Pretreatment Prostate-specific Antigen Research Articles

High-Dose Robotic Stereotactic Body Radiotherapy in the Treatment of Patients With Prostate Cancer: Preliminary Results in 26 Patients.

Stereotactic body radiotherapy (SBRT) can emulate high dose rate brachytherapy (HDR-BRT) dose fractionation. We report our preliminary results using SBRT in monotherapy or pre-external-beam radiotherapy (EBRT) boost in patients with localized prostate cancer (LpC). The primary end point was the evaluation of both acute and late toxicities; secondary end point was the observation of prostate-specific antigen (PSA) nadir. Patients with LpC having prostate volume ≤90 cm(3) were enrolled in the present study. Patients were treated with SBRT alone or in combined modality (SBRT + EBRT). SBRT was performed using a CyberKnife System (Accuray Incorporated, Sunnyvale, California) and fiducial tracking system. From February 2008 to July 2013, 21 patients for monotherapy (38 Gy/4 fractions) and 5 for combined modality (9.5 Gy/2 fractions plus 46 Gy/23 fractions EBRT) were enrolled. Androgen deprivation therapy (ADT) was administered in 16 of the 26 patients. The median pretreatment PSA was 9.4 (range, 4.5-14.3) ng/mL. All patients completed the planned therapy. Acute Grade 1 toxicity was observed in 18 patients, genitourinary (GU) in 12 / 26 patients, and gastrointestinal (GI) in 6 / 26 patients. Acute Grade 2 GU toxicity was reported in 1 / 26 patients, and Grade 2 GI toxicity was observed in 2 / 26 patients. The median PSA nadir was 0.15 (range, 0.02 = 1.4) ng/mL. Late toxicities were observed in 5 / 26 patients: Grade 1 GU (3 of 26), Grade 2 GU (1 of 26), and Grade 1 GI (1 of 26). Median follow-up was 21.5 (range, 8-65) months. Our preliminary results of SBRT "simulating" HDR for LpC confirm a minimal toxicity and an optimal PSA response. The PSA nadirs appear comparable with HDR-BRT.

Accelerated Hypofractioned Postoperative Radiotherapy for Prostate Cancer: A Prospective Phase I/II Study

AimsTo present the initial findings of a single institution, phase I/II study investigating hypofractionated radiotherapy in patients undergoing post-prostatectomy treatment. Materials and methodsPatients requiring postoperative radiotherapy were prospectively enrolled. Dose was prescribed to the prostate bed with 51 Gy in 17 daily fractions. Androgen deprivation was optional. Acute and late gastrointestinal/genitourinary toxicity were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 and quality of life was assessed using the Expanded Prostate Cancer Index Composite evaluation tool. Prostate-specific antigen (PSA) was evaluated at every follow-up. ResultsThirty patients were enrolled between 2009 and 2011. The median age was 65 years and most had Gleason 7 disease (86%) with pT2c or pT3a (82%). Positive margins were documented in 67% of the patients. The median pre-treatment PSA was 0.12 ng/ml. The median follow-up was 24 months. Overall toxicity was low, with >80% of patients having ≤ grade 1 acute toxicity in both genitourinary and gastrointestinal realms. Similarly, only two patients (6%) experienced grade 2/3 late gastrointestinal/genitourinary toxicity. Quality of life scores were also indicative of a well-tolerated treatment. PSA failure was seen in five patients (17%). ConclusionsWe present a hypofractionated schedule of postoperative prostate radiotherapy that is both well tolerated in terms of both toxicity and quality of life measures. Initial PSA control is encouraging. Further evaluation with a longer follow-up and a larger cohort is warranted.

A narrowing range of bone scan in newly diagnosed prostate cancer patients: A retrospective comparative study.

Objectives:The objective of the following study is to clarify a suitable group whereby a bone scan could be spared at the initial staging of prostate cancer, we wished to identify the possible relationship between bone metastasis and clinical and pathological parameters including serum total prostate specific antigen (PSA) concentration, alkaline phosphatase (ALP), biopsy Gleason Score (GS), and percentage of pathological cores.Materials and Methods:We reviewed the results of 220 bone scintigraphies, which were done between January 1, 2011 and June 30, 2013 in patients with newly diagnosed prostate cancer. These parameters were evaluated together with standard clinicopathological data to determine the prediction ability of the bone scan by univariate and multivariate analyses.Results:Bone metastases were seen in 44 patients of all 220 patients (20%, 95% confidence interval, 17-24%). In univariate analysis, PSA and biopsy GS were useful in predicting the bone scan result, but ALP and percentage of pathological cores was not. In multivariate analysis, the single most useful parameter in predicting the bone scan result was PSA (P < 0.001).Conclusions:A bone scan seems to be impractical in newly diagnosed prostate cancer patients with serum PSA level <20 ng/ml and GS up to seven and pre-treatment PSA is the best predictor of the need for the bone scan according to results of this study.

