Neuroendocrine Prostate Cancer (NEPC) Progressing From Conventional Prostatic Adenocarcinoma: Factors Associated With Time to Development of NEPC and Survival From NEPC Diagnosis—A Systematic Review and Pooled Analysis

2014 ◽  
Vol 32 (30) ◽  
pp. 3383-3390 ◽  
Author(s):  
Hai Tao Wang ◽  
Yan Hong Yao ◽  
Bao Guo Li ◽  
Yong Tang ◽  
Ji Wu Chang ◽  
...  

Purpose An often under-recognized late manifestation of prostate adenocarcinoma (PCa) is the development of treatment-related neuroendocrine prostate cancer (NEPC). The aim of this study is to identify the risk factors related to survival after NEPC diagnosis (NEPCS) and time from initial diagnosis of PCa to development of NEPC (TTNEPC). Patients and Methods A literature search on NEPC was performed using databases such as MEDLINE and EMBASE. Studies were eligible if outcomes data (NEPCS and/or TTNEPC) were reported in patients with a prior history of PCa and histopathologically confirmed NEPC. NEPCS and TTNEPC were evaluated using the Cox regression model with the robust sandwich estimates of the covariance matrix. Results There were 54 eligible publications, contributing 123 patients. The median TTNEPC was 20 months. In multivariable analyses, the Gleason score was significantly associated with shorter TTNEPC (hazard ratio [HR], 1.66; P = .032). The median NEPCS was 7 months. In multivariable analyses, the number of organs with metastatic disease at NEPC was significantly associated with shorter NEPCS (HR, 3.31; P = .001). Type of treatment after NEPC was significantly associated with longer NEPCS, with HRs of 0.66 (radiotherapy v palliative therapy; P = .034), 0.38 (chemotherapy v palliative therapy; P = .018), and 0.29 (chemoradiotherapy v palliative therapy; P = .012), respectively. Conclusion Treatment-related NEPC is an often under-recognized late manifestation of PCa with poor prognosis. Our study found that Gleason score was the only independent factor contributing to TTNEPC. Once NEPC is diagnosed, type of treatment and the number of organs with metastatic disease were the most important factors related to survival.

2021 ◽  
Author(s):  
Shiyam Kumar ◽  
Ikram A. Burney ◽  
Joseph Kunju ◽  
Mohammed Salim Al-Marhoon ◽  
Khurrum Mutahir Siddiqui

Objectives: Prostate cancer is the third most common cancer worldwide. The incidence is rising in the middle east. There is paucity of data about the clinicopathological features and outcomes of metastatic prostate cancer (mPCa) from the middle-east. We report the outcomes of mPCa from Oman.Methods: Consecutive men diagnosed with mPCa and treated at the university hospital in Oman between January 2006 and December 2017 were included in this study. Information about demographics, clinical, laboratory, pathological and radiological features at presentation, treatment, and survival outcomes was collected. Data were gathered until April 2019 or until patient’s death for progression-free survival (PFS) and overall survival (OS), whichever came first. Survival rates were estimated using the method of Kaplan and Meier. Univariate and multivariate analysis and Cox regression analyses were performed to study factors affecting the PFS and the OS. Results: Out of the 239 men diagnosed with PC over the study period, 62 were diagnosed with mPCa. The median age was 71 (range 57 – 92) years. Majority of patients (61.3%) had a Gleason score ≥8. Median PSA level was 100. Bone was the most common site of metastatic disease (90.3%). Majority of patients with hormone-sensitive disease were treated with testosterone suppression only, while abiraterone, enzalutamide and docetaxel were added for treating castrate resistant mPCa (mCRPC). After a median follow up of 34.5 months, the median PFS was 17 months, while the median OS was 43 months. Median survival post mCRPC was 17 months. Conclusion: Omani patients with mPCa present with high PSA and Gleason score and with widespread metastatic disease burden. Treatments offered are according to internationally accepted standards and have comparable PFS and OS as reported elsewhere.


2021 ◽  
Vol 27 ◽  
Author(s):  
Yuqing Wu ◽  
Saisai Chen ◽  
Minhao Zhang ◽  
Kuangzheng Liu ◽  
Jibo Jing ◽  
...  

