Risk of Biochemical Recurrence in Patients With Grade Group 1 Prostate Cancer With Extraprostatic Extension Treated With Radical Prostatectomy.

PURPOSE: We sought to examine the association of extraprostatic extension (EPE) with biochemical recurrence (BCR) separately in men with Grade Group (GG) 1 and GG2 prostate cancer (PCa) treated with radical prostatectomy. MATERIALS AND METHODS: We reviewed our institutional database of patients who underwent radical prostatectomy for PCa between 2005 and 2022 and identified patients with GG1 and GG2 disease on final pathology. Fine-Gray competing risk models with an interaction between EPE (yes vs no) and GG (GG1 vs GG2) were used to examine the relationship between disease group and BCR-free survival. RESULTS: The cohort consisted of 6309 men, of whom 169/2740 (6.2%) with GG1 disease had EPE while 1013/3569 (28.4%) with GG2 disease had EPE. Median follow-up was 4 years. BCR occurred in 400/6309 (6.3%) patients. For men with GG1, there was no statistically significant difference in BCR-free survival for men with vs without EPE (subdistribution HR = 0.88; 95% CI: 0.37-2.09). However, for GG2 patients BCR-free survival was significantly worse for those with vs without EPE (subdistribution HR = 1.97, 95% CI: 1.54-2.52). CONCLUSIONS: Although there is a subset of GG1 PCas capable of invading through the prostatic capsule, patients with GG1 PCa and EPE at prostatectomy experience similar biochemical recurrence and survival outcomes compared to GG1 patients without EPE. However, among men with GG2, EPE connotes a worse prognosis.

Large cribriform glands (> 0.25 mm diameter) as a predictor of adverse pathology in men with Grade Group 2 prostate cancer.

AIMS: A recent outcome-based, radical prostatectomy study defined > 0.25 mm diameter to distinguish large versus small cribriform glands, with > 0.25 mm associated with worse recurrence-free survival. This study evaluates whether identification of > 0.25 mm cribriform glands in Grade Group 2 patients at biopsy is associated with adverse pathology at radical prostatectomy. METHODS AND RESULTS: Tumours containing biopsy slides for 133 patients with Grade Group 2 prostate cancer with subsequent radical prostatectomy were re-reviewed for large cribriform glands (diameter > 0.25 mm). The primary outcome was adverse pathology (Grade Groups 3-5; stage pT3a or greater, or pN1). The secondary outcome was recurrence-free survival. Cribriform pattern was present in 52 of 133 (39%) patients; of these, 16 of 52 (31%) had large cribriform glands and 36 of 52 (69%) had only small cribriform glands. Patients with large cribriform glands had significantly more adverse pathology at radical prostatectomy compared to patients with small cribriform glands and no cribriform glands (large = 11 of 16, 69%; small = 12 of 36, 33%; no cribriform = 25 of 81, 31%; χ2 P-value 0.01). On multivariate analysis, large cribriform glands were also associated with adverse pathology, independent of age, prostate-specific antigen (PSA)/PSA density at diagnosis, year of diagnosis and biopsy cores percentage positive (global P-value 0.02). Large cribriform glands were also associated with increased CAPRA-S surgical risk score (Kruskal-Wallis P-value 0.02). CONCLUSIONS: Large cribriform glands using a diameter > 0.25 mm definition in Grade Group 2 patients on biopsy are associated with increased risk of adverse pathology at radical prostatectomy. The presence of large cribriform histology should be considered when offering active surveillance for those with Grade Group 2 disease.

The association of quantitative PSMA PET parameters with pathologic ISUP grade: an international multicenter analysis.

