Genetic testing practices among specialist physicians who treat prostate cancer A Canadian, cross-sectional survey.

INTRODUCTION: In patients with prostate cancer (PCa), the identification of an alteration in genes associated with homologous recombination repair (HRR) has implications for prognostication, optimization of therapy, and familial risk mitigation. The aim of this study was to assess the genomic testing landscape of PCa in Canada and to recommend an approach to offering germline and tumor testing for HRR-associated genes. METHODS: The Canadian Genitourinary Research Consortium (GURC) administered a cross-sectional survey to a largely academic, multidisciplinary group of investigators across 22 GURC sites between January and June 2022. RESULTS: Thirty-eight investigators from all 22 sites responded to the survey. Germline genetic testing was initiated by 34%, while 45% required a referral to a genetic specialist. Most investigators (82%) reported that both germline and tumor testing were needed, with 92% currently offering germline and 72% offering tissue testing to patients with advanced PCa. The most cited reasons for not offering testing were an access gap (50%), uncertainties around who to test and which genes to test, (33%) and interpreting results (17%). A majority reported that patients with advanced PCa (74-80%) should be tested, with few investigators testing patients with localized disease except when there is a family history of PCa (45-55%). CONCLUSIONS: Canadian physicians with academic subspecialist backgrounds in genitourinary malignancies recognize the benefits of both germline and somatic testing in PCa; however, there are challenges in accessing testing across practices and specialties. An algorithm to reduce uncertainty for providers when ordering genetic testing for patients with PCa is proposed.

Laparoscopic-guided radiofrequency ablation is safe for the treatment of enhancing renal masses among patients prescribed antithrombotic agents.

Patients undergoing laparoscopic-guided radiofrequency ablation (LRFA) for the treatment of a renal mass are commonly prescribed antithrombotic agents for the management of comorbid medical diseases. We retrospectively evaluated the safety of LRFA in this group. From October 2005 to June 2010, 109 patients underwent LRFA. Antithrombotic therapy was prescribed to 52 of these patients. Agents were managed the week of surgery per current practice guidelines from the American College of Chest Physicians. Intraoperatively, patients prescribed at least one antithrombotic agent lost a median of 10 mL of blood, while patients not on an antithrombotic agent also lost 10 mL of blood (P = .828). Both groups had a similar rate of procedure-related complications (intraoperative, P = 1.00; postoperative, P = .673). No patient required a blood transfusion or experienced a postoperative thromboembolic event. In conclusion, when current practice guidelines are followed, LRFA is safe among patients prescribed antithrombotic agents.

Oncological and functional outcomes following open radical prostatectomy: how patients may achieve the "Trifecta"?

PURPOSE: The desirable outcomes after open radical prostatectomy (RP) for localized prostate cancer (PC) are to: a) achieve disease recurrence free, b) urinary continence (UC), and c) maintain sexual potency (SP). These 3 combined desirable outcomes we called it the "Trifecta". Our aim is to assess the likelihood of achieving the Trifecta, and to analyze the influencing the Trifecta. MATERIALS AND METHODS: A total of 1738 men with localized PC underwent RP from 1992-2007 by a single surgeon. The exclusion criteria for this analysis were: preoperative hormonal or radiation therapy, preoperative urinary incontinence or erectile dysfunction, follow-up less than 24 months or insufficient data. Post-operative Trifecta factors were analyzed, including biochemical recurrence (BR). We defined: BR as PSA ≥ 0.2 ng/mL, urinary continence as wearing no pads, and sexual potency as having erections sufficient for intercourse with or without a phosphodiesterase-5 inhibitor. RESULTS: A total of 831 patients met the inclusion criteria. The mean age of the entire cohort was 59 years old. The median follow-up was 52 months (mean 60, range 24-202). The BR, UC and SP rates were 18.7%, 94.5%, and 71% respectively. Trifecta was achieved in 64% at 2 year follow-up, and 61% at 5 year follow-up. Multivariate analysis revealed age at time of surgery, pathologic Gleason score (PGS), pathologic stage, specimen weight, and nerve sparing (NS) were independent factors. CONCLUSIONS: Age at time of surgery, pathologic GS, pathologic stage, specimen weight and NS were independent predictors to achieve the Trifecta following radical prostatectomy. This information may help patients counseling undergoing radical prostatectomy for localized prostate cancer.

Oncological and functional outcomes following open radical prostatectomy: how patients may achieve the "trifecta"?