Exponential rise in prostate-specific antigen (PSA) during anti-androgen withdrawal predicts PSA flare after docetaxel chemotherapy in patients with castration-resistant prostate cancer.

PurposeTo investigate the relationship between rising patterns of prostate-specific antigen (PSA) before chemotherapy and PSA flare during the early phase of chemotherapy in patients with castration-resistant prostate cancer (CRPC).Materials and MethodsThis study included 55 patients with CRPC who received chemotherapy and in whom pre-treatment or post-treatment PSA levels could be serially obtained. The baseline parameters included age, performance, Gleason score, PSA level, and disease extent. PSA doubling time was calculated using the different intervals: the conventional interval from the second hormone manipulation following the nadir until anti-androgen withdrawal (PSADT1), the interval from the initial rise after anti-androgen withdrawal to the start of chemotherapy (PSADT2), and the interval from the nadir until the start of chemotherapy (PSADT3). The PSA growth patterns were analyzed using the ratio of PSADT2 to PSADT1.ResultsThere were two growth patterns of PSA doubling time: 22 patients (40.0%) had a steady pattern with a more prolonged PSADT2 than PSADT1, while 33 (60.0%) had an accelerating pattern with a shorter PSADT2 than PSADT1. During three cycles of chemotherapy, PSA flare occurred in 11 patients (20.0%); of these patients, 3 were among 33 (9.1%) patients with an accelerating PSA growth pattern and 8 were among 22 patients (36.4%) with a steady PSA growth pattern (p=0.019). Multivariate analysis showed that only PSA growth pattern was an independent predictor of PSA flare (p=0.034).ConclusionAn exponential rise in PSA during anti-androgen withdrawal is a significant predictor for PSA flare during chemotherapy in CRPC patients.

Prostate carcinoma: correlation of histopathology with serum prostate specific antigen

Prostate Specific Antigen (PSA) is the first line test in screening of prostate cancer. The increase in PSA depends on differentiation of tumour cells. Gleason grading is one of the most powerful predictors of biological behaviour and influential factors used to determine treatment. PSA, when combined with Gleason score and clinical stage, improves the prediction of pathological stage for prostate carcinoma. Aims of this study were to study the histopathological features and Gleason grading in Prostatic Carcinoma and to correlate pretreatment PSA levels with Gleason grade. The study was undertaken in a tertiary care hospital over a period of two years.Fifty one cases of prostatic carcinoma were studied. Grading done by Gleason grading system, was correlated with serum PSA levels. Software statistical package for social sciences (SPSS), version 16 was used. P value 10ng/ml). 5.9 % had PSA value in normal range (< 4 ng/ml). Though there was a comparative increase in PSA level with increase in Gleason grade, it was not statistically significant (‘p’ value = 0.75). To conclude, a proportion of tumours with Gleason score 8-10 are so poorly differentiated that they produce relatively little PSA. Refinement in estimation and interpretation of PSA values may be considered to improve the sensitivity and specificity of PSA. Gleason grading is a better predictor of biological behaviour of prostate cancer.

Metronomic oral cyclophosphamide plus prednisone in docetaxel-pretreated patients with metastatic castration-resistant prostate cancer.

We evaluated the efficacy and safety of metronomic oral cyclophosphamide (CTX) and prednisone in metastatic castration-resistant prostate cancer (mCRPC) patients. We analyzed retrospectively patients with mCRPC previously treated with docetaxel, and who received metronomic CTX (from 50mg PO daily to 150mg PO, 14days/7days off) and prednisone 10mg PO daily between September 2009 and April 2014 were analyzed. The primary endpoint was prostate-specific antigen (PSA) decrease ≥50%. Secondary analysis included PSA decrease ≥30%, time-to-treatment failure (TTF) and toxicity. Demographics and baseline characteristics were summarized using descriptive statistics. PSA response and adverse events were reported as relative rates. Kaplan-Meier estimates were calculated and plotted for time-to-event endpoints. Forty patients were evaluated. The median age was 69years old (52-86), 12 (30.0%) patients presented a Karnofsky performance status (KPS) of <80%, and 34 (85%) presented with bone with or without nodal metastases. Median pre-treatment PSA was 192ng/dL (7-2696ng/dL). All patients were previously exposed to docetaxel, including 33 (82.5%) with docetaxel-refractory disease. PSA response rate was achieved in eight (20.0%) out of 40 patients. Additionally, PSA declines of ≥30% occurred in 14 (35.0%) patients. The median TTF was 3months (95% confidence interval 2.5-3.5). The treatment was well tolerated. Grade 3/4 lymphopenia was reported in 11 (27.5%) patients and was the only grade 3-4 toxicity reported. Metronomic oral CTX showed activity and safety in docetaxel-pretreated mCRPC patients. This regimen deserves further investigation in this setting.

