Oncologic outcomes among Black and White men with grade group 4 or 5 (Gleason score 8-10) prostate cancer treated primarily by radical prostatectomy.

BACKGROUND: The aim of this study was to describe pathologic and short-term oncologic outcomes among Black and White men with grade group 4 or 5 prostate cancer managed primarily by radical prostatectomy. METHODS: This was a multi-institutional, observational study (2005-2015) evaluating radical prostatectomy outcomes by self-identified race. Descriptive analysis was performed via nonparametric statistical testing to compare baseline clinicopathologic data. Univariable and multivariable time-to-event analyses were performed to assess biochemical recurrence (BCR), metastasis, cancer-specific mortality (CSM), and overall survival between Black and White men. RESULTS: In total, 1662 men were identified with grade group 4 or 5 prostate cancer initially managed by radical prostatectomy. Black men represented 11.3% of the cohort (n = 188). Black men were younger, demonstrated a longer time from diagnosis to surgery, and were at a lower clinical stage (all P < .05). Black men had lower rates of pT3/4 disease (49.5% vs 63.5%; P < .05) but higher rates of positive surgical margins (31.6% vs 26.5%; P = .14) on pathologic evaluation. There was no difference in BCR, CSM, or overall survival over a median follow-up of 40.7 months. Black men had a lower 5-year cumulative incidence of metastasis-free survival (93.6%; 95% confidence interval [CI], 86.5%-97.0%) in comparison with White men (85.8%; 95% CI, 83.1%-88.0%), which did not persist in an age-adjusted analysis. CONCLUSIONS: Black and White men with high-grade prostate cancer at diagnosis demonstrated similar oncologic outcomes when they were managed by primary radical prostatectomy. Our findings suggest that racial disparities in prostate cancer mortality are not related to differences in the efficacy of extirpative therapy.

Testing-Related Health Impact of Transrectal and Transperineal Prostate Biopsy as Assessed by Health Utilities.

PURPOSE: We sought to assess the temporary health-related quality of life (health utility) of nonmagnetic resonance imaging-guided transrectal and transperineal prostate biopsy. MATERIALS AND METHODS: This is a 2-arm, prospectively enrolled, observational, patient-reported outcomes study, performed between June 2019 and November 2020 at a single academic medical center. Inclusion criteria were men undergoing an outpatient ultrasound-guided prostate biopsy (transrectal or transperineal approach, without magnetic resonance imaging guidance). Patients with a history of Gleason 7+ prostate cancer were excluded. Validated survey instruments were utilized to assess baseline (Short Form 12) and testing-related (Testing Morbidities Index [TMI]) health utility states. The primary outcome was the TMI summary testing-related quality-of-life score (summary utility score; scale: 0=death and 1=perfect health). The TMI is comprised of 7 domains, spanning before, during and after testing experiences. Each domain is scored from 1 (no health impact) to 5 (extreme health impact). Testing-related quality-of-life measures were compared with Mann-Whitney U test. RESULTS: Enrollment rates were 80% (60/75; transrectal) and 86% (60/70; transperineal). All patients (120/120) completed the questionnaire. The TMI summary score for transrectal biopsy was not significantly different from transperineal biopsy (0.86, 95% CI 0.84-0.88 vs 0.83, 95% CI 0.81-0.85; p=0.0774). The largest difference in the testing experiences was related to intraprocedural pain (transrectal biopsy: 2.3, 95% CI 2.1-2.4; transperineal biopsy: 2.9, 95% CI 2.6-3.1; p <0.001). CONCLUSIONS: Transperineal and transrectal prostate biopsies have similar effect on temporary health-related quality-of-life. Transient differences relate to intraprocedural pain. These data can inform clinical decision making and future cost-utility models.

Use of the MyProstateScore Test to Rule Out Clinically Significant Cancer: Validation of a Straightforward Clinical Testing Approach.

