Jinge Zhao

The impact of multifocal perineural invasion on biochemical recurrence and timing of adjuvant androgen-deprivation therapy in high-risk prostate cancer following radical prostatectomy

Background: Perineural invasion (PNI) is a distinct pathologic entity and a recognized source of tumor spread. However, the role of PNI in high‐risk prostate cancer (PCa) has not been explored. The aims of the study were to investigate the impact of PNI on biochemical recurrence (BCR) and optimal timing of adjuvant androgen‐deprivation therapy (ADT) after radical prostatectomy (RP).

The prognostic implication of intraductal carcinoma of the prostate in metastatic castration-resistant prostate cancer and its potential predictive value in those treated with docetaxel or abiraterone as first-line therapy

Intraductal carcinoma of the prostate (IDC-P) is recognized as a newly pathological entity in 2016 WHO classification. Its role in metastatic castration-resistant prostate cancer (CRPC) remains obscure. We aimed to explore the association of IDC-P with clinical outcome and to further identify its potential predictive role in making first-line treatment decisions for mCRPC. We retrospectively analyzed data of 131 mCRPC patients. IDC-P was diagnosed by re-biopsy at the time of mCRPC. Among total patients, 45 and 41 received abiraterone or docetaxel as first-line therapies, respectively. PSA response, PSA progression-free survival (PSA-PFS) and overall survival (OS) from mCRPC to death were analyzed using Kaplan-Meier curves, Log-rank test, Cox regression models and Harrells C-index. The incidence of IDC-P in mCRPC reached 47.3%. IDC-P was not only related to rapid PSA progression, but also associated with a 20-month decrease in OS. Among IDC-P(-) patients, PSA response, PSA-PFS and OS were comparable in abiraterone-treated and docetaxel-treated groups. In contrast, among IDC-P(+) patients, PSA response rate is higher in abiraterone-treated group vs. docetaxel-treated group (52.4% vs. 21.7%; p = 0.035). Also, PSA-PFS and OS were much longer in the IDC-P(+) abiraterone-treated group vs. the docetaxel-treated group (PSA-PFS: 13.5 vs.6.0 months, p = 0.012; OS: not reach vs.14.7 months, p = 0.128). Overall, IDC-P in mCRPC from re-biopsy was an independent prognosticator for clinical outcome. Abiraterone was observed having a better therapeutic efficacy than docetaxel as the first-line therapy in IDC-P(+) mCRPC patients. Thus, we suggest IDC-P should be considered as a novel predictive marker helping physicians making treatment decisions for mCRPC.Intraductal carcinoma of the prostate (IDC-P) is recognized as a newly pathological entity in 2016 WHO classification. Its role in metastatic castration-resistant prostate cancer (CRPC) remains obscure. We aimed to explore the association of IDC-P with clinical outcome and to further identify its potential predictive role in making first-line treatment decisions for mCRPC. We retrospectively analyzed data of 131 mCRPC patients. IDC-P was diagnosed by re-biopsy at the time of mCRPC. Among total patients, 45 and 41 received abiraterone or docetaxel as first-line therapies, respectively. PSA response, PSA progression-free survival (PSA-PFS) and overall survival (OS) from mCRPC to death were analyzed using Kaplan-Meier curves, Log-rank test, Cox regression models and Harrells C-index. The incidence of IDC-P in mCRPC reached 47.3%. IDC-P was not only related to rapid PSA progression, but also associated with a 20-month decrease in OS. Among IDC-P(-) patients, PSA response, PSA-PFS and OS were comparable in abiraterone-treated and docetaxel-treated groups. In contrast, among IDC-P(+) patients, PSA response rate is higher in abiraterone-treated group vs. docetaxel-treated group (52.4% vs. 21.7%; p = 0.035). Also, PSA-PFS and OS were much longer in the IDC-P(+) abiraterone-treated group vs. the docetaxel-treated group (PSA-PFS: 13.5 vs.6.0 months, p = 0.012; OS: not reach vs.14.7 months, p = 0.128). Overall, IDC-P in mCRPC from re-biopsy was an independent prognosticator for clinical outcome. Abiraterone was observed having a better therapeutic efficacy than docetaxel as the first-line therapy in IDC-P(+) mCRPC patients. Thus, we suggest IDC-P should be considered as a novel predictive marker helping physicians making treatment decisions for mCRPC.