A National Multicenter Phase 2 Study of Prostate-specific Antigen (PSA) Pox Virus Vaccine with Sequential Androgen Ablation Therapy in Patients with PSA Progression: ECOG 9802

BackgroundE9802 was a phase 2 multi-institution study conducted to evaluate the safety and effectiveness of vaccinia and fowlpox prostate-specific antigen (PSA) vaccine (step 1) followed by combination with androgen ablation therapy (step 2) in patients with PSA progression without visible metastasis. ObjectiveTo test the hypothesis that vaccine therapy in this early disease setting will be safe and have a biochemical effect that would support future studies of immunotherapy in patients with minimal disease burden. Design, setting, and participantsPatients who had PSA progression following local therapy were treated with PROSTVAC-V (vaccinia)/TRICOM on cycle 1 followed by PROSTVAC-F (fowlpox)/TRICOM for subsequent cycles in combination with granulocyte-macrophage colony-stimulating factor (step 1). Androgen ablation was added on progression (step 2). Outcome measurements and statistical analysisStep 1 primary end points included progression at 6 mo and characterization of change in PSA velocity pretreatment to post-treatment. Step 2 end points included PSA response with combined vaccine and androgen ablation. Results and limitationsIn step 1, 25 of 40 eligible patients (63%) were progression free at 6 mo after registration (90% confidence interval [CI], 48–75). The median pretreatment PSA velocity was 0.13 log(PSA)/mo, in contrast to median postregistration velocity of 0.09 log(PSA)/mo (p=0.02), which is an increase in median PSA doubling time from 5.3 mo to 7.7 mo. No grade ≥4 treatment-related toxicity was observed. In the 27 patients eligible and treated for step 2, 20 patients achieved a complete response (CR) at 7 mo (CR rate: 74%; 90% CI, 57–87). Although supportive of larger studies in the cooperative group setting, this study is limited by the small number of patients and the absence of a control group as in a phase 3 study. ConclusionsA viral PSA vaccine can be administered safely in the multi-institutional cooperative group setting to patients with minimal disease volume alone and combined with androgen ablation, supporting the feasibility of future phase 3 studies in this population. Patient summaryThese data support consideration of vaccine therapy earlier in the course of prostate cancer progression with minimal disease burden in future studies of vaccine approaches in earlier stages of disease.

Stereotactic body radiation therapy (SBRT) for prostate cancer in men with large prostates (≥50 cm(3)).

BackgroundPatients with large prostate volumes have been shown to have higher rates of genitourinary and gastrointestinal toxicities after conventional radiation therapy for prostate cancer. The efficacy and toxicity of stereotactic body radiation therapy (SBRT), which delivers fewer high-dose fractions of radiation treatment, is unknown for large prostate volume prostate cancer patients. We report our early experience using SBRT for localized prostate cancer in patients with large prostate volumes.Methods57 patients with prostate volumes ≥50 cm3 prior to treatment with SBRT for localized prostate carcinoma and with a minimum follow up of two years were included in this retrospective review of prospectively collected data. Treatment was delivered using Cyberknife (Accuray) with doses of 35–36.25 Gy in 5 fractions. Biochemical control was assessed using the Phoenix definition. Toxicities were scored using the CTCAE v.4. Quality of life was assessed using the American Urological Association (AUA) Symptom Score and the Expanded Prostate Cancer Index Composite (EPIC)-26.Results57 patients (23 low-, 25 intermediate- and 9 high-risk according to the D’Amico classification) at a median age of 69 years (range, 54–83 years) received SBRT with a median follow-up of 2.9 years. The median prostate size was 62.9 cm3 (range 50–138.7 cm3). 33.3% of patients received ADT. The median pre-treatment prostate-specific antigen (PSA) was 6.5 ng/ml and decreased to a median PSA of 0.4 ng/ml by 2 years (p <0.0001). A mean baseline AUA symptom score of 7.5 significantly increased to 13 at 1 month (p = 0.001) and returned to baseline by 3 months (p = 0.21). 23% of patients experienced a late transient urinary symptom flare in the first two years following treatment. Mean baseline EPIC bowel scores of 95.8 decreased to 78.1 at 1 month (p <0.0001), but subsequently improved to 93.5 three months (p = 0.08). The 2-year actuarial incidence rates of GU and GI toxicity ≥ grade 2 were 49.1% and 1.8%, respectively. Two patients (3.5%) experienced grade 3 urinary toxicity, and no patient experienced grade 3 gastrointestinal toxicity.ConclusionsSBRT for clinically localized prostate cancer was well tolerated in men with large prostate volumes.

