Measuring cancer burden in prostatic needle core biopsies: simplified assessments outperform complex measurements in assessing outcome: evidence to assist pathologist efficiency and minimize datasets.

AIMS: The optimal method of measuring cancer extent in prostate cancer (PCa) biopsies is unknown. METHODS AND RESULTS: Nine hundred eighty-one men with clinically localised PCa managed conservatively were reviewed with follow up. The number of positive cores (NPC), the Maximum Cancer Length in a core (MCL), Total Cancer Length (TCL), and percentage of positive cores (%+cores) was calculated and univariate and multivariate analysis performed using prostate-specific antigen (PSA), T-stage, and Gleason score. The presence of stromal gaps (SG) was recorded. Univariate models were run where SG made a difference to the MCL. All variables showed significant association with PCa death in univariate models. In multivariate models, incorporating PSA, T-stage, and Gleason score, only %+cores was a significant predictor of outcome, with a 10% increase in %+cores resulting in a hazard ratio (HR) of 1.07 (likelihood-ratio test P > Χ2  = 0.01). There were 120 patients where SG made a difference to the MCL and a total of 20 events in this group. Including SG, on univariate analysis the median MCL was 10 mm and HR was 1.16 (P = 0.007), not including SG, the median MCL was 6 mm and HR was 1.23 (P = 6.3 × 10-4 ). Inclusion or exclusion of SG made no significant difference to TCL as a predictor of outcome. CONCLUSION: Cancer extent is a strong predictor of PCa death but only %+cores added to the multivariate model. Expressed as a fraction of NPC/total number of cores, this is the simplest method of assessment, which we favour over more complicated methods in nontargeted biopsies.

Changes in Lower Urinary Tract Symptoms in Benign Prostatic Hyperplasia Patients Affected by Covid-19.

INTRODUCTION: Benign prostatic hyperplasia (BPH) is a histological diagnosis characterized by an increase in the number of epithelial and stromal cells in the transitional zone of the prostate gland. The clinical manifestation of BPH is associated with the appearance of so-called lower urinary tract symptoms (LUTS) which can also be a consequence of other conditions not related to the prostate. Covid-19, also known as severe acute respiratory syndrome coronavirus 2 was discovered as a disease in late 2019 in the city of Wuhan, China. MATERIALS AND METHODS: A case-control study was conducted between September 2021 and May 2022. Information was initially collected on 60 patients followed up and treated conservatively for BPH in two outpatient practices and recovered from Covid-19. After processing the received information, 27 patients were excluded from the study and 33 patients remained for observation The assessment of patients is carried out through an internationally validated questionnaire - international prostate symptom score (IPPS), prostate specific antigen, digital rectal examination (DRЕ), and ultrasound diagnostics of the prostate gland with consideration of its volume and the amount of residual urine. RESULTS: Our data show a strong correlation between the changes in LUTS in patients with BPH and Covid-19 infection. CONCLUSION: Although almost 3 years have passed since the beginning of this pandemic, there are still many unanswered questions surrounding this disease. We believe that with our experience we will enrich the information about the relationship between Covid-19 and LUTS, and the results obtained by us can serve as a basis for future large-scale and more in-depth studies on the subject.

Prostate MRI versus PSA screening for prostate cancer detection (the MVP Study): a randomised clinical trial.

