Systematic review of time to definitive treatment for intermediate-risk and high-risk prostate cancer: Are delays associated with worse outcomes?

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 233-233
Author(s):  
David-Dan Nguyen ◽  
Lorine Haeuser ◽  
Marco Paciotti ◽  
Chanan Reitblat ◽  
Jacqueline Cellini ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Systematic Review ◽  
Overall Survival ◽  
High Risk ◽  
Definitive Treatment ◽  
Intermediate Risk ◽  
Pathological Features ◽  
Pathological Findings ◽  
Treatment Delays ◽  
Oncological Outcomes

233 Background: Prostate cancer (PCa) is an indolent disease, especially when detected at a localized stage. Unlike other tumors that may benefit from timely receipt of definitive therapy, it is generally accepted that treatment delays for localized PCa are acceptable, especially for low-risk PCa. We sought to determine if treatment delays for intermediate-risk and high-risk PCa negatively impacted oncological outcomes. Methods: We conducted a systematic review of the literature with searches of Medline, EMBASE, and the Cochrane Database of Systematic Reviews, from inception to June 30, 2020. General study characteristics as well as study population and delay information were collected. The outcomes of interest extracted included biochemical recurrence (BCR), pathological features (positive surgical margins, upgrading, extracapsular extension, and other pathological features), cancer-specific survival, and overall survival. Due to significant heterogeneity between studies, a meta-analysis was not possible. Results: After identifying 1793 unique references, 24 manuscripts met criteria for data extraction, 15 of which were published after 2013. Based on our review, delays up to 3 months are safe for all PCa and are not associated with worse oncological outcomes. Some studies identified worse oncological outcomes as a result of delays beyond 6 to 9 months. However, these studies are counterbalanced by others finding no statistically significant association with delays up to 12 months. Studies that did find worse outcomes as a result of delays identified a higher risk of BCR and pathological findings, but not worse survival. Conclusions: Definitive treatment for intermediate-risk and high-risk PCa can be delayed up to 3 months without any oncological consequences. Some evidence suggests that delays beyond 6-9 months are associated with a higher risk of BCR and varying worse pathological findings; as such, care should be given to provide definitive treatment within 9 months. To date, there is no evidence of worse cancer-specific or overall survival as a result of delayed treatment for intermediate-risk and high-risk PCa.

Change in a 17-gene genomic prostate score over time in men with low- and intermediate-risk prostate cancer managed with active surveillance.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 124-124
Author(s):  
Michael S. Leapman ◽  
Janet E. Cowan ◽  
Hao Gia Nguyen ◽  
Matthew R. Cooperberg ◽  
Peter Carroll
Keyword(s):  
Prostate Cancer ◽  
Radical Prostatectomy ◽  
Active Surveillance ◽  
Small Sample ◽  
Definitive Treatment ◽  
Intermediate Risk ◽  
Pathological Findings ◽  
Clinical Risk ◽  
Risk Prostate Cancer ◽  
Over Time

124 Background: A biopsy-based RT-PCR assay (Oncotype DX Prostate Assay) providing a Genomic Prostate Score (GPS) as a measure of tumor aggressiveness has been validated as a predictor of adverse pathologic and oncologic outcomes. We sought to evaluate the change in GPS results among men with favorable-risk prostate cancer (PCa) managed with active surveillance (AS). Methods: We identified men with low and intermediate-clinical risk PCa managed with AS at our institution receiving a minimum of two GPS tests on serial prostate biopsy. GPS ranges from 0 (least) to 100 (most aggressive disease). We described the change in assay results and clinical risk designation over time and reported the subsequent clinical outcome (definitive treatment versus continued AS). For men receiving treatment with radical prostatectomy (RP) the occurrence of adverse pathological findings was defined by the presence of high grade (Gleason pattern ≥ 4+3) or non-organ confined disease ( ≥ pT3a). Results: 31 men were identified who underwent serial GPS testing at a median of 12 months. The median change in GPS was an increase of 1 point (IQR -7, 13). Fourteen (45%) patients experienced an increase in NCCN risk classification, including 3 from very-low to intermediate and 11 from low to intermediate risk. Following serial GPS testing 7 patients (23%) underwent radical prostatectomy. Among surgically treated patients, 3 had adverse pathology due to pT3a disease and the mean change in GPS prior to treatment was an increase of 13 points (IQR -7, 18); all of whom were intermediate clinical risk at the time of surgery. This study was limited by the small sample size and the uncontrolled decision to pursue definitive therapy. Conclusions: Serial change in a tissue based gene expression assay on serial biopsy during AS was non-static. Magnitude of GPS change may identify men at risk for adverse pathological findings, although larger series are required to validate such an endpoint during AS.

