Influence of body mass index on prostate-specific antigen failure after androgen suppression and radiation therapy for localized prostate cancer

BACKGROUND: Increasing body mass index (BMI) is associated with shorter time to prostate-specific antigen (PSA) failure after radical prostatectomy. Whether BMI is associated with time to PSA failure was investigated in men treated with androgen suppression therapy (AST) and radiation therapy (RT) for clinically localized prostate cancer. METHODS: The observational prospective cohort study consisted of 102 men with clinically localized prostate cancer who received 70 Gy RT with 6 months of AST on a single arm of a randomized trial between December 1995 and April 2001. Height and weight data were available at baseline for 99 (97%) of the men, from which BMI was calculated. Adjusting for age (continuous) and known prognostic factors including PSA level (continuous), Gleason score, and T-category, Cox regression analyses were performed to analyze whether BMI (continuous) was associated with time to PSA failure (PSA >1.0 ng/mL and increasing >0.2 ng/mL on 2 consecutive visits). RESULTS: Median age and median BMI (interquartile range [IQR]) at baseline was 72 (69.1-74.7) years and 27.4 (24.8-30.7) kg/m,(2) respectively. In addition to an increasing PSA level (P = .006) and Gleason 8-10 cancer (P = .024), after a median follow-up (IQR) of 6.9 (5.6-8.5) years, an increasing BMI was also significantly associated with a shorter time to PSA failure (adjusted hazard ratio [HR]: 1.10; 95% confidence interval [CI]: 1.01-1.19; P = .026) after RT and AST. CONCLUSIONS: After adjusting for known prognostic factors, baseline BMI is significantly associated with time to PSA failure after RT and AST for men with clinically localized prostate cancer. Further study is warranted to assess the impact of an increasing BMI after AST administration on PSA failure, prostate cancer-specific, and all-cause mortality.     

The influence of serial prostate-specific antigen (PSA) screening on the PSA velocity at diagnosis

BACKGROUND: A prostate-specific antigen (PSA) velocity (PSAV) >2 ng/mL during the year before diagnosis has been associated with an increased risk of prostate cancer-specific mortality (PCSM) after radical prostatectomy (RP) or radiation therapy. The objective of the current study was to examine whether the proportion of men with a PSAV >2 ng/mL per year has changed significantly during the PSA era. METHODS: The authors evaluated 1095 men from a prospective prostate cancer screening study who underwent RP between 1989 and 2002. For the purposes of this analysis, clinicopathologic features were compared between men who were treated during the following 3 periods: before 1995, from 1995 to 1998, and after 1998. Logistic regression analysis was used to evaluate for an association between the year of diagnosis and the proportion of men with a PSAV >2 ng/mL per year. RESULTS: Two hundred sixty-two of 1095 men (24%) had a PSAV >2 ng/mL per year. There was a statistically significant reduction in the proportion of men presenting with a PSAV >2 ng/mL per year over the study period. Specifically, 35% of men presented with a PSAV >2 ng/mL per year in the early period compared with only 22% and 12% in the middle and late periods, respectively (P < .001). Over the studied periods, there also was a significantly greater proportion of men with >2 PSA values obtained before diagnosis (P < .001). CONCLUSIONS: Men who were screened serially with PSA were less likely to present with a PSAV >2 ng/mL per year. This association lends support to the hypothesis that serial PSA-based screening may lead to a decrease in PCSM.     

Locally advanced prostate cancer--biochemical results from a prospective phase II study of intermittent androgen suppression for men with evidence of prostate-specific antigen recurrence after radiotherapy

BACKGROUND: Biochemical results from a prospective Phase II trial of intermittent androgen suppression for recurrent prostate cancer after radiotherapy were analyzed for correlations to the onset of hormone-refractory disease. METHODS: Patients with histologically confirmed adenocarcinoma of the prostate and a rising serum prostate-specific antigen (PSA) level after external beam irradiation of the prostate were treated intermittently with a 36-week course of cyproterone acetate and leuprolide acetate. Then, patients were stratified according to their serum PSA range at the start of each cycle and were followed with further biochemical testing until disease progression was evident. RESULTS: The mean PSA reduction was 95.2% irrespective of stratification group. A baseline serum PSA level <10 microg/L and a serum PSA nadir or=7.5 nmol/L was observed in 75%, 50%, 40%, and 30% of men in Cycles 1 to 4, respectively, and was sufficient to normalize the level of hemoglobin in each cycle, which dropped by an average of 10.8 g/L during treatment (P < .0001). CONCLUSIONS: The length of the off-treatment interval during cyclic androgen withdrawal therapy was related inversely to baseline and nadir levels of serum PSA. Nadir PSA was a powerful predictor of early progression to androgen independence.     

