Impact Of Gleason Score Research Articles

UnCHAARTED territory: The role of docetaxel rechallenge following chemohormonal therapy for metastatic castration-sensitive prostate cancer.

To assess the effectiveness of docetaxel rechallenge (DR) for metastatic castration-resistant prostate cancer (mCRPC) following chemohormonal therapy for metastatic castrate-sensitive prostate cancer (mCSPC). Additionally, we sought to define clinical factors predicting treatment response. Retrospective analysis of men treated with docetaxel for mCSPC and then rechallenged in the mCRPC setting from four cancer centers in Ontario, Canada. Prostate specific antigen (PSA) response, progression-free survival (PFS), and overall survival (OS) following DR were evaluated. Fifty five patients were identified between 2015 and 2020. Prior to DR, 94.5% of patients received androgen-receptor axis targeted therapy, 20% received radium-223, and 1.8% received cabazitaxel. Among 54 evaluable patients, 27.8% had a PSA decline ≥50%. Median PFS was 4.1 months (95% CI, 2.1-4.8) and median OS from androgen deprivation therapy initiation was 38.3 months (95% CI, 32.9-41.0). A Gleason Score of ≥8 was an independent predictor of prolonged PFS (HR 0.32, 95% CI, 0.12-0.81; P=0.02). DR following chemohormonal therapy for mCSPC produced a meaningful PSA response in approximately one-quarter of patients, with relatively short PFS. The impact of Gleason Score on docetaxel response warrants further investigation.

Oncological Outcomes After Radical Prostatectomy for High-Risk Prostate Cancer Based on New Gleason Grouping System: A Validation Study From University of Southern California With 3,755 Cases.

To assess the prognostic value of new Gleason grade grouping system in high-risk prostate cancer patients, we compared oncological outcomes after radical prostatectomy for patients with Gleason score 8 versus 9-10. Between 1987 and 2008, 3,755 men underwent radical prostatectomy with curative intent at University of Southern California. Patients who had Gleason score 8-10 at final histopathological evaluation (pT2-4N0) were included in this study. Eligible patients were divided into two groups; 226 with Gleason score 8 and 132 with Gleason score 9-10. Various patient and disease characteristics as well as oncological outcomes (biochemical recurrence, clinical recurrence, and overall survival) were compared between the groups. Impact of Gleason score on outcomes was controlled for preoperative prostate specific antigen, pathological stage, use of adjuvant radiotherapy, and neoadjuvant/adjuvant hormone therapy in multivariable analyses. A total of 358 patients (mean age: 65 years) were included in the analysis. Mean age and median duration of follow-up (9.6 years) were comparable between the study groups. Gleason 9-10 prostate cancer was associated with worse biochemical (HR 1.6; 95%CI [1.1-2.3]) and clinical recurrence free survival (HR = 1.9; 95%CI [1.1-3.3]); however, overall survival did not differ significantly between the groups. In addition, more patients with Gleason score 9-10 received adjuvant hormone therapy in the course of disease. Long-term follow-up after radical prostatectomy revealed significant differences in disease-specific outcomes between patients with Gleason score 8 versus 9-10. This sub-classification of high-risk patients might be helpful for patient counseling and determining therapeutic strategies. Prostate 77:743-748, 2017. © 2017 Wiley Periodicals, Inc.

Conditional Disease-free Survival After Radical Prostatectomy: Recurrence Risk Evolution Over Time