PURPOSE: The MyProstateScore test was validated for improved detection of clinically significant (grade group ≥2) prostate cancer relative to prostate specific antigen based risk calculators. We sought to validate an optimal MyProstateScore threshold for clinical use in ruling out grade group ≥2 cancer in men referred for biopsy. MATERIALS AND METHODS: Biopsy naïve men provided post-digital rectal examination urine prior to biopsy. MyProstateScore was calculated using the validated, locked multivariable model including only serum prostate specific antigen, urinary prostate cancer antigen 3 and urinary TMPRSS2:ERG. The MyProstateScore threshold approximating 95% sensitivity for grade group ≥2 cancer was identified in a training cohort, and performance was measured in 2 external validation cohorts. We assessed the 1) overall biopsy referral population and 2) population meeting guideline based testing criteria (ie, prostate specific antigen 3-10, or <3 with suspicious digital rectal examination). RESULTS: Validation cohorts were prospectively enrolled from academic (977 patients, median prostate specific antigen 4.5, IQR 3.1-6.0) and community (548, median prostate specific antigen 4.9, IQR 3.7-6.8) settings. In the overall validation population (1,525 patients), 338 men (22%) had grade group ≥2 cancer on biopsy. The MyProstateScore threshold of 10 provided 97% sensitivity and 98% negative predictive value for grade group ≥2 cancer. MyProstateScore testing would have prevented 387 unnecessary biopsies (33%), while missing only 10 grade group ≥2 cancers (3.0%). In 1,242 patients meeting guideline based criteria, MyProstateScore ≤10 provided 96% sensitivity and 97% negative predictive value, and would have prevented 32% of unnecessary biopsies, missing 3.7% of grade group ≥2 cancers. CONCLUSIONS: In a large, clinically pertinent biopsy referral population, MyProstateScore ≤10 provided exceptional sensitivity and negative predictive value for ruling out grade group ≥2 cancer. This straightforward secondary testing approach would reduce the use of more costly and invasive procedures after screening with prostate specific antigen.

Downgrading from Biopsy Grade Group 4 Prostate Cancer in Patients Undergoing Radical Prostatectomy for High or Very High Risk Prostate Cancer.

PURPOSE: We examined rates of Grade Group 4 downgrading at radical prostatectomy among men diagnosed with high and very high risk prostate cancer at biopsy. MATERIALS AND METHODS: A pooled cohort of 1,776 patients from 3 tertiary referral centers who underwent radical prostatectomy for National Comprehensive Cancer Network® high risk (prostate specific antigen greater than 20 ng/ml, or Grade Group 4-5, or clinical stage T3 or greater) or very high risk (primary Gleason pattern 5, or more than 4 biopsy cores with Grade Group 4-5, or 2 or more high risk features) disease from 2005 to 2015 were reviewed. Overall 893 patients with Grade Group 4 disease at biopsy were identified and 726 patients were available for analysis. Multivariable logistic regression models were fit to determine factors associated with downgrading to Grade Group 3 or less at radical prostatectomy. RESULTS: Overall 333 (45%) cases were downgraded to Grade Group 3 or less at radical prostatectomy. Of these cases 198 (27%) had concordant Grade Group 4 biopsy and radical prostatectomy pathology and 195 (27%) were upgraded at radical prostatectomy to Grade Group 5. Of high risk cases with biopsy Grade Group 4 disease 49% had any downgrading vs 29% of very high risk cases (p <0.0001). Downgrading to Grade Group 2 or less occurred in 16% (98 of 604) of high risk and 7% (8 of 122) of very high risk cases (p <0.01). Downgraded cases had a lower prostate specific antigen, fewer positive biopsy cores and lower clinical stage (p <0.01). On multivariable analysis fewer positive biopsy cores were significantly associated with downgrading at radical prostatectomy (p <0.01). CONCLUSIONS: In this cohort of patients with high risk/very high risk prostate cancer, downgrading from biopsy Grade Group 4 at radical prostatectomy occurred less frequently than in other published reports. Any downgrading was significantly less common in very high risk compared to high risk patients, and downgrading to Grade Group 2 or less occurred in a minority of cases in high risk and very high risk patients.

Prostate Health Index and multiparametric magnetic resonance imaging to predict prostate cancer grade reclassification in active surveillance.

