Association of extended core sampling with delayed intervention and pathologic outcomes for active surveillance patients: A population-based analysis.

INTRODUCTION: Combined systematic plus targeted biopsy sampling improves detection of clinically significant prostate cancer (PCa). Our objective was to evaluate whether extended core sampling at initial biopsy in active surveillance (AS) patients is associated with subsequent AS discontinuation and pathologic outcomes. METHODS: National Comprehensive Cancer Network (NCCN) low- and favorableintermediate-risk (FIR) AS patients diagnosed between 2010 and 2015 were identified from the Surveillance, Epidemiology, and End Results (SEER) Prostate with Watchful Waiting database. Prostate biopsy sampling was operationalized as: standard (10-12 cores), extended (13-20 cores), or super-extended (21+ cores). Sensitivity analyses using differing cutoffs was performed. Outcomes included delayed definitive intervention (radical prostatectomy [RP]/radiotherapy) and pathologic upgrading and/or downgrading in delayed RP patients. Multivariable logistic regression modelling adjusted for sociodemographic/oncologic variables was performed. RESULTS: This cohort included 42 459 patients (low-risk: 28 411; FIR:14 048); 25-29% and 3- 5% of patients underwent extended and super-extended core sampling, respectively, at diagnosis. Extended core sampling was associated with decreased odds of definitive intervention in low (odds ratio [OR] 0.89, p=0.003) and grade group 2 (GG2) FIR (OR 0.83, p=0.002) patients. Super-extended sampling was associated with decreased odds of definitive intervention in PSA 10-20 FIR patients (OR 0.65, p=0.02). Super-extended sampling was associated with decreased odds of upgrading to ≥GG2 disease in low-risk (OR 0.45, p=0.032) and to ≥GG3 disease in GG2 FIR patients (OR 0.67, p=0.044). CONCLUSIONS: This population-based analysis demonstrates that extended/super-extended sampling at diagnosis is associated with significantly decreased odds of AS discontinuation and pathologic upgrading in low/FIR AS patients. This highlights the significance of extended tissue sampling at initial biopsy to appropriately risk-stratify AS patients and minimize AS discontinuation rates.

Using active surveillance for Gleason 7 (3+4) prostate cancer: A narrative review.

The interest in broadening the application of active surveillance (AS) has been increasing, encompassing patients who may not strictly adhere to the conventional criteria for low-risk prostate cancer (PCa), particularly those diagnosed with small-volume Gleason grade group 2 disease. Nonetheless, accurately identifying individuals with low intermediate-risk PCa who can safely undergo AS without facing disease progression remains a challenge.This review aims to delve into the progression of this evolving trend specifically within this cohort of men, while also examining strategies aimed at minimizing irreversible disease advancement. Additionally, we address the criteria for patient selection, recommended followup schedules, and the indicators prompting intervention.

Intraductal Prostate Cancer Affinity for Lymphatic-Predominant Metastases Through 18F-DCFPyL‒Prostate-Specific Membrane Antigen‒Positron Emission Tomography/CT Scans in Pretreatment Prostate Cancer Patients.

PURPOSE: Intraductal prostate cancer (IDC) is linked to unfavorable oncologic outcomes, marked by distinctive cellular intrinsic pathway changes and intricate immunosuppressive microenvironments that could impact the way cancer spreads. The aim of this study was to determine whether the presence of IDC in prostate biopsy specimens obtained from patients before primary prostate cancer (PCa) treatment is associated with a lymph node metastatic propensity in prostate-specific membrane antigen (PSMA)‒positron emission tomography (PET)/CT. MATERIALS AND METHODS: This was a cross-sectional analysis of all PCa patients undergoing a pretreatment 18F-DCFPyL-PSMA-PET/CT between January 1, 2016, and August 2021 at The Princess Margaret Cancer Centre. Outcomes were presence of any metastasis in the overall cohort, presence of lymphatic vs no metastases, and presence of lymphatic vs bone metastasis among patients who underwent PSMA-PET/CT as PCa primary staging. The associations between IDC presence on the prostate biopsy and the study outcomes were evaluated using univariable and multivariable logistic regression analyses. RESULTS: The cohort consisted of 120 patients. IDC and cribriform pattern were observed in 55 (46%) and 48 (40%) prostate biopsies, respectively. Overall, 52 patients (43%) had evidence of metastasis. Presence of IDC on biopsy was associated with increased odds of overall metastasis (odds ratio: 2.47, 95% CI: 1.09-5.61, P = .03). Of the 52 patients with evidence of metastasis, 41 (79%) had evidence of lymphatic metastasis. Presence of IDC on biopsy was associated with significantly increased odds of lymphatic metastasis vs nonmetastases (odds ratio: 3.03, 95% CI: 1.24-7.40, P = .01). CONCLUSIONS: The identification of IDC morphology in prostate biopsy specimens has been observed to be significantly linked with lymph node metastasis on 18F-DCFPyL-PET/CT imaging in a PCa pretreatment staging setting. We found that presence of IDC in prostate biopsy appears to be a marker for lymph node metastasis on 18F-DCFPyL-PET/CT.

