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Nonsurgical treatments for prostate cancer include androgen-deprivation therapy (ADT), radiation therapy (RT), ablative therapies, chemotherapy, and newly emerging immunotherapies. These approaches can be used alone or in combination depending on the clinical scenario. ADT is typically reserved for high-risk locally or systemically advanced disease that is not amenable to curative surgery. Radiation therapy can be used instead of surgery as primary therapy with curative intent for low-intermediate-risk disease as well as for control of locally advanced disease not suitable for surgery. Ablative therapies can be used as primary therapy for low-intermediate-risk disease or as salvage therapy for clinically localized disease where RT has failed. Chemotherapy and immune-based therapies are currently used for androgen-independent disease, although the indications for these approaches may well change as new data from clinical trials accrue. Pathologists should be able to recognize tissue changes associated with these treatments to provide information that will optimize patient management. This is particularly true in situations where clinical history of recent or remote nonsurgical treatment is not provided with the specimen. In the absence of this information, pathologists encountering the features described herein are encouraged to review patient records or communicate directly with clinical colleagues to determine how a given patient was treated and when.

Key Points Prostate-specific membrane antigen (PSMA) is a promising and specific target for prostate cancer imaging PSMA–PET imaging can add molecular information to multiparametric MRI and, therefore, delineate suspicious lesions for targeted biopsies, especially in patients whose biopsy samples are tumour-negative PSMA–PET imaging shows increased specificity and sensitivity compared with current standard imaging (CT, MRI and bone scintigraphy) in patients with primary intermediate-risk or high-risk prostate cancer PSMA–PET imaging improves detection of metastatic lesions even at low serum PSA values in biochemically recurrent prostate cancer Enhanced detection of prostate cancer lesions might enable improved patient-tailored therapy planning and, therefore, lead to improved therapy outcomes Prostate-specific membrane antigen (PSMA) has gained increasing interest as target molecule for imaging. Several small compounds for labelling PSMA have been developed and are currently being investigated as imaging probes for PET. PSMA-based imaging has been reported to improve detection of metastatic disease compared with CT or multiparametric MRI and 68 Ga-PSMA–PET imaging has been shown to increase detection of metastatic sites, therefore, it holds great promise to improve prostate cancer management. Currently, the findings of imaging procedures used for detection or staging of prostate cancer depend on morphology of lymph nodes or bone metabolism and do not always meet diagnostic needs. Prostate-specific membrane antigen (PSMA), a transmembrane protein that has considerable overexpression on most prostate cancer cells, has gained increasing interest as a target molecule for imaging. To date, several small compounds for labelling PSMA have been developed and are currently being investigated as imaging probes for PET with the 68 Ga-labelled PSMA inhibitor Glu-NH-CO-NH-Lys(Ahx)-HBED-CC being the most widely studied agent. 68 Ga-PSMA–PET imaging in combination with multiparametric MRI (mpMRI) might provide additional molecular information on cancer localization within the prostate. In patients with primary prostate cancer of intermediate-risk to high-risk, PSMA-based imaging has been reported to improve detection of metastatic disease compared with CT or mpMRI, rendering additional cross-sectional imaging or bone scintigraphy unnecessary. Furthermore, in patients with biochemically recurrent prostate cancer, use of 68 Ga-PSMA–PET imaging has been shown to increase detection of metastatic sites, even at low serum PSA values, compared with conventional imaging or PET examination with different tracers. Thus, although current knowledge is still limited and derived mostly from retrospective series, PSMA-based imaging holds great promise to improve prostate cancer management.