Evaluation and management of prostate-specific antigen recurrence after radical prostatectomy for localized prostate cancer

A radical prostatectomy has been established as one of the standardmanagement options for localized prostate cancer. However, asubstantial proportion of patients who undergo a radical prostatectomydevelop prostate-specific antigen (PSA) recurrence which iscommonly defined as a PSA cut-off point value of 0.2 ng/ml.Although the management of PSA recurrence after radical prostatectomymay depend on the site of recurrence, it is quite difficultto identify the recurrent lesion accurately based on the currentlyavailable imaging technology. Patients who have surgical margininvolvement or a Gleason score 7 based on the radical prostatectomyspecimens, who do not have nodal or seminal vesicle involvement,and who develop a PSA recurrence >1–2 years after surgerywith a doubling time of >1 year, and whose pre-treatmentPSA is <1.0–1.5 ng/ml are considered to benefit fromlocal treatment with at least 64 Gy of salvage radiotherapy.Patients with different characteristics are considered to havedistant metastases or both local lesions and distant metastases,and thus may be candidates for hormonal manipulation ratherthan radiotherapy. Since local recurrent lesions are consideredto be quite small at the early stage of PSA recurrence, hormonalmanipulation may be sufficient to prevent disease progressioninstead of radiotherapy. However, the optimal type and timingof hormonal manipulation remain to be elucidated. As a result,no consensus regarding the treatment for PSA recurrence afterradical prostatectomy has yet been reached.     

Algorithms based on prostate-specific antigen (PSA), free PSA, digital rectal examination and prostate volume reduce false-positive PSA results in prostate cancer screening

Our objective was to determine whether multivariate algorithms based on serum total PSA, the free proportion of PSA, age, digital rectal examination and prostate volume can reduce the rate of false-positive PSA results in prostate cancer screening more effectively than the proportion of free PSA alone at 95% sensitivity. A total of 1,775 consecutive 55- to 67-year-old men with a serum PSA of 4-10 microg/l in the European Randomized Study of Screening for Prostate Cancer were included. To predict the presence of cancer, multivariate algorithms were constructed using logistic regression (LR) and a multilayer perceptron neural network with Bayesian regularization (BR-MLP). A prospective setting was simulated by dividing the data set chronologically into one set for training and validation (67%, n = 1,183) and one test set (33%, n = 592). The diagnostic models were calibrated using the training set to obtain 95% sensitivity. When applied to the test set, the LR model, the BR-MLP model and the proportion of free PSA reached 92%, 87% and 94% sensitivity and reduced 29%, 36% and 22% of the false-positive PSA results, respectively. At a fixed sensitivity of 95% in the test set, the LR model eliminated more false-positive PSA results (22%) than the proportion of free PSA alone (17%) (p < 0.001), whereas the BR-MLP model did not (19%) (p = 0.178). The area under the ROC curve was larger for the LR model (0.764, p = 0.030) and the BR-MLP model (0.760, p = 0.049) than for the proportion of free PSA (0.718). A multivariate algorithm can be used to reduce unnecessary prostate biopsies in screening more effectively than the proportion of free PSA alone, but the algorithms will require updating when clinical practice develops with time.     

Prostate cancer progression in the presence of undetectable or low serum prostate-specific antigen level

