Change in serum prostate-specific antigen as a marker of response to cytotoxic therapy for hormone-refractory prostate cancer.

PURPOSE Prostate-specific antigen (PSA) has been used as a marker of advanced prostate cancer but remains controversial. To evaluate PSA as a predictor of survival, we analyzed data from sequential phase II trials of estramustine and etoposide. METHODS A landmark analysis that used data from 62 men with PSA levels at baseline and 8 weeks was conducted. The best PSA measure (of six evaluated) was incorporated into a multiple regression model with performance status (PS); relative change in PSA level; and pretreatment PSA, alkaline phosphatase, and hemoglobin values. RESULTS A decrease in PSA of 50% or greater at 8 weeks was associated with a significantly increased survival (P=.0005, two-sided log-rank test). Median survival from the landmark was 91 weeks in patients with a 50% or greater decrease at 8 weeks versus 38 weeks in those without this decrease. Modeling showed that PS, pretreatment hemoglobin level, and relative change in PSA level were significant prognostic factors, with a significant interaction between PS and pretreatment hemoglobin level. In the final model, a relative change in PSA level at 8 weeks of less than 50% had an adjusted relative risk of 2.20 (95% confidence interval, 1.21 to 4.00). A decrease in PSA level of 50% or greater at any time during therapy was associated with a response in measurable disease (P=.0369, two-sided Fisher's exact test). CONCLUSION The PSA value after 8 weeks of this cytotoxic regimen does predict survival. A decrease in PSA level is associated with both survival and response in soft tissue lesions and should be incorporated into the response criteria and reporting of trials of cytotoxic agents in prostate cancer.

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Phase II study of intravenous vinorelbine plus hormone therapy in hormone-refractory prostate cancer

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.14601 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 14601-14601

Author(s):

E. Silva ◽

F. Silva

Keyword(s):

Prostate Cancer ◽

Elderly Patients ◽

Prostate Specific Antigen ◽

Phase Ii ◽

Performance Status ◽

Specific Antigen ◽

Hormone Refractory Prostate Cancer ◽

Phase Ii Studies ◽

Hormone Refractory ◽

Grade 3

14601 Background: Vinorelbine (VRL) has been shown to be active in hormone-refractory prostate cancer (HRPC) in Phase II studies, alone or in combination. Its moderate toxicity profile is well tolerated in elderly patients. The purpose of this study was the investigation of the efficacy of vinorelbine and its toxicity. Methods: Patients with metastatic prostate cancer, progressive after hormonal therapy, receive intravenous VRL 30 mg/m2 on days 1 and 8 every 3 weeks, and hydrocortisone 40 mg/day. Previous chemotherapy was allowed if stopped 6 months before. 44 received VRL according to the protocol. Inclusion criteria: hormone refractory prostate cancer patients PSA >20; performance status WHO < 2. The primary endpoint was prostate specific antigen (PSA) levels, pain, and WHO performance status. Their mean (range) age was 71 (45–80) years, their median prostate specific antigen (PSA) level was 286 (38–950) ng/ml, and the median Gleason score was 8 (7 to 9). 38 patients had had previous chemotherapy. Results: Among the 44 patients, 7 with less than 3 cycles were not evaluated. Patients received a mean (range) of 9 (3–44) cycles of therapy. 6 patients (14%) had not been dispensed prior chemotherapy and 38 (86%) had; 19 (43%) had 2 lines of chemotherapy and 19 (43%) had 1 line. The median follow-up was 13 months. There were no reported drug related Grade 3 toxicities. Only 2 patients required a blood transfusion. Tumour responses: 7 (16%); 17 (39%) PSA stable; 13 (29%) PSA progression, 7 not evaluated. Time of PSA response was 7 months; time to progression: 7 months. Conclusions: Vinorelbine (VRL) is a safe regimen in previous poly-chemotherapy treated hormone-refractory prostate cancer elderly patients and even with response and efficacy. No significant financial relationships to disclose.

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Efficacy of lower cut off value of serum prostate specific antigen in diagnosis of prostate cancer

Bangladesh Medical Research Council Bulletin ◽

10.3329/bmrcb.v38i3.14333 ◽

2013 ◽

Vol 38 (3) ◽

pp. 90-93 ◽

Cited By ~ 3

Author(s):

MM Rashid ◽

AKMK Alam ◽

AKMK Habib ◽

H Rahman ◽

AKMS Hossain ◽

...