scholarly journals Overall survival and adverse events after treatment with darolutamide vs. apalutamide vs. enzalutamide for high-risk non-metastatic castration-resistant prostate cancer: a systematic review and network meta-analysis

2021 ◽  
Author(s):  
Mike Wenzel ◽  
Luigi Nocera ◽  
Claudia Collà Ruvolo ◽  
Christoph Würnschimmel ◽  
Zhe Tian ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Systematic Review ◽  
Overall Survival ◽  
High Risk ◽  
Meta Analysis ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Pubmed Search ◽  
Grade 3 ◽  
Meta Analyses

Abstract Background The most recent overall survival (OS) and adverse event (AE) data have not been compared for the three guideline-recommended high-risk non-metastatic castration-resistant prostate cancer (nmCRPC) treatment alternatives. Methods We performed a systematic review and network meta-analysis focusing on OS and AE according to the most recent apalutamide, enzalutamide, and darolutamide reports. We systematically examined and compared apalutamide vs. enzalutamide vs. darolutamide efficacy and toxicity, relative to ADT according to PRISMA. We relied on PubMed search for most recent reports addressing prospective randomized trials with proven predefined OS benefit, relative to ADT: SPARTAN, PROSPER, and ARAMIS. OS represented the primary outcome and AEs represented secondary outcomes. Results Overall, data originated from 4117 observations made within the three trials that were analyzed. Regarding OS benefit relative to ADT, darolutamide ranked first, followed by enzalutamide and apalutamide, in that order. In the subgroup of PSA-doubling time (PSA-DT) ≤ 6 months patients, enzalutamide ranked first, followed by darolutamide and apalutamide in that order. Conversely, in the subgroup of PSA-DT 6–10 months patients, darolutamide ranked first, followed by apalutamide and enzalutamide, in that order. Regarding grade 3+ AEs, darolutamide was most favorable, followed by enzalutamide and apalutamide, in that order. Conclusion The current network meta-analysis suggests the highest OS efficacy and lowest grade 3+ toxicity for darolutamide. However, in the PSA-DT ≤ 6 months subgroup, the highest efficacy was recorded for enzalutamide. It is noteworthy that study design, study population, and follow-up duration represent some of the potentially critical differences that distinguish between the three studies and remained statistically unaccounted for using the network meta-analysis methodology. Those differences should be strongly considered in the interpretation of the current and any network meta-analyses.

Incidental Prostate Cancer in Radical Cystoprostatectomy Specimens is Associated with Worse Overall Survival

2021 ◽  
pp. 1-7
Author(s):  
Takahiro Kimura ◽  
Hajime Onuma ◽  
Shun Sato ◽  
Hiroyuki Inaba ◽  
Wataru Fukuokaya ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Bladder Cancer ◽  
Statistical Significance ◽  
Pathological Features ◽  
Incidental Prostate Cancer ◽  
P Values ◽  
Radical Cystoprostatectomy ◽  
Oncological Outcomes ◽  
The Impact

