The Gleason grading system is one of the most important factors in clinical decision-making for prostate
cancer patients, and is entirely based on the classification of tumour growth patterns. In recent years it
has become clear that some individual growth patterns themselves have independent prognostic value,
and could be used for better personalised risk
stratification. In this review we summarise recent literature on the clinicopathological value and molecular characteristics of individual prostate cancer
growth patterns, and show how these, most particularly cribriform architecture, could alter treatment
decisions for prostate cancer patients.

/pdf/prostate-cancer-growth-patterns-beyond-the-gleason-score-5a0mz8n8xf.pdf

Prostate cancer growth patterns beyond the Gleason score: entering a new era of comprehensive tumour grading.

Underactive bladder (UAB) is a prevalent but under-researched lower urinary tract symptom that typically occurs alongside detrusor underactivity (DU). Unlike UAB, DU is a urodynamic diagnosis which the International Continence Society (ICS) defines as “a contraction of reduced strength and/or duration, resulting in prolonged bladder emptying and/or a failure to achieve complete bladder emptying within a normal time span”. Despite the widespread prevalence of UAB/DU, there are significant gaps in our understanding of its pathophysiological mechanisms, diagnosis, and treatment compared with overactive bladder (OAB) and detrusor overactivity (DO). These gaps are such that clinicians regard UAB/DU as an incurable condition. In recent years, the understanding of UAB has increased. The definition of UAB has been clarified, and the diagnostic criteria for DU have been considered more comprehensively. Meanwhile, a number of non-invasive diagnostic methods have also been reported. Clinical trials involving novel drugs, electrical stimulation, and stem cell therapy have shown promising results. Therefore, this review summarizes recent reports on UAB and DU and highlights the latest advances in their diagnosis and treatment.

Underactive Bladder and Detrusor Underactivity: New Advances and Prospectives

BACKGROUND To explore whether metastatic castration-resistant prostate cancer (mCRPC) patients with distinct intraductal carcinoma of the prostate (IDC-P) subtypes respond differently to abiraterone and docetaxel treatment. METHODS We retrospectively analyzed data of 170 mCRPC patients receiving abiraterone or docetaxel as first-line therapy. PSA response, PSA progression-free survival (PSA-PFS), radiographic progression-free survival (rPFS), and overall survival (OS) were analyzed based on the presence of IDC-P and its subpatterns. RESULTS IDC-P was confirmed in 91/170 (53.5%) patients. Among them 36/91 (39.6%) and 55/91 (60.4%) harbored IDC-P patterns 1 and 2, respectively. Patients with IDC-P pattern 1 shared similar clinical outcomes to those without IDC-P in both abiraterone and docetaxel treatment. However, against cases without IDC-P or with IDC-P pattern 1, patients with IDC-P pattern 2 had markedly poorer prognosis in either abiraterone (mPSA-PFS: 11.9 vs. 11.1 vs. 6.1 months, p < 0.001; mrPFS: 18.9 vs. 19.4 vs. 9.6 months, p < 0.001) or docetaxel (mPSA-PFS: 6.2 vs. 6.6 vs. 3.0 months, p < 0.001; mrPFS: 15.1 vs. 12.6 vs. 5.5 months, p < 0.001) treatment. For patients without IDC-P, docetaxel had comparable therapeutic efficacy with abiraterone. However, the efficacy of docetaxel was significantly inferior to abiraterone in patients with either IDC-P pattern 1 (mPSA-PFS: 6.6 vs. 11.1 months, p = 0.021; mrPFS: 12.6 vs. 19.4 months, p = 0.027) or pattern 2 (mPSA-PFS: 3.0 vs. 6.1 months, p = 0.003; mrPFS: 5.5 vs. 9.6 months, p = 0.007). CONCLUSION Compared to docetaxel, abiraterone exhibited better efficacy in patients with IDC-P of either pattern. However, IDC-P pattern 2 responded unsatisfactorily to either abiraterone or docetaxel therapy. Novel therapeutic strategies for IDC-P pattern 2 need further investigations.