PURPOSE: To assess if PSMA PET quantitative parameters are associated with pathologic ISUP grade group (GG) and upgrading/downgrading. METHODS: PCa patients undergoing radical prostatectomy with or without pelvic lymph node dissection staged with preoperative PSMA PET at seven referral centres worldwide were evaluated. PSMA PET parameters which included SUVmax, PSMAvolume, and total PSMA accumulation (PSMAtotal) were collected. Multivariable logistic regression evaluated the association between PSMA PET quantified parameters and surgical ISUP GG. Decision-tree analysis was performed to identify discriminative thresholds for all three parameters related to the five ISUP GGs The ROC-derived AUC was used to determine whether the inclusion of PSMA quantified parameters improved the ability of multivariable models to predict ISUP GG ≥ 4. RESULTS: A total of 605 patients were included. Overall, 2%, 37%, 37%, 10% and 13% patients had pathologic ISUP GG1, 2, 3, 4, and 5, respectively. At multivariable analyses, all three parameters SUVmax, PSMAvolume and PSMAtotal were associated with GG ≥ 4 at surgical pathology after accounting for PSA and clinical T stage based on DRE, hospital and radioligand (all p < 0.05). Addition of all three parameters significantly improved the discrimination of clinical models in predicting GG ≥ 4 from 68% (95%CI 63 - 74) to 74% (95%CI 69 - 79) for SUVmax, 72% (95%CI 67 - 76) for PSMAvolume, 74% (70 - 79) for PSMAtotal and 75% (95%CI 71 - 80) when all parameters were included (all p < 0.05). Decision-tree analysis resulted in thresholds that discriminate between GG (SUVmax 0-6.5, 6.5-15, 15-28, > 28, PSMAvol 0-2, 2-9, 9-20 and > 20 and PSMAtotal 0-12, 12-98 and > 98). PSMAvolume was significantly associated with GG upgrading (OR 1.03 95%CI 1.01 - 1.05). In patients with biopsy GG1-3, PSMAvolume ≥ 2 was significantly associated with higher odds for upgrading to ISUP GG ≥ 4, compared to PSMAvolume < 2 (OR 6.36, 95%CI 1.47 - 27.6). CONCLUSION: Quantitative PSMA PET parameters are associated with surgical ISUP GG and upgrading. We propose clinically relevant thresholds of these parameters which can improve in PCa risk stratification in daily clinical practice.

A novel grading approach predicts worse outcomes in stage pT1 non-muscle-invasive bladder cancer.

OBJECTIVE: To develop a prognostically relevant scoring system for stage pT1 non-muscle-invasive bladder cancer (NMIBC) incorporating tumour budding, growth pattern and invasion pattern because the World Health Organisation grading system shows limited prognostic value in such patients. PATIENTS AND METHODS: The tissue specimens and clinical data of 113 patients with stage pT1 NMIBC who underwent transurethral resection of bladder tumour were retrospectively investigated. Tumour budding, and growth and invasion patterns were evaluated and categorised into two grade groups (GGs). GGs and other clinical and histopathological variables were investigated regarding recurrence-free survival (RFS), progression-free survival (PFS), cancer-specific survival (CSS) and overall survival (OS) using univariable and multivariable Cox regression analyses. RESULTS: The integration of two tumour budding groups, two growth patterns, and two invasion patterns yielded an unfavourable GG (n = 28; 24.7%) that had a high impact on oncological outcomes. The unfavourable GG was identified as an independent RFS and OS predictor (P = 0.004 and P = 0.046, respectively) and linked to worse PFS (P = 0.001) and CSS (P = 0.001), irrespective of the European Association of Urology risk group. The unfavourable GG was associated with higher rates of BCG-unresponsive tumours (P = 0.006). Study limitations include the retrospective, single-centre design, diverse therapies and small cohort. CONCLUSIONS: We present a morphology-based grading system for stage pT1 NMIBC that correlates with disease aggressiveness and oncological patient outcomes. It therefore identifies a highest risk group of stage pT1 NMIBC patients, who should be followed up more intensively or receive immediate radical cystectomy. The grading incorporates objective variables assessable on haematoxylin and eosin slides and immunohistochemistry, enabling an easy-to-use low-cost approach that is applicable in daily routine. Further studies are needed to validate and confirm these results.

International Society of Urological Pathology (ISUP) Gleason Grade Groups stratify outcomes in the CHHiP Phase 3 prostate radiotherapy trial.

OBJECTIVES: To compare the results of Gleason Grade Group (GGG) classification following central pathology review with previous local pathology assessment, and to examine the difference between using overall and worst GGG in a large patient cohort treated with radiotherapy and short-course hormone therapy. PATIENTS AND METHODS: Patients with low- to high-risk localized prostate cancer were randomized into the multicentre CHHiP fractionation trial between 2002 and 2011. Patients received short-course hormone therapy (≤6 month) and radical intensity-modulated radiotherapy (IMRT). Of 2749 consented patients, 1875 had adequate diagnostic biopsy tissue for blinded central pathology review. The median follow-up was 9.3 years. Agreement between local pathology and central pathology-derived GGG and between central pathology-derived overall and worst GGG was assessed using kappa (κ) statistics. Multivariate Cox regression and Kaplan-Meier methods were used to compare the biochemical/clinical failure (BCF) and distant metastases (DM) outcomes of patients with GGG 1-5. RESULTS: There was poor agreement between local pathology- and central pathology-derived GGG (κ = 0.19) but good agreement between overall and worst GGG on central pathology review (κ = 0.89). Central pathology-derived GGG stratified BCF and DM outcomes better than local pathology, while overall and worst GGG on central pathology review performed similarly. GGG 3 segregated with GGG 4 for BCF, with BCF-free rates of 90%, 82%, 74%, 71% and 58% for GGGs 1-5, respectively, at 8 years when assessed using overall GGG. There was a progressive decrease in DM-free rates from 98%, 96%, 92%, 88% and 83% for GGGs 1-5, respectively, at 8 years with overall GGG. Patients (n = 57) who were upgraded from GGG 2-3 using worst GS had BCF-free and DM-free rates of 74% and 92% at 8 years. CHHiP eligibility criteria limit the interpretation of these results. CONCLUSION: Contemporary review of International Society of Urological Pathology GGG successfully stratified patients treated with short-course hormone therapy and IMRT with regard to both BCF-free and DM-free outcomes. Patients upgraded from GGG 2 to GGG 3 using worst biopsy GS segregate with GGG 3 on long-term follow-up. We recommend that both overall and worst GS be used to derive GGG.

