Long-Term Follow-Up of HLA-A2+ Patients with High-Risk, Hormone-Sensitive Prostate Cancer Vaccinated with the Prostate Specific Antigen Peptide Homologue (PSA146-154)

Twenty-eight HLA-A2+ patients with high-risk, locally advanced or metastatic, hormone-sensitive prostate cancer were immunized with a peptide homologue of prostate-specific antigen, PSA146-154, between July 2002 and September 2004 and monitored for clinical and immune responses. Fifty percent of the patients developed strong PSA146-154-peptide-specific delayed-type hypersensitivity skin responses, tetramer and/or IFN-γ responses within one year. Thirteen patients had stable or declining serum levels of PSA one year post-vaccination. A decreased risk of biochemical progression was observed in patients who developed augmented tetramer responses at six months compared to pre-vaccination levels (P=.02). Thirteen patients have died while 15 patients remain alive with a mean overall survival of 60 months (95% CI, 51 to 68 months) per Kaplan-Meier analysis. A trend towards greater overall survival was detected in men with high-risk, hormone-sensitive CaP who developed specific T-cell immunity following vaccination with PSA146-154 peptide.

Download Full-text

Three-month early change in prostate-specific antigen levels as a predictive marker for overall survival during hormonal therapy for metastatic hormone-sensitive prostate cancer

10.21203/rs.3.rs-322308/v1 ◽

2021 ◽

Author(s):

Shotaro Nakanishi ◽

Masato Goya ◽

Mitsuyoshi Tamaki ◽

Takuma Oshiro ◽

Seiichi Saito

Keyword(s):

Prostate Cancer ◽

Overall Survival ◽

Prostate Specific Antigen ◽

Characteristic Curve ◽

Specific Antigen ◽

Predictive Marker ◽

Castration Resistant Prostate Cancer ◽

Pretreatment Level ◽

Castration Resistant ◽

Hormone Sensitive

Abstract Objective: To date, there are no useful markers for predicting the prognosis of metastatic hormone-sensitive prostate cancer (mHSPC). We evaluated the effect of early changes in prostate-specific antigen (PSA) levels after androgen deprivation therapy (ADT) on castration-resistant prostate cancer (CRPC) progression and overall survival (OS) in mHSPC patients. Results: In 71 primary mHSPC patients treated with ADT, the median times to CRPC and OS were 15 months and 92 months, respectively. In multivariate analysis, a Gleason score of ≥8 (p = 0.004), an extent of disease value (EOD) of ≥2 (p = 0.004), and a 3-month PSA level >1% of the pretreatment level (p = 0.017) were independent predictors of shorter time to CRPC. The area under the receiver operating characteristic curve was feasible at 0.822. For OS, a 3-month PSA level >1% of the pretreatment level was an independent predictor of time to CRPC (p = 0.004).Three factors were independent predictors of shorter time to CRPC. A 3-month PSA level >1% of the pretreatment level correlated with poor a prognosis.

Download Full-text

Seven-Month Prostate-Specific Antigen Is Prognostic in Metastatic Hormone-Sensitive Prostate Cancer Treated With Androgen Deprivation With or Without Docetaxel

Journal of Clinical Oncology ◽

10.1200/jco.2017.75.3921 ◽

2018 ◽

Vol 36 (4) ◽

pp. 376-382 ◽

Cited By ~ 30

Author(s):

Lauren C. Harshman ◽

Yu-Hui Chen ◽

Glenn Liu ◽

Michael A. Carducci ◽

David Jarrard ◽

...

Keyword(s):