OBJECTIVE: To identify the value of combining the Prostate Health Index (PHI) and multiparametric magnetic resonance imaging (mpMRI), tools which have previously been shown to be independently predictive of prostate cancer (PCa) grade reclassification (GR; Gleason score >6), for the purpose of predicting GR at the next surveillance biopsy to reduce unnecessary prostate biopsies for men in PCa active surveillance (AS). PATIENTS AND METHODS: Between 2014 and 2019, we retrospectively identified 253 consecutive men in the Johns Hopkins AS programme who had mpMRI and PHI followed by a systematic ± targeted biopsy. PHI and PHI density (PHID) were evaluated across Prostate Imaging-Reporting and Data System version 2.0 (PI-RADSv2) scores and compared to those with and without GR. Next, the negative predictive value (NPV) and area under the receiver operating curve (AUC) were calculated to compare the diagnostic value of PI-RADSv2 score combined with PHI, PHID, or prostate-specific antigen density (PSAD) for GR using their respective first quartile as a cut-off. RESULTS: Of the 253 men, 38 men (15%) had GR. Men with GR had higher PHI values (40.7 vs 32.0, P = 0.001), PHID (0.83 vs 0.57, P = 0.007), and PSAD (0.12 vs 0.10, P = 0.037). A PI-RADSv2 ≤3 alone had a NPV of 91.6% for GR (AUC 0.67). Using a PHI cut-off of 25.6 in addition to PI-RADSv2 ≤3, the NPV and AUC were both increased to 98% and 0.70, respectively. Using a PSAD cut-off of 0.07 ng/mL/mL with PI-RADSv2 had an AUC of 0.69 and NPV of 95.4%. PHI and PI-RADSv2 together could have avoided 20% of biopsies at the cost of missing 2.6% of GRs. CONCLUSIONS: The combination of PHI and mpMRI can aid in the prediction of GR in men on AS and may be useful for decreasing the burden of surveillance prostate biopsies.

Outcomes of very high-risk prostate cancer after radical prostatectomy: Validation study from 3 centers.

BACKGROUND: Among men with localized high-risk prostate cancer (PCa), patients who meet very high-risk (VHR) criteria have been shown to experience worse outcomes after radical prostatectomy (RP) in a previous study. Variations of VHR criteria have been suggested to be prognostic in other single-center cohorts, but multicenter outcomes validating VHR criteria have not been described. This study was designed to validate VHR criteria for identifying which PCa patients are at greatest risk for cancer progression. METHODS: Patients with high-risk PCa undergoing RP (2005-2015) at 3 tertiary centers were pooled. The outcomes of men with VHR PCa were compared with the outcomes of those who did not meet VHR criteria. The high-risk criteria were a clinical stage of T3 to T4, a prostate-specific antigen level > 20 ng/mL, or a biopsy Gleason grade sum of 8 to 10. The VHR criteria were multiple high-risk features, >4 biopsy cores with a Gleason grade sum of 8 to 10, or primary Gleason grade pattern 5. Biochemical recurrence, metastasis (METS), and cancer-specific mortality (CSM) were assessed with competing risks regressions. Overall mortality was assessed with Cox survival models. RESULTS: Among 1981 patients with high-risk PCa, men with VHR PCa (n = 602) had adverse pathologic outcomes: 37% versus 25% for positive margins and 37% versus 15% for positive lymph nodes (P < .001 for both comparisons). Patients with VHR PCa also had higher adjusted hazard ratios for METS (2.78; 95% confidence interval [CI], 2.08-3.72), CSM (6.77; 95% CI, 2.91-15.7), and overall mortality (2.44; 95% CI, 1.56-3.80; P < .001 for all comparisons). CONCLUSIONS: In a validation study of patients who underwent treatment for high-risk PCa, VHR criteria were strongly associated with adverse pathologic and oncologic outcomes.

Older Age Predicts Biopsy and Radical Prostatectomy Grade Reclassification to Aggressive Prostate Cancer in Men on Active Surveillance.

