Post-treatment Prostate-specific Antigen Levels Research Articles

The impact of the apparent diffusion coefficient for the early prediction of the treatment response after definitive radiotherapy in prostate cancer patients

PurposeWe assessed early changes in apparent diffusion coefficient (ADC) and serum prostate specific antigen (PSA) values after definitive radiotherapy (RT) without androgen deprivation treatment in low- and intermediate-risk prostate cancer (PC) patients. Materials and MethodsThe clinical data and ADC parameters of 229 PC patients were retrospectively evaluated. Pre-treatment and post-treatment serum PSA and primary tumor ADC values were calculated. Post-treatment DW-MRI was performed median 4.1 months after completion of definitive RT. The prognostic factors predicting freedom from biochemical failure (FFBF) and progression-free survival (PFS) were analyzed using univariable and multivariable analyses. ResultsWith a median follow-up time of 80.8 months, the 5-year FFBF and PFS rates were 95.9% and 89.3%, respectively. Eleven patients (4.8%) had PSA relapse, with a median of 34.4 months after the completion of RT. A statistically significant difference in post-treatment ADC values was noted between patients with and without recurrence (0.94 ± 0.07 vs. 1.10 ± 0.20 × 10-3 mm2/sec; p< 0.001). Patients with a Gleason score (GS) of 6 and low-risk disease had significantly higher post-treatment tumor ADC and PSA levels than patients with a GS of 7 and intermediate-risk disease. The 5-year FFBF rate in patients with tumor ADC ≤ 0.96 × 10-3 mm2/sec was significantly lower than patients with tumor ADC > 0.96 × 10-3 mm2/sec (85.5% vs. 100; p< 0.001). In the multivariable analysis, a lower ADC value, GS 4 + 3 and intermediate-risk disease were independent predictors of worse FFBF. In the multivariate analysis, a lower post-treatment ADC value and a GS of 4 + 3 were significant prognostic factors for a lower PFS. ConclusionThese findings suggest that the post-treatment tumor ADC value could be used for early treatment response evaluation after definitive RT in PC patients.

Proton Therapy for Localized Prostate Cancer: Long-Term Clinical Outcomes at a Comprehensive Cancer Center

<h3>Purpose/Objective(s)</h3> To assess the effectiveness and toxicity of proton therapy for patients with localized prostate cancer at a comprehensive cancer center. <h3>Materials/Methods</h3> Patients (n=2773) participating in two prospective clinical trials were treated from May 2006 through January 2020 at a comprehensive care center and stratified according to the National Comprehensive Cancer Network guidelines (n=640 low-risk [LR], n=850 favorable-intermediate risk [F-IR], n=851 unfavorable-intermediate risk [U-IR], n=315 high risk [HR], and n=117 very high risk [VHR]). Median patient age was 66 years; median follow-up time was 7.0 years. Median prostate-specific antigen (PSA) level at 7 years was 0.3 ng/mL (interquartile range [IQR] 0.2–0.4). Pelvic lymph node irradiation was given to 29 of 2773 patients (1%) (2/851 [0.2%] U-IR, 11/315 [3.5%] HR, and 16/117 [13.7%] VHR). The median PT dose was 78 Gy in 1.8–2.0 Gy(RBE) per fraction; 63% of patients received 78 Gy(RBE) in 39 fractions, and 29% received 76 Gy(RBE) in 38 fractions. Androgen deprivation therapy (ADT) was used in 1471 patients (53%) (68/640 [10.6%] LR, 329/850 [38.7%] F-IR, 642/851 [75.4%] U-IR, 315/315 [100%] HR, and 117/117 [100%] VHR), with a median duration of 6 months for U-IR and 24 months for HR and VHR groups. Biochemical failure was defined as post-treatment nadir PSA level + 2 ng/mL. Toxicity was graded according to the modified RTOG/EORTC morbidity scale. Descriptive statistics and Kaplan-Meier estimates were used to assess toxicity and survival. <h3>Results</h3> Freedom from biochemical relapse (FFBR) rates at 5 and 10 years were 98.3% (95% confidence interval [CI] 96.9-99.1%) and 97% (95% CI 94.8-98.3%) for the LR group; 98.3% (95% CI 97.0-99.0%) and 93.6% (95% CI 90.6-95.7%) for the F-IR; 94.2% (95% CI 92.1-95.7%) and 90.2% (95% CI 87.3-92.5%) for the U-IR; 94.3% (95% CI 90.1-96.8%) and 85.2% (95% CI 77.1-90.8%) for the HR; and 86.1% (95% CI, 74.7-92.9%) and 68.5% (95% CI, 50.9-82.1%) for the VHR group. Two patients died of prostate cancer, one VHR (at 19.5 months) and the other U-IR (at 28.5 months). The overall rate of acute grade ≥3 genitourinary (GU) toxicity was 6/2773 (0.22%). The overall rates of late grade ≥3 GU and gastrointestinal (GI) toxicities were 23/2773 (0.83%) and 26/2773 (0.94%). Maximum toxicities experienced were grade 4 acute GU in 1 patient, grade 4 late GU in 2 patients, and grade 4 late GI in 6 patients. <h3>Conclusion</h3> Long-term clinical outcomes for men treated with proton therapy for localized prostate cancer were excellent in all risk groups. The benefits of pelvic lymph node radiation therapy may be greatest in the VHR group, whereas the benefits of ADT may be highest in the U-IR, HR, and VHR groups.