Purpose: Xp11.2 translocation renal cell carcinoma (Xp11.2 tRCC) is a rare subtype of renal cell carcinoma (RCC), characterized by translocations of Xp11.2 breakpoints, involving of the transcription factor three gene (TFE3). The aim of our study was to comprehensively characterize the clinical characteristics and outcomes, and to identify risk factors associated with OS and PFS in Xp11.2 tRCC patients.Methods: Literature search on Xp11.2 tRCC was performed using databases such as pubmed EMBASE and Web of Science. Studies were eligible if outcomes data (OS and/or PFS) were reported for patients with a histopathologically confirmed Xp11.2 tRCC. PFS and OS were evaluated using the univariable and multivariable Cox regression model.Results: There were 80 eligible publications, contributing 415 patients. In multivariable analyses, the T stage at presentation was significantly associated with PFS (HR: 3.87; 95% CI: 1.70 to 8.84; p = 0.001). The median time of PFS was 72 months. In the multivariable analyses, age at diagnosis (HR: 2.16; 95% CI: 1.03 to 4.50; p = 0.041), T stage at presentation (HR: 4.44; 95% CI: 2.16 to 9.09; p < 0.001) and metastasis status at presentation (HR: 2.67; 95% CI: 1.12 to 6.41; p = 0.027) were all associated with OS, with a median follow-up time of 198 months.Conclusion: T stage at presentation is the only factor that is associated with both PFS and OS in patients with Xp11.2 tRCC. Also, patients over 45 or with metastases are more likely to have poorer OS.


2011 ◽  
Vol 18 (3) ◽  
pp. 113-119
Author(s):  
Daimantas MILONAS ◽  
Giedrė SMAILYTĖ ◽  
Darius TRUMBECKAS ◽  
Mindaugas JIEVALTAS

Background. The aim of the study was to present the oncologic outcomes and to determine the prognostic factors of overall (OS) and cancer-specific survival (CSS) as well as disease-progression-free survival (DPFS) after surgery for pT3b prostate cancer. Materials and methods. In 2002–2007, a pT3b stage after radical prostatectomy was detected in 56 patients. Patients were divided into groups according to the prostate-specific antigen (PSA) level (20 ng/ml), lymph nodes status (N0 vs. Nx vs. N1) and the Gleason score (6–7 vs. 8–10). The Kaplan–Meier analysis was used to calculate OS, CSS and DPFS. The Cox regression was used to identify the predictive factors of survival. Results. Five-year OS, CSS and DPFS rates were 75.1%, 79.6% and 79.3%, respectively. The survival was significantly different when comparing the Gleason 6–7 and 8–10 groups. The 5-year OS, CSS and DPFS were 91.2% vs. 48.6%, 97.1% vs. 51.1% and 93.8 vs. 51.1%, respectively. There was no difference in survival among the groups with a different PSA level. The OS and CSS but not DPFS were significantly different when comparing the N0 and N1 groups. The 5-year OS and CSS was 84.4% vs. 37.5% and 87.3% vs. 47.6%, respectively. The specimen Gleason score was a significant predictor of OS and CSS. The risk of death increased up to 4-fold when a Gleason score 8–10 was present at the final pathology. Conclusions. Radical prostatectomy may offer acceptable CSS, DPFS and OS rates in pT3b PCa. However, outcomes in patients with N1 and specimen Gleason ≥8 were significantly worse, suggesting the need of multimodality treatment in such cases. Keywords: prostate cancer, locally advanced, surgery, outcome


2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 242-242 ◽  
Author(s):  
Gustavo Jankilevich ◽  
Luciana Gennari ◽  
Matias Salazar ◽  
Claudio Graziano ◽  
Eduardo Saravia ◽  
...  