BACKGROUND: The serum prostate-specific antigen (PSA) level after definitive treatment for prostate cancer (PC) is a powerful predictor of outcome. Occasionally, PC progression can occur despite low or undetectable PSA levels. The authors report on the clinical and pathologic characteristics of patients who experienced PC progression with undetectable or low PSA levels. METHODS: From an electronic database of all patients with PC who were treated at The University of Texas M. D. Anderson Cancer Center between 1999 and 2004, a group of 46 patients was identified who had progression to metastatic PC detected with concomitant PSA levels from 0.1 ng/mL to 2 ng/mL. Patient charts were reviewed for tumor stage, Gleason score, pretreatment PSA level, and the presence of atypical histologic variants (ie, ductal, sarcomatoid, or small cell cancers). The nadir PSA level after treatment and the PSA level at the time metastatic PC was detected were determined. The patients were followed semiannually, and imaging studies were obtained at the discretion of treating physicians. The sites of metastasis and histologic confirmation were reported when available. RESULTS: Twenty-three of 46 patients underwent radical prostatectomy, 11 patients received radiation therapy, and 12 received hormone treatment as their initial form of therapy. Progression to metastatic disease with concomitant, undetectable PSA levels occurred in 10 patients, including 3 patients who had not received treatment with hormones. The sites of metastasis included bone (n = 35 patients), liver (n = 7 patients), retroperitoneal lymph nodes (n = 5 patients), lungs (n = 4 patients), and brain (n = 1 patient). Aggressive and locally advanced PC were common features in these patients: Eighty-five percent had Gleason scores >or=7, 63% had clinical T3 or T4 tumors, and 41% had pretreatment PSA levels >10 ng/mL. Atypical histologic variants were observed in 21 patients (46%) and in 8 of 10 patients who progressed with undetectable PSA levels. In 10 patients (22%), metastasis were detected in the presence of an undetectable PSA level. Eight of those patients had small cell carcinoma. In 19 patients (41%), progression to metastasis occurred without any increase in their PSA from the nadir level. Thirty-one patients (67%) were asymptomatic at the time metastasis was detected, and the detection of metastasis in these patients occurred only because of routine imaging studies. CONCLUSIONS: Progression of PC may occur despite undetectable or low PSA levels. Complete physical evaluation and imaging studies may be indicated in the surveillance of patients with high-grade, locally advanced tumors, especially when atypical histologic variants are present.     

Percent free prostate-specific antigen (PSA) is an accurate predictor of prostate cancer risk in men with serum PSA 2.5 ng/mL and lower

BACKGROUND: Up to 17% of men with a prostate-specific antigen (PSA) level below the accepted prostate biopsy cutoff of 2.5 ng/mL may have prostate cancer. Because identification of these patients represents a difficult task, we assessed the ability of percent free PSA to discriminate between benign and malignant prostate biopsy outcomes in men with PSA < or =2.5 ng/mL. METHODS: Between 1999 and 2006, 543 men with a PSA < or =2.5 ng/mL were referred for initial prostate biopsy. Age, total PSA, percent free PSA, and digital rectal examination findings represented predictors of prostate cancer at biopsy in logistic regression models. The area under the receiver operating characteristics curve (AUC) quantified the discriminative ability of the predictors. The pathological characteristics of the detected cancers were assessed in individuals treated with radical prostatectomy. RESULTS: Of all, 23% had prostate cancer on biopsy, 16.5% of patients treated with radical prostatectomy had pT3 stage, and 35.6% had a pathological Gleason score of 3 + 4 or higher. The most accurate predictor of prostate cancer on biopsy was percent free PSA (0.68) versus age (0.50), total PSA (0.57), or rectal examination findings (0.58). Of patients with percent free PSA below 14%, 59% had prostate cancer. In multivariate models, percent free PSA (P < .001) and rectal examination findings (P = .001) were the only independent predictors of prostate cancer. The combined AUC of all predictors (0.69) was not significantly (P = .7) higher than that of percentage of free PSA alone (0.68). CONCLUSIONS: The risk of prostate cancer is clearly non-negligible in patients with PSA < or =2.5 ng/mL. The percent free PSA can accurately predict the prevalence of prostate cancer at prostate biopsy in these individuals.     

Patient selection, cancer control, and complications after salvage local therapy for postradiation prostate-specific antigen failure: a systematic review of the literature

Among men who experience prostate-specific antigen (PSA) failure after external beam radiation or brachytherapy (RT), many will harbor occult micrometastases; however, a significant minority will have a true local-only failure and, thus, potentially may benefit from a salvage local therapy. Those most likely to have a local-only failure initially have low-risk disease (PSA < 10 ng/mL, Gleason score < or =6, clinical T1c or T2a tumor status), pretreatment PSA velocity < 2.0 ng/mL per year at the time of initial presentation, interval to PSA failure > 3 years, PSA doubling time > 12 months, negative bone scan and pelvic imaging, and positive rebiopsy. In addition, men with presalvage PSA levels > 10 ng/mL, presalvage T3/T4 disease, or presalvage Gleason scores > or =7 on a rebiopsy sample without significant RT effects are unlikely to be cured by salvage local therapy. Based on a review of all series of post-RT salvage prostatectomy, cryosurgery, and brachytherapy published in English since 1990, morbidity can be substantial. Although urinary incontinence appeared to be greater after salvage prostatectomy (41%) or cryosurgery (36%) than after brachytherapy (6%), patients who received salvage brachytherapy faced a 17% risk of grade 3 or 4 genitourinary complications and a fistula risk that averaged 3.4% across all series. From this review, the authors concluded that prospective randomized studies are needed to determine the relative efficacy of the 3 major local salvage modalities and that additional research is needed to identify factors associated with an increased risk of significant complications to improve patient selection and to augment the benefit/risk ratio associated with attempts to cure local-only recurrences after radiation therapy.     