OBJECTIVES: Our objective was to compare prostate cancer detection rates between patients undergoing serum prostate-specific antigen (PSA) vs magnetic resonance imaging (MRI) for prostate cancer screening. DESIGN: Phase III open-label randomised controlled trial. SETTING: Single tertiary cancer centre in Toronto, Canada. PARTICIPANTS: Men 50 years of age and older with no history of PSA screening for ≥3 years, a negative digital rectal exam and no prior prostate biopsy. INTERVENTIONS: Patients were recommended to undergo a prostate biopsy if their PSA was ≥2.6 ng/mL (PSA arm) or if they had a PIRADS score of 4 or 5 (MRI arm). Patients underwent an end-of-study PSA in the MRI arm. PRIMARY AND SECONDARY OUTCOME MEASURES: Adenocarcinoma on prostate biopsy. Prostate biopsy rates and the presence of clinically significant prostate cancer were also compared. RESULTS: A total of 525 patients were randomised, with 266 in the PSA arm and 248 in the MRI arm. Due to challenges with accrual and study execution during the COVID-19 pandemic, the study was terminated early. In the PSA arm, 48 patients had an abnormal PSA and 28 (58%) agreed to undergo a prostate biopsy. In the MRI arm, 25 patients had a PIRADS score of 4 or 5 and 24 (96%) agreed to undergo a biopsy. The relative risk for MRI to recommend a prostate biopsy was 0.52 (95% CI 0.33 to 0.82, p=0.005), compared with PSA. The cancer detection rate for patients in the PSA arm was 29% (8 of 28) vs 63% (15 of 24, p=0.019) in the MRI arm, with a higher proportion of clinically significant cancer detected in the MRI arm (73% vs 50%). The relative risk for detecting cancer and clinically significant with MRI compared with PSA was 1.89 (95% CI 0.82 to 4.38, p=0.14) and 2.77 (95% CI 0.89 to 8.59, p=0.07), respectively. CONCLUSIONS: Prostate MRI as a stand-alone screening test reduced the rate of prostate biopsy. The number of clinically significant cancers detected was higher in the MRI arm, but this did not reach statistical significance. Due to early termination, the study was underpowered. More patients were willing to follow recommendations for prostate biopsy based on MRI results. TRIAL REGISTRATION NUMBER: NCT02799303.

How I Use It: The Exosome Diagnostics (EPI) prostate cancer biomarker utility in urology and primary care.

Prostate-specific antigen (PSA) screening remains the mainstay for early detection of prostate cancer. Although PSA is a nonspecific prostate cancer biomarker, its specificity for high grade prostate cancer can be enhanced by pre-biopsy liquid biomarkers including the Exosome Dx Prostate IntelliScore (EPI) test. EPI is a stand-alone urine genomic test that measures 3 exosome-derived gene expression signatures without the need for digital rectal examination (DRE) or inclusion of standard of care parameters in the test algorithm. EPI has broad clinical utility as a risk stratification tool for clinically significant high grade prostate cancer in men considering diagnostic prostate biopsy (MRI-targeted and systematic biopsy). During the COVID-19 pandemic, the EPI At-Home Collection Kit was introduced and quickly became an important component of tele-urology. The EPI test has emerged as a prioritization tool for primary care referral to urologists and for prostate biopsy scheduling. EPI provides an objective and actionable genomic risk assessment tool for high grade prostate cancer and is a critical part of the informed decision-making regarding biopsy (targeted, systematic or both) in both urology and primary care practices.

Lessons learned after one year of COVID-19 from a urologist and radiotherapist view: A German survey on prostate cancer diagnosis and treatment.

INTRODUCTION: Since the beginning of the pandemic in 2020, COVID-19 has changed the medical landscape. International recommendations for localized prostate cancer (PCa) include deferred treatment and adjusted therapeutic routines. MATERIALS AND METHODS: To longitudinally evaluate changes in PCa treatment strategies in urological and radiotherapy departments in Germany, a link to a survey was sent to 134 institutions covering two representative baseline weeks prior to the pandemic and 13 weeks from March 2020 to February 2021. The questionnaire captured the numbers of radical prostatectomies, prostate biopsies and case numbers for conventional and hypofractionation radiotherapy. The results were evaluated using descriptive analyses. RESULTS: A total of 35% of the questionnaires were completed. PCa therapy increased by 6% in 2020 compared to 2019. At baseline, a total of 69 radiotherapy series and 164 radical prostatectomies (RPs) were documented. The decrease to 60% during the first wave of COVID-19 particularly affected low-risk PCa. The recovery throughout the summer months was followed by a renewed reduction to 58% at the end of 2020. After a gradual decline to 61% until July 2020, the number of prostate biopsies remained stable (89% to 98%) during the second wave. The use of RP fluctuated after an initial decrease without apparent prioritization of risk groups. Conventional fractionation was used in 66% of patients, followed by moderate hypofractionation (30%) and ultrahypofractionation (4%). One limitation was a potential selection bias of the selected weeks and the low response rate. CONCLUSION: While the diagnosis and therapy of PCa were affected in both waves of the pandemic, the interim increase between the peaks led to a higher total number of patients in 2020 than in 2019. Recommendations regarding prioritization and fractionation routines were implemented heterogeneously, leaving unexplored potential for future pandemic challenges.