BACKGROUND: The impact of incidental prostate cancer (IPC) on oncological outcomes after radical cystoprostatectomy (RCP) specimens from patients with bladder cancer (BC) remains controversial. This relationship has not been well elucidated in Asian countries, where the incidence of prostate cancer has recently shown dramatic increases. OBJECTIVES: This study retrospectively compared pathological features and oncological outcomes between BC patients with and without IPC in the RCP specimens. METHODS: This study included 142 men who underwent RCP for BC. Men who were previously diagnosed with prostate cancer were excluded. Each prostate gland and seminal vesicle was processed as whole mounts and 4-mm close-step sectioning was performed. A single genitourinary pathologist diagnosed IPC. The pathological features and oncological outcomes such as overall survival (OS), bladder cancer-specific survival (BCSS), and progression-free survival (PFS) were compared between patients with IPC (IPC+group, n = 45) and without IPC (IPC- group, n = 97). P values less than 0.05 considered to indicate statistical significance for patients’ characteristics. Because of multi-primary endpoint, P values less than 0.0167 was considered statistical significance for oncological outcomes. RESULTS: We detected IPC in 45 RCP specimens (31.6%). Patients in the IPC- group were significantly younger at surgery than those in the IPC+group (P <  0.001). The pathological features of the RCP specimens did not differ significantly. In multivariable analyses, presence of IPC was significantly associated with worse OS (P = 0.005), but not with either BCSS or PFS (P = 0.038 and 0.326, respectively). In Kaplan–Meier analyses, OS tended to be longer in the IPC- group than that in the IPC+group (NR vs 65 months, P = 0.0017). CONCLUSIONS: Our results suggested significantly better OS in patients without IPC than that in those with IPC.

Neoadjuvant versus concurrent androgen deprivation therapy plus radiotherapy for unfavorable intermediate-risk and high-risk prostate cancer with low PSA.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 243-243
Author(s):  
Neal Andruska ◽  
Temitope Agabalogun ◽  
Benjamin Walker Fischer-Valuck ◽  
Randall Brenneman ◽  
Hiram Alberto Gay ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Androgen Deprivation Therapy ◽  
Gleason Score ◽  
Androgen Deprivation ◽  
Recent Analysis ◽  
Definitive Treatment ◽  
Intermediate Risk ◽  
High Risk Prostate Cancer ◽  
Risk Prostate Cancer

243 Background: Dose-escalated radiotherapy (RT) with androgen-deprivation therapy (ADT) is a standard definitive treatment for localized prostate cancer (LPCa), but the optimal sequencing of hormone therapy with RT is unclear, with most patients treated with neoadjuvant ADT. Clinical trials addressing this question have not yielded definitive results. During COVID-19, there has been greater interest in neoadjuvant ADT as a way to delay initiation of RT to reduce risk of COVID transmission from daily RT visits with recent analysis from the NCDB showing that RT can be delayed for up to 6 months after neoadjuvant ADT. It is unclear if neoadjuvant ADT is appropriate for all patients or if select cohorts may benefit from concurrent ADT and upfront RT, such as patients with higher grade disease and low PSA who may have less hormone-responsive disease. Methods: Using the NCDB, we identified men diagnosed from 2004 to 2015 with NCCN unfavorable intermediate risk or high-risk adenocarcinoma of the prostate with a presenting PSA ≤ 5 ng/mL treated with definitive RT and either ADT initiated 2-4 months prior to RT (neoadjuvant ADT) or ADT started within 7 days of RT (concurrent ADT). OS was the primary endpoint. OS was estimated using the Kaplan-Meier method. Multivariable Cox proportional hazards analyses was performed using age, facility type, Charlson-Deyo comorbidity score, clinical T stage, and Gleason score. Results: 2393 patients were identified, with 2103 receiving neoadjuvant ADT and 290 receiving concurrent ADT. Multivariable analysis (MVA) showed that concurrent ADT was associated with a lower risk of death relative to patients receiving neoadjuvant ADT {hazard ratio (HR): 0.58 [95% confidence interval: 0.36-0.94], p = 0.02}. The number of days from diagnosis to the start of RT was not associated with worse OS (HR:[0.99-1.01], p = 0.61) on MVA. Age (HR = 1.03 [1.01-1.05], p = 0.002) and treatment at an academic center (HR: 0.71 [0.53-0.94], p = 0.02) were also significantly associated with OS on MVA. The benefit of concurrent ADT relative to neoadjuvant ADT was greatest in patients with Gleason 4 and Gleason 5 disease (HR: 0.31 [0.14-0.71], p = 0.005). Conclusions: For patients with unfavorable intermediate-risk or high-risk prostate cancer and a PSA ≤ 5 ng/mL, concurrent ADT and upfront RT was associated with improved OS compared to neoadjuvant ADT and RT. The associated benefit appeared to be more pronounced for Gleason Score ≥ 8. Results are hypothesis generating and require validation in a randomized trial.