The impact of PSA and digital rectal examination on the risk of prostate cancer specific mortality in men with a PSA level

IntroductionIt is unknown whether a normal range, diagnostic serum prostate specific antigen (PSA) level's influence on prostate cancer specific mortality (PCSM) is dependent upon digital rectal examination (DRE) findings. MethodsBetween 2004 and 2007, 9081 men diagnosed with non-palpable (T1c, N=1710) or palpable (T2–T4, N=7371) and non-metastatic prostate cancer (PC) were identified from surveillance, epidemiology, and end results data, selected based on pre-treatment PSA<2.5ng/ml. A multivariable competing risks regression model evaluated whether DRE findings interacted with PSA level in predicting risk of PCSM. ResultsAfter median follow-up of 2.83 years, 118 of 548 deaths (21.5%) were due to PC. Increasing diagnostic PSA was associated with increased risk of PCSM (AHR=3.52; 95% CI: 1.25–9.89; P=.017) in men with T1c, Gleason score 7–10 PC, but decreased PCSM risk (AHR=0.66; 95% CI: 0.52–0.83; P<.001) for men with T2–T4 PC and any Gleason score. DiscussionFor men with diagnostic PSA level <2.5ng/ml and palpable PC, risk of early PCSM increases by 34% for a 1 point decrease in PSA from 2. This suggests the existence of clinically detectable, low PSA secreting disease with an elevated risk of early PCSM, highlighting the importance of the DRE in men with PC and normal range, diagnostic PSA.

Outcomes of men with an elevated prostate-specific antigen (PSA) level as their sole preoperative intermediate- or high-risk feature.

To investigate the post-prostatectomy and long-term outcomes of men presenting with an elevated pretreatment prostate-specific antigen (PSA) level (>10 ng/mL), but otherwise low-risk features (biopsy Gleason score ≤6 and clinical stage ≤T2a). PSA-incongruent intermediate-risk (PII) cases were defined as those patients with preoperative PSA >10 and ≤20 ng/mL but otherwise low-risk features, and PSA-incongruent high-risk (PIH) cases were defined as men with PSA >20 ng/mL but otherwise low-risk features. Our institutional radical prostatectomy database (1992-2012) was queried and the results were stratified into D'Amico low-, intermediate- and high risk, PSA-incongruent intermediate-risk and PSA-incongruent high-risk cases. Prostate cancer (PCa) features and outcomes were evaluated using appropriate comparative tests. Multivariable analyses were adjusted for age, race and year of surgery. Of the total cohort of 17 608 men, 1132 (6.4%) had PII-risk disease and 183 (1.0%) had PIH-risk disease. Compared with the low-risk group, the odds of upgrading at radical prostatectomy (RP) were 2.20 (95% CI 1.93-2.52; P < 0.001) for the PII group and 3.58 (95% CI 2.64-4.85; P < 0.001) for the PIH group, the odds of extraprostatic disease at RP were 2.35 (95% CI 2.05-2.68; P < 0.001) for the PII group and 6.68 (95% CI 4.89-9.15; P < 0.001) for the PIH group, and the odds of positive surgical margins were 1.97 (95% CI 1.67-2.33; P < 0.001) for the PII group and 3.54 (95% CI 2.50-4.95, P < 0.001) for the PIH group. Compared with low-risk disease, PII-risk disease was associated with a 2.85-, 2.99- and 3.32-fold greater risk of biochemical recurrence (BCR), metastasis and PCa-specific mortality, respectively, and PIH-risk disease was associated with a 5.32-, 6.14- and 7.07-fold greater risk of BCR, metastasis and PCa-specific mortality, respectively (P ≤ 0.001 for all comparisons). For the PII group, the higher risks of positive surgical margins, upgrading, upstaging and BCR were dependent on PSA density (PSAD): men in the PII group who had a PSAD <0.15 ng/mL/g were not at higher risk compared with those in the low-risk group. Men in the PII group with a PSAD ≥0.15 ng/mL/g and men in the PIH group were more likely to have an anterior component of the dominant tumour (59 and 64%, respectively) compared with those in the low- (35%) and intermediate-risk group (39%) and those in the PII-risk group with PSAD <0.15 ng/mL/g (29%). Men with PSA >20 ng/mL or men with PSA >10 and ≤20 ng/mL with a PSAD ≥0.15 ng/mL/g, but otherwise low-risk PCa, are at greater risk of adverse pathological and oncological outcomes and may be inappropriate candidates for active surveillance. These men are at greater risk of having anterior tumours that are undersampled at biopsy, so if treatment is deferred, ancillary testing such as anterior zone sampling or magnetic resonance imaging should be strongly encouraged. Men with elevated PSA levels >10 and ≤20 ng/mL but low PSAD have outcomes similar to those in the low-risk group, and consideration of surveillance is appropriate in these cases.