To assess changes in conditional disease-free survival (DFS) rates after radical prostatectomy (RP) and how the impact of well-known prognostic factors evolves over time. There were 2813 patients treated with RP and postoperatively followed with clinical and prostate-specific antigen assessments. Estimation of conditional survival (CS) probabilities used the Kaplan-Meier method. Multivariable Cox regression model was used to calculate proportional hazard ratios for prediction of DFS after stratification by prognostics characteristics. The 5-year DFS rate was 71.2%. The DFS rate 5 years after RP increased to 77.4% (+8.7%), 82.1% (+15.3%), 88.0% (+23.6%), and 94.0% (+32.0%) for patients surviving without recurrence 1, 2, 3, and 4 years after RP, respectively. This represented a relatively stable survival gain per survived year ranging from 5.6% to 8.7%. The conditional 5-year DFS improves mainly for disease-free surviving patients with adverse pathologic factors. Among patients with pT3b-4 disease, the probability of surviving without recurrence to year 5 increased from 20.7% at the time of presentation to 78.9% for patients surviving 4 years without recurrence (+281%) as compared to +12.5% in pT2 disease. The impact of Gleason score and pT stage on CS estimates remained stable over time. Findings were confirmed upon multivariable analyses. The period elapsed from RP is associated with DFS. The risk of recurrence decreases with increasing survivorship, mainly in patients with adverse pathologic factors. CS can provide relevant information for clinicians and patients giving an update of their risk of subsequent recurrence.

Oncological outcomes in high-risk prostate cancer after radical prostatectomy based on Gleason score: USC experience with 3,755 cases.

60 Background: Gleason score is an important predictor of oncological outcomes after radical prostatectomy. However, it remains unclear whether there is a difference in outcomes between Gleason score (GS) 8 and 9-10 disease. We compare oncological outcomes after open radical prostatectomy for prostate cancer patients with GS of 8 versus 9-10. Methods: Of 3,755 radical prostatectomy patients (1987-2008), 360 patients with final pathology of GS 8, 9 or 10 and N0M0 were included. No significant differences between age, race and surgical margins between the two groups. Impact of GS on outcomes was controlled for preoperative PSA, pathological stage, use of adjuvant radiation therapy and use of neoadjuvant/adjuvant hormone deprivation therapy in multivariable analyses. Outcomes of interest were biochemical recurrence free survival (BCRFS), clinical recurrence free survival (CRFS) and overall survival (OS). Kaplan Meier plots, log rank tests and multivariable Cox regression model were used to analyze the data. Results: Median follow-up for GS 8 and GS 9-10 were 10.0 years and 8.6 years, respectively (p=0.43). Conclusions: Long term follow up after radical prostatectomy reveals significant differences in BCRFS and CRFS but not OS between patients with GS 8 vs. 9-10 prostate cancers. Further studies may examine sub-stratification of GS 8 tumors into a lower risk category than GS 9-10 tumors. [Table: see text] [Table: see text]

1051 Detection rate of Real-Time-Elastography (RTE) guided biopsy of the prostate: Impact of Gleason score (GS) and comparison to multiple core biopsy

1051 Detection rate of Real-Time-Elastography (RTE) guided biopsy of the prostate: Impact of Gleason score (GS) and comparison to multiple core biopsy

Does Gleason score (GS) predict efficacy of abiraterone acetate (AA) therapy in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC)? An analysis of AA phase 3 trials.

20 Background: GS is strongly prognostic in localized PC but is less so in mCRPC (Halabi S, J Clin Oncol 2003; Armstrong AJ, Eur J Cancer 2010). Pts with high-risk localized PC and high GS who undergo radiation therapy benefit from long-term androgen deprivation therapy (Horwitz EM, J Clin Oncol 2008). In mCRPC, the impact of GS at initial diagnosis on response to AA therapy is unknown. We retrospectively evaluated efficacy outcomes in pts with mCRPC treated with AA plus prednisone (P) vs P alone in pivotal studies COU-AA-301 (post-docetaxel) and COU-AA-302 (chemo-naive) by GS (≥ 8 or < 8). Methods: 1,048 pts in COU-AA-301 and 996 in COU-AA-302 with mCRPC treated with AA 1 g + P 5 mg po BID or placebo + P had GS data at diagnosis. Efficacy end points evaluated: overall survival (OS), radiographic progression free survival (rPFS), and time to prostate-specific antigen progression (TTPP) (de Bono JS, NEJM 2011; Fizazi K, Lancet Oncol 2012; Ryan CR, NEJM 2013). Distributions and medians were estimated by the Kaplan-Meier method, and hazard ratio (HR) and 95% confidence interval were estimated by the Cox model. Results: Proportion of pts with GS ≥ 8 and GS < 8 was similar across treatment groups and studies. Outcomes by GS are summarized in the Table. Conclusions: GS (≥ 8 or < 8) at initial diagnosis was not predictive of treatment benefit of AA + P vs P alone in post-docetaxel and chemo-naïve pts with mCRPC, with both groups benefiting. In this era of novel androgen signaling targeted agents, GS may not be relevant in predicting efficacy with AA for pts with mCRPC. Clinical trial information: NCT00638690, NCT00887198. [Table: see text]