PURPOSE: The desirable outcomes after open radical prostatectomy (RP) for localized prostate cancer (PC) are to: a) achieve disease recurrence free, b) urinary continence (UC), and c) maintain sexual potency (SP). These 3 combined desirable outcomes we called it the "Trifecta". Our aim is to assess the likelihood of achieving the Trifecta, and to analyze the influencing the Trifecta . MATERIALS AND METHODS: A total of 1738 men with localized PC underwent RP from 1992-2007 by a single surgeon. The exclusion criteria for this analysis were: preoperative hormonal or radiation therapy, preoperative urinary incontinence or erectile dysfunction, follow-up less than 24 months or insufficient data. Post-operative Trifecta factors were analyzed, including biochemical recurrence (BR).. We defined: BR as PSA > 0.2 ng/mL, urinary continence as wearing no pads, and sexual potency as having erections sufficient for intercourse with or without a phosphodiesterase-5 inhibitor. RESULTS: A total of 831 patients met the inclusion criteria. The mean age of the entire cohort was 59 years old. The median follow-up was 52 months (mean 60, range 24-202). The BR, UC and SP rates were 18.7 percent, 94.5 percent, and 71 percent respectively. Trifecta was achieved in 64 percent at 2 year follow-up, and 61 percent at 5 year follow-up. Multivariate analysis revealed age at time of surgery, pathologic Gleason score (PGS), pathologic stage, specimen weight, and nerve sparing (NS) were independent factors. CONCLUSIONS: Age at time of surgery, pathologic GS, pathologic stage, specimen weight and NS were independent predictors to achieve the Trifecta following radical prostatectomy. This information may help patients counseling undergoing radical prostatectomy for localized prostate cancer.

Population-based analysis of normal Total PSA and percentage of free/Total PSA values: results from screening cohort.

OBJECTIVES: To examine the distribution of total prostate-specific antigen (tPSA) and percentage of free/total PSA (%f/tPSA) values in patients undergoing prostate cancer screening in Canada. METHODS: The data from 4 consecutive annual prostate cancer screening events held in Montreal, Canada were examined with respect to age, tPSA, and %f/tPSA in 3222 men. RESULTS: Within the entire cohort, the median PSA level was 1.0 ng/mL and the median %f/tPSA was 26%. Using the interquartile range around the median, the upper bound for tPSA was situated at 1.9 ng/mL and the lower bound for %f/tPSA was at 19%. The 90th percentile for the median tPSA was 3.8, and the 10th percentile for the median %f/tPSA was 14. PSA and %f/tPSA showed a relation with age. The 75th percentile for the median tPSA level in the age category 40-49, 50-59, 60-69, and 70-79 years was 1.1, 1.4, 2.6, and 3.6 ng/mL, respectively. The 25th percentile for the median %f/tPSA level in the age category 40-49, 50-59, 60-69, and 70-79 years was 19, 21, 18 and 19 ng/mL, respectively. CONCLUSIONS: Our results can guide clinicians regarding the population-based distribution of serum tPSA and %f/tPSA values. Those values can be used for the purpose of counseling, as well as in the informed consent process before prostate biopsy.

Radical versus partial nephrectomy: effect on overall and noncancer mortality.

BACKGROUND: Relative to radical nephrectomy (RN), partial nephrectomy (PN) performed for renal cell carcinoma (RCC) may protect from non-cancer-related deaths. The authors tested this hypothesis in a cohort of PN and RN patients. METHODS: The Surveillance, Epidemiology, and End Results-9 database allowed identification of 2198 PN (22.4%) and 7611 RN (77.6%) patients treated for T1aN0M0 RCC between 1988 and 2004. Analyses matched for age, year of surgery, tumor size, and Fuhrman grade addressed the effect of nephrectomy type (RN vs PN) on overall mortality (Cox regression models) and on non-cancer-related mortality (competing-risks regression models). RESULTS: Relative to PN, RN was associated with 1.23-fold (P = .001) increased overall mortality rate, which translated into a 4.9% and 3.1% absolute increase in mortality at 5 and 10 years after surgery, respectively. Similarly, non-cancer-related death rate was significantly higher after RN in competing-risks regression models (P < .001), which translated into a 4.6% and 4.5% absolute increase in non-cancer-related mortality at 5 and 10 years after surgery, respectively. CONCLUSIONS: Relative to PN, RN predisposes to an increase in overall mortality and non-cancer-related death rate in patients with T1a RCC. In consequence, PN should be attempted whenever technically feasible. Selective referrals should be considered if PN expertise is unavailable.

A critical assessment of the prognostic value of clear cell, papillary and chromophobe histological subtypes in renal cell carcinoma: a population-based study.