The role of COVID-19 in prostate tissue inflammation: first pathological evidence.

According to current studies, COVID-19 might have an impact on semen quality. Therefore, SARS-CoV-2 may affect other traits of male reproductive system, including the prostate. Thus, we recruited patients who experienced COVID-19 infection in-between prostate biopsy and radical prostatectomy and compared prostate samples inflammation, measured with IRANI score, to those who did not. Indeed, we recruited 20 patients, aged 69 (62-73) years, finding no difference between the 10 patients with COVID-19 infection and the others in IRANI score and all its sub-scores. Hence, according to our exploratory and limited results, COVID-19 infection might have no gross effect on prostate inflammation.

The Impact of the Ongoing COVID-19 Epidemic on the Increasing Risk of Adverse Pathology in Prostate Cancer Patients Undergoing Radical Prostatectomy.

We aimed to assess whether the ongoing course of the COVID-19 epidemic has been associated with an increased risk of adverse pathology (AP) findings in prostate cancer (PC) patients treated with radical prostatectomy (RP). We performed a retrospective data analysis which included 408 consecutive, non-metastatic, previously untreated PC patients who underwent RP in our institution between March 2020 and September 2021. Patients were divided into two equally numbered groups in regard to the median surgery date (Early Epidemic [EE] and Late Epidemic [LE]) and compared. Adverse pathology was defined as either grade group (GG) ≥ 4, pT ≥ 3a or pN+ at RP. Patients in the LE group demonstrated significantly higher rates of AP than in the EE group (61 vs. 43% overall and 50 vs. 27% in preoperative non-high-risk subgroup, both p < 0.001), mainly due to higher rates of upgrading. On multivariable analysis, consecutive epidemic week (odds ratio: 1.02, 95% confidence interval: 1.00-1.03, p = 0.009) as well as biopsy GG ≥ 2 and a larger prostate volume (mL) were associated with AP in non-high-risk patients. The study serves as a warning call for increased awareness of risk underassessment in contemporarily treated PC patients.

Association of the COVID-19 Pandemic With Rates of Prostate Cancer Biopsies and Diagnoses in Black vs White US Veterans.

Importance: Several studies have assessed the negative effect of the COVID-19 pandemic on cancer screening and diagnosis rates. However, this has not been evaluated for prostate biopsy and prostate cancer (PC) diagnosis in an equal-access health care system. Objective: To determine the association of the pandemic with prostate biopsy and PC diagnosis rates among Black vs White patients in the Veterans Affairs Health Care System (VAHCS). Design, Setting, and Participants: This cohort study included a retrospective analysis of all prostate biopsies performed on patients in the VAHCS without a preexisting PC diagnosis between January 2018 and March 2021. The base population included all living male patients who had at least 1 visit to the VAHCS during the 3 years prior to each month of the study. Exposure: The COVID-19 pandemic. Main Outcomes and Measures: The main outcomes were the number of prostate biopsies and PC diagnoses by month. The influence of the pandemic on prostate biopsy volume and the incidence of PC diagnoses was modeled using an interrupted time-series analysis. Poisson generalized linear models were fitted to project the expected number of prostate biopsies and PC diagnoses had there been no pandemic interruption. Additional models were used to test for differences by race. Results: Prior to the pandemic (January 2018 through February 2020), monthly biopsy numbers among 51 606 included men ranged between 1230 and 1695, of which 56% to 60% of results were positive for PC. The estimated number of missed PC diagnoses from March 2020 through March 2021 ranged from 97 cases (October 2020: 752 cases expected, 655 cases observed) to 573 cases (April 2020: 794 cases expected, 221 cases observed). Prior to the pandemic, biopsy rates were statistically significantly higher among Black vs White men (incidence rate ratio, 2.25; 95% CI, 2.06-2.46; P < .001). There was no change in biopsy rates associated with race at the onset of the pandemic nor during the recovery period from March 2020 to March 2021. Similar trends were observed for PC diagnosis rates. Conclusions and Relevance: Results of this cohort study demonstrate that during the COVID-19 pandemic, prostate biopsy and PC diagnosis rates decreased, particularly during the peak of the pandemic. However, there were no statistically significant changes in rates by race.