Prostate Cancer ◽

Overall Survival ◽

Prostate Specific Antigen ◽

Multivariable Analysis ◽

Specific Antigen ◽

Androgen Deprivation ◽

Androgen Ablation ◽

Hormone Sensitive ◽

Low Volume

Purpose We evaluated the relationship between prostate-specific antigen (PSA) and overall survival in the context of a prospectively randomized clinical trial comparing androgen-deprivation therapy (ADT) plus docetaxel with ADT alone for initial metastatic hormone-sensitive prostate cancer. Methods We performed a landmark survival analysis at 7 months using the E3805 Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer (CHAARTED) database ( ClinicalTrials.gov identifier: NCT00309985). Inclusion required at least 7 months of follow-up and PSA levels at 7 months from ADT initiation. We used the prognostic classifiers identified in a previously reported trial (Southwest Oncology Group 9346) of PSA ≤ 0.2, > 0.2 to 4, and > 4 ng/mL. Results Seven hundred nineteen of 790 patients were eligible for this subanalysis; 358 were treated with ADT plus docetaxel, and 361 were treated with ADT alone. Median follow-up time was 23.1 months. On multivariable analysis, achieving a 7-month PSA ≤ 0.2 ng/mL was more likely with docetaxel, low-volume disease, prior local therapy, and lower baseline PSAs (all P ≤ .01). Across all patients, median overall survival was significantly longer if 7-month PSA reached ≤ 0.2 ng/mL compared with > 4 ng/mL (median survival, 60.4 v 22.2 months, respectively; P < .001). On multivariable analysis, 7-month PSA ≤ 0.2 and low volume disease were prognostic of longer overall survival (all P < 0.01). The addition of docetaxel increased the likelihood of achieving a PSA ≤ 0.2 ng/mL at 7 months (45.3% v 28.8% of patients on ADT alone). Patients on ADT alone who achieved a 7-month PSA ≤ 0.2 ng/mL had the best survival and were more likely to have low-volume disease (56.7%). Conclusion PSA ≤ 0.2 ng/mL at 7 months is prognostic for longer overall survival with ADT for metastatic hormone-sensitive prostate cancer irrespective of docetaxel administration. Adding docetaxel increased the likelihood of a lower PSA and improved survival.

Download Full-text

Identification of low prostate-specific antigen, high Gleason prostate cancer as a unique hormone-resistant entity with poor survival: A contemporary analysis of 640,000 patients.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.5080 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 5080-5080

Author(s):

David Dewei Yang ◽

Brandon Arvin Virgil Mahal ◽

Christopher Sweeney ◽

Quoc-Dien Trinh ◽

Felix Yi-Chung Feng ◽

...

Keyword(s):

Prostate Cancer ◽

High Risk ◽

Prostate Specific Antigen ◽

Locally Advanced ◽

Specific Antigen ◽

Molecular Classification ◽

High Grade ◽

Biological Insight ◽

Cancer Specific Mortality ◽

New Treatment

5080 Background: The clinical implications of a low prostate-specific antigen (PSA) in high-grade prostate cancer are unclear. We examined the prognostic and predictive value of a low PSA in high-grade prostate cancer. Methods: We identified 642,975 patients in the National Cancer Database (n = 491,505) and Surveillance, Epidemiology, and End Results program (n = 151,470) with localized or locally advanced prostate cancer from 2004-2013. Patients were stratified by Gleason score (8-10 vs. ≤7) and PSA (≤2.5, 2.6-4.0, 4.1-10.0, 10.1-20.0, and > 20.0 ng/mL) for analyses. Multivariable Fine-Gray competing risks and Cox regressions were used to analyze prostate-cancer specific mortality (PCSM) and all-cause mortality (ACM), respectively. Results: 5.6% of Gleason 8-10 tumors were diagnosed with PSA ≤2.5 ng/mL. Among Gleason 8-10 disease using PSA 4.1-10.0 ng/mL as referent, PCSM was U-shaped with respect to PSA, with adjusted hazard ratio (AHR) of 1.75 (95% CI 1.05-2.92, P = 0.032) for PSA ≤2.5 ng/mL vs. 1.31, 0.88, and 1.60 for PSA 2.6-4.0, 10.1-20.0, and > 20.0 ng/mL. In contrast, PCSM was linear for Gleason ≤7 disease with AHR of 0.32 (95% CI 0.10-1.00, P = 0.050) for PSA ≤2.5 ng/mL vs. 1.13, 1.69, and 3.22 for PSA 2.6-4.0, 10.1-20.0, and > 20.0 ng/mL (PGleason*PSA interaction< 0.001). Gleason 8-10 disease with PSA ≤2.5 ng/mL had a much higher risk of PCSM than standard NCCN high-risk disease (AHR 1.92, 95% CI 1.18-3.14, P = 0.009; 47-month PCSM 14.0% vs. 10.5%). For Gleason 8-10 tumors treated with definitive radiotherapy, androgen deprivation therapy (ADT) was associated with decreased ACM for PSA > 2.5 ng/mL (AHR 0.87, 95% CI 0.81-0.94, P < 0.001) but trended toward increased ACM for PSA ≤2.5ng/mL (AHR 1.27, 95% CI 0.89-1.81, P = 0.194; PADT*PSA interaction= 0.026). Conclusions: Low PSA, high-grade prostate cancer appears to be a unique hormone-resistant entity with a high risk of PCSM that responds poorly to standard treatment. Further molecular classification and trials are urgently needed to develop biological insight into this entity and establish new treatment paradigms, potentially including chemotherapy or novel systemic agents.