How long is long enough to secure disease control after low-dose-rate brachytherapy in combination with other modalities in intermediate-risk, localized prostate cancer?

Previous studies have demonstrated excellent overall outcomes in patients who underwent low-dose-rate brachytherapy (LDR-BT) in intermediate-risk, localized prostate cancer (PCa). We thus investigated the appropriate length of time before completing prostate-specific antigen (PSA) monitoring after treatment. Between 2003 and 2014, 710 localized, intermediate-risk PCa patients underwent LDR-BT with or without supplemental external beam radiotherapy (EBRT). Data from 567 of those patients was analyzed in this study. Neoadjuvant hormonal therapy (NHT) was administered to 315 patients (55.6 %) and NHT with adjuvant hormonal therapy (AHT) to 59 patients (10.4 %), as per the protocol of a prospective randomized controlled trial (SHIP0804). We stratified patients by posttreatment PSA levels at specific times and assessed the factors for association with biochemical recurrence (BCR) and for clinical progression (CP). The median follow-up was 109 months (range, 60-205 months). Of 529 patients who were BCR-free at 3 years after treatment, 56 subsequently developed BCR, and 47 developed CP. PSA at 3 and 5 years after treatment were significantly correlated with long-term oncological outcomes. No patients with 5-year PSA levels ≤0.1 ng/mL subsequently developed BCR or CP. Discontinuation of PSA monitoring could be discussed with patients with intermediate-risk PCa as a reasonable option if PSA levels remain ≤0.1 ng/mL at 5 years after LDR-BT, either alone or with other combined modalities, as subsequent recurrences are quite rare.

CRISP3 glycoprotein: a good biomarker for prostate cancer?

ABSTRACT Introduction: Cysteine-rich secretory protein 3 (CRISP3) is expressed at low levels in normal human prostate but often overexpressed in prostate cancer (PCa). The relevance of this overexpression for the malignancy of PCa is still unclear. The prognostic value of the currently used prostate specific antigen (PSA) test can be misleading under certain circumstances, resulting in overtreatment of indolent tumors. New biomarkers are needed to reduce overtreatment and improve quality of life of men. Objective: Evaluate if CRISP3 expression could be a good biomarker for PCa. Methods: CRISP3 expression was determined by immunohistochemistry in tissue sections of prostate cancer from twenty-five patients subjected to radical prostatectomy. Gleason grading system was used as prognostic indicator and the staging of PCa was defined using the TNM system. Clinical parameters and PSA levels before and after surgery were determined. Results: CRISP3 expression was strong in 14 (56%), moderate in four (16%) and weak in seven (28%) specimens. There was no correlation between the intensity of CRISP3 expression and pre- and post-treatment PSA levels. Fifteen (60%) of PCa biopsies showed extension of the primary tumor pT2. Seven patients (28%) showed Gleason score higher than 7; thirteen (52%) equal to 7, and five (20%) lower than 7. There were no significant statistical differences between Gleason score and CRISP3 expression. Conclusion: CRISP3 is expressed in prostate cancer at different levels. Additional studies are required to better evaluate if CRISP3 could be used as a biomarker.

Localization and restaging of carcinoma prostate by 68Gallium prostate-specific membrane antigen positron emission tomography computed tomography in patients with biochemical recurrence.