242 Background: Tumor stage, Gleason score, PSA, Performance Status have been identified as important predictors of survival in prostate cancer. The Charlson Comorbidity Index (CCI) is a validated score used to stratify patients according to comorbidities. To evaluate the prognostic role of CCI in patients with CPRC. Methods: A retrospective study based on an analysis of medical records of 212 patients with CRPC treated at Durand Hospital between 2010-2015. The CCI was calculated for each patient and a correlation with overall survival was performed. Statistical analysis included univariate analysis and multivariate analysis (Cox regression). Patients were stratified according CCI ≤ 7.6 or ≥ 7.6. Survival analysis was performed using the Kaplan-Meier curve. Results: We analyzed records of 212 patients with prostate cancer, of which 59 were resistant to castration. Median age 69 years, the PFS with androgen blockade was 32.4 months. Patients with CPRC 54% perform chemotherapy as first-line treatment of castration resistance and 46% performed treatment of hormonal manipulation (Enzalutamide or Abiraterone Acetate). Median overall survival of patients with CCI < 7.6 was 75 months versus 62 months for those with CCI > 7.6 HR: 1.19 (1.03 to 1.36) p: 0.01. In multivariate analysis the ICC was an independent predictor of mortality in these patients HR: 1.23 (1.03 to 1.48) p: 0.02. (Table 1) CCI ≤ 7,6 was predictor to subsequent lines in CPRC setting. Gleason score, PS were independent predictors of survival. Conclusions: Based on our results we can consider the CCI as an independent predictor of survival in CPRC patients. CCI could be an useful tool useful to select patients in clinical trial and community settings. [Table: see text]


2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 41-41
Author(s):  
Daniel Canter ◽  
Julia E. Reid ◽  
Maria Latsis ◽  
Margaret Variano ◽  
Shams Halat ◽  
...  

41 Background: Prostate cancer (PC) is the most common male malignancy. Prior data has suggested that African American (AA) men present with more aggressive disease relative to men of other ancestries. Here, we examined the effects of ancestry on clinical and molecular measures of disease aggressiveness as well as pathologic outcomes in men treated with radical prostatectomy (RP) for localized PC. Methods: Data was collected from patients undergoing RP at the Ochsner Clinic from 2006 to 2011. Formalin−fixed paraffin embedded biopsy tissue was analyzed for the RNA expression of 31 cell cycle progression (CCP) genes and 15 housekeeping genes to obtain a CCP score (a validated molecular measure of PC aggressiveness). Cancer of the Prostate Risk Assessment (CAPRA) scores were also determined based on clinicopathologic features at the time of diagnosis. Clinical (Gleason score, tumor stage, CAPRA score) and molecular (CCP score) measures of disease aggressiveness were compared based on ancestry (AA versus non−AA). Cox proportional hazards models were used to test association of ancestry to biochemical recurrence (BCR) and progression to metastatic disease. Fisher’s exact and Wilcoxon rank sum tests were used to compare ancestries. Results: A total of 384 patients were treated with RP, including 133 (34.8%) AA men. At the time of diagnosis, the median age was 62 years (interquartile range (IQR) 56, 66) and PSA was 5.4 ng/mL (IQR 4.2, 7.6). When compared by ancestry, there were no significant differences in biopsy Gleason score (p = 0.26), clinical stage (p = 0.27), CAPRA score (p = 0.58), or CCP score (p = 0.87). In addition, there was no significant difference in the risk of BCR between ancestries (p = 0.55). Only non−AA men progressed to metastatic disease within the ten years of follow−up. Conclusions: Contrary to prior reports, these data appears to indicate that men of AA ancestry do not necessarily present with or develop a more biologically aggressive form of PC. Although these data represents only one institution’s experience, it contains a highly robust AA population compared to prior reports. Further research is required to account for the discrepancy in the previously published literature.


2017 ◽  
Vol 35 (17) ◽  
pp. 1898-1904 ◽  
Author(s):  
Michael S. Leapman ◽  
Janet E. Cowan ◽  
Hao G. Nguyen ◽  
Katsuto K. Shinohara ◽  
Nannette Perez ◽  
...  