Mosquito (Diptera: Culicidae) Fauna of a Zoological Park in an Urban Setting: Analysis of Culex pipiens s.l. and Their Biotypes.

Mosquito-borne diseases (MBDs) are important emerging diseases that affect humans and animals. Zoological parks can work as early warning systems for the occurrence of MBDs. In this study, we characterized the mosquito fauna captured inside Lisbon Zoo from May 2018 to November 2019. An average of 2.4 mosquitos per trap/night were captured. Five mosquito species potentially causing MBDs, including Culex pipiens biotypes, were found in the zoo. The sympatric occurrence of Culex pipiens biotypes represents a risk factor for the epizootic transmission of West Nile virus and Usutu virus. The mosquito occurrence followed the expected seasonality, with the maximum densities during summer months. However, mosquito activity was detected in winter months in low numbers. The minimum temperature and the relative humidity (RH) on the day of capture showed a positive effect on Culex pipiens abundance. Contrary, the RH the week before capture and the average precipitation the week of capture had a negative effect. No invasive species were identified, nor have flaviviruses been detected in the mosquitoes. The implementation of biosecurity measures regarding the hygiene of the premises and the strict control of all the animals entering the zoo can justify the low prevalence of mosquitoes and the absence of flavivirus-infected mosquitoes.

Limitations of Prostate Biopsy in Detection of Cribriform and Intraductal Prostate Cancer.

BACKGROUND: The presence of cribriform morphology and intraductal carcinoma (IDC) in prostate biopsies and radical prostatectomy specimens is an adverse prognostic feature that can be used to guide treatment decisions. OBJECTIVE: To assess how accurately biopsies can detect cribriform morphology and IDC cancer by examining matched biopsy and prostatectomy samples. DESIGN, SETTING, AND PARTICIPANTS: Patients who underwent radical prostatectomy at The Princess Margaret Cancer Centre between January 2015 and December 2022 and had cribriform morphology and/or IDC in the surgical specimen were included in the study. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We used detection sensitivity to evaluate the level of agreement between biopsy and prostatectomy samples regarding the presence of cribriform morphology and IDC. RESULTS AND LIMITATIONS: Of the 287 men who underwent radical prostatectomy, 241 (84%) had cribriform morphology and 161 (56%) had IDC on final pathology. The sensitivity of prostate biopsy, using radical prostatectomy as the reference, was 42.4% (95% confidence interval [CI] 36-49%) for detection of cribriform morphology and 44.1% (95% CI 36-52%) for detection of IDC. The sensitivity of prostate biopsy for detection of either IDC or cribriform morphology was 52.5% (95% CI 47-58%). Among patients who underwent multiparametric magnetic resonance imaging-guided biopsies, the sensitivity was 54% (95% CI 39-68%) for detection of cribriform morphology and 37% (95% CI 19-58%) for detection of IDC. CONCLUSIONS: Biopsy has low sensitivity for detecting cribriform morphology and IDC. These limitations should be incorporated into clinical decision-making. Biomarkers for better detection of these histological patterns are needed. PATIENT SUMMARY: Prostate biopsy is not an accurate method for detecting two specific types of prostate cancer cells, called cribriform pattern and intraductal prostate cancer, which are associated with unfavorable prognosis.

Mesorectal nodal metastasis with seminal vesicle invasion in biochemically recurrent prostate cancer.