Introduction:Radical prostatectomy (RP) and radical radiotherapy (RT) are well established primary curative options for localized prostate cancer. Despite technical improvements, prostate-specific antigen (PSA)-recurrence after RP and RT is a common clinical scenario. We aimed to assess the role of 68Gallium (68Ga) prostate-specific membrane antigen positron emission tomography computed tomography (PSMA PET/CT) in patients with biochemical recurrence of prostate cancer after RP or RT for the detection and localization recurrent and metastatic disease.Materials and Methods:We ambispectively (70 retrospective and 100 prospective) analyzed the data of men with biochemical recurrence post-RP and post-RT who were evaluated by 68Ga PSMA PET/CT at our institute. We aimed to assess the relationship between serum PSA levels and the probability of having a positive scan in patients with recurrent prostate cancer.Results:The study included 170 men, all had adenocarcinoma of the prostate, 124/170 had previous RP and 46/170 had prior RT. The median serum PSA in the RP group was 1.8 ng/ml and 5.2 ng/ml in the RT group. In the post-RP cohort, the detection rate of 68Ga PSMA PET/CT was 39.3% for PSA 0.2 to <0.5 ng/ml, 47.3% for PSA 0.5 to <1 ng/ml, 68.4% for PSA 1 to <2 ng/ml and 93.1% for PSA ≥2 ng/ml. In the post-RT group, the detection rate was 88.8% for PSA 2 to <4 ng/ml and 100% for PSA ≥4 ng/ml.Conclusions:68Ga PSMA PET/CT provides a novel imaging modality for the detection of prostate cancer recurrence and metastases at low posttreatment PSA levels, which may help in directing appropriate salvage treatments.

Prognostic Association of Prostate-specific Antigen Decline with Clinical Outcomes in Men with Metastatic Castration-resistant Prostate Cancer Treated with Enzalutamide in a Randomized Clinical Trial

BackgroundIn the PREVAIL study, enzalutamide provided significant improvements versus placebo in clinical outcomes in chemotherapy-naïve men with metastatic castration-resistant prostate cancer (mCRPC). The association of post-treatment prostate-specific antigen (PSA) decline with clinical outcomes may provide important prognostic information. ObjectiveTo evaluate associations between the magnitude of PSA decline from baseline to month 3 and clinical outcomes among enzalutamide recipients. Design, setting, and participantsThis was a post hoc retrospective analysis of PREVAIL, an international, randomized, double-blind, placebo-controlled phase 3 study. Men with mCRPC and no prior chemotherapy from the enzalutamide arm were included (n=872). Patients were grouped by confirmed maximal PSA decline from baseline to month 3 of treatment (n=795 evaluable). Outcome measurements and statistical analysisPrimary outcomes were overall survival and radiographic progression-free survival. Secondary outcomes included PSA progression-free survival, radiographic response, and degradation of Functional Assessment of Cancer Therapy-Prostate score, which were estimated using the Kaplan-Meier method. Results and limitationsFollowing 3mo of enzalutamide treatment, 88% (701/795), 80% (639/795), and 39% (307/795) of patients had postbaseline confirmed maximal PSA declines of ≥30%, ≥50%, and ≥90%, respectively, whereas 12% (94/795) had no confirmed maximal PSA decline or a decline of <30%. Greater degrees of PSA decline within the first 3mo of enzalutamide treatment were increasingly associated with longer overall survival, time to PSA and radiographic progression, higher objective soft-tissue responses, and longer time to quality-of-life deterioration than no PSA decline or declines of <30% from baseline. PSA flares (rise followed by fall) after enzalutamide treatment were rare (<1%). ConclusionsThe magnitude of PSA decline after 3mo of enzalutamide therapy was strongly associated with better clinical and patient-reported outcomes. This updated prognostic information is of clinical value to this patient population and their health care providers. Patient summaryWe report that decreases in PSA levels are closely linked to better health and survival after 3mo of enzalutamide treatment in men with metastatic prostate cancer.The PREVAIL trial is registered at clinicaltrials.gov as NCT01212991.

Early PSA Kinetics for Low- and Intermediate-Risk Prostate Cancer with Favorable Treatment Response Treated with HDR Brachytherapy, SBRT, Hfrt, and Cfrt