OBJECTIVE To assess the magnitude of the effect of histological subtype (HS, the three most common being clear cell, papillary and chromophobe) on cause-specific mortality (CSM) from renal cell carcinoma (RCC). PATIENTS AND METHODS Univariable and multivariable Cox regression models included data from 11 618 patients treated with nephrectomy between 1988 and 2004 in nine Surveillance Epidemiology and End Results registries. We tested whether HS represents an independent predictor of CSM, and whether HS adds to the ability of other variables to predict CSM. The covariates comprised age, year of surgery, T stage, nodal status, M stage and Fuhrman grade. RESULTS In a multivariable model predicting CSM, HS was an independent predictor (P = 0.03), but failed to improve the accuracy of the model (+0.1% gain when HS was included in the model). CONCLUSION Although we confirmed that HS is an independent predictor for CSM, there was no gain in accuracy when HS was added to standard predictors of CSM. From a practical perspective, this implies that patients with clear cell, papillary and chromophobe HS share similar natural histories after nephrectomy, provided that other cancer characteristics are accounted for. From a statistical perspective, in multivariable models of CSM, the clear cell, papillary and chromophobe HS might be included as a single entity.

Obesity does not predispose to more aggressive prostate cancer either at biopsy or radical prostatectomy in European men.

Many investigators suggested that obesity predisposes to adverse prostate cancer characteristics and outcomes. We tested the effect of obesity on the rate of aggressive prostate cancer at either prostate biopsy or radical prostatectomy (RP). Clinical and pathological data were available for 1,814 men. Univariable and multivariable logistic regression models addressed the rate of high grade prostate cancer (HGPCa) at either biopsy or final pathology. Clinical stage, prostate-specific antigen (PSA), percentage of free PSA and prostate volume were the base predictors. All models were fitted with and without body mass index (BMI), which quantified obesity. BMI and its reciprocal (InvBMI) were coded as cubic splines to allow nonlinear effects. Predictive accuracy (PA) was quantified with area under curve estimates, which were subjected to 200 bootstrap re-samples to reduce overfit bias. Gains in PA related to the inclusion of BMI were compared using the Mantel-Haenszel test. HGPCa at biopsy was detected in 562 (31%) and HGPCa at RP pathology was present in 931 (51.3%) men. In either univariable or multivariable models predicting HGPCa at biopsy, BMI or InvBMI failed to respectively reach statistical significance or add to multivariable PA (BMI gain = 0%, p = 1.0; InvBMI gain = -0.2%, p = 0.9). Conversely, in models predicting HGPCa at RP, BMI and InvBMI represented independent predictors but failed to increase PA (BMI gain = 0.7%, p = 0.6; InvBMI gain = 0.5, p = 0.7%). Obesity does not predispose to more aggressive prostate cancer at biopsy. Similarly, obesity does not change the ability to identify those who may harbor HGPCa at RP.

Surgical volume is related to the rate of positive surgical margins at radical prostatectomy in European patients.

OBJECTIVE: To assess the association between surgical volume (SV) and the rate of positive surgical margins (PSM) after radical prostatectomy (RP) in a large single-institution European cohort of patients. PATIENTS AND METHODS: In all, 2402 men had a RP by a group of 11 surgeons, all of whom were trained by the surgeon with the highest SV; all surgeons used the same surgical technique. Variables assessed before RP were prostate-specific antigen (PSA) level, clinical stage and biopsy Gleason sum; variables assessed after RP were PSA level, extracapsular extension, seminal vesicle invasion, lymph node invasion and pathological Gleason sum. These were used to predict the rate of PSM in models before or after RP. Multivariate models were complemented with SV to test its independent and multivariate statistical significance and to quantify its impact on the model's overall (and 200 bootstrap-corrected) predictive accuracy. RESULTS: The mean (range) SV was 201 (1-1293) RPs; the mean (median, range) rate of PSM was 20.2 (21.4, 0-32.9)%. In multivariate models, SV was a highly statistically significant independent predictor of PSM (P < 0.001) and increased the predictive accuracy in multivariate models both before (2.0%) and after RP (1.5%, both P < 0.001). However, when the surgeon with the highest SV, who contributed to 1293 cases, was removed from the analyses, the multivariate independent prediction and the gains in predictive accuracy related to adding SV, disappeared in the models both before (P = 0.9, accuracy gain 0.1%) and after (P = 0.4, accuracy gain - 0.3%) RP. CONCLUSIONS: These results indicate that patients treated by surgeons with a very high volume can expect to have a significantly lower rate of PSM, after accounting for clinical and pathological case-mix differences. However, SV is not a predictor of PSM when analyses are restricted to intermediate- and low-volume surgeons.