Is there an association between a history of military service and cancer diagnosis? Results from a US national-level study of self-reported outcomes.

PURPOSE: To examine cancer prevalence in men with and without military service history, using national-level self-reported outcomes. METHODS: A cross-sectional survey-based US study, including men aged 18 and above from the Health Information National Trends Survey database between 2011 and 2014. The primary endpoint was self-reported cancer prevalence. Multivariable logistic regression analyses assessed the association of various covariates with the prevalence of cancer. RESULTS: A total of 4,527 men were analyzed, with 1,352 (29.9%) reporting a history of military service. Compared to men with no military service history, men with a military service history were older (median of 65 [IQR 56, 74] vs. 53 [IQR 41, 62] years, p < 0.0001), more commonly Caucasian (71.4% vs. 61.4%, p < 0.0001), born in the US (95.6% vs. 79.5%, p < 0.0001), attained higher education level and annual household income (p < 0.0001), and consisted of more smokers(58.3% vs. 44.5%, p < 0.0001). The age-adjusted comparison demonstrated a higher cancer prevalence in men with military service history (20.5% vs. 7.6%, p < 0.0001). Specifically, genitourinary, dermatological, gastrointestinal, and hematological cancers were generally more prevalent. Adjusting for all available confounders, multivariable models showed that military service history was associated with 1.56 (95% CI 1.20-2.03), and 1.57 (95% CI 1.07-2.31) increased odds of having any cancer, and specifically genitourinary cancer, respectively. CONCLUSIONS: Further research is needed to ascertain whether the association between military service and increased cancer diagnosis results from better screening programs or increased exposure to risk factors during military service.

Can post-treatment free PSA ratio be used to predict adverse outcomes in recurrent prostate cancer?

OBJECTIVES: To assess whether free PSA ratio (FPSAR) at biochemical recurrence (BCR) can predict metastasis, castrate-resistant prostate cancer (CRPC), and cancer-specific survival (CSS), following therapy for localised disease. PATIENTS AND METHODS: A single-centre retrospective cohort study (NCT03927287) including a discovery cohort composed of patients with an FPSAR after radical prostatectomy (RP) or radiotherapy (RT) between 2000 and 2017. For validation, an independent Biobank cohort of patients with BCR after RP was tested. Using a defined FPSAR cut-off, the metastasis-free-survival (MFS), CRPC-free survival, and CSS were compared. Multivariable Cox models determined the association between post-treatment FPSAR, metastases, and CRPC. RESULTS: Overall, 822 patients (305 RP- and 363 RT-treated patients and 154 Biobank patients) were analysed. In the RP cohort, a total of 272/305 (89.1%) and 33/305 (10.9%) had a FPSAR test incidentally and reflexively, respectively. In the RT cohort, 155/363 (42.7%) and 208/263 (57.3%) had a FPSAR test incidentally and reflexively, respectively. However, in the prospective Biobank RP cohort, FPSAR testing was done on all samples of patients diagnosed with BCR. A FPSAR cut-off of 0.10 was determined using receiver operating characteristic analyses in both the RP and RT cohorts. A FPSAR of <0.10 resulted in longer median MFS (14.8 vs 9.3 years and 14.8 vs 13 years, respectively), and longer median CRPC-free survival (median not reached vs 9.9 years and 20.7 vs 13.8 years, respectively). Multivariable analyses showed that a FPSAR of ≥0.10 was associated with increased metastasis in the RP cohort (hazard ratio [HR] 1.915, 95% confidence interval [CI] 1.241-2.955) and RT cohort (HR 1.754, 95% CI 1.112-2.769), and increased CRPC in the RP cohort (HR 2.470, 95% CI 1.493-4.088). Findings were validated in the Biobank cohort. CONCLUSIONS: A post-treatment FPSAR of ≥0.10 is associated with more aggressive disease, suggesting a potentially novel role for this biomarker.

Attitude is everything: keep probe pitch neutral during side-fire prostate biopsy. A simulator study.