Keyword(s):

Prostate Cancer ◽

Prostate Specific Antigen ◽

Prostate Biopsy ◽

Performance Status ◽

Specific Antigen ◽

Significant Proportion ◽

Digital Rectal Examination ◽

High Serum ◽

Serum Prostate Specific Antigen ◽

Sensitivity Specificity

Indications of prostate biopsy are high serum prostate specific antigen (PSA) value and or abnormal digital rectal examination (DRE) findings. Although serum PSA value of 4 ng/ml is the most commonly used threshold for recommending prostate biopsy, significant proportion of men harbor prostate cancer even when their serum PSA values are less than 4.0 ng/ml. Therefore present study was designed to determine the performance status of serum PSA in lower cut-off values. This hospital based prospective study was conducted in the Department of Urology of Bangabandhu Sheikh Mujib Medical University (BSMMU) and Comfort Nursing Home Pvt. Ltd, Dhaka from July 2009 to October 2010. Two hundred six male patients aged over 50 years having lower urinary tract symptoms (LUTS) and serum PSA more than 2.5 ng/ml were prepared for prostate biopsy. Trans rectal ultrasound (TRUS) guided biopsy was done. The test statistics used to analyze the data were descriptive statistics, sensitivity, specificity, positive and negative predictive value, ROC curve. For all analytical tests, the level of significance was set at 0.05 and p<0.05 was considered significant. In 2.5-4 serum PSA range, 28.26% (13 out of 46) of all malignancy were found, which would be missed if we take cut off value 4. At 2.5 PSA cut-off, Sensitivity 91.3%, Specificity 14.37%, PPV 23.46%, NPV 85.18%, Efficacy 31.55%. At 4 PSA cut-off value, Sensitivity 71.73%, Specificity 46.25%, PPV 27.73%, NPV 85.05%, Efficacy 51.94%. So it can be concluded that, for early diagnosis of prostate cancer cut-off value of serum PSA of 2.5 ng/ml can be recommended as an indication for prostate biopsy. DOI: http://dx.doi.org/10.3329/bmrcb.v38i3.14333 Bangladesh Med Res Counc Bull 2012; 38(3): 90-93 (December)

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Randomized Phase II Trials and Prostate-Specific Antigen Endpoints in Prostate Cancer: Much Ado About Nothing?

Journal of Clinical Oncology ◽

10.1200/jco.2005.03.2458 ◽

2005 ◽

Vol 23 (31) ◽

pp. 8124-8125 ◽

Cited By ~ 2

Author(s):

Walter M. Stadler ◽

Laura C. Michaelis ◽

Mark J. Ratain

Keyword(s):

Prostate Cancer ◽

Prostate Specific Antigen ◽

Phase Ii ◽

Specific Antigen ◽

Phase Ii Trials ◽

Much Ado About Nothing ◽

Randomized Phase Ii

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The GP Score, a Simplified Formula (Bioptic Gleason Score Times Prostate Specific Antigen) as a Predictor for Biochemical Failure after Prostatectomy in Prostate Cancer

Current Urology ◽

10.1159/000499298 ◽

2019 ◽

Vol 13 (1) ◽

pp. 25-30

Author(s):

Norihito Soga ◽

Yuji Ogura ◽

Toshiaki Wakita ◽

Takumi Kageyama ◽

Jun Furusawa

Keyword(s):