Pretreatment prostate-specific antigen velocity is associated with development of distant metastases and prostate cancer mortality in men treated with radiotherapy and androgen-deprivation therapy

BACKGROUND: In men with prostate cancer, pretreatment prostate-specific antigen (PSA) velocity (PSAV) has been demonstrated as a predictor of biochemical and survival outcomes in patients undergoing radical prostatectomy (RP). The utility of pretreatment PSAV in predicting outcomes after radiotherapy (RT), with or without androgen-deprivation therapy (ADT), is less certain. This study was undertaken to determine whether pretreatment PSAV is associated with biochemical disease-free survival, patterns of recurrence, and survival outcomes in men treated with radiation therapy and ADT. METHODS: Two hundred seventy-seven patients with intermediate- and high-risk prostate cancer treated with RT and ADT formed the study cohort. Kaplan-Meier survival estimates and Cox regression analyses were used to evaluate whether PSAV was associated with disease outcomes. RESULTS: The median age of diagnosis was 70 years, and the median follow-up was 6.8 years. Men with a PSAV in the highest quartile tended to have higher risk disease at presentation (P = .028). After adjustment for known prognostic factors and duration of ADT, men who had a PSAV in the highest quartile had an increased risk of distant metastasis (hazard ratio [HR], 4.0; 95% confidence interval [95% CI], 1.61-9.9 [P = .003]) and prostate cancer-specific mortality (HR, 2.75; 95% CI, 1.27-5.95 [P = .01]) compared with men who had a lower PSAV, but had no increase in the risk of local recurrence (P = .76). CONCLUSIONS: A high pretreatment PSAV was associated with distant metastasis and prostate cancer-specific mortality but not with local recurrence. A high pretreatment PSAV may signify the presence of occult metastatic disease. Randomized trials are needed to determine whether more aggressive intervention is required in men who present with high pretreatment PSAV.     

Impact of postoperative prostate‐specific antigen disease recurrence and the use of salvage therapy on the risk of death

BACKGROUND:

This report evaluated whether biochemical recurrence (BCR) as a time‐dependent covariate (t) after radical prostatectomy (RP) for prostate cancer was associated with the risk of death and whether salvage therapy with radiotherapy (RT) and/or hormonal therapy (HT) can lessen this risk

METHODS:

This was a retrospective cohort study of 3071 men who underwent RP at Duke University between 1988 and 2008 and had complete follow‐up data. A Cox regression multivariable analysis was used to determine whether BCR (t) was associated with the risk of death in men after adjusting for age, prostatectomy findings, and the use of salvage RT and/or HT.

RESULTS:

After a median follow‐up of 7.4 years, 546 (17.8%) men experienced BCR and 454 (14.8%) died. The median follow‐up after prostate‐specific antigen (PSA) failure was 11.2 years (interquartile range, 5.8‐16.0 years). BCR (t) was associated with an increased risk of death (adjusted hazards ratio [AHR], 1.03; 95% confidence interval [95% CI], 1.004‐1.06 [P = .025]). In men who experienced BCR, a PSA doubling time <6 months was associated with an increased risk of death (AHR, 1.55; 95% CI, 1.15‐2.1 [P = .004]); whereas a decrease in the risk of death was observed in men who received RT (AHR, 0.58; 95% CI, 0.40‐0.58 [P = .002]) or HT (AHR, 0.56; 95% CI, 0.37‐0.84 [P = .005]) after BCR.

CONCLUSIONS:

The occurrence of BCR was found to increase the risk of death in men undergoing RP for prostate cancer, and this risk appeared to increase as the time to BCR shortened. However, the addition of RT and/or HT in men with BCR significantly lowered this risk. Cancer 2010. © 2010 American Cancer Society.     