Should we abstain from Gleason score 2–4 in the diagnosis of prostate cancer? Results of a German multicentre study

The present study analysed the loss of prognostic information related to the abandonment of Gleason score (GS) 2-4 by the International Society of Urological Pathology (ISUP-2005). Within a 10-year period prior to the modification of GS, 856 patients (mean age 64.2 years) underwent radical prostatectomy (RP). The grade of agreement between GS in biopsy and definitive histology was calculated by Kappa statistics (κ). Univariable and multivariable influence of different preoperatively available parameters on disease-free survival (DFS) were assessed. The mean follow-up period was 39 months. Concordance between GS in biopsy versus RP samples was 58% (κ-value 0.354) and was improved by an increased number of biopsy cores. Undergrading in biopsy was present in 38% and not significantly enhanced by an extended time-period between biopsy and RP (threshold 90 d). PSA level, clinical tumour stage, fraction of positive cores (dichotomized at 34%), cases of RP per year and institution (dichotomized at 75), and GS independently influenced DFS. An upgrading to GS ≥ 7 was found in only 5.7% of patients presenting with GS 2-4 in the biopsy. Independent from definitive histology, patients with GS 2-4 had a significantly better prognosis compared to patients with a higher GS. The present study shows an independent prognostic impact of GS in biopsy samples classified according to the previous classification. The elimination of GS 2-4 by the ISUP 2005 results in a considerable loss of pretherapeutic prognostic information and therefore should be questioned in particular with regard to the increasing demand for active surveillance regimens.

Impact of Gleason score 4+3 on biochemical treatment failure in Japanese patients treated with monotherapeutic permanent interstitial brachytherapy.

e15108 Background: The permanent prostate brachytherapy (PPB) with iodine-125 seeds has an indication in patients with organ-confined prostate cancer. Our objective is to reveal pretreatment factors which have impact on the biochemical freedom from failure (bFFF) in patients with permanent interstitial seed implants as monotherapy. Methods: Between January 2004 and July 2009, 414 consecutive prostate cancer patients with low or intermediate risk in criteria of NCCN guideline underwent PPB at single institution. All of the pre-treatment pathological diagnoses were made by a central pathologist. Biochemical recurrence was defined using the Phoenix definition. Multivariate analysis was performed for pathological/clinical features and bFFF. The Kaplan-Meier method was used to calculate rates of bFFF with the log rank test. Results: The median follow-up length was 36.0 months (range, 1.0-68.6 months). The 2 and 3-year bFFF rates were 98.3% and 96.0%, respectively, for the entire cohort. Pretreatment Gleason score (p<0.0001) had strong impact on bFFF while risk group (p=0.0534) and clinical stage (p=0.563) did not. Especially, patients with GS 4+3 showed lower bFFF than patients with GS 3+4 (p=0.0267 ). Conclusions: Although clinical risk classification has contributed to predict biochemical failure rate in patients with PPB, the patients with Gleason sum score 7 should be divided to group 3+4 and group 4+3 since the clinical outcome may be different between these groups. Therefore, an indication of PPB for patients with Gleason 4+3 may be controversial. No significant financial relationships to disclose.

1423: The Impact of Gleason Score on the Predictive Value of PSA Doubling Time

1423: The Impact of Gleason Score on the Predictive Value of PSA Doubling Time