Long-term outcomes from dose-escalated image-guided intensity-modulated radiotherapy with androgen deprivation: encouraging results for intermediate- and high-risk prostate cancer.

PurposeDose-escalated (DE) radiotherapy in the setting of localized prostate cancer has been shown to improve biochemical disease-free survival (bDFS) in several studies. In the same group of patients, androgen deprivation therapy (ADT) has been shown to confer a survival benefit when combined with radiotherapy doses of up to 70 Gy; however, there is currently little long-term data on patients who have received high-dose intensity-modulated radiotherapy (IMRT) with ADT. We report the long-term outcomes in a large cohort of patients treated with the combination of DE image-guided IMRT (IG-IMRT) and ADT.Methods and materialsPatients with localized prostate cancer were identified from a centralized database across an integrated cancer center. All patients received DE IG-IMRT, combined with ADT, and had a minimum follow up of 12 months post-radiotherapy. All relapse and toxicity data were collected prospectively. Actuarial bDFS, metastasis-free survival, prostate cancer-specific survival, and multivariate analyses were calculated using the SPSS v20.0 statistical package.ResultsSeven hundred and eighty-two eligible patients were identified with a median follow up of 46 months. Overall, 4.3% of patients relapsed, 2.0% developed distant metastases, and 0.6% died from metastatic prostate cancer. At 5-years, bDFS was 88%, metastasis-free survival was 95%, and prostate cancer-specific survival was 98%. Five-year grade 2 genitourinary and gastrointestinal toxicity was 2.1% and 3.4%, respectively. No grade 3 or 4 late toxicities were reported. Pretreatment prostate specific antigen (P=0.001) and Gleason score (P=0.03) were significant in predicting biochemical failure on multivariate analysis.ConclusionThere is a high probability of tumor control with DE IG-IMRT combined with androgen deprivation, and this is a technique with a low probability of significant late toxicity. Our long term results corroborate the safety and efficacy of treating with IG-IMRT to high doses and compares favorably with published series for the treatment of prostate cancer.

PREDICTORS OF SURVIVAL IN DISSEMINATED PROSTATE CANCER PATIENTS RECEIVING HORMONAL THERAPY

Background and objective. The division of patients with disseminated prostate cancer (PC) into prognostic groups may be potentially used for a differential approach to choosing the hormonal therapy (HT) option and regimen. This study was conducted to identify factors influencing survival, as well as prognostic groups in this category of patients. Subjects. The study enrolled 113 patients with verified cT2b–4N0–1M0–1 stage PC. Their median age was 70.0 ± 7.3 years. The median pretreatment prostate-specific antigen (PSA) concentration was 309.8 ng/ml. The stage cT2 was diagnosed in 12 (10.6 %) patients; cT3 was in 85 (75.2 %); cT4 in 16 (14.2 %); cN+ in 32 (28.3 %); М+ in 74 (65.5 %). The median baseline Gleason score was 3.0± 0.8 ± 4.0± 0.9 =7.0± 1.6. All the patients received emergency HT: castration was carried out in 2 (1.8 %) patients; maximum androgenic block and antiandrogen monotherapy were performed in 96 (85.0 %) and 15 (13.3 %), patients, respectively. The median follow-up was 31.9± 17.7 months. Results. Five-year progression-free, hormone-refractory prostate cancer-free, specific, and overall survivals (OS) were 29.7, 31.8, 39.3, and 26.0 %, respectively. Multivariate analysis has shown that OS is negatively influenced by the following factors: bone pain, stages cT4, М+, a nadir of PSA of  4 ng/ml (p < 0.05) and its baseline level of  100 ng/ml (р = 0.057). Good (no bone pain, a PSA level of < 100 ng/ml, сТ < T4, and М0) and poor (bone pain and/or a PSA level of  100 ng/ml, and/or stages cT4 and/or М+) prognostic groups were identified. The median OS in the groups was 39.8± 3.9 and 29.8± 4.2 months, respectively (р = 0.048). Conclusion. In disseminated PC, bone pain, a PSA level of 100 ng/ml, cT4 and M+, and a PSA nadir of  4 ng/ml are poor predictors of OS. The patients without these indicators belong to a good prognostic group; those have one sign or more do to a poor prognostic one.