/pdf/the-heterogeneity-of-intraductal-carcinoma-of-the-prostate-4tuu3fkboo.pdf

The heterogeneity of intraductal carcinoma of the prostate is associated with different efficacy of standard first-line therapy for patients with metastatic castration-resistant prostate cancer

The CHAARTED and LATITUDE trials demonstrated a survival benefit of docetaxel and abiraterone for hormone-sensitive prostate cancer. In this study, we examined the impact of the risk stratification criteria used in the CHAARTED and LATITUDE trials on the prognosis of castration-resistant prostate cancer (CRPC). We also tested whether these risk stratification criteria could help in selecting effective initial treatment for CRPC.Japanese patients with CRPC who were treated with docetaxel or androgen receptor pathway inhibitors such as abiraterone acetate or enzalutamide between 2014 and 2018 were included in this study. Clinicopathological factors, progression-free survival, and overall survival were investigated.Of 215 patients, 110 men (51.2%) and 93 men (43.3%) were grouped as high volume by CHAARTED criteria and high risk by LATITUDE criteria, respectively. Median progression-free survival was 10.3/4.5 months (P < 0.0001) for low/high volume (CHAARTED criteria) and 9.9/4.8 months (P = 0.0032) for low/high risk (LATITUDE criteria). The median overall survival was 44.8/17.4 months (P < 0.0001) for low/high volume (CHAARTED criteria) and 37.4/17.4 months (P = 0.0011) for low/high risk (LATITUDE criteria). The prognostic impact of CHAARTED and LATITUDE criteria was comparable between androgen receptor pathway inhibitors and docetaxel as first-line treatment for CRPC.The CHAARTED and LATITUDE criteria were prognostic, but not useful to discriminate the therapeutic outcome between androgen receptor pathway inhibitors and docetaxel for CRPC. 

https://doi.org/10.1016/j.prnil.2022.01.001

Prognostic significance of risk stratification in CHAARTED and LATITUDE studies among Japanese men with castration-resistant prostate cancer

OBJECTIVES To investigate predictive factors of survival of metastatic castration-resistant prostate cancer patients undergoing first-line treatment with androgen receptor pathway inhibitors or docetaxel. METHODS Japanese patients with metastatic castration-resistant prostate cancer treated with androgen receptor pathway inhibitor or docetaxel between 2008 and 2018 were included. The differential impact of various clinicopathological factors on the outcome, including progression-free survival and overall survival, was compared between treatment with androgen receptor pathway inhibitor and docetaxel. RESULTS Of 254 patients with metastatic castration-resistant prostate cancer, 119 (46.9%) and 135 (53.2%) were treated with androgen receptor pathway inhibitor and docetaxel, respectively. The multivariate analysis showed that androgen receptor pathway inhibitor was an independent prognostic factor for better progression-free survival (hazard ratio 0.62, 95% confidence interval 0.42-0.92, P = 0.016) and overall survival (hazard ratio 0.61, 95% confidence interval 0.41-0.93, P = 0.021), compared with docetaxel. Pretreatment prostate-specific antigen levels and time to castration-resistant prostate cancer were differentially associated with progression-free survival and overall survival between androgen receptor pathway inhibitor or docetaxel. In patients who presented <6 months to castration-resistant prostate cancer, progression-free survival was shorter in those treated with androgen receptor pathway inhibitor (median 1.1 months, 95% confidence interval 0.2-2.8 months) compared with those who received docetaxel (median 5.0 months, 95% confidence interval 1.8-6.7 months; P = 0.014). CONCLUSIONS First-line therapy with androgen receptor pathway inhibitor is associated with a better prognosis when compared with docetaxel, even after adjustment for prognostic factors. However, a shorter time to castration-resistant prostate cancer is associated with better progression-free survival for patients receiving docetaxel, suggesting that docetaxel is the preferred option for patients with a shorter time to castration-resistant prostate cancer.

Predictive factors of survival outcomes in first-line therapy for metastatic castration-resistant prostate cancer.