OBJECTIVES: To develop and validate on a simulator a learnable technique to decrease deviation of biopsied cores from the template schema during freehand, side-fire systematic prostate biopsy (sPBx) with the goal of reducing prostate biopsy (PBx) false-negatives, thereby facilitating earlier sampling, diagnosis and treatment of clinically significant prostate cancer. PARTICIPANTS AND METHODS: Using a PBx simulator with real-time three-dimensional visualization, we devised a freehand, pitch-neutral (0°, horizontal plane), side-fire, transrectal ultrasonography (TRUS)-guided sPBx technique in the left lateral decubitus position. Thirty-four trainees on four Canadian and US urology programmes learned the technique on the same simulator, which recorded deviation from the intended template location in a double-sextant template as well as the TRUS probe pitch at the time of sampling. We defined deviation as the shortest distance in millimeters between a core centre and its intended template location, template deviation as the mean of all deviations in a template, and mastery as achieving a template deviation ≤5.0 mm. RESULTS: All results are reported as mean ± sd. The mean absolute pitch and template deviation before learning the technique (baseline) were 8.2 ± 4.1° and 8.0 ± 2.7 mm, respectively, and after mastering the technique decreased to 4.5 ± 2.7° (P = 0.001) and 4.5 ± 0.6 mm (P < 0.001). Template deviation was related to mean absolute pitch (P < 0.001) and increased by 0.5 mm on average with each 1° increase in mean absolute pitch. Participants achieved mastery after practising 3.9 ± 2.9 double-sextant sets. There was no difference in time to perform a double-sextant set at baseline (277 ± 102 s) and mastery (283 ± 101 s; P = 0.39). CONCLUSION: A pitch-neutral side-fire technique reduced template deviation during simulated freehand TRUS-guided sPBx, suggesting it may also reduce PBx false-negatives in patients in a future clinical trial. This pitch-neutral technique can be taught and learned; the University of Florida has been teaching it to all Urology residents for the last 2 years.

Does Time Spent on Active Surveillance Adversely Affect the Pathological and Oncologic Outcomes in Patients Undergoing Delayed Radical Prostatectomy?

PURPOSE: Pathological and oncologic outcomes of delayed radical prostatectomy following prostate cancer active surveillance are not well established. We determined the pathological and oncologic outcomes of favorable risk, Grade Group 1, prostate cancer managed with active surveillance and progressing to radical prostatectomy for clinically significant prostate cancer (Grade Group 2 or greater). MATERIALS AND METHODS: Between 1992 and 2015, 170 men with favorable risk prostate cancer underwent delayed radical prostatectomy for clinically significant prostate cancer (ASRP) at the Princess Margaret Cancer Centre. Pathological and oncologic outcomes of the ASRP cohort were compared with a matched cohort treated with up-front radical prostatectomy (405) immediately before surgery. Biochemical recurrence-free survival, overall survival and cancer specific survival were compared. We examined the association between delayed radical prostatectomy and adverse pathology at radical prostatectomy and biochemical recurrence using logistic and Cox regression analyses, respectively. RESULTS: Median time spent on active surveillance before radical prostatectomy was 31.0 months. At radical prostatectomy pT3 (extraprostatic extension, seminal vesicle invasion), positive surgical margin and pN1 rates were comparable between the 2 cohorts. Median followup after radical prostatectomy was 5.6 years. The 5-year biochemical recurrence-free survival rate in the ASRP cohort and up-front radical prostatectomy cohort were 85.8% and 82.4%, respectively (p=0.38). Overall survival and cancer specific survival were comparable between the 2 groups. Delayed radical prostatectomy was not associated with adverse pathological outcomes and biochemical recurrence on regression analyses. CONCLUSIONS: Curative intent radical prostatectomy after a period of active surveillance results in excellent pathological and oncologic outcomes at 5 years. A period of active surveillance does not result in inferior outcomes compared to patients with similar risk characteristics undergoing up-front radical prostatectomy.

Comparison of Magnetic Resonance Imaging and Transrectal Ultrasound Informed Prostate Biopsy for Prostate Cancer Diagnosis in Biopsy Naïve Men: A Systematic Review and Meta-Analysis.