Improved Outcomes with Advancements in High Intensity Focused Ultrasound Devices for the Treatment of Localized Prostate Cancer

We evaluated the association between long-term clinical outcomes and morbidity with high intensity focused ultrasound. We included patients with stage T1c-T3N0M0 prostate cancer who were treated with Sonablate® (SB) devices during 1999 to 2012 and followed for more than 2 years. Risk stratification and complication rates were compared among the treatment groups (ie SB200/500 group, SB500 version 4 group and SB500 tissue change monitor group). Primary study outcomes included overall, cancer specific and biochemical disease-free survival rates determined using Kaplan-Meier analysis (Phoenix definition). Secondary outcomes included predictors of biochemical disease-free survival using Cox models. A total of 918 patients were included in the study. Median followup in the SB200/500, SB500 version 4 and the SB500 tissue change monitor groups was 108, 83 and 47 months, respectively. The 10-year overall and cancer specific survival rates were 89.6% and 97.4%, respectively. The 5-year biochemical disease-free survival rate in the SB200/500, SB500 version 4 and SB500 tissue change monitor group was 48.3%, 62.3% and 82.0%, respectively (p < 0.0001). The overall negative biopsy rate was 87.3%. On multivariate analysis pretreatment prostate specific antigen, Gleason score, stage, neoadjuvant androgen deprivation therapy and high intensity focused ultrasound devices were significant predictors of biochemical disease-free survival. Urethral stricture, epididymitis, urinary incontinence and rectourethral fistula were observed in 19.7%, 6.2%, 2.3% and 0.1% of cases, respectively. Long-term followup of patients with high intensity focused ultrasound demonstrated improved clinical outcomes due to technical, imaging and technological advancements.

Prostate-specific antigen density predicts extracapsular extension and increased risk of biochemical recurrence in patients with high-risk prostate cancer who underwent radical prostatectomy.

Patients with advanced local-stage, high-grade prostate cancer (Pca) and high pretreatment prostate-specific antigen (PSA) levels have inferior outcomes compared to their counterparts with more favorable clinical characteristics. However, some patients exhibit favorable pathological features or experience long-term PSA-free survival after radical prostatectomy (RP). We retrospectively examined the ability of preoperative characteristics to predict pathological and oncological outcomes in high-risk Pca patients who underwent RP. We examined data of 1,268 consecutive Pca patients treated with RP alone at 4 hospitals from the Michinoku Urological Cancer Study Group database. Preoperative predictors included age, PSA level, biopsy Gleason score, clinical T stage, and PSA density (PSAD). The outcome measures pathological T stage and PSA-free survival were evaluated by multivariate analysis. We identified 380 high-risk Pca patients, of which 44 % patients had extracapsular extension. Logistic regression analysis indicated that PSAD was an independent predictor of adverse pathologic stage. The 5-year PSA-free survival rates were 82.9 % for patients with PSAD ≤0.468 ng mL(-1) cm(-2) and 50.7 % for those with PSAD >0.468 ng mL(-1) cm(-2) (P < 0.0001). Multivariate analyses revealed that PSAD, cT, and the number of preoperative high-risk Pca criteria were independent predictors of PSA-free survival. PSAD may be an independent predictor of advanced pathological features and biochemical recurrence in high-risk Pca patients treated with RP alone. PSAD may be used for further risk stratification of high-risk Pca patients.

Correlation of pretreatment clinical parameters and PSA nadir after high-intensity focused ultrasound (HIFU) for localised prostate cancer

To determine which pretreatment clinical parameters were predictive of a low prostate-specific antigen (PSA) nadir following high-intensity focused ultrasound (HIFU) treatment. Retrospective study of patients with clinically localised prostate cancer undergoing HIFU at a single centre between December 1997 and September 2009. Whole-gland treatment was applied. Patients also included if they had previously undergone transurethral resection of the prostate (TURP). TURP was also conducted simultaneously to HIFU. Biochemical failure based on Phoenix definition (PSA nadir + 2). Univariate and multivariate analysis of pretreatment clinical parameters conducted to assess those factors predictive of a PSA nadir ≤0.2 and >0.2 ng/ml. Mean (SD) follow-up was 6.2 (2.8) years; median (range) was 6.3 (1.1-12.2) years. Kaplan-Meier estimate of biochemical disease-free survival rate at 8 years was 83 and 48 % for patients achieving a PSA nadir of ≤0.2 and >0.2 ng/ml, respectively. Prostate volume and incidental finding of cancer were significant predictors of low PSA nadir (≤0.2 ng/ml). Prostate volume and incidental finding of cancer could be predictors for oncologic success of HIFU based on post-treatment PSA nadir.