Objective To evaluate the efficacy of docetaxel and androgen receptor axis-targeted (ARAT) agents in patients with castration-resistant prostate cancer (CRPC) with intraductal carcinoma of the prostate (IDC-P) using a propensity score-matched analysis. Patients and methods We retrospectively identified 309 patients with CRPC from February 2007 to February 2016 at Nagoya University and its affiliated hospitals. All patients received initial androgen-deprivation therapy (ADT). After progression to CRPC, they received docetaxel or ARAT (abiraterone or enzalutamide) as first-line life-prolonging therapy. Docetaxel (70-75 mg/m2 ) every 3 weeks vs enzalutamide (160 mg) once daily orally or abiraterone (1 g) once daily plus prednisone (5 mg) twice daily orally was administered. The primary outcome of interest was overall survival (OS) from the time of CRPC diagnosis. A propensity score analysis with a 1:1 ratio using an optimal matching algorithm was used to adjust for confounding factors. Results Overall, 234 patients were analysed. Propensity score-matching identified 85 patients in each group. There were no significant differences in patient characteristics between the groups. The median OS in the docetaxel group was 38.2 vs 58.3 months in the ARAT group (P = 0.03). For patients with IDC-P, OS was significantly longer in the ARAT group than the docetaxel group (P = 0.01), and there was no significant difference in each group, as in patients without IDC-P (P = 0.67). A multivariate analysis showed that the presence of IDC-P, duration of primary ADT, visceral metastasis, and administration of ARAT as the first-line treatment for CRPC were independent prognostic factors for OS. Conclusion Administration of ARAT as the first-line treatment for CRPC may prolong OS more than that of docetaxel, especially in patients with IDC-P.

Propensity score-matched comparison of docetaxel and androgen receptor axis-targeted agents in patients with castration-resistant intraductal carcinoma of the prostate.

Adiponectin can be a good predictor of urodynamic detrusor underactivity: a prospective study in men with lower urinary tract symptoms

Background The optimal sequential therapy for castration-resistant prostate cancer (CRPC) remains unknown. In recent years, some doubts have emerged regarding the clinical benefit of sequential therapy with androgen receptor axis-targeted agents (ART) such as abiraterone (ABI) or enzalutamide (ENZ) for patients with CRPC. We compared the effect of ART-to-ART (AA) sequential therapy after castration resistance with that of docetaxel (DTX)-combined sequential therapy (ART to DTX or DTX to ART) in patients with CRPC. Methods We retrospectively identified and analyzed the data of 315 patients with CRPC treated in our seven affiliated institutions between 2009 and 2019. All patients received either DTX or ART (ABI or ENZ) as the first- or second-line therapy after castration resistance. We compared the overall survival (OS) and the second progression-free survival (PFS2), calculated from the initiation of first-line therapy after castration resistance, between the AA sequence group and the DTX-combined sequence group. PFS2 was defined as the period from the start of first-line treatment after castration resistance to progression on second-line treatment. To minimize selection bias from possible confounders, we performed propensity score matching using one-to-one nearest neighbor matching without replacement. Results Overall, 106 and 209 patients were administered the AA sequential therapy and DTX-combined sequential therapy, respectively. The clinicopathological variables of patients were well balanced after propensity score matching, and there were no significant differences between the two groups. In the propensity score-matched cohort, OS was not significantly different between the two groups (median, 37.9 vs. 45.4 months; hazard ratio [HR], 1.10; 95% confidence interval [CI], 0.68-1.79; p = .701), while PFS2 was significantly shorter in the AA group than in the DTX-combined group (median, 12.9 vs. 21.6 months; HR, 1.70; 95% CI, 1.16-2.48; p = .007). Conclusions Certain patients with CRPC can benefit from ART-to-ART sequential therapy in a daily clinical setting.

The clinical benefit of sequential therapy with androgen receptor axis-targeted agents alone in patients with castration-resistant prostate cancer: A propensity score-matched comparison study

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Propensity score-matched comparison of docetaxel and androgen receptor axis-targeted agents in patients with castration-resistant intraductal carcinoma of the prostate.

Adiponectin can be a good predictor of urodynamic detrusor underactivity: a prospective study in men with lower urinary tract symptoms

The clinical benefit of sequential therapy with androgen receptor axis-targeted agents alone in patients with castration-resistant prostate cancer: A propensity score-matched comparison study