The impact of socioeconomic status on stage specific prostate cancer survival and mortality before and after introduction of PSA test in Finland

Socioeconomic status (SES) has an impact on prostate cancer (PCa) outcomes. Men with high SES have higher incidence and lower mortality of PCa versus lower SES males. PCa cases diagnosed in Finland in 1985–2014 (N = 95,076) were identified from the Finnish Cancer Registry. Information on education level (EL) was obtained from Statistics Finland. EL was assessed with three‐tiered scale: basic, upper secondary and higher education. PCa stage at diagnosis was defined as localized, metastatic or unknown. Years of diagnosis 1985–1994 were defined as pre‐PSA period and thereafter as post‐PSA period. We report PCa‐specific survival (PCSS) and relative risks (RR) for PCa specific mortality (PCSM) among cancer cases in Finland, where healthcare is 100% publicly reimbursed and inequality in healthcare services low. Men with higher EL had markedly better 10‐year PCSS: 68 versus 63% in 1985–1994 and 90 versus 85% in 1995–2004 compared to basic EL in localized PCa. The RR for PCSM among men with localized PCa and higher EL compared to basic EL was 0.76(95%confidence interval (CI) 0.66–0.88) in 1985–1994 and 0.61(95%CI 0.53–0.70) in 1995–2004. Variation in PCSS and PCSM between EL categories was evident in metastatic PCa, too. The difference in PCSM between EL categories was larger in the first 10‐year post‐PSA period than before that but decreased thereafter in localized PCa, suggesting PSA testing became earlier popular among men with high EL. In summary, higher SES/EL benefit PCa survival both in local and disseminated disease and the effect of EL was more pronounced in early post‐PSA period.     

Transrectal ultrasound in detecting prostate cancer compared with serum total prostate-specific antigen levels

We carried out a retrospective study to review the efficiency of grey-scale transrectal ultrasonography (TRUS) in detecting prostate cancer compared with the data in recent published work, including alternative imaging methods of the prostate gland. Our study group consisted of 830 patients who underwent TRUS-guided biopsy of the prostate between May 2000 and June 2004. The relation between abnormal TRUS findings and serum total prostate-specific antigen (tPSA) levels was evaluated in patients with prostate cancer who were divided into three different groups according to serum tPSA levels. Group I included patients with tPSA levels of 4-9.9 ng/mL, group II included tPSA levels of 10-19.9 ng/mL and group III included patients with tPSA levels of 20 ng/mL or more. In general, TRUS detected 185 (64%) of 291 cancers with a specificity of 89%, a PPV of 76% and an accuracy of 80%. TRUS findings enabled the correct identification of 22 (56%) of the 39 cancers in group I, 28 (30%) of the 93 cancers in group II and 135 (85%) of the 159 cancers in group III. In conclusion, TRUS alone has a limited potential to identify prostate cancer, especially in patients with tPSA levels lower than 20 ng/mL. Therefore, increased numbers of systematically placed biopsy cores must be taken or alternative imaging methods are required to direct TRUS-guided biopsy for improving prostate cancer detection.     

Changing face and different countenances of prostate cancer: racial and geographic differences in prostate-specific antigen (PSA), stage, and grade trends in the PSA era.

The purpose of this investigation was to examine changes in pretreatment prostate-specific antigen (PSA), stage, and grade over the past decade as a function of race and geographic region. A multiinstitutional database representing 6,790 patients (1,417 African-American, 5,373 white) diagnosed with nonmetastatic prostate cancer between 1988 and 1997 was constructed. PSA, stage, and grade data were tabulated by calendar year and region, and time trend analyses based on race and region were performed. There was an overall decline of PSA of 0.8%/year, which was significant (P = 0.0001), with a faster rate of decline in African-Americans (1.9%/year) than for whites (0.6%/year). The odds ratio (OR) for a stage shift was 1.09, which was significant (P < 0.0001), and this shift was greater in whites. The OR for an overall grade shift was 1.15, which was significant (P < 0.0001). Although grade and PSA trends were similar for the different regions, there were significant regional differences in stage trends. The implications are that the face of prostate cancer has changed over the past decade; i.e., the distributions of stage, grade, and PSA (the most important prognosticators) have changed. In addition, the countenances of that face are different for whites and African-Americans. For African-Americans, this is good news: the stage, grade, and PSA distributions are more favorable now than before. For whites, the trends are more complex and more dependent on region. These findings should be used for future clinical and health-policy decisions in the screening and treatment of prostate cancer.     