Pretreatment Tables Predicting Pathologic Stage of Locally Advanced Prostate Cancer

BackgroundPretreatment tables for the prediction of pathologic stage have been published and validated for localized prostate cancer (PCa). No such tables are available for locally advanced (cT3a) PCa. ObjectiveTo construct tables predicting pathologic outcome after radical prostatectomy (RP) for patients with cT3a PCa with the aim to help guide treatment decisions in clinical practice. Design, setting, and participantsThis was a multicenter retrospective cohort study including 759 consecutive patients with cT3a PCa treated with RP between 1987 and 2010. InterventionRetropubic RP and pelvic lymphadenectomy. Outcome measurements and statistical analysisPatients were divided into pretreatment prostate-specific antigen (PSA) and biopsy Gleason score (GS) subgroups. These parameters were used to construct tables predicting pathologic outcome and the presence of positive lymph nodes (LNs) after RP for cT3a PCa using ordinal logistic regression. Results and limitationsIn the model predicting pathologic outcome, the main effects of biopsy GS and pretreatment PSA were significant. A higher GS and/or higher PSA level was associated with a more unfavorable pathologic outcome. The validation procedure, using a repeated split-sample method, showed good predictive ability. Regression analysis also showed an increasing probability of positive LNs with increasing PSA levels and/or higher GS. Limitations of the study are the retrospective design and the long study period. ConclusionsThese novel tables predict pathologic stage after RP for patients with cT3a PCa based on pretreatment PSA level and biopsy GS. They can be used to guide decision making in men with locally advanced PCa. Patient summaryOur study might provide physicians with a useful tool to predict pathologic stage in locally advanced prostate cancer that might help select patients who may need multimodal treatment.

Prostate-specific antigen decline during salvage radiation therapy following prostatectomy is associated with reduced biochemical failure

PurposeTo evaluate the prognostic value of prostate-specific antigen (PSA) decline during salvage radiation therapy (SRT) after prostatectomy. Methods and materialsWe reviewed an institutional database and identified all prostate cancer patients who were treated with SRT between the years 2003 and 2010, had at least 1 PSA measurement during their SRT course, and had no history of androgen deprivation therapy use prior to or during SRT. Disease characteristics, treatment information, and clinical outcomes data were tabulated for each patient. The PSA response during SRT was defined as a PSA decline of at least 0.2 ng/mL compared with the pretreatment PSA level. Bivariate and multivariate analyses using Cox proportional hazards modeling were performed to identify predictors of biochemical recurrence. ResultsSixty-four patients met eligibility criteria for this analysis. Median PSA before SRT was 0.63 ng/mL (interquartile range: 0.42-1.00). With a median follow-up time of 70 months after SRT, 5-year actuarial rates for biochemical control and metastasis-free survival were 61% (95% confidence interval [CI], 48%-75%) and 88% (95% CI, 79%-97%), respectively. The median number of PSA measurements per patient during SRT was 3 (range, 1-5). On bivariate analysis, PSA response during SRT and positive surgical margins were significantly associated with a decreased risk of biochemical recurrence (BR), with hazard ratios of 0.160 (95% CI, 0.059-0.431, P < .001) and 0.396 (95% CI, 0.168-0.935, P = .035). On multivariate analysis, PSA response during SRT and positive surgical margin were independent, favorable predictors for BR, with hazard ratios of 0.171 (95% CI, 0.063-0.463, P < .001) and 0.411 (95% CI, 0.177-0.956, P = .039). The 5-year biochemical control rate for PSA responders was 81%, compared with 37% for nonresponders (P < .001). ConclusionsProstate-specific antigen decline during SRT may be a valuable prognostic factor for subsequent clinical outcomes. Future studies should investigate the value of monitoring PSA during SRT and how PSA response may be used to personalize therapy.

An arranged marriage for precision medicine: hypoxia and genomic assays in localized prostate cancer radiotherapy

Prostate cancer (CaP) is the most commonly diagnosed malignancy in males in the Western world with one in six males diagnosed in their lifetime. Current clinical prognostication groupings use pathologic Gleason score, pre-treatment prostatic-specific antigen and Union for International Cancer Control-TNM staging to place patients with localized CaP into low-, intermediate- and high-risk categories. These categories represent an increasing risk of biochemical failure and CaP-specific mortality rates, they also reflect the need for increasing treatment intensity and justification for increased side effects. In this article, we point out that 30-50% of patients will still fail image-guided radiotherapy or surgery despite the judicious use of clinical risk categories owing to interpatient heterogeneity in treatment response. To improve treatment individualization, better predictors of prognosis and radiotherapy treatment response are needed to triage patients to bespoke and intensified CaP treatment protocols. These should include the use of pre-treatment genomic tests based on DNA or RNA indices and/or assays that reflect cancer metabolism, such as hypoxia assays, to define patient-specific CaP progression and aggression. More importantly, it is argued that these novel prognostic assays could be even more useful if combined together to drive forward precision cancer medicine for localized CaP.