A gene expression signature to predicit overall, prostate cancer, and non–prostate cancer survival.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 51-51
Author(s):  
Chunde Li ◽  
Zhuochun Peng ◽  
Lambert Skoog ◽  
Henrik Hellborg ◽  
Inga-lill Wingmo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
High Risk ◽  
Cancer Patients ◽  
Survival Data ◽  
Embryonic Stem ◽  
Low Risk ◽  
Intermediate Risk ◽  
Cancer Specific Survival ◽  
Expression Signature

51 Background: For prostate cancer patients, prostate cancer specific and non-prostate cancer specific survival have the same importance. This study aimed at identifying expression biomarkers that can predict prostate cancer specific, non-prostate cancer specific and overall survival at diagnosis. Methods: Selected ESCGPs (embryonic stem cell gene predictors) and control genes were analyzed by multiplex quantitative PCR using prostate fine-needle aspiration samples taken at diagnosis from a Swedish cohort of 189 prostate cancer patients diagnosed between 1986 and 2000. Of all patients, 97.9% had overall and cancer-specific survival data and 77.9% were primarily treated only by hormone therapy. The cohort was divided into one discovery and two validation subsets. Univariate and multivariate Cox proportional hazard ratios and Kaplan-Meier plots were used for the survival analysis. A published dataset was used for external validation. Results: An expression signature of F3, VGLL3 and IGFBP3, was sufficient to categorize the patients into high-risk, intermediate-risk and low-risk subtypes. The median overall survival of the subtypes was 3.23, 4.00 and 9.85 years respectively. The difference corresponded to HRs of 5.86 (95% CI 2.91-11.78, P<0.001) for the high-risk and 3.45 (95% CI 1.79-6.66, P<0.001) for the intermediate-risk compared to the low-risk subtype. This signature is significant in correlation to overall, cancer-specific and non-cancer specific survival in both univariate and multivariate analyses including common clinical parameters. Conclusions: These results suggest that these novel expression biomarkers and the expression signature could be used to improve the accuracy of the currently available clinical tools for predicting overall, cancer-specific and non-cancer specific survival and selecting patients with potential survival benefit from hormone treatment.

scholarly journals Effects of Delayed Radical Prostatectomy and Active Surveillance on Localised Prostate Cancer—A Systematic Review and Meta-Analysis

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3274
Author(s):  
Vinson Wai-Shun Chan ◽  
Wei Shen Tan ◽  
Aqua Asif ◽  
Alexander Ng ◽  
Olayinka Gbolahan ◽  
...  
Keyword(s):  
High Risk ◽  
Radical Prostatectomy ◽  
Meta Analysis ◽  
Expectant Management ◽  
Intermediate Risk ◽  
Active Monitoring ◽  
High Risk Patients ◽  
Oncological Outcomes ◽  
Risk Patients ◽  
Randomised Controlled

External factors, such as the coronavirus disease 2019 (COVID-19), can lead to cancellations and backlogs of cancer surgeries. The effects of these delays are unclear. This study summarised the evidence surrounding expectant management, delay radical prostatectomy (RP), and neoadjuvant hormone therapy (NHT) compared to immediate RP. MEDLINE and EMBASE was searched for randomised controlled trials (RCTs) and non-randomised controlled studies pertaining to the review question. Risks of biases (RoB) were evaluated using the RoB 2.0 tool and the Newcastle–Ottawa Scale. A total of 57 studies were included. Meta-analysis of four RCTs found overall survival and cancer-specific survival were significantly worsened amongst intermediate-risk patients undergoing active monitoring, observation, or watchful waiting but not in low- and high-risk patients. Evidence from 33 observational studies comparing delayed RP and immediate RP is contradictory. However, conservative estimates of delays over 5 months, 4 months, and 30 days for low-risk, intermediate-risk, and high-risk patients, respectively, have been associated with significantly worse pathological and oncological outcomes in individual studies. In 11 RCTs, a 3-month course of NHT has been shown to improve pathological outcomes in most patients, but its effect on oncological outcomes is apparently limited.

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