What is cancer? A focus on Grade Group 1 prostate cancer.

Since the widespread adoption of prostate-specific antigen-based screening for prostate cancer, the prevalence of Grade Group 1 (GG1) prostate cancer has risen. Historically, these patients were subjected to overtreatment of this otherwise indolent disease process, leading to significant quality-of-life detriments. Active surveillance as a primary management strategy has allowed for a focus on early detection while minimising morbidity from unnecessary intervention. Here we provide a comprehensive overview of the characteristics of GG1 prostatic adenocarcinoma, including its histological features, genomic differentiators, clinical progression, and implications for treatment guidelines, all supporting the movement to reclassify GG1 disease as a non-cancerous entity.

Prognostic factors among patients with pathological Grade Group 5 prostate cancer based on robot-associated radical prostatectomy specimens from a large Japanese cohort (MSUG94).

PURPOSE: There are no definitive prognostic factors for patients with pathological Grade Group 5 (pGG 5) prostate cancer (PCa) undergoing robot-associated radical prostatectomy (RARP). This study aimed to explore the prognostic factors among patients with pGG 5 PCa in a large Japanese cohort (MSUG94). METHODS: This retrospective, multi-institutional cohort study was conducted between 2012 and 2021 at ten centers in Japan and included 3195 patients. Patients with clinically metastatic PCa (cN1 or cM1) and those receiving neoadjuvant and/or adjuvant therapy were excluded. Finally, 217 patients with pGG5 PCa were analyzed. RESULTS: The median follow-up period was 28.0 months. The 3- and 5-year biochemical recurrence-free survival (BCRFS) rates of the overall population were 66.1% and 57.7%, respectively. The optimal threshold value (47.2%) for the percentage of positive cancer cores (PPCC) with any GG by systematic biopsy was chosen based on receiver operating characteristic curve analysis. Univariate analysis revealed that the prostate-specific antigen level at diagnosis, pT, pN, positive surgical margins (PSMs), lymphovascular invasion, and PPCC were independent prognostic factors for BCRFS. A multivariate analysis revealed that PSMs and PPCC were independent prognostic factors for BCRFS. Using these two predictors, we stratified BCRFS, metastasis-free survival (MFS), and castration-resistant PCa-free survival (CRPC-FS) among patients with pGG 5 PCa. CONCLUSION: The combination of PSMs and PPCC may be an important predictor of BCRFS, MFS, and CRPC-FS in patients with pGG 5 PCa undergoing RARP.

Effect of positive surgical margins at radical prostatectomy on cancer-specific mortality in high/very high-risk prostate cancer patients with Gleason Grade Group 4-5.

BACKGROUND: The effect of positive surgical margins (PSM) on cancer specific mortality (CSM) in high/very high-risk (HR/VHR) prostate cancer (PCa) with aggressive Gleason Grade Group (GGG) is unknown. We tested PSM effect on CSM in this setting, in addition to testing of radiotherapy (RT) benefit in PSM patients. METHODS: We relied on Surveillance, Epidemiology, and End Results database (2010-2015), focusing on HR/VHR patients with exclusive GGG 4-5 at radical prostatectomy (RP). Kaplan-Meier plots and multivariable Cox regression models tested the relationship between PSM and CSM. Moreover, the effect of RT on CSM was explored in PSM patients. RESULTS: Of 3383 HR/VHR patients, 15.1% (n = 511) exhibited PSM. Patients with PSM harbored higher rates of GGG 5 (60.1% vs. 50.9%, p < 0.001), pathologic tumor stage T3a (69.1% vs. 45.2%, p < 0.001) and lymph node involvement (14.1% vs. 9.4%, p < 0.001), relative to patients without PSM. PSM rates decreased over time (2010-2015) from 16.0% to 13.6%. Seven-year CSM-free survival rates were 91.6% versus 95.7% in patients with and without PSM, respectively. In multivariable Cox regression models, PSM was an independent predictor of CSM (hazard ratio = 1.6, p = 0.040) even after adjustment for age, prostate specific antigen, pathologic tumor stage and lymph node status. Finally, in PSM patients, RT delivery did not reduce CSM in either univariable or multivariable Cox regression models. CONCLUSIONS: In HR/VHR PCa patients with exclusive GGG 4-5, PSM at RP adversely affect survival. Moreover, RT has no protective effect on CSM. In consequence, lowest possible PSM rates are crucial in such patients.