Download Full-text

Time to prostate-specific antigen nadir independently predicts overall survival in patients who have metastatic hormone-sensitive prostate cancer treated with androgen-deprivation therapy

Cancer ◽

10.1002/cncr.24064 ◽

2009 ◽

Vol 115 (5) ◽

pp. 981-987 ◽

Cited By ~ 79

Author(s):

Toni K. Choueiri ◽

Wanling Xie ◽

Anthony V. D'Amico ◽

Robert W. Ross ◽

Jim C. Hu ◽

...

Keyword(s):

Prostate Cancer ◽

Overall Survival ◽

Prostate Specific Antigen ◽

Androgen Deprivation Therapy ◽

Specific Antigen ◽

Androgen Deprivation ◽

Hormone Sensitive

Download Full-text

Three-month early change in prostate-specific antigen levels as a predictive marker for overall survival during hormonal therapy for metastatic hormone-sensitive prostate cancer

BMC Research Notes ◽

10.1186/s13104-021-05641-5 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Shotaro Nakanishi ◽

Masato Goya ◽

Mitsuyoshi Tamaki ◽

Takuma Oshiro ◽

Seiichi Saito

Keyword(s):

Prostate Cancer ◽

Overall Survival ◽

Prostate Specific Antigen ◽

Characteristic Curve ◽

Specific Antigen ◽

Predictive Marker ◽

Castration Resistant Prostate Cancer ◽

Pretreatment Level ◽

Castration Resistant ◽

Hormone Sensitive

Abstract Objective To date, there are no useful markers for predicting the prognosis of metastatic hormone-sensitive prostate cancer (mHSPC). We evaluated the effect of early changes in prostate-specific antigen (PSA) levels after androgen deprivation therapy (ADT) on castration-resistant prostate cancer (CRPC) progression and overall survival (OS) in mHSPC patients. Results In 71 primary mHSPC patients treated with ADT, the median times to CRPC and OS were 15 months and 92 months, respectively. In multivariate analysis, a Gleason score of ≥ 8 (p = 0.004), an extent of disease value (EOD) of ≥ 2 (p = 0.004), and a 3-month PSA level > 1% of the pretreatment level (p = 0.017) were independent predictors of shorter time to CRPC. The area under the receiver operating characteristic curve was feasible at 0.822. A 3-month PSA level > 1% of the pretreatment level was an independent predictor of OS (p = 0.004). Three factors were independent predictors of shorter time to CRPC. A 3-month PSA level > 1% of the pretreatment level correlated with a poor prognosis.

Download Full-text

Early change in prostate-specific antigen levels as a predictive marker for overall survival during vintage hormonal therapy for metastatic hormone-sensitive prostate cancer

10.21203/rs.3.rs-79980/v1 ◽

2020 ◽

Author(s):

Shotaro Nakanishi ◽

Masato Goya ◽

Mitsuyoshi Tamaki ◽

Takuma Oshiro ◽

Seiichi Saito

Keyword(s):

Prostate Cancer ◽

Overall Survival ◽

Prostate Specific Antigen ◽

Proportional Hazards ◽

Specific Antigen ◽

Predictive Marker ◽

Cox Proportional Hazards ◽

Castration Resistant Prostate Cancer ◽

Castration Resistant ◽

Hormone Sensitive

Abstract Background The effect of early changes in prostate-specific antigen (PSA) levels after androgen deprivation therapy (ADT) in metastatic hormone-sensitive prostate cancer (mHSPC) patients has not been well investigated. Here, we evaluated the effect of factors that lead to castration-resistant prostate cancer (CRPC) progression and overall survival (OS) in mHSPC. Methods Medical records of 71 consecutive primary mHSPC patients treated with ADT were analyzed. Factors predicting the time to CRPC and OS in these patients were evaluated at 3 months after ADT induction. Results The median times to CRPC and OS were 15 months and 92 months, respectively. In multivariate analysis using Cox proportional hazards regression, a Gleason score of 8 or more (p = 0.004), extent of disease value (EOD) of 2 or more (p = 0.004), and a PSA level of 1% or more of the pretreatment levels after 3 months of ADT (p = 0.017) were independent predictors of shorter time to CRPC. For OS, a PSA level of 1% or more after 3 months of ADT was the independent predictor (p = 0.004). Conclusion % PSA was an important factor that correlated with poor prognosis at 3 months after ADT induction.

Download Full-text