PURPOSE: Multiparametric magnetic resonance imaging with informed targeted biopsies has changed the paradigm of prostate cancer diagnosis. Randomized studies have demonstrated a diagnostic benefit of clinical significance for targeted biopsy compared to standard systematic biopsies. We evaluated whether multiparametric magnetic resonance imaging informed targeted biopsy has superior diagnosis rates of any, clinically significant, high grade and clinically insignificant prostate cancer compared to systematic biopsy in biopsy naïve men. MATERIALS AND METHODS: Data were searched in Medline®, Embase®, Web of Science and Evidence-Based Medicine Reviews-Cochrane Database of Systematic Reviews from database inception until 2019. Studies were selected by 2 authors independently, with disagreements resolved by consensus with a third author. Overall 1,951 unique references were identified and 100 manuscripts underwent full-text review. Data were pooled using random effects models. The meta-analysis is reported according to the PRISMA statement and the study protocol is registered with PROSPERO (CRD42019128468). RESULTS: Overall 29 studies (13,845 patients) were analyzed. Compared to systematic biopsy, use of multiparametric magnetic resonance imaging informed targeted biopsy was associated with a 15% higher rate of any prostate cancer diagnosis (95% CI 10-20, p <0.00001). This relationship was not affected by the study methodology (p=0.11). Diagnoses of clinically significant and high grade prostate cancer were more common in the multiparametric magnetic resonance imaging informed targeted biopsy group (risk difference 11%, 95% CI 0-20, p=0.05 and 2%, 95% CI 1-4, p=0.005, respectively) while there was no difference in diagnosis of clinically insignificant prostate cancer (risk difference 0, 95% CI -3 to 3, p=0.96). Notably, the exclusion of systematic biopsy in the multiparametric magnetic resonance imaging informed targeted biopsy arm significantly modified the association between a multiparametric magnetic resonance imaging strategy and lower rates of clinically insignificant prostate cancer diagnosis (p=0.01) without affecting the diagnosis rates of clinically significant or high grade prostate cancer. CONCLUSIONS: Compared to systematic biopsy a multiparametric magnetic resonance imaging informed targeted biopsy strategy results in a significantly higher diagnosis rate of any, clinically significant and high grade prostate cancer. Excluding systematic biopsy from multiparametric magnetic resonance imaging informed targeted biopsy was associated with decreased rates of clinically insignificant prostate cancer diagnosis without affecting diagnosis of clinically significant or high grade prostate cancer.

Gender-based psychological and physical distress differences in patients diagnosed with non-metastatic renal cell carcinoma.

OBJECTIVES: To analyze gender-based differences in distress symptoms in patients with non-metastatic renal cell carcinoma (RCC) at different stages of disease. METHODS: The Edmonton Symptom Assessment System-revised (ESAS-r) questionnaire includes a physical (PHSDSS) and a psychological distress sub-score (PDSS). The ESAS-r was used to measure psychological and physical distress symptoms in localized RCC patients in a major cancer referral center between 2014 and 2017 at four predefined time points: (a) diagnosis, (b) biopsy, (c) surgery, and (d) last follow-up. Results were gender stratified, and multivariable linear regression models were used to determine associations with increased sub-scores. RESULTS: Overall, 495 patients were included with 37.2% females. No significant gender differences were seen in mean age, relevant clinical parameters, and treatment. PDSS was significantly higher in females after diagnosis (8.5 vs. 5.1, p = 0.018), biopsy (8.9 vs. 4.1, p = 0.003), and surgery (6.5 vs. 4.4, p = 0.007), while being similar at the last follow-up. The multivariable model demonstrated a statistically significant association of female gender with higher PDSS after diagnosis (B = 3.755, 95% CI 0.761-6.750), biopsy (B = 6.076, 95% CI 2.701-9.451), and surgery (B = 1.974, 95% CI 0.406-3.542). PHSDSS was significantly higher in females after biopsy (10.0 vs. 5.7, p = 0.028) and surgery (8.6 vs. 6.1, p = 0.022). In the multivariable model, female gender conferred a higher PHSDSS only after surgery (B = 2.384, 95% CI 0.208-4.560). CONCLUSIONS: Gender-associated psychological distress differences exist in non-metastatic RCC patients throughout treatment, while dissipating at last follow-up. Emphasis should be placed on screening for distress symptoms and providing psychological support continuously, particularly for female patients.

Predictors of prostate-specific antigen testing in men aged ≥55 years: A cross-sectional study based on patient-reported outcomes.