Prostate magnetic resonance imaging-targeted biopsy global grade correlates better than highest grade with prostatectomy grade.

BACKGROUND: Magnetic resonance imaging (MRI)-targeted prostate biopsy has become an increasingly common method of diagnosing prostate cancer. A previous study from our institution demonstrated that the biopsy global Grade Group (gGG, aggregate GG of all positive cores) and highest Grade Group (hGG in any core) both show substantial concordance with the Grade Group at radical prostatectomy (RPGG) while the discordance predominantly consists of upgrading in gGG and downgrading in hGG. We performed a larger cohort study focused on biopsy cases in which gGG and hGG differ, to determine their relative concordance with RPGG. METHODS: We conducted a retrospective review of radical prostatectomy specimens with prior MRI-targeted biopsies from our institution between 2016 and 2020. Separate gGG and hGG were assigned to each MRI-targeted lesion. Targeted lesions with different gGG versus hGG were segregated from those with identical gGG and hGG. The concordance of biopsy GG with RPGG was evaluated using κ coefficient analysis. RESULTS: Of the 489 lesions with MRI-targeted biopsies, 82 (17%) differed in gGG versus hGG. The gGG of 46 (56%), 33 (40%), and 3 (4%) lesions were unchanged, upgraded, and downgraded at radical prostatectomy, respectively (κ= 0.302, weighted κ = 0.334). The hGG of 24 (29%), 9 (11%), and 49 (60%) lesions were unchanged, upgraded, and downgraded at radical prostatectomy, respectively (κ = 0.040, weighted κ = 0.198). When stratified by the biopsy GG, gGG showed the highest concordance in GG2 (61%) and GG3 (54%) lesions. The hGG resulted in substantial downgrading (60%) with less optimal concordance regardless of the biopsy GG. Neither the prebiopsy prostate specific antigen level nor the PI-RADS score was predictive of upgrading of gGG. CONCLUSIONS: When gGG and hGG differ, gGG method more accurately predicts the RPGG than hGG, particularly in GG2 and GG3 lesions which comprised the majority of targeted lesions.

Cribriform morphology is associated with higher risk of biochemical recurrence after radical prostatectomy in patients with Grade Group 5 prostate cancer.

AIMS: Grade Group 5 (GG5) prostate cancer (PCa) is associated with a high risk of disease recurrence after radical prostatectomy (~75% at 5 years). However, this is a heterogeneous category that includes neoplasms with different combinations of Gleason pattern (GP) 4 and 5. Within GP4, large cribriform growth has been associated with adverse disease-specific outcomes in GG2-4 PCa. Less is known about the significance of cribriform morphology and the different histologic patterns of GP5 in GG5 PCa. METHODS AND RESULTS: In this study we evaluated the prognostic implications of cribriform morphology (either invasive or intraductal, henceforth "cribriform") and large solid growth or comedonecrosis (comedo/solid) in patients with GG5 PCa. One-hundred and thirty prostatectomies from a single institution were analysed. The presence of comedo/solid components was associated with a higher frequency of concurrent cribriform PCa (85.7% versus 45.9%, P < 0.001), lymphovascular invasion (44.6% versus 27%, P = 0.04), and biochemical recurrence (48.2% versus 28.4%, P = 0.03). The presence of large cribriform growth was associated with a higher frequency of extraprostatic involvement (i.e. pT3a-b; 85.3% versus 68.7%, P = 0.02), positive surgical margins (47.6% versus 29.2%, P = 0.04) and biochemical recurrence (47.6% versus. 18.7%, P = 0.001). Kaplan-Meier analysis demonstrated that GG5 PCa with cribriform or comedo/solid components had a higher probability of biochemical recurrence. Multivariable analysis showed that only cribriform components were an independent predictor of a higher risk of biochemical recurrence in this series. CONCLUSION: These findings highlight the importance of reporting the presence of cribriform components in GG5 PCa and suggest that cribriform morphology might help decide postsurgical management in these patients.