Prostate Cancer ◽

Multivariate Analysis ◽

High Risk ◽

Prostate Specific Antigen ◽

Gleason Score ◽

Specific Antigen ◽

Biochemical Failure ◽

Rank Test ◽

Failure Group ◽

Significant Independent Risk Factor

Objectives: We used a new GP score (Gleason score multiplied by prostate-specific antigen) without the T stage as a predictive value for biochemical failure (BCF) after prostatectomy. Materials and Methods: We assessed 459 prostate cancer patients who underwent prostatectomies at our institution. Three sub-groups were defined in terms of D'Amico classification risk (low, intermediate, and high) and Gleason score (low, < 50; intermediate, 50-100; and high GP score, > 100). Risk factors for BCF were evaluated by multivariate analysis with a Cox hazard model. A log-rank test was used to compare the BCF rate in the 2 groups. Results: There was nosignificant difference in the non-BCF rate between the lowrisk and low GP score subgroups or the intermediate risk andintermediate GP score subgroups. In contrast, the non-BCFrate of the high GP score subgroup (42.1%) was significantlylower than that of the high-risk subgroup (66.1%, log-rankp = 0.008). Based on multivariate analysis, a high GP score(p = 0.001; HR 3.78; 95%CI 1.95-7.35) was a significant independent risk factor for BCF after prostatectomy. Conclusion: The GP score, consisting of two absolute numbers, may be a valuable predictive factor for BCF after prostatectomy, especially in the high-risk failure group.

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Prognostic Significance of Extent of Disease in Bone in Patients With Androgen-Independent Prostate Cancer

Journal of Clinical Oncology ◽

10.1200/jco.1999.17.3.948 ◽

1999 ◽

Vol 17 (3) ◽

pp. 948-948 ◽

Cited By ~ 160

Author(s):

P. Sabbatini ◽

S. M. Larson ◽

A. Kremer ◽

Z.-F. Zhang ◽

M. Sun ◽

...

Keyword(s):

Prostate Cancer ◽

Lactate Dehydrogenase ◽

Prostate Specific Antigen ◽

Performance Status ◽

Prognostic Significance ◽

Specific Antigen ◽

Bone Scan Index ◽

Skeletal Involvement ◽

Multiple Variable ◽

Androgen Independent

PURPOSE: To evaluate the prognostic significance of a bone scan index (BSI) based on the weighted proportion of tumor involvement in individual bones, in relation to other factors and to survival in patients with androgen-independent prostate cancer. PATIENTS AND METHODS: Baseline radionuclide bone scans were reviewed in 191 assessable patients with androgen-independent disease who were enrolled onto an open, randomized trial of liarozole versus prednisone. The extent of skeletal involvement was assessed by scoring each scan using the BSI and independently according to the number of metastatic lesions. The relationship of the scored bone involvement to other known prognostic factors was explored in single- and multiple-variable analyses. RESULTS: In single-variable analyses, the pretreatment factors found to be associated with survival were age (P = .0446), performance status (P = .0005), baseline prostate-specific antigen (P = .0001), hemoglobin (P = .0001), alkaline phosphatase (P = .0002), AST (P = .0021), lactate dehydrogenase (P = .0001), and treatment (P = .0098). The extent of osseous disease was significant using both the BSI (P = .0001) and the number of lesions present (P = .0001). In multiple-variable proportional hazards analyses, only BSI, age, hemoglobin, lactate dehydrogenase, and treatment arm were associated with survival. When the patient population was divided into three equal groups, with BSI values of < 1.4%, 1.4% to 5.1%, and > 5.1%, median survivals of 18.3, 15.5, and 8.1 months, respectively, were observed (P = .0079). CONCLUSION: The BSI quantifies the extent of skeletal involvement by tumor. It allows the identification of patients with distinct prognoses for stratification in clinical trials. Further study is needed to assess the utility of serial BSI determinations in monitoring treatment effects. The BSI may be particularly useful in the evaluation of agents for which prostate-specific antigen changes do not reflect clinical outcomes accurately.

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Prostate-Specific Antigen and Pain Surrogacy Analysis in Metastatic Hormone-Refractory Prostate Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2007.11.4769 ◽

2007 ◽

Vol 25 (25) ◽

pp. 3965-3970 ◽

Cited By ~ 215

Author(s):

Andrew J. Armstrong ◽

Elizabeth Garrett-Mayer ◽

Yi-Chun Ou Yang ◽

Michael A. Carducci ◽

Ian Tannock ◽

...