OBJECTIVES: To examine the predictors of prostate-specific antigen discussion with a physician and prostate-specific antigen testing in men aged ≥55 years. METHODS: Utilizing the USA Health Information National Trends Survey, 4th Ed., a cross-sectional study from 2011 to 2014 was carried out to analyze the factors predicting prostate-specific antigen testing and discussion in men ≥55 years. Associations between each covariate and prostate-specific antigen discussion/testing were determined. Multivariable logistic regression models were used to determine clinically relevant predictors of prostate-specific antigen discussion/testing. Due to multiple comparisons, the Bonferroni correction was used. RESULTS: A total of 2731 men included in the Health Information National Trends Survey were analyzed. Several socioeconomic parameters were found to increase the likelihood of men aged ≥55 years to undergo prostate-specific antigen testing: living with a spouse, a higher level of education (college graduate or above), a higher income (>$50 000 annually) and previous history of any cancer. In contrast, current smokers were less likely to undergo prostate-specific antigen testing. Having a prostate-specific antigen discussion with a physician was more likely for men surveyed in 2014, for men who were living with a spouse, who had a higher annual income (>$50 000 annually) and those with a history of any cancer. CONCLUSIONS: Significant inequalities in prostate-specific antigen testing and discussion exist among men in the USA, mainly driven by socioeconomic factors. Ideally, prostate-specific antigen testing and discussion should be based on relevant clinical factors with a shared decision-making approach for every man. Therefore, a better understanding of the socioeconomic factors influencing prostate-specific antigen testing/discussions can inform strategies to reduce existing gaps in care.

Natural History of Complex Renal Cysts: Clinical Evidence Supporting Active Surveillance.

PURPOSE: We evaluated intervention rates, progression and cancer specific survival outcomes in patients with complex renal cysts in a single center experience. MATERIALS AND METHODS: We used the Montage™ radiology data mining system to retrospectively identify all reported cases of complex renal cyst at our institution from 2001 to 2013. The primary study end points were overall and cancer specific survival. The secondary end points included radiographic progression and upgrading, clinical progression and final histology on surgical pathology. RESULTS: We identified 336 patients with a complex renal cyst, of whom 185 (55.1%), 122 (36.3%) and 29 (8.6%) had Bosniak IIF, III and IV cysts, respectively. Median followup was 67.1 months (range 34.4 to 101.6). In the 332 patients with followup there was 1 cancer specific death (0.3%) and overall mortality was 6.2%. Ten (5.4%), 37 (30.3%) and 18 patients (62.1%) with Bosniak IIF, III and IV, respectively, underwent surgical or ablative intervention. The indication for intervention was predominantly age (intervention vs no intervention mean ± SD age 50.1 ± 15.9 vs 62.5 ± 13.9 years) and complexity. Surgery with radical and partial nephrectomy (23 patients or 35% and 37 or 57%, respectively) was most common and favorable final pathology was identified. Two treated patients experienced recurrence during followup. When excluding patients with von Hippel-Lindau syndrome, the cancer specific survival rate was 100%. CONCLUSIONS: Cancer survival and overall survival in patients with Bosniak IIF to IV renal cysts was high with only 1 cancer specific death. No cancer deaths were recorded in patients who did not undergo intervention. Reconsidering management guidelines for complex renal cysts is warranted, particularly consideration for initial surveillance of Bosniak III cysts.

Serum miRNA Predicts Viable Disease after Chemotherapy in Patients with Testicular Nonseminoma Germ Cell Tumor.

PURPOSE: Retroperitoneal lymph node dissection is recommended for residual masses greater than 1 cm after chemotherapy of nonseminomatous germ cell tumors. Currently there is no reliable predictor of post-chemotherapy retroperitoneal lymph node dissection histology. Up to 50% of patients harbor necrosis/fibrosis only so that a potentially morbid surgery has limited therapeutic value. In this study we evaluated the ability of defined serum miRNAs to predict residual viable nonseminomatous germ cell tumors after chemotherapy. MATERIALS AND METHODS: Levels of serum miRNA, including miR-371a-3p, miR-373-3p and miR-367-3p, were measured using the ampTSmiR (amplification targeted serum miRNA) test in 82 patients, including 39 in cohort 1 and 43 in cohort 2, who were treated with orchiectomy, chemotherapy and post-chemotherapy retroperitoneal lymph node dissection. miRNA levels were compared to clinical characteristics and serum tumor markers, and correlated with the presence of viable germ cell tumor vs fibrosis/necrosis and teratoma. ROC analysis was done to determine miRNA discriminative capacity. RESULTS: miRNA levels were significantly associated with disease extent at chemotherapy and they decreased significantly after chemotherapy. Conventional serum tumor marker levels were uninformative after chemotherapy. However, after chemotherapy miRNA levels remained elevated in patients harboring viable germ cell tumor in post-chemotherapy retroperitoneal lymph node dissection specimens. miR-371a-3p demonstrated the highest discriminative capacity for viable germ cell tumors (AUC 0.874, 95% CI 0.774-0.974, p <0.0001). Using an adapted hypothetical cutoff of 3 cm or less for surgical intervention miR-371a-3p correctly stratified all patients with viable residual retroperitoneal germ cell tumors with 100% sensitivity (p = 0.02). CONCLUSIONS: Our study demonstrates for the first time the potential value of miR-371a-3p to predict viable germ cell tumors in residual masses after chemotherapy. Prospective studies are required to confirm clinical usefulness.