Accurate diagnosis and grading of needle biopsies are crucial for prostate cancer management. A uropathologist-level artificial intelligence (AI) system could help make unbiased decisions and improve pathologists' efficiency. We previously reported an artificial neural network-based, automated, diagnostic software for prostate biopsy, DeepDx® Prostate (DeepDx). Using an independent external dataset, we aimed to validate the performance of DeepDx at the levels of prostate cancer diagnosis and grading and evaluate its potential value to the general pathologist. A dataset composed of 593 whole-slide images of prostate biopsies (130 normal and 463 adenocarcinomas) was assembled, including their original pathology reports. The Gleason scores (GSs) and grade groups (GGs) determined by three uropathology experts were considered as the reference standard. A general pathologist conducted user validation by scoring the dataset with and without AI assistance. DeepDx was accurate for prostate cancer detection at a similar level to the original pathology report, whereas it was more concordant than the latter with the reference GGs and GSs (kappa/quadratic-weighted kappa = 0.713/0.922 vs. 0.619/0.873 for GGs and 0.654/0.904 vs. 0.576/0.858 for GSs). Notably, it outperformed the original report, especially in the detection of Gleason patterns 4/5, and achieved excellent agreement in quantifying the Gleason pattern 4. When the general pathologist used AI assistance, the concordance of GG between the user and the reference standard increased (kappa/quadratic-weighted kappa, 0.621/0.876 to 0.741/0.925), while the average slide examination time was substantially decreased (55.7 to 36.8 s/case). Overall, DeepDx was capable of making expert-level diagnosis in prostate core biopsies. In addition, its remarkable performance in detecting high-grade Gleason patterns and enhancing the general pathologist's diagnostic performance supports its potential value in routine practice.

BackgroundPsychiatric implications of prostate cancer are increasingly recognised, having important effects on oncological and functional outcomes. However, findings for co-occurring depression, anxiety, and suicidality remain variable. Therefore, this review of observational studies aimed to establish best estimates of the prevalence and rates of these outcomes in prostate cancer patients.MethodsA systematic literature search was conducted using MEDLINE, Scopus, PsycInfo, and Cochrane Library databases from inception up to 26 May 2020. Observational studies using validated methods for evaluating prevalences of depression, anxiety and suicidal ideation, or suicide mortality rates post prostate cancer diagnosis were included. Random effect models were used to calculate pooled prevalences of depressive and anxiety symptoms or disorders, and suicidal ideation post diagnosis. Additionally, pooled crude suicide mortality rates per 100,000 person years were calculated. Heterogeneity was explored using a stratified analysis.ResultsOf 3537 articles screened, 117 were included. Pooled prevalence for depressive disorders was 5.81% (95% CI 4.36–7.46) in 11 studies, representing 655,149 patients. Significant depressive symptoms were identified in 17.07% (15.14–19.09) across 32,339 patients and 76 studies. In total, 16.86% (14.92–18.89) had significant anxiety symptoms in 56 studies combining 24,526 patients. In 6,173 patients and eight studies, recent suicidal ideation was present in 9.85% (7.31–12.70). Crude suicide mortality rate after diagnosis was 47.1 (39.85–54.96) per 100,000 person years in 12 studies. Significant heterogeneity was seen with potential sources identified through our sensitivity analysis including diagnostic method utilised, study size and location of study.ConclusionsThe mental health impact in patients with prostate cancer is significant. Depressive, anxiety, and suicidal symptoms were common. Additionally, a high suicide mortality rate was identified when compared to general population estimates. Screening of patients and integration of physical and mental health care should be evaluated further to improve quality of life and functional outcomes.