OBJECTIVES: To determine the prevalence and predictors of mesorectal lymph node (MLN) metastases on prostate-specific membrane antigen (PSMA)-based positron emission tomography/computed tomography (PET/CT) in patients with biochemically recurrent prostate cancer (PCa) following radical therapy. MATERIALS AND METHODS: This was a cross-sectional analysis of all PCa patients with biochemical failure following radical prostatectomy or radiotherapy who underwent an 18 F-DCFPyL-PSMA-PET/CT at the Princess Margaret Cancer Centre between December 2018 and February 2021. Lesions with PSMA scores ≥2 were considered positive for PCa involvement (PROMISE classification). Predictors of MLN metastasis were evaluated using univariable and multivariable logistic regression analyses. RESULTS: Our cohort consisted of 686 patients. The primary treatment method was radical prostatectomy and radiotherapy in 528 (77.0%) and 158 patients (23.0%), respectively. The median serum PSA level was 1.15 ng/mL. Overall, 384 patients (56.0%) had a positive scan. Seventy-eight patients (11.3%) had MLN metastasis, with 48/78 (61.5%) having MLN involvement as the only site of metastasis. On multivariable analysis, presence of pT3b disease (odds ratio 4.31, 95% confidence interval 1.44-14.2; P = 0.011) was significantly associated with increased odds of MLN metastasis, whereas surgical factors (radical prostatectomy vs radiotherapy; performance/extent of pelvic nodal dissection), surgical margin positivity, and Gleason Grade were not. CONCLUSIONS: In this study, 11.3% of PCa patients with biochemical failure had MLN metastasis on 18 F-DCFPyL-PET/CT. pT3b disease was associated with 4.31-fold significantly increased odds of MLN metastasis. These findings suggest alternate drainage routes for PCa cells, either via alternate lymphatic drainage from the seminal vesicles themselves or secondary to direct extension from posteriorly located tumours invading the seminal vesicles.

Poly(adenosine diphosphate-ribose) polymerase inhibitor combinations in first-line metastatic castrate-resistant prostate cancer setting: a systematic review and meta-analysis.

OBJECTIVES: To compare radiographic progression-free survival (rPFS), overall survival (OS), and treatment-emergent adverse events (TEAEs) among patients with metastatic castrate-resistant prostate cancer (mCRPC) receiving a combination of first-line poly(adenosine diphosphate-ribose) polymerase inhibitors (PARPi) plus androgen receptor axis-targeted agents (ARAT) vs placebo/ARAT. MATERIALS AND METHODS: We conducted a systematic review/meta-analysis of all published Phase III randomised controlled trials using EMBASE, MEDLINE, and Cochrane (inception until 6 June 2023). Published full-text manuscripts and conference abstracts were inclusion eligible. Study selection/data extraction were independently performed by two authors. The Cochrane Risk-of-Bias 2 Tool was used, and certainty of evidence assessed using the Grading of Recommendations, Assessment, Development, and Evaluations framework. Pooled hazard ratios (HRs) and relative risks, with corresponding confidence intervals (CIs), were generated using random-effects models. RESULTS: Three trials were identified: PROpel, MAGNITUDE, and TALAPRO-2. Compared to placebo/ARAT, the PARPi/ARAT combination was associated with a 35% rPFS improvement in the overall cohort (HR 0.65, 95% CI 0.56-0.76), with 68%, 45%, and 26% improvements in the BReast CAncer gene 1/gene 2 (BRCA1/2)-mutated (BRCA1/2m; P < 0.001), homologous recombination repair-mutated (HRRm; P < 0.001), and non-HRRm cohorts (P = 0.003), respectively. OS data maturity ranged from 31% to 48%, with overall cohort OS data unavailable from MAGNITUDE. The PROpel/TALAPRO-2 pooled analysis demonstrated a 16% OS improvement in the overall cohort (HR 0.84, 95 CI 0.72-0.98; P = 0.02). OS in the HRRm (HR 0.76, 95% CI 0.61-0.95) and the BRCA1/2m cohorts (HR 0.53, 95% CI 0.18-1.56) were improved, with a higher effect magnitude compared to the overall cohort. This combination was associated with a 45% relative risk increase in Grade ≥3 TEAEs, including 6.22-fold for Grade ≥3 anaemia (31.9% vs 4.9%). CONCLUSIONS: The addition of PARPi to ARAT in the first-line mCRPC setting is associated with rPFS benefits across subgroups, with the greatest magnitude of benefit in BRCA1/2m patients. OS benefits remain inconsistent irrespective of HRRm status, with significant increases in Grade ≥3 TEAEs, particularly anaemia. Currently, we suggest this combined approach be selectively offered to HRRm patients, preferentially BRCA1/2m.