Radical Prostatectomy for Patients With Oligometastatic Prostate Cancer.

Cancer progresses in a stepwise fashion. Oligometastatic cancer is an intermediate stage of tumor spread between localized disease and disseminated metastases. Oligometastatic prostate cancer is defined as up to five extrapelvic lesions on conventional imaging. There are controversies surrounding the management of this malignancy, but retrospective and population-based studies suggest a role for radical prostatectomy. Despite insufficient data to draw conclusions regarding the effectiveness of aggressive therapies on overall or cancer-specific survival of patients with oligometastatic prostate cancer, current studies suggest that surgery decreases tumor burden, disease-related morbidity, and the need for palliative surgical intervention, while increasing the period of time to development of castration-resistant disease.

Should Small Renal Masses Be Biopsied?

Over the last few decades, the incidence of renal cell carcinomas (RCCs) has been steadily increasing. This is primarily due to an increase in detection of small renal masses (SRMs) as a result of widespread utilization of abdominal imaging. Interestingly, up to 30% of incidentally discovered SRMs (solid lesions measuring ≤4 cm) are benign, and consequently, the definitive treatment of all SRMs is associated with a considerable risk of overtreatment. To decrease the overtreatment rate, renal tumour biopsy (RTB) has been advocated as a safe alternative to identify the pretreatment histology of these SRMs. Although initially fraught with high non-diagnostic rates, more recent series from centres of experience have demonstrated that RTB is safe, reliable and accurate. The future of SRM management will combine pathological, molecular and genetic information to improve our ability to predict the behaviour of these lesions and herald risk-adapted personalized treatment.

Manufacturers' data show increasing implanted cylinder sizes and measured corporal lengths in inflatable penile implants.

INTRODUCTION: We sought to determine whether measured corporal length (MCL) or implanted device size (IDS) has changed. METHODS: Data were obtained from the two major penile implant companies from the years of 2005-2010 and analyzed. While we requested similar data, companies supplied information at their discretion with MCL provided by American Medical Systems and IDS provided by Coloplast. Intra-patient corporal discrepancies, disease state effects, rear tip extenders (RTEs) use and place of implantation were also provided in some part by companies. RESULTS: MCL and IDS increased during the study period. Despite the general trend of MCL/IDS, clinically significant (0.5 cm or greater) decreases in MCLs were noted in patients with Peyronie's disease (PD) or a history of radical pelvic surgery (excludes prostatectomy). In only 2.7 % of cases was there an intra-patient discrepancy in cylinder size (>1 cm). IDS was longer in the USA (US, 19.4 cm) compared to outside the US (OUS, 17.7 cm, p < 0.0001). Cylinders were implanted without RTEs in 48.3 % of US cases and 73.7 % of OUS cases (p < 0.0001). In Coloplast devices there was an overall statistically significant change in the use of 16 cm (less utilized) and 20 and 22 cm (more utilized) cylinder lengths during the study period in US implants. CONCLUSION: MCL and IDS increased during the study period. Men with a history of PD or radical pelvic surgery are at highest risk to have shorter MCL and to possibly receive shorter implants. Intra-patient IDS inconsistency is rare and should prompt investigation.

Primary Whole-gland Ablation for the Treatment of Clinically Localized Prostate Cancer: A Focal Therapy Society Best Practice Statement.