Inhibition of prostate-specific membrane antigen (PSMA)-positive tumor growth by vaccination with either full-length or the C-terminal end of PSMA

For experimental immunotherapy of prostate cancer, we used a model system to target a defined region of the extracellular domain of prostate-specific membrane antigen (PSMA). PSMA is a surface antigen expressed by prostate epithelium that is upregulated approximately 10-fold in most prostate tumors. We vaccinated BALB/c mice with NIH3T3 cells cotransfected with pST/neo plus pEF-BOS-based vectors expressing either the full-length 750-amino acid human PSMA or only the C-terminal 180-amino acid region (PSMc). PSMc lies C-terminal to the transferrin receptor-like sequence in the extracellular domain of PSMA. BALB/c mice were injected i.p. 4 times at weekly intervals with vaccine cells. Vaccinated mice were then challenged s.c. with Renca/PSMA, a BALB/c renal cell carcinoma line transfected to express human PSMA. Growth of Renca/PSMA tumors was substantially retarded and host survival significantly prolonged in mice prevaccinated with either 3T3/PSMA or 3T3/PSMc. Furthermore, antiserum from vaccinated mice intensely immunocytochemically stained LNCaP, a PSMA-positive human prostate cancer cell line. In contrast, control mice similarly prevaccinated i.p. with 3T3/neo (NIH3T3 cells transfected with pST/neo alone) developed Renca/PSMA tumors, which were palpable within 2 weeks and lethal by 5 weeks. Serum from 3T3/neo-vaccinated mice did not immunocytochemically stain LNCaP cells. The antitumor activity induced by vaccination with 3T3/PSMc was also demonstrated via growth inhibition of established LNCaP tumors xenografted in athymic mice following passive transfer of immune serum from vaccinated mice. Our results suggest that vaccination with PSMc induces adaptive humoral activity, which is directed against the extracellular region of human PSMA and can significantly inhibit human prostate cancer growth in athymic mice, and that administration of antibodies to PSMA may provide a passive treatment modality for immunocompromised patients.     

Combining 33 genetic variants with prostate-specific antigen for prediction of prostate cancer: longitudinal study

The aim of this study was to investigate if a genetic risk score including 33 common genetic variants improves prediction of prostate cancer when added to measures of prostate-specific antigen (PSA). We conducted a case-control study nested within the Northern Sweden Health and Disease Cohort (NSHDC), a prospective cohort in northern Sweden. A total of 520 cases and 988 controls matched for age, and date of blood draw were identified by linkage between the regional cancer register and the NSHDC. Receiver operating characteristic curves with area under curve (AUC) estimates were used as measures of prostate cancer prediction. The AUC for the genetic risk score was 64.3% [95% confidence interval (CI) = 61.4-67.2], and the AUC for total PSA and the ratio of free to total PSA was 86.2% (95% CI = 84.4-88.1). A model including the genetic risk score, total PSA and the ratio of free to total PSA increased the AUC to 87.2% (95% CI = 85.4-89.0, p difference = 0.002). The addition of a genetic risk score to PSA resulted in a marginal improvement in prostate cancer prediction that would not seem useful for clinical risk assessment.     

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

BACKGROUND:

The objective of this study was to evaluate the relation between the kinetics of prostate‐specific antigen (PSA) decline after the initiation of androgen‐deprivation therapy (ADT) and overall survival (OS) in men with metastatic, hormone‐sensitive prostate cancer (HSPC).

METHODS:

The authors' institutional database was used to identify a cohort of men with metastatic HSPC who were treated with ADT. Patients were included if they had at least 2 serum PSA determinations before PSA nadir and at least 1 serum PSA value available within 1 month of ADT initiation. Patient characteristics, PSA at ADT initiation, nadir PSA, time to PSA nadir (TTN), and PSA decline (PSAD) in relation to OS were analyzed.

RESULTS:

One hundred seventy‐nine patients were identified, and they had a median follow‐up after ADT initiation of 4 years. The median OS after ADT initiation was 7 years. The median PSA level at ADT initiation and PSA nadir were 47 ng/mL and 0.28 ng/mL, respectively. On univariate analysis: TTN <6 months, PSAD >52 ng/mL per year, PSA nadir ≥0.2 ng/mL, PSA ≥47.2 ng/mL at ADT initiation, and Gleason score >7 were associated with shorter OS. On multivariate analysis, TTN <6 months, Gleason score >7, and PSA nadir ≥0.2 ng/mL independently predicted shorter OS.

CONCLUSIONS:

To the authors' knowledge, this was the first report to demonstrate that a faster time to reach a PSA nadir after the initiation of ADT was associated with shorter survival duration in men with metastatic HSPC. These results need confirmation but may indicate that a rapid initial response to ADT indicates more aggressive disease. Cancer 2009. © 2009 American Cancer Society.