Lymphotropic Pattern of Prostate-specific Membrane Antigen-detected Metastases Among Biochemically Recurrent Radical Prostatectomy Patients with Cribriform Disease.

BACKGROUND: Cribriform morphology portends worse oncologic outcomes, and has unique cellular intrinsic pathway alterations and tumor microenvironments that may impact metastatic spread patterns. OBJECTIVE: To determine whether the presence of cribriform morphology in prostatectomy specimens of patients with biochemical recurrence after radical prostatectomy (RP) is associated with the presence of metastasis on prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) and a distinct pattern of spread. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional analysis was conducted of all prostate cancer patients with biochemical recurrence after RP undergoing 18F-DCFPyL-PET/CT between December 2018 and February 2021 at the Princess Margaret Cancer Centre. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Outcomes were presence of any metastasis in the overall cohort and lymphatic versus bone/visceral metastases among patients with metastatic disease. The associations between the presence of intraductal (IDC) and/or invasive cribriform (ICC) carcinoma on the RP specimen and study outcomes were evaluated using logistic regression analyses. RESULTS AND LIMITATIONS: The cohort included 176 patients. IDC and ICC were observed in 77 (43.8%) and 80 (45.5%) RP specimens, respectively. The median time from RP to PSMA-PET/CT was 5.0 yr. The median serum prostate-specific antigen level at PSMA-PET/CT was 1.12 ng/ml. Overall, metastasis was observed in 77 patients, of whom 58 were had lymphatic-only metastasis. On a multivariable analysis, presence of IDC on RP was associated with increased odds of overall metastasis (odds ratio [OR]: 2.17; 95% confidence interval [CI]: 1.07-4.45; p = 0.033). Presence of ICC on RP was associated with significantly increased odds of lymphatic versus bone/visceral metastases (OR: 3.13; 95% CI: 1.09-21.7; p = 0.004). CONCLUSIONS: Presence of cribriform morphology on RP specimens of patients with biochemical failure after RP is associated with increased odds of PSMA-PET/CT-detected metastases with a lymphatic predominant pattern of spread. These findings have implications for the design and evaluation of post-RP salvage therapies. PATIENT SUMMARY: We found that microscopic cribriform appearance correlates with disease spread on imaging in prostate cancer patients with recurrence and has a predilection for spread to lymph nodes, as opposed to bone or visceral organs.

Small Renal Masses: The Evolving Histologic, Imaging, and Genomic Landscapes.

According to the American Cancer Society, it is currently estimated that approximately 81,800 new cases of kidney cancer will be diagnosed in the United States in 2023 [...].

A Multinational Study of The Impact of Covid-19 On Urologic Surgery Residency and Wellbeing.

OBJECTIVE: To assess changes to the experiences and wellbeing of urology trainees in the United States (US) and European Union (EU) during the COVID-19 pandemic. METHODS: A 72-item anonymous online survey was distributed September 2020 to urology residents of Italy, France, Portugal, and the US. The survey assessed burnout, professional fulfillment, loneliness, depression and anxiety as well as 38 COVID specific questions. RESULTS: Two hundred twenty-three urology residents responded to the survey. Surgical exposure was the main educational concern for 81% of US and 48% of EU residents. E-learning was utilized by 100% of US and 57% of EU residents with two-thirds finding it equally or more useful than traditional didactics. No significant differences were seen comparing burnout, professional fulfillment, depression, anxiety, or loneliness among US or EU residents, 73% of US and 71% of EU residents reported good to excellent quality of life during the pandemic. In the US and EU, significantly less time was spent in the hospital, clinic, and operating room (P <.001) and residents spent more time using telehealth and working from home during the pandemic and on research projects, didactic lectures, non-medical hobbies and reading. The majority of residents reported benefit from more schedule flexibility, improved work life balance, and increased time for family, hobbies, education, and research. CONCLUSION: The COVID-19 pandemic has resulted in significant restructuring of residents' educational experience around the globe. Preservation of beneficial changes such as reduction of work hours and online learning should be pursued within this pandemic and beyond it.