CONTEXT: Whole-gland ablation is a feasible and effective minimally invasive treatment for localized prostate cancer (PCa). Previous systematic reviews supported evidence for favorable functional outcomes, but oncological outcomes were inconclusive owing to limited follow-up. OBJECTIVE: To evaluate the real-world data on the mid- to long-term oncological and functional outcomes of whole-gland cryoablation and high-intensity focused ultrasound (HIFU) in patients with clinically localized PCa, and to provide expert recommendations and commentary on these findings. EVIDENCE ACQUISITION: We performed a systematic review of PubMed, Embase, and Cochrane Library publications through February 2022 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. As endpoints, baseline clinical characteristics, and oncological and functional outcomes were assessed. To estimate the pooled prevalence of oncological, functional, and toxicity outcomes, and to quantify and explain the heterogeneity, random-effect meta-analyses and meta-regression analyses were performed. EVIDENCE SYNTHESIS: Twenty-nine studies were identified, including 14 on cryoablation and 15 on HIFU with a median follow-up of 72 mo. Most of the studies were retrospective (n = 23), with IDEAL (idea, development, exploration, assessment, and long-term study) stage 2b (n = 20) being most common. Biochemical recurrence-free survival, cancer-specific survival, overall survival, recurrence-free survival, and metastasis-free survival rates at 10 yr were 58%, 96%, 63%, 71-79%, and 84%, respectively. Erectile function was preserved in 37% of cases, and overall pad-free continence was achieved in 96% of cases, with a 1-yr rate of 97.4-98.8%. The rates of stricture, urinary retention, urinary tract infection, rectourethral fistula, and sepsis were observed to be 11%, 9.5%, 8%, 0.7%, and 0.8%, respectively. CONCLUSIONS: The mid- to long-term real-world data, and the safety profiles of cryoablation and HIFU are sound to support and be offered as primary treatment for appropriate patients with localized PCa. When compared with other existing treatment modalities for PCa, these ablative therapies provide nearly equivalent intermediate- to long-term oncological and toxicity outcomes, as well as excellent pad-free continence rates in the primary setting. This real-world clinical evidence provides long-term oncological and functional outcomes that enhance shared decision-making when balancing risks and expected outcomes that reflect patient preferences and values. PATIENT SUMMARY: Cryoablation and high-intensity focused ultrasound are minimally invasive treatments available to selectively treat localized prostate cancer, considering their nearly comparable intermediate- to long term cancer control and preservation of urinary continence to other radical treatments in the primary setting. However, a well-informed decision should be made based on one's values and preferences.

The association of statin subgroups with lower urinary tract symptoms following a prostate biopsy.

INTRODUCTION: This was a secondary analysis aiming to assess whether hydrophilic or hydrophobic statins have a differential effect on urinary retention (UR) and lower urinary tract symptoms (LUTS) in men following a prostate biopsy (PBx), who were at risk for prostate cancer development. METHODS: This was a population-based cohort study with data incorporated from the Institute for Clinical and Evaluative Sciences database to identify all Ontarian men aged 66 and above with a history of a single negative PBx between 1994 and 2016, with no drug prescription history of any of several putative chemo-preventative medications (statins, proton pump inhibitors, five-alpha-reductase inhibitors, and alpha-blockers). Multivariable Cox regression models with time-dependent covariates were used to assess the association of hydrophilic and hydrophobic statins with UR and LUTS within 30 days of a PBx. All models were adjusted for other known putative chemopreventive medications, age, rurality, pharmacologically treated diabetes, comorbidity score, and study inclusion year. RESULTS: Overall, 21 512 men were included, with a median followup time of 9.4 years (interquartile range [IQR] 5.4-13.4 years). Hydrophobic and hydrophilic statins were initiated by 30.7% and 19.6% of men, respectively, after the first negative PBx. UR and LUTS were experienced by 2.2% and 10% of men, respectively. Cox models demonstrated hydrophilic statins were associated with a lower risk of UR (hazard ratio [HR] 0.56, 95% confidence interval [CI] 0.38-0.83, p=0.0038) and LUTS (HR 0.86, 95% CI 0.76-0.98, p=0.022), while no such association was shown for hydrophobic statins. CONCLUSIONS: Initiation of hydrophilic statins in men older than 66 appears to be inversely associated with the risk of UR and LUTS within 30 days of a PBx.

Management of urologic cancers during the pandemic and potential impact of treatment deferrals on outcomes.

The COVID-19 pandemic-related constraints on healthcare access have raised concerns about adverse outcomes from delayed treatment, including the risk of cancer progression and other complications. Further, concerns were raised about a potentially significant backlog of patients in need of cancer care due to the pandemic-related delays in healthcare, further exacerbating any potential adverse outcomes. Delayed access to surgery is particularly relevant to urologic oncology since one-third of new cancers in men (20% overall) arise from the genitourinary (GU) tract and surgery is often the primary treatment. Herein, we summarize the prepandemic literature on deferred surgery for GU cancers and risk of disease progression. The aforementioned data on delayed surgery were gathered in the context of systemic delays present in certain healthcare systems, or occasionally, due to planned deferral in suboptimal surgical candidates. These data provide indirect, but sufficient insight to develop triage schemas for prioritization of uro-oncological cases. Herein, we outline the extent to which the pandemic-related triage guidelines had influenced urologic practice in various regions. To study the adverse outcomes in the pandemic-era, a survey of urologic oncologists was conducted regarding modifications in their initial management of urologic cancers and any delay-related adverse outcomes. While the adverse effects directly from COVID-19 related delays will become apparent in the coming years, the results showing short-term outcomes are quite instructive. Since cancer care was assigned a higher priority at most centers, this strategy may have avoided significant delays in care and limited the anticipated negative impact of pandemic-related constraints.