PURPOSE: Age at prostate cancer diagnosis has been positively associated with prostate cancer specific mortality and in men on active surveillance with a higher risk of biopsy grade reclassification to Gleason score 3 + 4 or greater (Grade Group 2 or greater). However, to our knowledge the association between age and biopsy grade reclassification to an aggressive phenotype (Gleason score 4 + 3 or greater [Grade Group 3 or greater]) has not been explored. MATERIALS AND METHODS: From 1995 to 2016 we followed 1,625 men 41 to 81 years old with NCCN® (National Comprehensive Cancer Network®) very low (68%) or low (32%) risk prostate cancer on active surveillance. We determined the rate of biopsy grade reclassification to Grade Group 3 or greater. Competing risk analysis was applied to evaluate the association between age at enrollment and the risk of biopsy grade reclassification. Additionally, in men who underwent radical prostatectomy after biopsy grade reclassification we assessed the rate of radical prostatectomy grade reclassification (ie radical prostatectomy Grade Group greater than biopsy Grade Group). RESULTS: The 5-year incidence of biopsy grade reclassification to Grade Group 3 or greater was 4%, 7% and 14% in men younger than 60, 60 to 69 and 70 years old or older, respectively (p <0.001). On univariate analysis older age was associated with biopsy grade reclassification to Grade Group 3 or greater (per 10-year increase HR 2.43, p <0.001). On multivariable analysis adjusting for year of diagnosis, race, prostate specific antigen density and cancer volume at diagnosis older age remained associated with biopsy grade reclassification to Grade Group 3 or greater (per 10-year increase HR 2.19, p <0.001). In men who underwent radical prostatectomy after biopsy grade reclassification those who were older had a higher rate of radical prostatectomy grade reclassification (p <0.05). CONCLUSIONS: In men on active surveillance older age at diagnosis was positively associated with biopsy grade reclassification to Grade Group 3 or greater and radical prostatectomy grade reclassification. These observations imply that for many older men, active surveillance as opposed to watchful waiting remains a more appropriate management strategy.

Clinical, Pathological and Oncologic Findings of Radical Prostatectomy with Extraprostatic Extension Diagnosed on Preoperative Prostate Biopsy.

PURPOSE: Prostatic adenocarcinoma with extraprostatic extension detected on prostate needle biopsy is an uncommon finding. We describe clinical and pathological findings in a large cohort of patients with prostatic adenocarcinoma who were treated with radical prostatectomy and in whom extraprostatic extension was identified on prostate needle biopsy. MATERIALS AND METHODS: Using our institutional pathology database we identified 83 patients with prostatic adenocarcinoma and with extraprostatic extension on prostate needle biopsy between 2000 to 2018 who underwent radical prostatectomy and had clinical followup information. Clinical and pathological outcomes were examined. RESULTS: Of the 83 patients 54 (65%) presented with clinical stage T2 or greater disease. On biopsy 50 of the 83 patients (60%) had Grade Group 4-5 and 66 (81%) had perineural invasion. Extraprostatic extension was confirmed in the radical prostatectomy specimen in 81 of 83 cases (98%). At radical prostatectomy 49 of 83 patients (59%) had positive surgical margins, 37 (45%) had seminal vesicle invasion and 30 (37%) had lymph node involvement. Median followup after radical prostatectomy was 2 years. Overall 34 of 76 men (45%) received postoperative radiation a median of 1 year after radical prostatectomy and 8 (11%) received chemotherapy a median of 2 years after radical prostatectomy. The 3-year biochemical recurrence-free survival rate was 48.4% (95% CI 0.345-0.610) and the 3-year metastasis-free survival rate was 75.2% (95% CI 0.603-0.851). CONCLUSIONS: Patients in whom extraprostatic extension is detected on prostate needle biopsy almost always have extraprostatic disease and markedly adverse pathology findings at radical prostatectomy. Many of them experience biochemical recurrence and most will require multimodal therapy. These data can be useful to counsel such patients in regard to the treatment approach and the expected outcomes after surgery.

Tissue-based genomics: which test and when.

PURPOSE OF REVIEW: The clinical course of localized prostate cancer varies widely, ranging from indolent disease unlikely to require treatment to aggressive cancers meriting intensive, multimodal therapy. Management recommendations have traditionally been determined based on clinical and pathologic factors, including serum prostate - specific antigen (PSA), clinical stage, and Gleason score. Unfortunately, these factors have limited ability to describe the underlying biology of a given tumor. Tissue-based genomic tests have emerged as a promising tool to more accurately characterize prostate cancer biology and projected clinical course. The current review article summarizes available data describing the clinical use of genomic assays, with a specific focus on three critical scenarios. RECENT FINDINGS: We reviewed the potential role of tissue-based genomic assays in determining: the appropriateness of active surveillance versus definitive therapy, patients that will benefit from adjuvant radiation therapy following radical prostatectomy, and men most likely to benefit from concurrent androgen deprivation therapy with primary radiotherapy. SUMMARY: Current literature suggests that commercially available genomic tests provide prognostic information independent of traditional risk factors that may augment clinical decision-making. Additional data will better clarify the optimal use of each test across common clinical scenarios.