The Percentage of [-2]Pro-Prostate-Specific Antigen and the Prostate Health Index Outperform Prostate-Specific Antigen and the Percentage of Free Prostate-Specific Antigen in the Detection of Clinically Significant Prostate Cancer and Can Be Used as Reflex Tests.

CONTEXT.­: There is a need to avoid the overdiagnosis of prostate cancer (PCa) and to find more specific biomarkers. OBJECTIVE.­: To evaluate the clinical utility of [-2]pro-prostate-specific antigen ([-2]proPSA) derivatives in detecting clinically significant PCa (csPCa) and to compare it with prostate-specific antigen (PSA) and with the percentage of free PSA (%fPSA). DESIGN.­: Two hundred thirty-seven men (PSA: 2-10 ng/mL) scheduled for a prostate biopsy were enrolled. Parametric and nonparametric tests, receiver operating characteristic curves, and logistic regression analysis were applied. Outcomes were csPCa and overall PCa. RESULTS.­: Both [-2]proPSA derivatives were significantly higher in csPCa and overall PCa (P < .001). The areas under the curves for the prediction of csPCa were higher for the percentage of [-2]proPSA (%[-2]proPSA) (0.781) and the prostate health index (PHI) (0.814) than for PSA (0.651) and %fPSA (0.724). There was a gain of 11% in diagnostic accuracy when %[-2]proPSA or PHI were added to a base model with PSA and %fPSA. Twenty-five percent to 29% of biopsies could have been spared with %[-2]proPSA (cutoff: ≥1.25%) and PHI (cutoff: ≥27), missing 10% of csPCas. The same results could have been achieved by using [-2]proPSA as a reflex test, when %fPSA was 25% or less (cutoffs: ≥1.12% and ≥24 for %[-2]proPSA and PHI, respectively). CONCLUSIONS.­: The [-2]proPSA derivatives improve the diagnostic accuracy of csPCa when the PSA value is between 2 and 10 ng/mL, sparing unnecessary biopsies and selecting patients for active surveillance. [-2]proPSA can be used as a reflex test when %fPSA is 25% or less, without reducing the diagnostic accuracy for csPCa and the number of spared biopsies.

Tumour markers in prostate cancer: The post-prostate-specific antigen era.

Although prostate-specific antigen-based prostate cancer screening had a positive impact in reducing prostate cancer mortality, it also led to overdiagnosis, overtreatment and a significant number of unnecessary biopsies. In the post-prostate-specific antigen era, new biomarkers have emerged that can complement the information given by prostate-specific antigen, towards a better cancer diagnostic specificity, and also allowing a better estimate of the aggressiveness of the disease and its clinical outcome. That means those markers have the potential to assist the clinician in the decision-making processes, such as whether or not to perform a biopsy, and to make the best treatment choice among the new therapeutic options available, including active surveillance in lower risk disease. In this article, we will review several of those more recent diagnostic markers (4Kscore®, [-2]proPSA and Prostate Health Index, SelectMDx®, ConfirmMDx®, Progensa® Prostate Cancer Antigen 3, Mi-Prostate Score, ExoDx™ Prostate Test, the Stockholm3 test and ERSPC risk calculators) and prognostic markers (OncotypeDX® Genomic Prostate Score, Prolaris®, Decipher® and ProMark®). We will also address some new liquid biopsy approaches - circulating tumour cells and cell-free DNA - with a potential role in metastatic castration-resistant prostate cancer and will briefly give some future perspectives, mostly outlooking epigenetic markers.

Extracellular Vesicle Proteome in Prostate Cancer: A Comparative Analysis of Mass Spectrometry Studies.