Change from transrectal to transperineal ultrasound-guided prostate biopsy under local anaesthetic eliminates sepsis as a complication.

Transrectal ultrasound-guided (TRUS) biopsy of the prostate is associated with increased risk of post-procedural sepsis with associated morbidity, mortality, re-admission to hospital, and increased healthcare costs. In the study institution, active surveillance of post-procedural infection complications is performed by clinical nurse specialists for prostate cancer under the guidance of the infection prevention and control team. To protect hospital services for acute medical admissions related to the coronavirus disease 2019 (COVID-19) pandemic, TRUS biopsy services were reduced nationally, with exceptions only for those patients at high risk of prostate cancer. In the study institution, this change prompted a complete move to transperineal (TP) prostate biopsy performed in outpatients under local anaesthetic. TP biopsies eliminated the risk of post-procedural sepsis and, consequently, sepsis-related admission while maintaining a service for prostate cancer diagnosis during the COVID-19 pandemic.

Effect of COVID-19 on Male Reproductive System - A Systematic Review.

Background: Angiotensin-converting enzyme II (ACE2), a receptor for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) to enter host cells, is widely expressed in testes and prostate tissues. The testis and prostate produce semen. At present, there are contradictory reports about whether SARS-CoV-2 can exist in the semen of infected men. Objective: To provide a comprehensive overview of the topic of whether COVID-19 can impact on male reproductive system. Methods: We reviewed the relevant publications on the possible impact of Coronavirus Disease 2019 (COVID-19) on male reproductive system and summarized the latest and most important research results so far. Literature published in English from December 2019 to January 31, 2021 regarding the existence of SARS-CoV-2 in semen, testis, and prostatic fluid and the effects of COVID-19 on male reproductive were included. Results: We identified 28 related studies, only one of which reported the presence of SARS-CoV-2 in semen. The study found that the semen quality of patients with moderate infection was lower than that of patients with mild infection and healthy controls. The impaired semen quality may be related to fever and inflammation. Pathological analysis of the testis/epididymis showed that SARS-CoV-2 viral particles were positive in 10 testicular samples, and the spermatogenic function of the testis was impaired. All 94 expressed prostatic secretion (EPS) samples were negative for SARS-CoV-2 RNA. Conclusion: The likelihood of SARS-CoV-2 in the semen of COVID-19 patients is very small, and semen should rarely be regarded as a carrier of SARS-CoV-2 genetic material. However, COVID-19 may cause testicular spermatogenic dysfunction via immune or inflammatory reactions. Long-term follow-up is needed for COVID-19 male patients and fetuses conceived during the father's infection period.

Cauda equina compression in metastatic prostate cancer.

A 67-year-old man presented to his general practitioner with intermittent episodes of unilateral sciatica over a 2-month period for which he was referred for an outpatient MRI of his spine. This evidenced a significant lumbar vertebral mass that showed tight canal stenosis and compression of the cauda equina. The patient was sent to the emergency department for management by orthopaedic surgeons. He was mobilising independently, pain free on arrival and without neurological deficit on assessment. Clinically, this patient presented with no red flag symptoms of cauda equina syndrome or reason to suspect malignancy. In these circumstances, National Institute for Health and Care Excellence guidelines do not support radiological investigation of the spine outside of specialist services. However, in this case, investigation helped deliver urgent care for cancer that otherwise may have been delayed. This leads to the question, do the current guidelines meet clinical requirements?

Surgical Delay and Pathological Outcomes for Clinically Localized High-Risk Prostate Cancer.