Decade-long trends in prostate cancer biopsy grade groups and treatment within a population-based registry.

OBJECTIVE: To assess changes in diagnosis prostate cancer (PCa) grade, biopsy and treatment approach over a decade (2011-2020) at a population level within a clinical quality cancer registry. PATIENTS AND METHODS: Patients diagnosed by prostate biopsy between 2011 and 2020 were retrieved from the Victorian Prostate Cancer Outcomes Registry, a prospective, state-wide clinical quality registry in Australia. Distributions of each grade group (GG) proportion over time were modelled with restricted cubic splines, separately by biopsy technique, age group and subsequent treatment method. RESULTS: From 2011 to 2020, 24 308 men were diagnosed with PCa in the registry. The proportion of GG 1 disease declined from 36-23%, with commensurate rises in GG 2 (31-36%), GG 3 (14-17%) and GG 5 (9.3-14%) disease. This pattern was similar for men diagnosed by transrectal ultrasonography or transperineal biopsy. Patients aged <55 years had the largest absolute reduction in GG 1 PCa, from 56-35%, compared to patients aged 55-64 (41-31%), 65-74 (31-21%), and ≥75 years (12-10%). The proportion of prostatectomies performed for patients with GG 1 disease fell from 28% to 7.1% and, for primary radiation therapy, the proportion fell from 22% to 3.5%. CONCLUSION: From 2011 to 2020, there has been a substantial decrease in the proportion of GG 1 PCa diagnosed, particularly in younger men. The percentage of interventional management performed in GG 1 disease has fallen to very low levels. These results reflect the implementation of major changes to diagnostic and treatment guidelines and inform the future allocation of treatment methods.

Active surveillance should be considered for select men with Grade Group 2 prostate cancer.

BACKGROUND: Treatment decisions for localized prostate cancer must balance patient preferences, oncologic risk, and preservation of sexual, urinary and bowel function. While Active Surveillance (AS) is the recommended option for men with Grade Group 1 (Gleason Score 3 + 3 = 6) prostate cancer without other intermediate-risk features, men with Grade Group 2 (Gleason Score 3 + 4 = 7) are typically recommended active treatment. For select patients, AS can be a possible initial management strategy for men with Grade Group 2. Herein, we review current urology guidelines and the urologic literature regarding recommendations and evidence for AS for this patient group. MAIN BODY: AS benefits men with prostate cancer by maintaining their current quality of life and avoiding treatment side effects. AS protocols with close follow up always allow for an option to change course and pursue curative treatment. All the major guideline organizations now include Grade Group 2 disease with slightly differing definitions of eligibility based on risk using prostate-specific antigen (PSA) level, Gleason score, clinical stage, and other factors. Selected men with Grade Group 2 on AS have similar rates of deferred treatment and metastasis to men with Grade Group 1 on AS. There is a growing body of evidence from randomized controlled trials, large observational (prospective and retrospective) cohorts that confirm the oncologic safety of AS for these men. While some men will inevitably conclude AS at some point due to clinical reclassification with biopsy or imaging, some men may be able to stay on AS until transition to watchful waiting (WW). Magnetic resonance imaging is an important tool to confirm AS eligibility, to monitor progression and guide prostate biopsy. CONCLUSION: AS is a viable initial management option for well-informed and select men with Grade Group 2 prostate cancer, low volume of pattern 4, and no other adverse clinicopathologic findings following a well-defined monitoring protocol. In the modern era of AS, urologists have tools at their disposal to better stage patients at initial diagnosis, risk stratify patients, and gain information on the biologic potential of a patient's prostate cancer.

Optimized grade group for reporting prostate cancer grade in systematic and MRI-targeted biopsies.