Purpose The suitability of younger patients with prostate cancer (PCa) for initial active surveillance (AS) has been questioned on the basis of eventual treatment necessity and concerns of safety; however, the role of age on surveillance outcomes has not been well defined. Patients and Methods We identified men managed with AS at our institution with a minimum follow-up of 6 months. The primary study objective was to examine the association of age with risk of biopsy-based Gleason score upgrade during AS. We also examined the association of age with related end points, including overall biopsy-determined progression, definitive treatment, and pathologic and biochemical outcomes after delayed radical prostatectomy (RP), using descriptive statistics, the Kaplan-Meier method, and multivariable Cox proportional hazards regression. Results A total of 1,433 patients were followed for a median of 49 months; 74% underwent initial biopsy at a referring institution. Median age at diagnosis was 63 years, including 599 patients (42%) ≤ 60 years old and 834 (58%) > 60 years old. The 3- and 5-year biopsy-based Gleason score upgrade-free rates were 73% and 55%, respectively, for men ≤ 60 years old compared with 64% and 48%, respectively, for men older than 60 years ( P < .01). On Cox regression analysis, younger age was independently associated with lower risk of biopsy-based Gleason score upgrade (hazard ratio per 1-year decrease, 0.969 [95% CI, 0.956 to 0.983]; P < .01), and persisted upon restriction to men meeting strict AS inclusion criteria. There was no significant association between younger age and risk of definitive treatment or risk of biochemical recurrence after delayed RP. Conclusion Younger patient age was associated with decreased risk of biopsy-based Gleason score upgrade during AS but not with risk of definitive treatment in the intermediate term. AS represents a strategy to mitigate overtreatment in young patients with low-risk PCa in the early term.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15594-15594
Author(s):  
A. Banu ◽  
E. Banu ◽  
D. Dionysopoulos ◽  
J. Medioni ◽  
F. Scotte ◽  
...  

15594 Background: Clinical studies suggested that the extent of neuro-endocrine differentiation in prostate cancer increases with tumor progression and the development of androgen refractory status. Chromogranine (CgA) and neuron-specific enolase (NSE) are currently explored as surrogate markers. Methods: Eligible chemonaive HRPC patients (pts) were required to have an ECOG performance status (PS) ≤ 2. Before chemotherapy initiation, we quantified NSE, CgA and PSA in the venous blood using commercial kits. We evaluated the impact of baseline NSE, CgA and PSA on overall survival (OS) using multivariate Cox regression analysis, stratified by chemotherapy regimen. Secondary, we studied the correlation between NSE, CgA, PSA and other important variables as age, Gleason score, hemoglobin, number of metastatic sites and ECOG PS. Results: Data of 39 consecutive HRPC pts treated between December 01–06 in a single French center were analyzed. Chemotherapy was docetaxel-based in 92% of pts. Median age was 71 years (range 51–86) and 79% of pts had bone metastases. Elevated NSE, CgA and PSA were observed in 6, 9 and 30% of pts and median levels were 10.8, 67 and 23.3 ng/mL, respectively. Gleason 8–10 was present in 49% of pts. Significant correlations were observed between NSE and the number of metastatic sites and between CgA and age, hemoglobin and ECOG PS. The baseline PSA was only correlated with Gleason score. Median OS for the entire cohort was 24.4 months (95% CI, 18.8–29.9). Two-year OS was 15% and only 19% of patients are dead. Univariate Cox regression analysis showed only a significant relationship between OS and baseline NSE: hazard ratio= 1.09 (95% CI, 1.03–1.16), P=0.006. No other known prognostic factors are related to outcome. A multivariate model including baseline NSE, CgA, ECOG PS and Gleason score showed a 15% rise of the risk of death related to NSE (borderline P value). Conclusions: NSE was the most powerful predictor of survival for HRPC pts. Our results emphasize the theory that cells secreting NSE are chemoresistant, with a negative impact on OS. No significant financial relationships to disclose.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS5097-TPS5097 ◽  
Author(s):  
Karim Fizazi ◽  
Julie S. Larsen ◽  
Shannon Matheny ◽  
Arturo Molina ◽  
Jinhui Li ◽  
...  