The roles of prostate‐specific antigen (PSA) density, prostate volume, and their zone‐adjusted derivatives in predicting prostate cancer in patients with PSA less than 20.0 ng/mL

The aim of this study was to develop nomograms for predicting prostate cancer and its zonal location using prostate‐specific antigen density, prostate volume, and their zone‐adjusted derivatives. A total of 928 consecutive patients with prostate‐specific antigen (PSA) less than 20.0 ng/mL, who underwent transrectal ultrasound‐guided transperineal 12‐core prostate biopsy at West China Hospital between 2011 and 2014, were retrospectively enrolled. The patients were randomly split into training cohort (70%, n = 650) and validation cohort (30%, n = 278). Predicting models and the associated nomograms were built using the training cohort, while the validations of the models were conducted using the validation cohort. Univariate and multivariate logistic regression was performed. Then, new nomograms were generated based on multivariate regression coefficients. The discrimination power and calibration of these nomograms were validated using the area under the ROC curve (AUC) and the calibration curve. The potential clinical effects of these models were also tested using decision curve analysis. In total, 285 (30.7%) patients were diagnosed with prostate cancer. Among them, 131 (14.1%) and 269 (29.0%) had transition zone prostate cancer and peripheral zone prostate cancer. Each of zone‐adjusted derivatives‐based nomogram had an AUC more than 0.75. All nomograms had higher calibration and much better net benefit than the scenarios in predicting patients with or without different zones prostate cancer. Prostate‐specific antigen density, prostate volume, and their zone‐adjusted derivatives have important roles in detecting prostate cancer and its zonal location for patients with PSA 2.5–20.0 ng/mL. To the best of our knowledge, this is the first nomogram using these parameters to predict outcomes of 12‐core prostate biopsy. These instruments can help clinicians to increase the accuracy of prostate cancer screening and to avoid unnecessary prostate biopsy.

What kind of patients with castration-naïve prostate cancer can benefit from upfront docetaxel and abiraterone: A systematic review and a network meta-analysis

We conducted a systematic network meta-analysis to review the relevant literature evaluating the therapeutic efficacy of upfront docetaxel (Doc) or abiraterone (Abi) plus androgen deprivation therapy (ADT) on oncological outcome in patients with castration-naïve prostate cancer (CNPC). An attempt to identify subgroups of patients who would benefit most either from Doc or Abi plus ADT and further compare the efficacy and safety between these two combination therapies was made. A comprehensive search of the PubMed/Medline, Embase databases, International Clinical Trial Registration Platform (ICTRP), Clinical Trial, and Cochrane Central Register of Controlled Trials to December 2017 was performed. Six studies, involving 6480 patients, were included in this meta-analysis, consisting of over 60% (4462/6480) of patients with metastatic CNPC (mCNPC, M1), and 31.1% (2018/6480) of patients with non-metastatic CNPC (M0). In total, combination therapies (ADT plus Doc or Abi) significantly improved overall survival (OS) and failure-free survival (FFS) for all CNPC patients. For M1 patients, combination therapies were dramatically associated with improved OS and FFS, but for M0 patients, only with moderate improvement in FFS. M1 patients < 70 years old, Eastern Cooperative Oncology Group (ECOG) performance status (ECOG PS) 0-1, Gleason score (< 8), or visceral metastases could realize better survival benefit from either combination therapy. In indirect comparisons among M1 patients with younger age (< 70 years), ECOG PS 0-1 or aggressive Gleason score (GS ≥ 8), upfront Abi showed superiority to Doc in prolonging FFS. The incidence of severe adverse events (AEs ≥ 3) was comparable between these two therapeutic regimens. In conclusion, upfront Doc or Abi plus ADT should be considered a standard of care in selected patients with mCNPC. For a subset of populations, Abi may be the first choice for men who start treatment for the first time.

The prognostic value of the proportion/architectural patterns of intraductal carcinoma of the prostate (IDC-P) in patients with de novo metastatic prostate cancer