Impact of obesity on outcomes after definitive dose escalated intensity modulated radiation therapy for localized prostate cancer.

50 Background: Multiple retrospective studies have investigated the association between body mass index (BMI) and biochemical failure (BF) after definitive external beam radiotherapy (EBRT) of localized prostate cancer (CaP) prior to the dose escalation era, with conflicting results. The purpose of this study is to determine whether increasing BMI is associated with CaP outcomes in patients treated with dose escalated radiotherapy. Methods: From 2000 to 2010, we identified 1,291 patients with localized (T1b-T4N0M0) CaP who were treated with definitive intensity modulated radiation therapy (IMRT). BMI was categorized using World Health Organization classification. Multivariable competing risk and Cox proportional hazards regression models were used to assess the risk of BF, distant metastasis (DM), cause-specific mortality (CSM) and overall mortality (OM). BF was defined as prostate-specific antigen (PSA) greater than or equal to nadir + 2 ng/mL. Covariates included age, androgen deprivation therapy (ADT), pre-treatment PSA (iPSA), Gleason score, and T stage. For OM, self-reported history of diabetes, heart disease, and hypertension were included. Results: Of the 1,291 patients identified, there were 20% normal (BMI&lt;25 kg/m2), 47% overweight (BMI 25-29.9), 23% obese class I (BMI 30-34.9), 6% obese class II (BMI 35-39.9), and 4% obese class III (BMI &gt;40). Median follow-up was 43.7 months (range 1.1-127) with median age of 68 (range 36 to 88). Median dose was 78 Gy (range 76-80) and 33% of patients received ADT. Increasing BMI was inversely associated with age (p&lt;0.0001) and iPSA (p=0.047). There were 128 BF, 51 DM, 15 CSM, and 119 OM. Risk of BF, CSM, and OM were increased for obese class II and III compared to normal (all p&lt;0.05). On multivariable analysis, for BF, HR was 2.1(p=0.057) for obese class II and 2.5 (p=0.043) for class III. For CSM, HR was 5.1 (p=0 .028) for class II and 5.15 (p=0.014) for class III. For OM, HR was 2.3 (p=0.022) for class II and 2.6(p=0.023) for class III. There was a trend toward increased DM for class III (p=0.057). Conclusions: For CaP patients receiving IMRT, those with higher levels of obesity may be at increased risk of BF and prostate cancer mortality, and should be considered for more aggressive treatment.

Prospective evaluation of low-dose ketoconazole plus hydrocortisone (HC) in chemotherapy-pretreated castration-resistant prostate cancer (CRPC) patients.

227 Background: Ketoconazole (keto), a known CYP17 inhibitor, is a traditional systemic treatment for CRPC. However, most of the published data has been in the pre-chemo setting; its efficacy in the post-chemo setting has not been as widely reported. Chemo-naive patients treated with attenuated doses of keto (200-300 mg TID) had prostate specific antigen (PSA) response rate (&gt; 50% decline) ranges from 21%-62% and treatment was well tolerated. We hypothesized that low dose keto would likewise possess efficacy and tolerability in the CRPC post-chemo state. Methods: CRPC patients with ECOG PS 0-3, adequate end organ function, who had received at least one chemo were treated with low-dose keto (200 mg PO TID) and HC (20 mg PO q AM and 10 mg PO q PM) until progression, as defined by either RECIST or PSA rise &gt; 50% from nadir or baseline. Primary endpoint was PSA response rate (&gt; 50% reduction from baseline). A Simon minimax design was used. PSA response of &gt; 25% was to be considered promising for further study (versus null rate of &lt; 5%); 25 patients were required. Secondary endpoints included PSA response &gt; 30%, progression-free survival (PFS), duration of stable disease, and evaluation of adverse events (AE). Results: 29 patients were accrued: median age was 71 (range 55-86) and median pretreatment PSA was 76 ng/mL (range 7-11,420 ng/ml); all had prior docetaxel-based chemotherapy. 28 patients were evaluable for response; all were evaluable for toxicity. PSA response of &gt;50% was seen in 48% of patients and 59% of patients had a PSA response of &gt; 30%. Median PFS was 138 days; median duration of stable disease was 123 days. 12 patients had grade 3 or 4 toxicity on treatment. Of the 17 grade 3 AEs, only 3 were considered ‘probably’ or ‘possibly’ related to treatment, while none of the 2 grade 4 AEs were considered related to treatment. Conclusions: In docetaxel pre-treated CRPC patients, low-dose keto + HC is a well-tolerated, relatively inexpensive and clinically active treatment option. PSA response with low-dose keto appears comparable to that of abiraterone in this patient context. A prospective randomized study of available post-chemo options is needed to assess comparative efficacy. Clinical trial information: NCT00895310.