It is not well understood how the various modern radiation techniques influence post-treatment prostate specific antigen (PSA) kinetics. We examine initial PSA kinetics with a decay rate model to determine how to assess treatment response for patients treated with HDR, SBRT, hypofractionated (HFRT), and conventionally fractionated IMRT (CFRT). This retrospective study uses a prospective database at a single institution. We included patients with low or intermediate risk prostate cancer (T1-T2; GS 6 or 7; PSA < 20 ng/mL), treated without androgen deprivation therapy between 2002 and 2017, and free from biochemical failure per Phoenix criteria. Only patients with at least 2 PSA measurements in the first 2 years of follow-up were included. Treatment techniques included HDR, SBRT, HFRT (70.2 Gy in 2.7 Gy/fx) and CFRT. Pre-treatment PSA (iPSA) obtained within 90 days of RT start. Time to nadir was measured from RT completion date. iPSA was compared to PSA levels at subsequent follow ups at 6-month intervals. PSA decay rate was modeled using longitudinal regression analysis with generalized estimating equation (GEE) methods to adjust for within patient correlations; we considered the influence of age, Gleason Score (GS), iPSA, and T-stage on decay rates in multivariable models. PSA half-life, i.e. time for PSA to drop to 50% of a given time period’s initial PSA, was estimated from decay rate coefficients. A shorter follow-up for SBRT and HDR cohorts limited analysis to a 2-year interval. Of 628 patients in this study, 81 received HDR, 65 SBRT, 67 HFRT, and 415 CFRT. Patients receiving HDR and SBRT more frequently were younger and had lower T-stage, while CFRT patients were more likely to have higher iPSA and GS 4+3. In the first year of follow-up, lowest PSA levels, as absolute value (ng/mL) and relative to iPSA (PSA%), were lower among HFRT (1.1, 16%) and CFRT (1.0, 17%) when compared with SBRT (1.8, 29%) and HDR (1.4, 26%) (p=0.056). PSA half-lives during the 1-year interval were also shorter among HFRT and CFRT when compared with SBRT and HDR, 4.2 and 4.1 months for CFRT and HFRT compared with 5.4 and 5.3 months for SBRT and HDR (p=0.015). Using PSA measured within a 2-year interval, both absolute PSA and relative to iPSA values were lowest in HFRT (0.58, 9%) and CFRT (0.51, 10%) when compared with SBRT (1.5, 24%) and HDR (1.1, 23%) (p=0.015). However, PSA half-lives within the 2-year interval did not differ between all four treatments (p=0.22). Notably, HDR and SBRT decay rates did not significantly differ at either follow-up interval (p=0.84). Based on PSA decay modeling, adjusting for within patient correlations, both HFRT and CFRT show more rapid early PSA response within 1 year compared to HDR and SBRT. At the 2-year interval PSA decay rates are similar among all four treatments.

Effect of Patient Demographic Characteristics and Radiation Timing on PSA Reduction in Patients Treated With Definitive Radiation Therapy for Prostate Cancer

IntroductionThe purpose of this study was to assess how demographic characteristics and temporal factors including time to treatment (TTT) and elapsed time of treatment (ETT) affect prostate-specific antigen (PSA) levels during and after radiation treatment for low- and intermediate-risk prostate cancer. Patients and MethodsA retrospective review of 1584 patients was conducted on patients diagnosed with prostate cancer between 2005 and 2013, from which 147 patients were found to have completed definitive external beam radiation therapy (EBRT) monotherapy. Demographic data, TTT (days between diagnosis and EBRT start date), ETT (days between EBRT start and stop date), and Gleason score were collected on these patients and analysis of variance was performed to analyze the relationship of these factors with PSA changes. PSA changes were calculated during treatment as the difference between pre- and posttreatment PSA levels and after treatment as 3-year and overall PSA velocities. ResultsPatients who spoke Haitian Creole (P = .039) and those with a longer ETT (P = .029) had significantly greater PSA decline during treatment, primarily as a result of higher pretreatment PSA levels. Patients with Gleason score 4+3 disease had significantly greater 3-year (P = .033) and overall (P = .019) PSA velocities. Race and/or ethnicity, insurance type, marital status, and age were not associated with any PSA variable. ConclusionDisparities in prostate cancer are not reflected in PSA dynamics during or after radiation treatment, but are evident in PSA level at presentation. Timeliness of treatment was not found to affect true PSA change due to EBRT in low- and intermediate-risk prostate cancer patients.

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 specific antigen. Current clinical application and future prospects.