Importance: There is a lack of data evaluating the association of surgical delay time (SDT) with outcomes in patients with localized, high-risk prostate cancer. Objective: To investigate the association of SDT of radical prostatectomy and final pathological and survival outcomes. Design, Setting, and Participants: This cohort study used data from the US National Cancer Database (NCDB) and identified all patients with clinically localized (cT1-2cN0cM0) high-risk prostate adenocarcinoma diagnosed between 2006 and 2016 who underwent radical prostatectomy. Data analyses were performed from April 1 to April 12, 2020. Exposures: SDT was defined as the number of days between the initial cancer diagnosis and radical prostatectomy. SDT was categorized into 5 groups: 31 to 60, 61 to 90, 91 to 120, 121 to 150, and 151 to 180 days. Main Outcomes and Measures: The primary outcomes were predetermined as adverse pathological outcomes after radical prostatectomy, including pT3-T4 disease, pN-positive disease, and positive surgical margin. The adverse pathological score (APS) was defined as an accumulated score of the 3 outcomes (0-3). An APS of 2 or higher was considered a separate outcome to capture cases with more aggressive pathological features. The secondary outcome was overall survival. Results: Of the 32 184 patients included in the study, the median (interquartile range) age was 64 (59-68) years, and 25 548 (79.4%) were non-Hispanic White. Compared with an SDT of 31 to 60 days, longer SDTs were not associated with higher risks of having any adverse pathological outcomes (odds ratio [OR], 0.95; 95% CI, 0.80-1.12; P = .53), pT3-T4 disease (OR, 0.99; 95% CI, 0.83-1.17; P = .87), pN-positive disease (OR, 0.79; 95% CI, 0.59-1.06; P = .12), positive surgical margin (OR, 0.88; 95% CI, 0.74-1.05; P = .17), or APS greater than or equal to 2 (OR, 0.90; 95% CI, 0.74-1.05; P = .17). Longer SDT was also not associated with worse overall survival (for SDT of 151-180 days, hazard ratio, 1.12; 95% CI, 0.79-1.59, P = .53). Subgroup analyses performed for patients with very high-risk disease (primary Gleason score 5) and sensitivity analyses with SDT considered as a continuous variable yielded similar results. Conclusions and Relevance: In this cohort study of patients who underwent radical prostatectomy within 180 days of diagnosis for high-risk prostate cancer, radical prostatectomy for high-risk prostate cancer could be safely delayed up to 6 months after diagnosis.

The effect of delaying transperineal fusion biopsy of the prostate for patients with suspicious MRI findings-Implications for the COVID-19 era.

OBJECTIVE: Image guided biopsies are an integral part of prostate cancer evaluation. The effect of delaying biopsies of suspicious prostate mpMRI lesions is uncertain and clinically relevant during the COVID-19 crisis. We evaluated the association between biopsy delay time and pathologic findings on subsequent prostate biopsy. MATERIALS AND METHODS: After obtaining IRB approval we reviewed the medical records of 214 patients who underwent image-guided transperineal fusion biopsy of the prostate biopsy between 2017 and 2019. Study outcomes included clinically significant (ISUP grade group ≥2) and any prostate cancer on biopsy. Logistic regression was used to evaluate the association between biopsy delay time and outcomes while adjusting for known predictors of cancer on biopsy. RESULTS: The study cohort included 195 men with a median age of 68. Median delay between mpMRI and biopsy was 5 months, and 90% of patients had a ≤8 months delay. A significant association was found between PI-RADS 5 lesions and no previous biopsies and shorter delay time. Delay time was not associated with clinically significant or any cancer on biopsy. A higher risk of significant cancer was associated with older age (P = 0.008), higher PSA (0.003), smaller prostate volume (<0.001), no previous biopsy (0.012) and PI-RADS 5 lesions (0.015). CONCLUSIONS: Our findings suggest that under current practice, where men with PI-RADS 5 lesions and no previous biopsies undergo earlier evaluation, a delay of up to 8 months between imaging and biopsy does not affect biopsy findings. In the current COVID-19 crisis, selectively delaying image-guided prostate biopsies is unlikely to result in a higher rate of significant cancer.