Keyword(s):

Prostate Cancer ◽

Overall Survival ◽

Prostate Specific Antigen ◽

Treatment Effect ◽

Specific Antigen ◽

Cytotoxic Agents ◽

Phase Iii ◽

Pain Response ◽

Hormone Refractory Prostate Cancer ◽

Hormone Refractory

Purpose It is currently unclear if early prostate-specific antigen (PSA) or pain improvements are adequate surrogates for overall survival in men with metastatic hormone-refractory prostate cancer (HRPC). Here we examined various degrees of PSA decline and pain response as surrogates for the survival benefit observed in the TAX327 trial. Patients and Methods In the TAX327 trial, 1,006 men with HRPC were randomly assigned to receive docetaxel in two schedules, or mitoxantrone, each with prednisone: 989 men provided data on 3-month PSA decline. Surrogacy was examined for post-treatment changes in PSA and pain response using Cox proportional hazards models to calculate the proportion of treatment effect (PTE) explained by each potential surrogate. Results A ≥ 30% PSA decline within 3 months of treatment initiation provides the highest degree of surrogacy, with a PTE of 0.66 (95% CI, 0.23 to 1.0), and was associated with a hazard ratio (HR) of 0.50 (95% CI, 0.43 to 0.58) for overall survival after adjusting for treatment effect. Introduction of a ≥ 30% PSA decline is predictive of survival regardless of treatment arm. Other changes in PSA or PSA kinetics, PSA normalization, and pain responses were highly prognostic but weaker surrogates for survival. Conclusion In the TAX327 trial, a PSA decline of ≥ 30% within 3 months of chemotherapy initiation had the highest degree of surrogacy for overall survival, confirming data from the Southwest Oncology Group 9916 trial. However, given the wide CIs around the estimate of this moderate surrogate effect, overall survival should remain the preferred end point for phase III trials of cytotoxic agents in HRPC.

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Association between early PSA increase and clinical outcome in patients treated with enzalutamide for metastatic castration resistant prostate cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.2_suppl.231 ◽

2016 ◽

Vol 34 (2_suppl) ◽

pp. 231-231

Author(s):

Vincenza Conteduca ◽

Simon J. Crabb ◽

Emanuela Scarpi ◽

Catherine Hanna ◽

Francesca Maines ◽

...

Keyword(s):

Prostate Cancer ◽

Multivariate Analysis ◽

Clinical Outcome ◽

Performance Status ◽

Specific Antigen ◽

Response To Treatment ◽

Rank Test ◽

Castration Resistant Prostate Cancer ◽

Primary Resistance ◽

Castration Resistant

231 Background: Prostate specific antigen (PSA) decline by 50% from the baseline to 12 weeks (PSA50w12) is currently used to predict response to treatment and clinical outcome of patients with metastatic castration resistant prostate cancer (mCRPC). However, in clinical practice, PSA changes are monitored monthly in several centers. We evaluated the association between PSA changes at 4 weeks and clinical outcome. Methods: We retrospectively evaluated mCRPC patients treated with enzalutamide after docetaxel. Early PSA increase was defined as a PSA level at 4 weeks ≥ 20% (PSA+20w4) from baseline. Early PSA decline was defined as a PSA response at 4 weeks ≥ 30% (PSA30w4) and ≥ 50% (PSA50w4) from baseline.Progression-free survival (PFS), overall survival (OS) and their 95% Confidence Interval (95% CI) were evaluated by the Kaplan-Meier method and compared with the log-rank test. A multivariate analysis was performed including the following variables: PSA+20w4, PSA30w4, PSA50w4 and PSA50w12, baseline PSA, performance status, LDH values, sites of metastases, age. Results: We assessed 193 patients with median age of 73.1 years (range, 42.8 to 90.7). The median follow-up was 11.7 months. PSA+20w4 was associated with shorter PFS (median PFS 2.0 vs. 6.1 months; HR 4.03; 95% CI 2.62-6.19; p < 0.0001) and shorter OS (median OS 5.9 vs. 15.6 months; HR 3.48; 95% CI 2.12-5.69; p < 0.0001). At multivariate analysis, PSA+20w4 remained predictive of both PFS and OS [HR 4.03 (95% CI 0.2.62-6.19; p < 0.0001) and HR 3.48 (95% CI 2.12-5.69; p < 0.0001), respectively], whereas PSA30w4 and PSA50w4 predicted only PFS [HR 0.37 (95% CI 0.21-0.67; p = 0.0009) and HR 0.34 (95% CI 0.19-0.60; p = 0.0003), respectively]. No cases of PSA flare were reported. Conclusions: An early PSA increase, defined as a PSA level at 4 weeks ≥ 20% (PSA+20w4), could be useful to identify patients unlikely to benefit from enzalutamide. Larger studies are needed to confirm PSA+20W4 as an early and cheap biomarker of primary resistance to enzalutamide.

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