Molecular diagnostics based on discovery research holds the promise of improving screening methods for prostate cancer (PCa). Furthermore, the congregated information prompts the question whether the urinary extracellular vesicles (uEV) proteome has been thoroughly explored, especially at the proteome level. In fact, most extracellular vesicles (EV) based biomarker studies have mainly targeted plasma or serum. Therefore, in this study, we aim to inquire about possible strategies for urinary biomarker discovery particularly focused on the proteome of urine EVs. Proteomics data deposited in the PRIDE archive were reanalyzed to target identifications of potential PCa markers. Network analysis of the markers proposed by different prostate cancer studies revealed moderate overlap. The recent throughput improvements in mass spectrometry together with the network analysis performed in this study, suggest that a larger standardized cohort may provide potential biomarkers that are able to fully characterize the heterogeneity of PCa. According to our analysis PCa studies based on urinary EV proteome presents higher protein coverage compared to plasma, plasma EV, and voided urine proteome. This together with a direct interaction of the prostate gland and urethra makes uEVs an attractive option for protein biomarker studies. In addition, urinary proteome based PCa studies must also evaluate samples from bladder and renal cancers to assess specificity for PCa.

The impact of multidisciplinary team conferences in urologic cancer in a tertiary hospital.

PURPOSE: Multidisciplinary team (MDT) conferences are currently the standard of care in cancer patients' management. Despite evidence supporting benefits to the majority of malignancies, a paucity of data exists examining the impact in urinary and male genital cancers. This study aims to evaluate the impact of MDT conferences in urologic cancer practice. METHODS: Clinical plans discussed in urologic MDT conferences in Centro Hospitalar Universitário de Lisboa Central between January 2019 and December 2019 were retrospectively analysed. Clinical plans were categorized as accepted, changed, rejected (cases that had to be re-presented to the MDT because of insufficient staging or administrative issues) or no plan. MDT conferences' impact was assessed according to type of consultation, referral medical specialty and primary tumour type. RESULTS: 710 clinical plans were discussed at the MDT conferences. 61.8% were accepted, 10.6% were changed, 16.5% were rejected and 11.1% of cases referred to MDT discussion had no defined clinical plan. First consultations had a higher rate of accepted clinical plans (63.4%) versus subsequent consultations (56.4%). Referrals by the urology specialty had the highest rate of acceptances (64.3%). On the stratification by primary tumour site, testicular cancer had the highest acceptance rate (70.3%), whereas bladder cancer had the lowest (47.8%). CONCLUSIONS: MDT conferences had an important impact in the management of 38.2% of cases. Therefore, all patients with urologic malignancies should be referred to MDT review to ensure optimal clinical care.

Prostate cancer with cribriform pattern: Exclusion criterion for active surveillance?

INTRODUCTION: Following the 2014 International Society of Urological Pathology meeting, a rapidly growing body of evidence by several researchers has been demonstrating a poor prognosis in association with cribriform morphology. The aim of our study was to describe the presence of cribriform foci in specimens of radical prostatectomies and to evaluate whether demographic and clinical characteristics are associated with the presence of cribriform pattern. MATERIALS AND METHODS: This cohort study was based on 70 radical retropubic prostatectomies specimens collected between 2012 and 2016 and evaluated for the association of the cribriform pattern with age, prostate-specific antigen at surgery day, Gleason on biopsy, Gleason after radical prostatectomy, extracapsular extension, vesicles invasion, margins, multiparametric magnetic resonance imaging, and post-operative radiotherapy. Results; From the univariable analysis, biochemical prostatespecific antigen recurrence (p = 0.001), extracapsular extension (p = 0.003), pre-operative prostate-specific antigen (p = 0.017), vesicles invasion, (p = 0.038) and post-operative radiotherapy (p < 0.001) showed an association with the presence of cribriform pattern. There was also a significant difference of cribriform pattern and Gleason 7 in needle biopsy (p = 0.020) and cribriform pattern and Gleason 8 or 9 in radical prostatectomy specimen (p = 0.036). CONCLUSIONS: In our study, the increase in preoperative prostate-specific antigen had a high association with cribriform pattern. Further evidence is needed to discriminate preoperative prostate specific antigen values that might potentially be associated with the presence of cribriform pattern. Raising our knowledge about the cribriform pattern can be an excellent opportunity to correctly identify and treat patients who will eventually die from prostate cancer, sparing treatment in those who will not.