Association of tumor-infiltrating T-cell density with molecular subtype, racial ancestry and clinical outcomes in prostate cancer.

The inflammatory microenvironment plays an important role in the pathogenesis and progression of tumors and may be associated with somatic genomic alterations. We examined the association of tumor-infiltrating T-cell density with clinical-pathologic variables, tumor molecular subtype, and oncologic outcomes in surgically treated primary prostate cancer occurring in patients of European-American or African-American ancestry. We evaluated 312 primary prostate tumors, enriched for patients with African-American ancestry and high grade disease. Tissue microarrays were immunostained for CD3, CD8, and FOXP3 and were previously immunostained for ERG and PTEN using genetically validated protocols. Image analysis for quantification of T-cell density in tissue microarray tumor spots was performed. Automated quantification of T-cell densities in tumor-containing regions of tissue microarray spots and standard histologic sections were correlated (r = 0.73, p < 0.00001) and there was good agreement between visual and automated T-cell density counts on tissue microarray spots (r = 0.93, p < 0.00001). There was a significant correlation between CD3+, CD8+, and FOXP3+ T-cell densities (p < 0.00001), but these were not associated with most clinical or pathologic variables. Increased T-cell density was significantly associated with ERG positivity (median 309 vs. 188 CD3+ T cells/mm2; p = 0.0004) and also with PTEN loss (median 317 vs. 192 CD3+ T cells/mm2; p = 0.001) in the combined cohort of matched European-American and African-American ancestry patients. The same association or a similar trend was present in patients of both ancestries when analyzed separately. When the African-American patients from the matched race set were combined with a separate high grade set of African-American cases, there was a weak association of increased FOXP3+ T-cell densities with increased risk of metastasis in multivariable analysis. Though high T-cell density is associated with specific molecular subclasses of prostate cancer, we did not find an association of T-cell density with racial ancestry.

Tumor Volume on Biopsy of Low Risk Prostate Cancer Managed with Active Surveillance.

PURPOSE: Contemporary clinical guidelines recommend active surveillance of men with low risk prostate cancer. Low risk disease spans any potential volume of Gleason score 6 cancer without sufficient attention to tumor volume in the past. Therefore, we compared tumor characteristics in men at low risk on active surveillance to men treated with radical prostatectomy. MATERIALS AND METHODS: We evaluated an institutional cohort of 1,633 men with very low risk disease (clinical stage T1c, prostate specific antigen density less than 0.15 ng/ml/cm3, 2 or more positive cores and 50% or greater core involvement) and low risk disease (clinical stage T2a or less, prostate specific antigen less than 10 ng/ml and Gleason score 6 or less). Among patients at low risk we calculated the proportion who failed to meet very low risk volume criteria (greater than 2 positive cores or greater than 50% core involvement). Clinical and pathological metrics in the active surveillance cohort were compared to those in a cohort of men at low risk who underwent radical prostatectomy in the current era of 2011 to 2016. RESULTS: In the active surveillance cohort 1,119 men (69%) met very low risk criteria and 514 (31%) had low risk disease. In the low risk population only 138 men (27%) harbored higher volume cancer exceeding very low risk criteria compared to 815 (82%) at low risk who underwent radical prostatectomy (p <0.001). Overall the low risk active surveillance population had fewer positive biopsy cores (median 1 vs 3, p <0.001) and a lower maximum percent of core involvement (median 10% vs 40%, p <0.001) compared to patients at low risk who underwent radical prostatectomy. CONCLUSIONS: Data supporting the safety of active surveillance in men at low risk at our institution were derived from a distinct subgroup harboring a limited cancer volume. Until acceptable outcomes are confirmed for higher volume tumors it is important to remain mindful of these limitations before broadly recommending active surveillance to all low risk men.

Subtyping the Risk of Intermediate Risk Prostate Cancer for Active Surveillance Based on Adverse Pathology at Radical Prostatectomy.