Prostate-specific antigen (PSA) is a glycoprotein produced by the prostate gland and its production can be enhanced in benign and malignant diseases. The introduction of PSA testing has greatly increased the detection of prostate cancer. However there is continuing controversy and confusion over the most appropriate application of the PSA test. PubMed and Web of Science databases were used to search original and review articles on the historical aspects, clinical utilization and possible future directions in PSA. After its discovery, PSA was quickly established as an exquisitely sensitive tumor marker for prostate cancer detection, assessment of treatment responses and follow-up among patients with prostate cancer. Nevertheless, controversy exists about the proper threshold for recommending prostate biopsy. If this limit is lowered to improve the sensitivity even more, patients with low-risk prostate cancer would be subsequently detected. Post-treatment PSA levels can certainly provide valuable information about the effectiveness of the therapy given. Recently introduced ultrasensitive PSA detection techniques are offering new insight into the changes in serum PSA at very low concentrations. This has resulted in identification of valuable postoperative prognostic variables together with the possibility of earlier cancer relapse detection. The development of assays that may show superior sensitivity and specificity in prostate cancer diagnosis is focused on proteins possibly complexed with PSA and other potential markers detectable both in serum and urine. The goal of newly discovered prostate cancer biomarkers is greater cancer specificity in order to reduce the overdiagnosis, overtreatment and financial cost.

Prostate-Specific Antigen Kinetics under Androgen Deprivation Therapy and Prostate Cancer Prognosis

Objectives: To compare the difference in characteristics of post-treatment prostate-specific antigen (PSA) kinetics among respective patients and their influence on disease prognosis. Methods: A cohort of totally 332 eligible patients with histologically confirmed and hormonally naïve prostate cancer, identified from the patients' database of Huashan Hospital, all received combined androgen deprivation therapy including bilateral orchiectomy or luteinizing hormone-releasing hormone antagonists with the oral administration of flutamide 250 mg t.i.d. All patients had their serum PSA level tested at least every 3 months in the first 2 years and at least once a half year from the third year on. PSA nadir, time to PSA nadir (TTPN), PSA normalization (<4 ng/ml), undetectable PSA level (<0.2 ng/ml), biochemical failure, overall survival and cancer-specific survival were analyzed. Results: PSA normalization, TTPN, and reaching the undetectable PSA level perhaps were the independent risk factors for predicting the three types of prognosis. Probably the best cut-off of PSA nadir was 0.2 ng/ml (sensitivity 65.7%, specificity 80.6%) and the best cut-off of TTPN was 10 months (sensitivity 71.6%, specificity 63.9%). Conclusions: These results implied that a lower level of PSA nadir and longer TTPN can predict a better disease prognosis.

Miliary Tuberculosis Following Transrectal Ultrasonography (TRUS)-Guided Prostate Biopsy

Miliary tuberculosis (TB) after transrectal ultrasonography (TRUS)-guided prostate biopsy is an extremely rare complication. A 75-year-old patient who presented with high fever and cough following TRUS-guided prostate biopsy for his high serum prostate-specific antigen (PSA) level (13.104 ng/ml) was diagnosed with miliary TB after clinical, laboratory, and radiological assessments. Histopathological examination of the prostate revealed TB with acid-fast bacilli. He was treated with chemotherapy for 9 months. The patient is now symptom-free, and his post-treatment PSA level was 5.023 ng/ml. This case is reported to acknowledge the possibility that miliary TB can occur as a complication of prostate biopsy if the patient suffers from prostate TB.

High-Risk Prostate Cancer With Gleason Score 8–10 and PSA Level ≤15 ng/ mL Treated With Permanent Interstitial Brachytherapy

With widespread prostate-specific antigen (PSA) screening, there has been an increase in men diagnosed with high-risk prostate cancer defined by a Gleason score (GS) ≥8 coupled with a relatively low PSA level. The optimal management of these patients has not been defined. Cause-specific survival (CSS), biochemical progression-free survival (bPFS), and overall survival (OS) were evaluated in brachytherapy patients with a GS ≥8 and a PSA level ≤15 ng/mL with or without androgen-deprivation therapy (ADT). From April 1995 to October 2005, 174 patients with GS ≥8 and a PSA level ≤15 ng/mL underwent permanent interstitial brachytherapy. Of the patients, 159 (91%) received supplemental external beam radiation, and 113 (64.9%) received ADT. The median follow-up was 6.6 years. The median postimplant Day 0 minimum percentage of the dose covering 90% of the target volume was 121.1% of prescription dose. Biochemical control was defined as a PSA level ≤0.40 ng/mL after nadir. Multiple parameters were evaluated for impact on survival. Ten-year outcomes for patients without and with ADT were 95.2% and 92.5%, respectively, for CSS (p = 0.562); 86.5% and 92.6%, respectively, for bPFS (p = 0.204); and 75.2% and 66.0%, respectively, for OS (p = 0.179). The median post-treatment PSA level for biochemically controlled patients was <0.02 ng/mL. Multivariate analysis failed to identify any predictors for CSS, whereas bPFS and OS were most closely related to patient age. Patients with GS ≥8 and PSA level ≤15 ng/mL have excellent bPFS and CSS after brachytherapy with supplemental external beam radiotherapy. The use of ADT did not significantly impact bPFS, CSS, or OS.