Defining oligometastatic hormone sensitive prostate cancer and clinically significant outcomes: Implications on clinical trials?

PURPOSE: With the current movement toward treating oligometastatic hormone sensitive prostate cancer (OMPC), we design a study with the objective of gathering opinions regarding what would be considered a clinically significant benefit from such treatments. METHODS: Data was collected from physicians of the Society of Urologic Oncology using a self-administered questionnaire using SurveyMonkey. The questionnaire was designed to obtain characteristics on clinical practice of the respondents, definitions used for OMPC and also what would be considered a clinically significant benefit according to the respondents. We present a descriptive analysis of the responses obtained. RESULTS: We obtained 119 responses (response rate of 12.6%) after sending the questionnaire twice with one month apart. Most of them being staff/faculty (89%) practicing in the United States of America (84.87%). Most of the responders referred that a significant proportion of their practice comes from PC patients. Most defined OMPC <3 bone/lymph node metastasis seen with conventional imaging, only 26.9% of the responders used positron emission tomography. Regarding the clinical benefit of metastasis-oriented treatment, a curing rate >10% or an increase in 1 year of androgen deprivation therapy-free survival would make the treatment worthwhile. We present examples of sample size calculations for future clinical trials using these parameters as an expected "clinically-significant" benefit. CONCLUSION: This study shows that most clinicians still support the use of conventional imaging to define OMPC. Our findings show that a curing rate of a minimum of 11% and an androgen deprivation therapy-free survival at 1 year are considered clinically significant and this should be used for estimating the sample size in future clinical trials.

The suggested chemopreventive association of metformin with prostate cancer in diabetic patients.

PURPOSE: Metformin, an insulin sensitizer, is the most common first-line antidiabetic therapy. There is increasing evidence suggesting metformin can prevent the emergence of prostate cancer (CaP). We aimed to analyze the chemopreventive role of metformin, in conjunction with other putative chemopreventive medications (statins, proton-pump-inhibitors, alpha-blockers, 5-alpha-reductase inhibitors, diabetic medications) in a population-based cohort study. METHODS: Data were incorporated from the Institute for Clinical and Evaluative Sciences to identify all diabetic men aged 66 and above with prior history of a negative prostate biopsy (PB) between 1994 and 2016, who were not on any of the medications prior to study inclusion. Multivariable Cox regression models with time-dependent covariates were used to assess the association of metformin to CaP diagnosis, subsequent PB, and use of androgen deprivation therapy (ADT). All models were adjusted for age, rurality, comorbidity, and year of study inclusion. RESULTS: Overall, 2,332 diabetic men were included, with a median follow-up time of 9.4 years (interquartile range 5.4-13.4 years). A total of 2,036 patients (87.3%) received metformin. Compared to non-metformin users, metformin use was associated with decreased CaP diagnosis rate (HR 0.69, 95%CI 0.54-0.88, P = 0.003), lower hazard of undergoing an additional PB (HR 0.64, 95%CI 0.44-0.95, P = 0.03), and receiving ADT (HR 0.72, 95%CI 0.54-0.96, P = 0.003). CONCLUSION: Men receiving metformin were less likely to have suspected or diagnosed CaP, and in those with CaP, the use of ADT was less common. Ongoing prospective randomized studies will determine if these findings correspond to the suggested associations of metformin in the emergence and/or progression of CaP.

Clinical-genomic Characterization Unveils More Aggressive Disease Features in Elderly Prostate Cancer Patients with Low-grade Disease.