PURPOSE: Intermediate risk prostate cancer is a heterogenous classification with favorable proposed criteria based on men treated with radiation therapy. However, there is uncertain application to active surveillance. We quantified the rate of adverse surgical pathology and implications for survival in patients at favorable intermediate risk compared to those with low risk prostate cancer. MATERIALS AND METHODS: We performed a comparative cohort study of men with prostate cancer from 2009 to 2013 in the National Cancer Database who underwent radical prostatectomy. The study primary end point was adverse pathology, defined as Grade Group 3 or greater/pT3b/pN1. Various favorable intermediate risk definitions were evaluated, including the Memorial Sloan Kettering Cancer Center definition of Grade Group 2 or less with only 1 intermediate risk factor (Grade Group 2/cT2b/prostate specific antigen 10 to 20 ng/ml), which we defined as type 1 intermediate risk. The remaining patients at intermediate risk were classified as type 2 intermediate risk. Log binomial, logistic and Cox proportional hazards regression models were applied. RESULTS: Adverse pathological findings were noted in 3,519 of the 51,688 patients (6.8%) at low risk and 8,888 of the 42,720 Grade Group 2 patients (20.8%) at intermediate risk (RR 3.06, 95% CI 2.95-3.17, p <0.001). Stratification by prostate specific antigen and volume minimally impacted the absolute rate. Results were similar for the Memorial Sloan Kettering Cancer Center definition (type 1 intermediate risk). Type 2 intermediate risk led to a greater risk of adverse pathology (RR 8.52, 8.23-8.82, p <0.001) and Grade Group 1 intermediate risk led to lower risk (RR 2.00, 1.86-2.16, p <0.001). Patients at favorable intermediate risk had worse overall survival than patients at low risk in adjusted models due to adverse pathology. CONCLUSIONS: Adverse pathology at radical prostatectomy was observed at a threefold higher rate in patients classified at favorable intermediate risk compared to low risk, leading to worse overall survival. Men at intermediate risk may be better classified as types 1 and 2 since none showed pathological outcomes similar to those of men at low risk.

Combining Prostate Health Index density, magnetic resonance imaging and prior negative biopsy status to improve the detection of clinically significant prostate cancer.

OBJECTIVES: To determine the performance of Prostate Health Index (PHI) density (PHID) combined with MRI and prior negative biopsy (PNB) status for the diagnosis of clinically significant prostate cancer (PCa). PATIENTS AND METHODS: Patients without a prior diagnosis of PCa, with elevated prostate-specific antigen and a normal digital rectal examination who underwent PHI testing prospectively prior to prostate biopsy were included in this study. PHID was calculated retrospectively using prostate volume derived from transrectal ultrasonography at biopsy. Univariable and multivariable logistic regression modelling, along with receiver-operating characteristic (ROC) curve analysis, was used to determine the ability of serum biomarkers to predict clinically significant PCa (defined as either grade group [GG] ≥2 disease or GG1 PCa detected in >2 cores or >50% of any one core) on biopsy. Age, PNB status and Prostate Imaging Reporting and Data System (PI-RADS) score were incorporated into the regression models. RESULTS: Of the 241 men who qualified for the study, 91 (37.8%) had clinically significant PCa on biopsy. The median (interquartile range) PHID was 0.74 (0.44-1.24); it was 1.18 (0.77-1.83) and 0.55 (0.38-0.89) in those with and without clinically significant PCa on biopsy, respectively (P < 0.001). On univariable logistic regression, age and PNB status were associated with clinically significant cancer. Of the tested biomarkers, PHID demonstrated the highest discriminative ability for clinically significant disease (area under the ROC curve [AUC] 0.78 for the univariable model). That continued to be the case in multivariable logistic regression models incorporating age and PNB status (AUC 0.82). At a threshold of 0.44, representing the 25th percentile of PHID in the cohort, PHID was 92.3% sensitive and 35.3% specific for clinically significant PCa; the sensitivity and specificity were 93.0% and 32.4% and 97.4% and 29.1% for GG ≥2 and GG ≥3 disease, respectively. In the 104 men who underwent MRI, PI-RADS score was complementary to PHID, with a PI-RADS score ≥3 or, if PI-RADS score ≤2, a PHID ≥0.44, detecting 100% of clinically significant disease. For that subgroup, of the biomarkers tested, PHID (AUC 0.90) demonstrated the highest discriminative ability for clinically significant disease on multivariable logistic regression incorporating age, PNB status and PI-RADS score. CONCLUSIONS: In this contemporary cohort of men undergoing prostate biopsy for the diagnosis of PCa, PHID outperformed PHI and other PSA derivatives in the diagnosis of clinically significant cancer. Incorporating age, PNB status and PI-RADS score led to even further gains in the diagnostic performance of PHID. Furthermore, PI-RADS score was found to be complementary to PHID. Using 0.44 as a threshold for PHID, 35.3% of unnecessary biopsies could have been avoided at the cost of missing 7.7% of clinically significant cancers. Despite these encouraging results, prospective validation is needed.

