was 12 and three, respectively. At 30 d, a higher proportion of patients in the SBx group had experienced pain than in the FBx group (70/203 [34%] vs 12/59 [20%]; p=0.043), whereas there was no difference in the median discomfort scores. Hematuria was less common in the FBx group (26/59 [44%] vs 140/203 [69%]; p<0.001). Patients willing to undergo rebiopsy immediately post-biopsy reported lower median NRS (3.0 [interquartile range 2.0-5.0] vs 5.0 [4.3-6.0]; p<0.001) and discomfort scores (4.0 [2.0-6.0] vs 7.0 [5.0-8.0]; p<0.001) than those unwilling. At 30 d, less discomfort (2.0 [interquartile range 1.0-2.0] vs 2.0 [2.0-3.0]; p=0.008) and fever (6/195 [3.1%] vs 6/28 [22%]; p=0.001) were experienced by patients willing to undergo rebiopsy. The nonrandomized design was a limitation. CONCLUSIONS: FBx is associated with less pain and hematuria than SBx during the 30-d interval after biopsy. PATIENT SUMMARY: Magnetic resonance imaging (MRI)-targeted prostate biopsy is associated with less pain, discomfort, and blood in the urine compared to the standard ultrasound-guided procedure. Performing MRI-targeted procedures may reduce biopsy-related complications and promote adherence to recommended repeat biopsy for patients on active surveillance for prostate cancer.

Loss of PTEN expression in ERG-negative prostate cancer predicts secondary therapies and leads to shorter disease-specific survival time after radical prostatectomy.

The clinical course of prostate cancer is highly variable. Current prognostic variables, stage, and Gleason score have limitations in assessing treatment regimens for individual patients, especially in the intermediate-risk group of Gleason score 7. ERG:TMPRSS2 fusion and loss of PTEN are some of the most common genetic alterations in prostate cancer. Immunohistochemistry of PTEN and ERG has generated interest as a promising method for more precise outcome prediction but requires further validation in population-based cohorts. We studied the predictive value of ERG and PTEN expression by immunohistochemistry in two large radical prostatectomy cohorts comprising 815 patients with extensive follow-up information. Clinical end points were initiation of secondary therapy, overall survival, and disease-specific survival. Predictions of clinical outcomes were also assessed according to androgen receptor (AR) activity. PTEN loss, especially in ERG-negative cancers, predicted initiation of secondary treatments and shortened disease-specific survival time, as well as stratifying Gleason score 7 patients into different prognostic groups with regard to secondary treatments and disease-specific survival. High AR immunoreactivity in ERG-negative cancers with PTEN loss predicted worse disease-specific survival. We also observed that in Gleason score 7 ERG-negative cases with PTEN loss and high AR expression have significantly shorter disease-specific survival time compared with ERG-positive cases. Our conclusion is that loss of PTEN is a strong determining factor for shorter disease-specific survival time and initiation of secondary therapies after radical prostatectomy. The predictive value of PTEN immunoreactivity is further accentuated in ERG-negative cancers with high AR expression. Negative PTEN expression, accompanied by ERG status, can be used to stratify patients with Gleason score 7 into different survival groups. Assessment of PTEN and ERG status could provide an additional tool for initial diagnostics when determining the prognosis and subsequent follow-up regimen for patients treated by radical prostatectomy.

Performance of transrectal prostate biopsies in detecting tumours and implications for focal therapy.

OBJECTIVE: The aim of this study was to investigate the performance of transrectal biopsies in predicting pathological outcomes after radical prostatectomy (RP) and in estimating possible candidates for focal therapies. MATERIAL AND METHODS: The study was a retrospective analysis of 96 prostate cancer patients treated by robot-assisted laparoscopic RP at Helsinki University Central Hospital in 2009-2010. Data from diagnostic biopsies were compared with data from reassessment of RP slides. At reanalysis, an index tumour was chosen for all patients and was determined as being the most dedifferentiated tumour or the largest tumour with Gleason pattern 3 in case Gleason patterns 4 or 5 were absent. The performance of prostate biopsies in predicting cancer laterality, tumour size and tumour location was analysed. Statistical methods included Spearman's correlation, linear regression analysis and Pearson's chi-squared test. Suitability for focal therapies was assessed based on tumour morphology and laterality. RESULTS: The extent of cancer in biopsies correlated with tumour size in the apex and middle of the prostate [standard coefficients in linear regression for the apex 2.479-2.553, 95% confidence interval (CI) 1.952-3.056, p < 0.001-0.007; and for the middle 1.936-2.388, 95% CI 1.504-2.861, p < 0.001]. Prostate biopsies performed moderately in predicting tumour location in RP slides (positive predictive value 34.1-90.9%). Thirty-six patients (37.5%) would possibly have been candidates for focal therapy and thirty-nine (40.6%) patients for hemiablation. CONCLUSIONS: Contemporary transrectal prostate biopsies are a suboptimal tool for predicting pathological findings at RP. Approximately 40% of patients would possibly have been suitable candidates for focal or hemiablative therapies.

Diffusion-weighted magnetic resonance imaging in prostate cancer patients on active surveillance one year after diagnosis and before repeat biopsy.

OBJECTIVE: The aim of this study was to evaluate prospectively whether diffusion-weighted magnetic resonance imaging (DW-MRI), interpreted in a routine clinical setting, can serve as a diagnostic and prognostic tool for prostate carcinoma patients on active surveillance (AS). MATERIAL AND METHODS: Eighty men enrolled in the Finnish arm of the PRIAS (Prostate Cancer Research International: Active Surveillance) study were followed for at least 1 year and had DW-MRI scans taken in addition to repeat biopsy. Spearman's correlations were analysed between tumour appearance on DW-MRI and clinical variables [age, prostate-specific antigen (PSA), free PSA, PSA doubling time, prostate volume, percentage of cancer at diagnostic biopsy]. The Pearson chi-squared test clarified associations between outcome factors (number of positive cores and Gleason score on repeat biopsy, treatment change) and DW-MRI results. Assumed predictors of deferred radical treatment were examined with logistic regression analysis. Accuracy of tumour localization by DW-MRI compared to repeat biopsy findings was analysed by the chi-squared test. RESULTS: DW-MRI revealed an anatomical lesion suggestive of cancer in 40 patients (50%). MRI positivity showed no significant correlation with clinical variables. No associations existed between tumour appearance on DW-MRI and biopsy findings or discontinuation of AS. The only variable predicting treatment change was higher PSA at discontinuation (p = 0.002). Appearance of tumour, either on T2-weighted MRI (p = 0.273) or on apparent diffusion coefficient maps (p = 0.691), was not a significant predictor of treatment change. CONCLUSIONS: Localized low-grade prostate cancer is challenging to visualize in DW-MRI, and this imaging technique provides no additional prognostic benefit compared to PSA and repeat biopsies.