BACKGROUND: Over 20% of men diagnosed with prostate cancer (PC) are ≥75 yr old. More objective disease-specific indices for predicting outcomes beyond chronological age are necessary. OBJECTIVE: To analyze age-related differences in clinical-genomic prognostic features of aggressiveness in localized PC. DESIGN, SETTING, AND PARTICIPANTS: A retrospective multicenter cross-sectional study reported the use of the Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK) guidelines. Clinical-genomic data of patients who underwent a prostate biopsy or radical prostatectomy (RP) were obtained from the Decipher Genomic Resource Information Database (NCT02609269). INTERVENTION: Our analyses focused on the 22-gene Decipher genomic classifier (GC) and 50-gene (PAM50) models in the biopsy and RP cohorts stratified by age. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was the impact of age on GC scores and PAM50 molecular subtypes. Prognostic indices including Decipher GC scores, PAM50 molecular subtypes, National Comprehensive Cancer Network risk categories, and ISUP grade groups (IGGs) were stratified by age using multivariable logistic regression analyses. RESULTS AND LIMITATIONS: Within histological low-risk IGGs, there were a higher proportion of patients with high-risk Decipher biopsy scores with age (age <60 yr: 10.1% IGG 1 and 29.9% IGG 2 vs age ≥80 yr: 22% IGG 1 and 37.7% IGG 2). The prevalence of the adverse phenotype luminal B (PAM50-defined) increased with age (age <60 yr: 22.7% and 40.2% vs age ≥80 yr: 29.7% and 49.1%, in patients with IGG 1 and IGG 2, respectively). In IGGs 3-5, no age differences were observed. Multivariable models demonstrated that each age decile entailed a 19% (odds ratio [OR] 1.19, 95% confidence interval [CI] 1.10-1.29, p < 0.001) and a 10% (OR 1.1, 95% CI 1.05-1.16) increased probability for a high-risk Decipher biopsy and RP score, respectively. Aside from an obvious selection bias, data on race, family history, prostate volume, and long-term follow-up outcomes were unavailable. CONCLUSIONS: These data demonstrated that elderly men with favorable pathology (IGG 1-2), might harbor more aggressive disease than younger patients based on validated GC scores. PATIENT SUMMARY: The presented clinical-genomic data demonstrate that elderly patients with low-risk prostate cancer might harbor more aggressive disease than their younger counterparts. This suggests that standard well-accepted paradigm of elderly prostate cancer patients not being aggressively treated, based solely on their chronological age, might need to be reconsidered.

The Suggested Unique Association Between the Various Statin Subgroups and Prostate Cancer.

BACKGROUND: The chemopreventive effect of various medications in prostate cancer (PCa) has gained interest. Specifically, the potential impact of statins on PCa incidence has been studied, but solely as a "drug family" overlooking the distinctive pharmacological properties of its two main subgroups: hydrophilic and hydrophobic statins. OBJECTIVE: To assess the impact of statin subgroups on PCa-specific mortality (PCSM), PCa diagnosis, and undergoing another prostate biopsy. DESIGN, SETTING, AND PARTICIPANTS: This is a population-based cohort study in Ontario identifying all men aged ≥66 yr with a history of a single negative prostate biopsy (representing healthy men at risk for PCa) between 1994 and 2016, who were not on any of the analyzed medications prior to the study, with a median follow-up of 9.42 yr (interquartile range 8.03 yr). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Using multivariable cause-specific hazard models with time-dependent covariates, the association of hydrophobic and hydrophilic statins with all study outcomes was analyzed. Other putative chemopreventive medications (including alpha-blockers, 5-alpha-reductase inhibitors, and proton-pump inhibitors), age, rurality, comorbidities, and study inclusion year were included in the models. RESULTS AND LIMITATIONS: Overall, 21 512 men were identified. Statins were taken by 11 401 patients (50.3%), 5184 men (24.1%) were diagnosed with PCa, and 805 (3.7%) died from it. Overall, 7556 patients (35.1%) underwent another biopsy. Any use of hydrophilic statins was associated with a 32.4% (95% confidence interval [CI] 12.9-47.5%), a 20% (95% CI 10-28%), and an 18% (95% CI 6.1-27.3%) decreased risk of PCSM, undergoing another prostate biopsy, and being diagnosed with PCa, respectively. Hydrophobic statins were associated with 17% (95% CI 2-31%) decreased PCSM. The study is limited by its retrospective nature, selection bias, and accompanying health-administrative database inaccuracies. CONCLUSIONS: Use of any statin may be associated with a lower hazard of PCSM, with hydrophilic statins showing a greater association with decreased PCa diagnosis rates. Preferentially prescribing one statin subgroup over another in men needs further exploration. PATIENT SUMMARY: Use of any statin may be associated with a lower probability of dying from prostate cancer. Hydrophilic statins (rosuvastatin and pravastatin) may also be more positively associated with a lower risk of undergoing an additional prostate biopsy and being diagnosed with prostate cancer in men aged ≥66 yr.