Radical Prostatectomy, External Beam Radiotherapy, or External Beam Radiotherapy With Brachytherapy Boost and Disease Progression and Mortality in Patients With Gleason Score 9-10 Prostate Cancer.

Importance: The optimal treatment for Gleason score 9-10 prostate cancer is unknown. Objective: To compare clinical outcomes of patients with Gleason score 9-10 prostate cancer after definitive treatment. Design, Setting, and Participants: Retrospective cohort study in 12 tertiary centers (11 in the United States, 1 in Norway), with 1809 patients treated between 2000 and 2013. Exposures: Radical prostatectomy (RP), external beam radiotherapy (EBRT) with androgen deprivation therapy, or EBRT plus brachytherapy boost (EBRT+BT) with androgen deprivation therapy. Main Outcomes and Measures: The primary outcome was prostate cancer-specific mortality; distant metastasis-free survival and overall survival were secondary outcomes. Results: Of 1809 men, 639 underwent RP, 734 EBRT, and 436 EBRT+BT. Median ages were 61, 67.7, and 67.5 years; median follow-up was 4.2, 5.1, and 6.3 years, respectively. By 10 years, 91 RP, 186 EBRT, and 90 EBRT+BT patients had died. Adjusted 5-year prostate cancer-specific mortality rates were RP, 12% (95% CI, 8%-17%); EBRT, 13% (95% CI, 8%-19%); and EBRT+BT, 3% (95% CI, 1%-5%). EBRT+BT was associated with significantly lower prostate cancer-specific mortality than either RP or EBRT (cause-specific HRs of 0.38 [95% CI, 0.21-0.68] and 0.41 [95% CI, 0.24-0.71]). Adjusted 5-year incidence rates of distant metastasis were RP, 24% (95% CI, 19%-30%); EBRT, 24% (95% CI, 20%-28%); and EBRT+BT, 8% (95% CI, 5%-11%). EBRT+BT was associated with a significantly lower rate of distant metastasis (propensity-score-adjusted cause-specific HRs of 0.27 [95% CI, 0.17-0.43] for RP and 0.30 [95% CI, 0.19-0.47] for EBRT). Adjusted 7.5-year all-cause mortality rates were RP, 17% (95% CI, 11%-23%); EBRT, 18% (95% CI, 14%-24%); and EBRT+BT, 10% (95% CI, 7%-13%). Within the first 7.5 years of follow-up, EBRT+BT was associated with significantly lower all-cause mortality (cause-specific HRs of 0.66 [95% CI, 0.46-0.96] for RP and 0.61 [95% CI, 0.45-0.84] for EBRT). After the first 7.5 years, the corresponding HRs were 1.16 (95% CI, 0.70-1.92) and 0.87 (95% CI, 0.57-1.32). No significant differences in prostate cancer-specific mortality, distant metastasis, or all-cause mortality (≤7.5 and >7.5 years) were found between men treated with EBRT or RP (cause-specific HRs of 0.92 [95% CI, 0.67-1.26], 0.90 [95% CI, 0.70-1.14], 1.07 [95% CI, 0.80-1.44], and 1.34 [95% CI, 0.85-2.11]). Conclusions and Relevance: Among patients with Gleason score 9-10 prostate cancer, treatment with EBRT+BT with androgen deprivation therapy was associated with significantly better prostate cancer-specific mortality and longer time to distant metastasis compared with EBRT with androgen deprivation therapy or with RP.