18F-choline PET/CT imaging of RECIST measurable lesions in hormone refractory prostate cancer

Apply measurability criteria based on the response evaluation criteria in solid tumors (RECIST) to lesions found on (18)F-choline positron emission tomography (PET)/computerized tomography (CT) in patients with hormone refractory prostate cancer. Whole-body PET followed by CT or in-line PET/CT using 3.3-4 MBq/kg of (18)F-choline was performed prospectively on 30 patients with prostate cancer, castrate testosterone levels, and rising post-treatment prostate specific antigen (PSA) levels. Lesions demonstrating increased (18)F-choline uptake were classified as measurable or non-measureable based on RECIST. Three patients were known previously to have RECIST measurable lesions, 10 patients had metastatic findings on radionuclide bone scan, and 17 patients had elevated serum PSA level as the only evidence of disease. Lesions demonstrating increased (18)F-choline uptake were found in 28 (93%) patients. Thirty-eight PET/CT lesions from 14 patients were measurable by RECIST. Lymph node maximum standardized uptake value (SUV(max)) correlated with lymph node diameter (Pearson r = 0.44, p < 0. 001). RECIST measurable lymph node SUV(max) was significantly higher than that of non-measurable nodes (8.1 vs. 3.7, p < 0.0001). Detection of skeletal, prostatic, or RECIST-compatible lesions was more likely with a PSA level greater than 4.0 ng/ml (Fisher exact p = 0.0005). Lesions detected with (18)F-choline PET/CT are frequently measurable by RECIST at baseline. Therefore, it may be feasible to include comparisons to RECIST in evaluations of (18)F-choline as a therapeutic response marker for hormone refractory prostate cancer.

Postradiotherapy 2-Year Prostate-Specific Antigen Nadir as a Predictor of Long-Term Prostate Cancer Mortality

To report the influence of posttreatment prostate-specific antigen (PSA) nadir response at 2 years after external beam radiotherapy (RT) on distant metastases (DM) and cause-specific mortality (CSM). Eight hundred forty-four patients with localized prostate cancer were treated with conformal RT. The median duration of follow-up was 9.1 years. A fixed landmark time point at 2 years was used to assess the influence of nadir PSA value as a time-dependent variable on long-term outcomes. Multivariate analysis demonstrated that nadir PSA <or=1.5 ng/mL at the landmark was an independent predictor of progression-free survival after adjusting for T stage, Gleason score, pre-RT PSA value, and RT dose (p = 0.03). The 5- and 10-year cumulative incidences of DM were 2.4% and 7.9%, respectively, in those with nadir PSA levels <or=1.5 ng/mL at the 2-year landmark, and were 10.3% and 17.5%, respectively, in patients with higher nadir values. Multivariate analysis showed that the higher nadir PSA value at the 2-year landmark (p = 0.002), higher Gleason scores (p < 0.001), and increasing T stage (p = 0.03) were predictors of DM after adjusting for pre-RT PSA values and RT dose. Multivariate analysis also showed that higher Gleason scores (p = 0.002), and higher nadir PSA values at the 2-year landmark (p = 0.03) were risk factors associated with CSM after adjusting for T stage and pre-RT PSA value. Nadir PSA values of <or=1.5 ng/mL at 2 years after RT for prostate cancer predict for long-term DM and CSM outcomes. Patients with higher absolute nadir levels at 2 years after treatment should be evaluated for the presence of nonresponding disease, and earlier salvage treatment interventions should be considered.

Interval to Biochemical Failure Highly Prognostic for Distant Metastasis and Prostate Cancer-Specific Mortality After Radiotherapy