Purpose: Intraductal carcinoma of the prostate is an adverse prognosticator of prostate cancer. However, the roles of proportion and architectural patterns of intraductal prostate carcinoma in patient outcomes remain unclear. Materials and Methods: We retrospectively analyzed data on 644 patients with de novo metastatic prostate cancer between 2010 and 2017. Intraductal carcinoma of the prostate was identified from 12-core prostate biopsy. We calculated the proportion of intraductal prostate carcinoma and identified patterns according to the 2016 WHO classification. Propensity score matching was performed to balance baseline characteristics between patients with and without intraductal prostate carcinoma. Kaplan-Meier curves and Cox regression were used for survival analyses. The end points were castration resistant prostate cancer-free survival and overall survival. Results: Of the 644 patients 180 (28.0%) harbored intraductal carcinoma of the prostate. A 10% or greater incidence of the carcinoma was independently associated with worse prognosis (castration resistant prostate cancer-free survival HR 2.06, 95% CI 1.51–2.81, p <0.001, and overall survival HR 2.52, 95% CI 1.52–4.16, p <0.001), as was pattern 2 intraductal carcinoma of the prostate (HR 1.86, 95% CI 1.40–2.49, p <0.001, and HR 2.12, 95% CI 1.29–3.46, p = 0.003, respectively). Based on these 2 risk factors all men were classified into 5 groups. Patients in group 0 (no intraductal carcinoma of the prostate) and prostate intraductal carcinoma group 1 (less than 10% intraductal carcinoma, pattern 1) had favorable median castration resistant prostate cancer-free survival (18.0 vs 16.9 months, p = 0.871) and median overall survival (neither reached, p = 0.698). Men in intraductal carcinoma of the prostate group 4 (10% or greater intraductal carcinoma, pattern 2) harbored the worst outcomes (median castration resistant prostate cancer-free and overall survival 8.4 and 29.9 months, respectively). Group 2 (less than 10% intraductal carcinoma, pattern 2, with median castration resistant prostate cancer-free and overall survival 14.2 and 45.9 months) and group 3 (10% or less prostate intraductal carcinoma, pattern 1, with median castration resistant prostate cancer-free and overall survival 11.9 and 39.7 months, respectively) had an intermediate prognosis. Conclusions: A 10% or greater proportion of intraductal carcinoma of the prostate and pattern 2 were 2 unfavorable prognosticators of metastatic prostate cancer. Pathological reporting criteria based on intraductal carcinoma of the prostate could improve the prediction of patient outcomes and optimize treatment decisions.

Improved Long-Term Clinical Outcomes And Safety Profile Of Sunitinib Dosing Schedule With 4/2 Switched To 2/1 In Patients With Metastatic Renal Cell Carcinoma

Purpose: This study aimed to identify the survival benefit and safety of alternative dosage schedules for sunitinib in metastatic renal cell carcinoma. Materials and Methods: Clinicopathologic and survival data of patients treated with sunitinib as first-line therapy were retrospectively reviewed. Patients were classified into three groups: a standard dosing schedule (4/2 schedule), alternative dosing schedule (2/1 schedule), and switched dosing schedule (4/2-2/1 schedule). Results: Ninety-nine patients were retrospectively included. Seventy-five (75.8%) patients were initially administrated with a 4/2 schedule of sunitinib, while 24 were started with the 2/1 schedule. During treatment, 45 (60.0%) patients with an initial 4/2 schedule switched to a 2/1 schedule (4/2-2/1 schedule) due to severe adverse events (AEs) or poor tolerance. Compared to that with a 4/2 schedule, patients with a 2/1 schedule had a much lower incidence of grade 3/4 AEs (69.6% vs. 40.6%, p=0.001). Overall, the 4/2-2/1 schedule was associated with the best survival benefits. Among the 4/2, 2/1, and 4/2-2/1 schedule groups, the median PFS was 12.5, 11.0, and 25.0 months, respectively (p=0.003), and the median OS was 21.0, 28.0, and 52.0 months, respectively (p=0.03). Multivariate analysis identified the 4/2-2/1 schedule as an independent factor predicting favorable PFS. Although without statistical significance, 4/2-2/1 schedule could decrease 55% risk of death. Furthermore, patients with unfavorable IMDC risk seemed to have more opportunity to achieve better survival from the 4/2-2/1 dosing schedule. Conclusion: Patients with a 4/2-2/1 schedule could minimize treatment-related toxicities; more importantly, patients with 4/2-2/1 schedule could achieve a superior survival benefit.

Comparison of the prognosis of primary and progressive muscle-invasive bladder cancer after radical cystectomy: A systematic review and meta-analysis