TPS5097 Background: Patients (pts) who initially present with metastatic prostate cancer (MPC) (up to 30% of men in Europe; 4% in US) typically progress to metastatic castration-resistant prostate cancer (mCRPC) with a poor prognosis. Prognostic factors impacting survival include high PSA concentration, high Gleason score, high volume of metastatic disease, and bone symptoms. AA decreases testosterone via CYP17 inhibition and is approved for treatment of mCRPC before and after docetaxel-based chemotherapy. Two recent reports (J Clin Oncol. 2012: 30 [suppl. abstr 4521 and 4556]) showed that AA + P in addition to ADT (LHRH agonist) in the neoadjuvant setting led to higher rates of undetectable PSA and complete pathologic response (cPR) or near-cPR in pts undergoing prostatectomy for high risk-localized prostate cancer than with ADT alone, suggesting a potential role for inhibiting extragonadal androgen synthesis prior to emergence of castration-resistance. Because of its benefit in mCRPC, as well as early activity in high risk-localized prostate cancer, AA is being evaluated in high risk mHNPC. Methods: Approximately 1,270 men with newly diagnosed (within 3 months of randomization) high risk mHNPC with at least 2 of 3 high risk factors (≥ 3 bone lesions, presence of visceral metastases or Gleason score ≥ 8) are being randomized to AA 1000 mg + P 5 mg daily + ADT or ADT alone. Pts are stratified by presence of visceral disease and ECOG PS (0-1 vs 2). Distant metastatic disease must be documented by positive bone scan or CT/MRI. ADT or orchiectomy within 3 mos of randomization is allowed. Continued use of anti-androgens after randomization is not allowed on study. The primary endpoint is overall survival. Secondary endpoints include radiographic PFS, time to next skeletal-related event, PSA progression, and subsequent therapy. Two interim analyses and a final analysis are planned. 300 sites from 36 countries will participate. As of February 4, 2013, one patient has entered screening. Clinical trial information: NCT01715285.


2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 158-158
Author(s):  
Tejas Suresh ◽  
Qi Gao ◽  
Mimi Kim ◽  
Sanjay Goel ◽  
Benjamin Adam Gartrell

158 Background: In the United States, prostate cancer (PCa) incidence and death rate differ among racial groups. Non-Hispanic Blacks (NHB) have a higher incidence and death rate than non-Hispanic Whites (NHW), whereas incidence and death rate are slightly lower in Hispanics (H) than in NHW. We sought to compare the socioeconomic, demographic and baseline prognostic factors at PCa diagnosis among different races at a large, urban academic center serving a diverse population. Methods: Following institutional review board approval, the Montefiore Medical Center Cancer Registry was used to generate a comprehensive list of patients diagnosed with PCa 2004 to 2013. Clinical Looking Glass (a searchable database of patient information) and individual patient chart review were used to obtain data including age at diagnosis, socioeconomic score (SES), Gleason score, stage at diagnosis and PSA at diagnosis. Patients were classified by self-identified race as H, NHB or NHW. For categorical variables the chi-square test was used, whereas the ANOVA or the Kruskal-Wallis tests were employed for continuous variables. Results: During the specified period 2352 patients were diagnosed with PCa among which 778 were self-classified as H, 1046 as NHB, 486 as NHW and 42 as other (O). The mean age at diagnosis differed between these groups (H 63.2, NHB 63.4, NHW 67, O 63.0, p < 0.0001). The proportion of men below the mean SES also differed between races (H 92.8%, NHB 91.3%, NHW 56.6%, O 75%, p < 0.0001). Median PSA (ng/ml) at diagnosis was similar (H 8.0, NHB 8.4 NHW 7.2, O 6.4, p = 0.0768) whereas Gleason score differed between racial groups (Gleason ≤ 6: H 42.8%, NHB 39.1%, NHW 52.2%, O 50%; Gleason 8-10: H 15.8%, NHB 17.6%, NHW 14.3%, O 16.7%, p = 0.0005). The proportion of men with metastatic disease at diagnosis also differed significantly in these groups (H 7.5%, NHB 9.0%, NHW 4.3%, O 9.5%, p = 0.0139). Conclusions: At our center, in patients with newly diagnosed PCa, there are significant differences among racial groups. These include age at diagnosis, SES, Gleason score and proportion with metastatic disease. Such differences at diagnosis suggest that minority patients are at risk for inferior PCa outcomes.


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