Few biochemical parameters have been related to mortality. The present study examined the clinical utility of the interval to biochemical failure (IBF) as a prognostic factor for distant metastasis (DM) and prostate cancer-specific mortality (PCSM) after radiotherapy. The study group consisted of 211 T1c-T3Nx-N0M0 patients who had experienced BF among 1,174 men treated with three-dimensional conformal radiotherapy alone. Biochemical failure was defined as a post-treatment prostate-specific antigen (PSA) level of at, or greater than, the PSA nadir plus 2 ng/mL. Cox proportional hazards modeling was used to identify independent predictors of DM and PCSM on multivariate analysis. An IBF of <18 months was independently predictive for DM (p = 0.008), as was a Gleason score of 7-10 (p = 0.0005), PSA nadir >or=2 ng/mL (p = 0.04), and decreasing radiation dose (p = 0.02) on multivariate analysis, including increasing pretreatment PSA level, PSA nadir >or=2.5 ng/mL, PSA doubling time of <3 months, and Stage T3 disease. An IBF of <18 months was the only predictor of PCSM (p = 0.0003) in the same model. The actuarial 5-year DM rate for an IBF of <18 vs. >or=18 months was 52% vs. 20% (p < 0.0001), and the actuarial PCSM rate was 36% vs. 6%, respectively (p = 0.0001). The IBF is an important descriptor of the PSA kinetics after radiotherapy to identify men at high risk of clinical failure and death. A IBF of <18 months could aid in selecting men for early, aggressive salvage therapy or participation in a clinical trial.

Biochemical and clinical significance of the posttreatment prostate‐specific antigen bounce for prostate cancer patients treated with external beam radiation therapy alone

The posttreatment prostate-specific antigen (PSA) bounce phenomenon has been recognized in at least 20% of all patients treated with radiation. The purpose of the current report was to determine if there was a difference in biochemical and clinical control between the bounce and nonbounce (NB) patients using pooled data on 4839 patients with T1-2 prostate cancer treated with external beam radiation therapy (RT) alone at 9 institutions between 1986 and 1995. The median follow-up was 6.3 years. A posttreatment PSA bounce was defined by a minimal rise of 0.4 ng/mL over a 6-month follow-up period, followed by a drop in PSA level of any magnitude. Endpoints included no biochemical evidence of disease (bNED) failure (BF) (ASTRO definition), distant failure (DF), cause-specific failure (CSF), and overall survival (OS). Patients were stratified by pretreatment PSA, Gleason score, T stage, age, dose, and risk group. In all, 978 (20%) patients experienced at least 1 posttreatment PSA bounce. Within 3 subgroups (risk group, pretreatment PSA, and age), statistically significant differences of remaining bounce-free were observed on univariate analysis. Patients < 70 years had a 72% chance of remaining bounce-free at 5 years compared with 75% for older patients (P = .04). The NB patients had 72% bNED control at 10 years compared with 58% for the bounce patients. The effect of a bounce remained statistically significant on multivariate analysis (P < .0001). No statistically significant difference in DF, CSF, or OS was observed. Patients treated with external beam radiation therapy alone who experience a posttreatment PSA bounce have increased risk of BF. However, this did not translate into a difference in clinical failure with the available follow-up in the current study.

PSA bounces after brachytherapy HDR and external beam radiation therapy for prostate cancer

Summary Background The serum prostate-specific antigen (PSA) test is the most commonly used method for confirming response of prostate cancer after definitive radiation therapy (RT). PSA levels are expected to decrease after radiotherapy but usually remain detectable. Three consecutive PSA rises above the post-treatment nadir have been defined as biochemical failure by the ASTRO consensus panel [1]. Rising serum PSA concentration after RT does not always indicate treatment failure. Some patients have a temporary PSA spike, usually within 12–30 months of radiation therapy [2–4]. Most PSA bounces have a magnitude of 1.0 ng/mL or less. This observation was first described by Wallner and colleagues in 1997 [5]. Although this phenomenon is a source of anxiety for both the patient and the physician, its relevance to biochemical failure is controversial. Aim To determine the clinical and dosimetric factors that predict prostate-specific antigen (PSA) bouncing following brachytherapy HDR and three-dimensional conformal radiation therapy (3D-CRT) for prostate cancer patients. Materials/Methods The evaluated population consisted of 71 hormone-naive patients with a minimum of 2 years of follow-up and at least 6 post-treatment PSA levels. All patients were treated using 3D-CRT combined with brachytherapy HDR. A bounce was defined as a PSA rise of ≥0.2 ng/mL above the nadir followed by a subsequent 120 decline of ≥0.2 ng/mL. Clinical factors evaluated included: patient age, Gleason score, maximum initial pretreatment PSA value (iPSAmax), clinical stage, prostate volume, median time to PSA nadir, median PSA nadir value and patient follow-up in months. Dosimetric factors evaluated included the percentage of the prostate volume receiving 100% (V100), 150% (V150) and 200% (V200) of the prescribed minimal peripheral dose. Results Statistically significant predictive factors for PSA bounce were age, V100, V150, V200, iPSAmax and median time to PSA nadir. Logistic regression model for multivariate analysis revealed that only age, iPSAmax and V200 were statistically significant predictors for PSA bounce. There were no statistical differences between median nadir among patients who exhibited a PSA bounce and those who did not, but non-bouncers reached PSA nadir earlier than bouncers; median time was 12.1 vs 17.2 months respectively. Conclusion PSA bouncing occurs in approximately one third (1/3) of patients treated with 3D-CRT and brachytherapy HDR. Bouncing is associated with age, higher pretreatment PSA level and increased V200 factor.