PURPOSE: To explore an optimized grade group (oGG) criterion from systematic biopsies (SB) and targeted biopsies (TB) and offer a better prediction of radical prostatectomy (RP) grade group (GG). METHODS: Positive needles were collected from 146 patients who underwent SB + TB followed by RP. The grade was assigned for two different kinds of biopsies with five GG criteria: (1) global GG (gGG); (2) most common GG (most common GG from SB + TB, mGG); (3) highest GG (highest numerical GG from SB + TB, hGG); (4) largest volume/linear length cancer GG (defined as GG from the SB + TB with the largest length of cancer in a needle, lGG). These biopsy grades were compared (equivalence, upgrade, or downgrade) with the final grade of the RP lesion, using weighted κ coefficients; (5) Then the best agreement of the (2) (3) (4) grading scores from SB or TB was combined to introduce an oGG. RESULTS: In this study, gGG showed generally poor agreement (47.2%) with RP GG (weighted κ: 0.43). Using the three criteria (mGG, hGG, and lGG) of SB, mGG had the best agreement (55.5%, weighted κ: 0.46), while hGG and lGG had a lower agreement (48.6% and 48.6%, weighted κ: 0.42 and 0.38). Using the three criteria (mGG, hGG and lGG) of TB: lGG had the best agreement (56.8%, weighted κ: 0.43), while mGG and hGG had lower agreement (50.0% and 49.3%, weighted κ: 0.40 and 0.40); Then oGG was generated (higher GG between mGG of SB and lGG of TB) and the agreement of oGG increased to 59.6% and weighted κ was 0.49. Additionally, oGG had a lower upgrade rate than gGG, while the downgrade rate remained unchanged. CONCLUSIONS: oGG showed better agreement with RP GG than gGG. oGG had a lower upgrade rate than gGG, while downgrade rate remained unchanged.

Non-organ confined stage and upgrading rates in exclusive PSA high-risk prostate cancer patients.

BACKGROUND: The pathological stage of prostate cancer with high-risk prostate-specific antigen (PSA) levels, but otherwise favorable and/or intermediate risk characteristics (clinical T-stage, Gleason Grade group at biopsy [B-GGG]) is unknown. We hypothesized that a considerable proportion of such patients will exhibit clinically meaningful GGG upgrading or non-organ confined (NOC) stage at radical prostatectomy (RP). MATERIALS AND METHODS: Within the Surveillance, Epidemiology, and End Results database (2010-2015) we identified RP-patients with cT1c-stage and B-GGG1, B-GGG2, or B-GGG3 and PSA 20-50 ng/ml. Rates of GGG4 or GGG5 and/or rates of NOC stage (≥ pT3 and/or pN1) were analyzed. Subsequently, separate univariable and multivariable logistic regression models tested for predictors of NOC stage and upgrading at RP. RESULTS: Of 486 assessable patients, 134 (28%) exhibited B-GGG1, 209 (43%) B-GGG2, and 143 (29%) B-GGG3, respectively. The overall upgrading and NOC rates were 11% and 51% for a combined rate of upgrading and/or NOC stage of 53%. In multivariable logistic regression models predicting upgrading, only B-GGG3 was an independent predictor (odds ratio [OR]: 5.29; 95% confidence interval [CI]: 2.21-14.19; p < 0.001). Conversely, 33%-66% (OR: 2.36; 95% CI: 1.42-3.95; p = 0.001) and >66% of positive biopsy cores (OR: 4.85; 95% CI: 2.84-8.42; p < 0.001), as well as B-GGG2 and B-GGG3 were independent predictors for NOC stage (all p ≤ 0.001). CONCLUSIONS: In cT1c-stage patients with high-risk PSA baseline, but low- to intermediate risk B-GGG, the rate of upgrading to GGG4 or GGG5 is low (11%). However, NOC stage is found in the majority (51%) and can be independently predicted with percentage of positive cores at biopsy and B-GGG.

Stratification of prostate cancer patients into low- and high-grade groups using multiparametric magnetic resonance radiomics with dynamic contrast-enhanced image joint histograms.

PURPOSE: This study aimed to investigate the potential of stratification of prostate cancer patients into low- and high-grade groups (GGs) using multiparametric magnetic resonance (mpMR) radiomics in conjunction with two-dimensional (2D) joint histograms computed with dynamic contrast-enhanced (DCE) images. METHODS: A total of 101 prostate cancer regions extracted from the MR images of 44 patients were identified and divided into training (n = 31 with 72 cancer regions) and test datasets (n = 13 with 29 cancer regions). Each dataset included low-grade tumors (International Society of Urological Pathology [ISUP] GG ≤ 2) and high-grade tumors (ISUP GG ≥ 3). A total of 137,970 features consisted of mpMR image (16 types of images in four sequences)-based and joint histogram (DCE images at 10 phases)-based features for each cancer region. Joint histogram features can visualize temporally changing perfusion patterns in prostate cancer based on the joint histograms between different phases or subtraction phases of DCE images. Nine signatures (a set of significant features related to GGs) were determined using the best combinations of features selected using the least absolute shrinkage and selection operator. Further, support vector machine models with the nine signatures were built based on a leave-one-out cross-validation for the training dataset and evaluated with receiver operating characteristic (ROC) curve analysis. RESULTS: The signature showing the best performance was constructed using six features derived from the joint histograms, DCE original images, and apparent diffusion coefficient maps. The areas under the ROC curves for the training and test datasets were 1.00 and 0.985, respectively. CONCLUSION: This study suggests that the proposed approach with mpMR radiomics in conjunction with 2D joint histogram computed with DCE images could have the potential to stratify prostate cancer patients into low- and high-GGs.