BackgroundRisk stratification in men with suspicion of prostate cancer (PCa) requires reliable diagnostic tests, not only to identify high-grade PCa, also to minimize the overdetection of low-grade PCa, and reduction of “unnecessary” prostate MRIs and biopsies. This study aimed to evaluate the SelectMDx test to detect high-grade PCa in biopsy-naïve men. Subsequently, to assess combinations of SelectMDx test and multi-parametric (mp) MRI and its potential impact on patient selection for prostate biopsy.MethodsThis prospective multicenter diagnostic study included 599 biopsy-naïve patients with prostate-specific antigen level ≥3 ng/ml. All patients underwent a SelectMDx test and mpMRI before systematic transrectal ultrasound-guided biopsy (TRUSGB). Patients with a suspicious mpMRI also had an in-bore MR-guided biopsy (MRGB). Histopathologic outcome of TRUSGB and MRGB was used as reference standard. High-grade PCa was defined as ISUP Grade Group (GG) ≥ 2. The primary outcome was the detection rates of low- and high-grade PCa and number of biopsies avoided in four strategies, i.e., (1) SelectMDx test-only, (2) mpMRI-only, (3) SelectMDx test followed by mpMRI when SelectMDx test was positive (conditional strategy), and (4) SelectMDx test and mpMRI in all (joint strategy). A positive SelectMDx test outcome was a risk score of ≥−2.8. Decision curve analysis (DCA) was performed to assess clinical utility.ResultsPrevalence of high-grade PCa was 31% (183/599). Thirty-eight percent (227/599) of patients had negative SelectMDx test in whom biopsy could be avoided. Low-grade PCa was not detected in 35% (48/138) with missing 10% (18/183) high-grade PCa. Yet, mpMRI-only could avoid 49% of biopsies, not detecting 4.9% (9/183) of high-grade PCa. The conditional strategy reduces the number of mpMRIs by 38% (227/599), avoiding biopsy in 60% (357/599) and missing 13% (24/183) high-grade PCa. Low-grade PCa was not detected in 58% (80/138). DCA showed the highest net benefit for the mpMRI-only strategy, followed by the conditional strategy at-risk thresholds >10%.ConclusionsSelectMDx test as a risk stratification tool for biopsy-naïve men avoids unnecessary biopsies in 38%, minimizes low-grade PCa detection, and misses only 10% high-grade PCa. Yet, using mpMRI in all patients had the highest net benefit, avoiding biopsy in 49% and missing 4.9% of high-risk PCa. However, if mpMRI availability is limited or expensive, using mpMRI-only in SelectMDx test positive patients is a good alternative strategy.

Limited evidence exists about preserving neurovascular bundles during radical prostatectomy (RP) for high-risk prostate cancer (HRPCa) patients. Hence, we validated an existing algorithm predicting contralateral extraprostatic extension (cEPE) risk in unilateral high-risk cases. This algorithm aims to assist in determining the suitability of unilateral nerve-sparing RP. Among 264 patients, 48 (18%) had cEPE. The risk of cECE varied: 8%, 17.2%, and 30.8% for the low, intermediate, and high-risk groups, respectively. Despite a higher risk of cECE among individuals classified as low-risk in the development group compared to the validation group, our algorithm’s superiority over always/never nerve-sparing RP was reaffirmed by decision curve analysis. Therefore, we conclude that bilateral excision may not always be justified in men with unilateral HRPCa. Instead, decisions can be based on our suggested nomogram.

The Gleason score is an important parameter for clinical outcome in prostate cancer patients. Gleason score 8 is a heterogeneous disease including Gleason score 3 + 5, 4 + 4, and 5 + 3 tumors, and encompasses a broad range of tumor growth patterns. Our objective was to characterize individual growth patterns and identify prognostic parameters in Gleason score 8 prostate cancer patients. We reviewed 1064 radical prostatectomy specimens, recorded individual Gleason 4 and 5 growth patterns as well as presence of intraductal carcinoma, and evaluated biochemical recurrence- and metastasis-free survival. Gleason score 8 disease was identified in 140 (13%) patients, of whom 76 (54%) had Gleason score 3 + 5, 46 (33%) 4 + 4, and 18 (13%) 5 + 3 disease. Invasive cribriform and/or intraductal carcinoma (n = 87, 62%) was observed more frequently in Gleason score 4 + 4 (93%) than 3 + 5 (47%; P < 0.001) and 5 + 3 (44%; P < 0.001) patients. Gleason pattern 5 was present in 110 (79%) men: as single cells and/or cords in 99 (90%) and solid fields in 32 (29%) cases. Solid field pattern 5 coexisted with cribriform architecture (23/32, 72%) more frequently than nonsolid pattern 5 cases (36/78, 46%, P = 0.02). In multivariable analysis including age, prostate-specific antigen, pT-stage, surgical margin status, and lymph node metastases, presence of cribriform architecture was an independent parameter for biochemical recurrence-free (hazard ratio (HR) 2.0, 95% confidence interval (CI) 1.0–3.7; P = 0.04) and metastasis-free (HR 3.5, 95% CI 1.0–12.3; P = 0.05) survival. In conclusion, invasive cribriform and/or intraductal carcinoma occurs more frequently in Gleason score 4 + 4 prostate cancer patients than in Gleason score 3 + 5 and 5 + 3, and is an independent parameter for biochemical recurrence and metastasis. Therefore, cribriform architecture has added value in risk stratification of Gleason score 8 prostate cancer patients.