Prognostic significance of perineural invasion on biochemical progression-free survival after prostate brachytherapy

Objectives To evaluate the influence of perineural invasion (PNI) in the biopsy specimen on biochemical progression-free survival in hormone-naive patients with prostate cancer undergoing brachytherapy. Methods A total of 512 consecutive hormone-naive patients (173 low risk, 212 intermediate risk, and 127 high risk) underwent brachytherapy for clinical Stage T1b-T2cNxM0 (2002 American Joint Committee on Cancer staging system) prostate cancer. No patient underwent seminal vesicle or pathologic lymph node staging. All patients had undergone brachytherapy at least 3 years before analysis. The median follow-up was 5.3 years. Biochemical progression-free survival was defined by a prostate-specific antigen (PSA) cutpoint of 0.4 ng/mL or less after nadir and by the American Society for Therapeutic Radiology and Oncology consensus definition. PNI was defined as carcinoma tracking along, or around, a nerve within the perineural space. Results PNI was documented in 133 patients (26.0%). For both biochemical progression-free definitions, 94.0% and 94.9% of patients with and without PNI, respectively, remained free of biochemical progression. The median time to failure in patients with and without PNI was 17.2 and 17.9 months, respectively. For the biochemically disease-free cohort, the median posttreatment PSA level was less than 0.1 ng/mL. On univariate Cox regression analysis, the pretreatment PSA level, percentage of positive biopsies, prostate volume, and Gleason score predicted for biochemical outcome. PNI did not approach statistical significance ( P = 0.671). On multivariate analysis, only pretreatment PSA ( P <0.001) and the percentage of positive biopsies ( P <0.001) maintained statistical significance. Conclusions In hormone-naive brachytherapy patients implanted with generous periprostatic treatment margins, the presence of PNI in the biopsy specimen did not adversely affect 8-year biochemical progression-free survival.

Defining biochemical failure after radiotherapy with and without androgen deprivation for prostate cancer

To compare several characteristics of alternative definitions of biochemical failure (BF) in men with extended follow-up after radiotherapy (RT) with or with androgen deprivation therapy (ADT) for prostate cancer. From December 1, 1991, to April 30, 1998, 688 men with Stage T1c-T3NX-N0M0 prostate cancer received RT alone (n = 586) or RT plus ADT (n = 102) with a minimal follow-up of 4 years and five or more "ADT-free" posttreatment prostate-specific antigen levels. BF was defined by three methods: (1) the ASTRO definition (three consecutive rises in prostate-specific antigen level); (2) a modified American Society for Therapeutic Radiology Oncology (ASTRO) definition requiring two additional consecutive rises when a decline immediately subsequent to three consecutive rises occurred; and (3) the "Houston" or nadir plus 2-ng/mL definition (a rise of at least 2 ng/mL greater than the nadir). The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy were determined for each using clinical progression as the endpoint. Furthermore, the misclassification rates for a steadily rising prostate-specific antigen level, ability to satisfy the proportional hazards (RT with or without ADT), effects of short follow-up, and intervals to the diagnosis of BF were compared. The misclassification rate for BF using the nadir plus 2-ng/mL definition was 2% for RT alone and 0% for RT plus ADT compared with 0% and 0% for the modified ASTRO definition, and 5% and 23% for the ASTRO definition, respectively. The hazard rates for RT alone and RT plus ADT were proportional only for the nadir plus 2 ng/mL definition and seemingly unaffected by the length of follow-up. For RT with or without ADT, the nadir plus 2 ng/mL definition was the most specific (RT, 80% vs. RT plus ADT, 75%) with the greatest positive predictive value (RT, 36% vs. RT plus ADT, 25%) and overall accuracy (RT, 81% vs. RT plus ADT, 77%). A greater proportion of BF was diagnosed in the first 2 years of follow-up with the nadir plus 2 ng/mL definition compared with the ASTRO definition (13% vs. 5%, p = 0.0138, chi-square test). The nadir plus 2 ng/mL definition was the best predictor of sustained, true, biochemical, and clinical failure, and was not affected by the use of ADT or follow-up length.