Prevalence of adverse pathology features in grade group 2 prostatectomy specimens with syn- or metachronous metastatic disease.

BACKGROUND: To validate the importance of recently established adverse histopathology features (cribriform pattern and intraductal carcinoma) as contra-indication for deferred treatment of Gleason score 7 (3 + 4) (grade group [GG] 2) prostate cancer, we investigated their frequency in GG2 radical prostatectomies with syn- or metachronous metastatic disease. METHODS: GG2 prostatectomy specimens of patients with concomitant lymph node metastasis or distant metastasis at follow-up were identified in a clinical database of a tertiary care center and their pathology was reviewed for pathological stage, lymphovascular invasion, Gleason grade 4 subpatterns, presence of tertiary grade 5, and ductal adenocarcinoma histology. A control group of 99 GG2 prostatectomy specimens who had no metastatic disease (controls) was reviewed for the same adverse pathological features. RESULTS: Of 1860 GG2 prostatectomy specimens (operated between 2002 and 2020), 45 (2.4%) had concurrent regional lymph node metastases or distant metastases at follow-up. Pathological stage distribution of cases and controls was 24% and 79% pT2, 42% and 15% pT3a, 33% and 6.1% pT3b -T4, respectively (p < 0.001). Eleven of 45 cases (24%) had ≤10% Gleason grade 4 component. Cribriform pattern or intraductal carcinoma was present in 84% of cases versus 34% of controls (p < 0.001), tertiary grade 5 in 16% of cases versus 5% controls (p = 0.05) and ductal adenocarcinoma in 16% of cases versus 2% of controls (p = 0.004). Among the seven cases without cribriform or intraductal carcinoma, two displayed ductal adenocarcinoma features. CONCLUSIONS: Well-established unfavorable histopathologic features (intraductal and cribriform pattern carcinoma, ductal adenocarcinoma) are represented in about 90% of GG2 prostate cancers with local or distant metastatic disease and are much less common (38%) in those without metastatic disease. Strikingly, about 25% of GG2 prostatectomy cases with metastatic disease had an organ-confined disease and/or a small percentage of Gleason grade 4 pattern. This further emphasizes the relative importance of these adverse histopathological features (cribriform, intraductal, and ductal adenocarcinoma) rather than percentage Gleason grade 4 as contra-indicator of deferred treatment for patients with GG2 prostate cancer.

Clinical utility of subclassifying positive surgical margins at radical prostatectomy.

OBJECTIVE: To determine whether subclassification of positive surgical margins (PSMs) increases predictive ability for biochemical recurrence (BCR) and aids clinical decision-making in patients undergoing radical prostatectomy. PATIENTS AND METHODS: We studied 2147 patients with pT2 and pT3a prostate cancer with detailed surgical margin parameters and BCR status. We compared a base model, a linear predictor calculated from the Memorial Sloan Kettering Cancer Center postoperative nomogram (prostate-specific antigen, pathological tumour grade and stage), with the addition of surgical margin status to five additional models (base model plus surgical margin subclassifications) to evaluate enhancement in predictive accuracy. Decision curve analysis (DCA) was performed to determine the clinical utility of parameters that enhanced predictive accuracy. RESULTS: Among 2147 men, 205 had PSMs, and 231 developed BCR. Discrimination for the base model with addition of surgical margin status was high (c-index = 0.801) and not meaningfully improved by adding surgical margin subclassification in the full cohort. In analyses considering only men with PSMs (N = 55 with BCR), adding surgical margin subclassification to the base model increased discrimination for total length of all PSMs - alone or with maximum Gleason grade at the margin (c-index improvement = 0.717 to 0.752 and 0.753, respectively). DCA demonstrated a modest benefit to clinical utility with the addition of these parameters. CONCLUSIONS: Specific subclassification parameters add predictive accuracy for BCR and may aid clinical utility in decision-making for patients with PSMs. These findings may be useful for patient counselling and future adjuvant therapy trial design.

Heterogeneity of contemporary grade group 4 prostate cancer in radical prostatectomy specimens.