OBJECTIVEnThe aim of the study was to systematically review the relevant studies to evaluate the prognosis of primary and progressive muscle-invasive bladder cancer (MIBC) after radical cystectomy (RC) and provide a clue for the timing of RC in patients with progressive MIBC early at the time of high-risk non-muscle-invasive bladder cancer (NMIBC).nnnMATERIAL AND METHODSnPubMed, MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched for eligible studies. We extracted hazard ratios (HRs) of overall survival (OS) and cancer-specific survival (CSS) and deaths at 5 and 10 years for each study and performed the meta-analysis using Review Manager 5.3.nnnRESULTSnA total of 11 retrospective studies with 4102 patients were included in the meta-analysis. The pooled analysis suggested a similar CSS (HR: 1.18; 95% CI, 0.74, 1.87; pu202f=u202f0.50) and OS (HR: 1.15; 95% CI, 0.82, 1.61; pu202f=u202f0.43) between primary and progressive MIBC patients treated with RC. The results further indicated no significant differences between the two populations in terms of 5-year CSS rate (OR: 1.32; 95% CI, 0.90, 1.95; pu202f=u202f0.16), 10-year CSS rate (OR: 0.83; 95% CI, 0.37, 1.83; pu202f=u202f0.64) as well as 5-year OS rate (OR: 1.02; 95% CI, 0.66, 1.56; pu202f=u202f0.94). Subgroup analysis according to the starting point of follow-up showed similar outcomes.nnnCONCLUSIONnThe meta-analysis demonstrates comparable CSS and OS in patients with primary and progressive MIBC following RC. Novel risk stratifications and prospective trials are urgently needed to investigate the prognosis after RC of these two groups of patients, which could finally aid clinician decision making and select patients who would actually benefit from early RC.

Novel nomograms for castration-resistant prostate cancer and survival outcome in patients with de novo bone metastatic prostate cancer

To develop nomograms predicting the incidence of castration‐resistant prostate cancer (CRPC) and overall survival (OS) for de novo metastatic prostate cancer (PCa).

Prior switching to a second-line nonsteroidal antiandrogen does not impact the therapeutic efficacy of abiraterone acetate in patients with metastatic castration-resistant prostate cancer: a real-world retrospective study

Even in the era of novel targeted agents, switching to a second-line nonsteroidal antiandrogen (NSAA) is still widely used in treating metastatic castration-resistant prostate cancer (mCRPC), especially in undeveloped countries. However, whether prior treatment with a second-line NSAA would impact the efficacy of abiraterone acetate (Abi) remains uncertain. In the current study, 87 mCRPC patients treated with Abi were analyzed. Among them, 21 were treated with a second-line NSAA (from bicalutamide to flutamide) before receiving abiraterone, while the remaining 66 received Abi directly. Therapeutic efficacy of Abi was compared between those with and without prior second-line NSAA using Kaplan–Meier curves, log-rank test, and Cox regression models. The therapeutic efficacy of Abi was similar between those with or without the prior switching treatment of flutamide, in terms of either prostate-specific antigen progression-free survival (PSA-PFS, 5.5 vs 5.6 months, P = 0.967), radiographic progression-free survival (rPFS, 12.8 vs 13.4 months, P = 0.508), overall survival (OS, not reached vs 30.6 months, P = 0.606), or PSA-response rate (71.4% [15/21] vs 60.6% [40/66], P = 0.370). This is the first time that the impact of prior switching of treatment to a second-line NSAA on the efficacy of Abi in mCRPC patients has been addressed. Our data support that, use of prior sequential bicalutamide and flutamide does not seem to preclude response to abiraterone, although larger cohort studies and, ideally, a randomized controlled trial are needed. These findings will facilitate doctors decision-making in the treatment of mCRPC patients, especially for those with previous experience of switching NSAA second-line treatments in the clinic.

Predictive efficacy of the 2014 International Society of Urological Pathology Gleason grading system in initially diagnosed metastatic prostate cancer.

We compared the predictive ability of the 2014 and 2005 Gleason grading systems in 568 patients initially diagnosed with metastatic prostate cancer (PCa). Outcomes included the duration of castration-resistant prostate cancer-free survival (CFS) and overall survival (OS). Univariate analyses and log-rank tests were used to identify prognosis indicators and assess univariable differences in CFS and OS in Gleason score (GS) groups. Cox proportional hazards and area under the curves of receiver operator characteristics methods were used to evaluate the predictive efficacy of the 2005 and 2014 ISUP grading systems. Univariate analyses showed that the 2005 and 2014 grading systems were prognosticators for CFS and OS; both systems could distinguish the clinical outcome of patients with GS 6, GS 7, and GS 8-10. Using the 2014 criteria, no statistical differences in patient survival were observed between GS 3 + 4 and GS 4 + 3 or GS 8 and GS 9-10. The predictive ability of the 2014 and 2005 grading systems was comparable for CFS and OS (P = 0.321). However, the 2014 grading system did not exhibit superior predictive efficacy in patients initially diagnosed with PCa and bone metastasis; trials using larger cohorts are required to confirm its predictive value. To the best of our knowledge, ours is the first study to compare the 2005 and 2014 grading systems in initially diagnosed PCa with bone metastasis. At present, we recommend that both systems should be used to predict the prognosis of patients with metastatic PCa.