PURPOSE: The aim was to evaluate the prognostic role of sub-categories of ISUP 4 prostate cancer (PCa) on final pathology, and assess the tumor architecture prognostic role for predicting biochemical recurrence (BCR) after radical prostatectomy. METHODS: From a prospectively-maintained database, we included 370 individuals with ISUP 4 on final pathology. The main outcomes were to evaluate the relationship between different ISUP patterns within the group 4 with pathological and oncological outcomes. Binary logistic regression and Kaplan-Meier estimator were used to evaluate the role of the different categories (3 + 5, 4 + 4, 5 + 3) and tumor architecture (intraductal and/or cribriform) on pathological and oncological outcomes. RESULTS: Among the 370 individuals with ISUP considered for the study, 9, 85 and 6% had grade 3 + 5, 4 + 4 and 5 + 3 PCa, respectively. Overall, 74% had extracapsular extension, while lymph node invasion (LNI) was documented in 9%. A total of 144 patients experienced BCR during follow-up. After adjusting for PSA, pT, grade group, LNI and positive surgical margins (PSM), grade 3 + 5 was a protective factor (HR: 0.30, 95% CI: 0.13,0.68, p = 0.004) in predicting BCR relative to grade 4 + 4. Intraductal or cribriform architecture was correlated with BCR (HR: 5.99, 95% CI: 2.68, 13.4, p < 0.001) after adjusting for PSA, pT, grade group, LNI and PSM. CONCLUSIONS: Patients with tumor grade 3 + 5 had better pathological and prognostic outcomes compared to 4 + 4 or 5 + 3. When accounting for tumor architecture, the sub-stratification into subgroups lost its prognostic role and tumor architecture was the sole predictor of poorer prognosis in terms of biochemical recurrence.

Prostate-specific antigen level, biopsy grade group, and tumor-capsular contact length on magnetic resonance imaging are independently associated with an extraprostatic extension.

OBJECTIVE: To define the clinicopathological and radiological factors independently associated with the existence of an extraprostatic extension in radical prostatectomy specimens. METHODS: A total of 202 patients who underwent robotic prostatectomy following biparametric magnetic resonance imaging were assessed. We evaluated the clinicopathological and magnetic resonance imaging variables. We performed receiver-operating characteristic curve analyses to identify factors associated with extraprostatic extension. We engaged in multivariate analysis to identify factors independently associated with such extension. RESULTS: Extraprostatic extensions were apparent in the final prostatectomy specimens of 62 patients (31%). The areas under the curves of the prostate-specific antigen level, the biopsy grade group, and the tumor-capsular contact length on magnetic resonance imaging were 0.76, 0.71, and 0.70, respectively, in receiver-operating characteristic analysis when used to predict extraprostatic extension; thus, higher than the areas under the curves of the other variables (0.61-0.68). The prostate-specific antigen level (odds ratio 1.090, p = 0.004), the biopsy grade group (odds ratios 2.678 and 6.358, p = 0.017 and p < 0.001 for grade group 3-4 and 5), and the tumor-capsular contact length (odds ratio 1.079, p = 0.001) were independently associated with extraprostatic extension. When the three factors were combined, the area under the receiver-operator characteristic curve increased to 0.79. CONCLUSIONS: The prostate-specific antigen level, the biopsy grade group, and the tumor-capsular contact length on magnetic resonance imaging were independently associated with extracapsular extension.

Twenty-year trends in prostate cancer stage and grade migration in a large contemporary german radical prostatectomy cohort.

BACKGROUND: A trend towards inverse stage migration in prostate cancer (PCa) was reported. However, previous analyses did not take into account potential differences in sampling strategies (number of biopsy cores), which might have confounded these reports. MATERIAL AND METHODS: Within our single-institutional database we identified PCa patients treated with radical prostatectomy (RP) between 2000 and 2020 (n = 21,646). We calculated the estimated annual percentage change (EAPC) for D'Amico risk groups, biopsy Gleason Grade Group (GGG), PSA and cT stage as well as postoperative RP GGG and pT stage relying on log linear regression methodology. Subsequently, we repeated the analyses after adjustment for number of cores obtained at biopsy. RESULTS: Absolute rates of D'Amico low risk decreased (-30.1%), while intermediate and high risk increased (+21.2% and +9.0%, respectively). Rates of GGG I decreased (-50.0%), while GGG II-V increased, with the largest increase in GGG II (+22.5%). This trend, albeit less pronounced, was also recorded after adjusted EAPC analyses (p < .05). Specifically, EAPC values for D'Amico low vs intermediate vs high risk were -1.07%, +0.37%, +0.45%, respectively, and EAPC values for GGG ranged between -0.71% (GGG I) and +0.80% (GGG IV). Finally, an increase in ≥cT2 (EAPC: +3.16%) was displayed (all p < .001). These trends were confirmed in EAPC calculations in RP GGG and pT stages (p < .001). CONCLUSION: Our findings confirm the trend towards less frequent treatment of low risk PCa and more frequent treatment of high risk PCa, also after adjustment for number of biopsy cores.