Prostate-specific Antigen Trends Research Articles

Serum prostate-specific antigen trends and prostate cancer detection on follow-up in men with a prior negative biopsy: A cohort study

ABSTRACT Introduction: Elevated serum prostate-specific antigen (PSA) is the most common trigger for a prostate biopsy. However, the range of normal PSA is poorly defined in many populations. Men with “elevated” PSA may not harbor cancer, and it is unclear if such men with a prior negative prostate biopsy should be biopsied again. We conducted a cohort study to assess the PSA trends and cancer detection rates in such men. Methods: In an Institutional Review Board-approved ambispective study, men who underwent prostate biopsy between January 2016 and December 2021 for PSA > 4 ng/mL were identified. Among them, those whose biopsy was negative for malignancy were contacted either telephonically or reviewed in person, and the most recent PSA and histopathology of any repeat prostate biopsy were determined. These were evaluated to assess the PSA trend, re-biopsy rate, and cancer detection rate. Results: During the study period, prostate biopsies were performed in a total of 1260 men; out of which 444 were negative for malignancy and 241 patients fulfilled the inclusion criteria. Their median prebiopsy PSA was 9.81 ng/mL (interquartile range [IQR]: 7.14–15.6), and the median follow-up PSA was 5.08 (IQR: 3.18–8.4). At a median follow-up of 53 months (range: 6–77 months), PSA had decreased in 177 (73.4%) patients, was static in 48 (19.9%) patients, and increased in only 16 (6.6%) patients. Repeat biopsy was performed on 20 patients; of whom seven had cancer (35%) with an overall positivity rate of 2.9% among the 241 patients. Although the positivity rate was higher in men with increased PSA, it was not statistically different from those with lower or similar PSA. No factors could be identified to predict a positive repeat biopsy. Conclusions: PSA, the sole trigger for a prostate biopsy, declined in nearly three-quarters of men with a negative first biopsy, and <3% of men were detected to have cancer on a repeat biopsy. This information could help appropriately counsel patients and allay anxiety after a negative biopsy.

Effect of Chronic Urinary Retention over Serum Prostate-Specific Antigen and Its Role in Histopathological Diagnosis

Background: Prostate-specific antigen (PSA) rises in all types of retentions and also in carcinoma prostate. The raised levels of PSA levels due to urinary retention may raise a false suspicion of carcinoma prostate in these patients. Unlike chronic urinary retention (CUR), the effect of acute urinary retention (AUR) on serum PSA levels had been studied in detail as evident from the past literature. Objectives: The objectives of the study were first to estimate and interpret serum PSA levels in adult males with CUR due to prostatic pathology, second to assess the need of taking prostatic biopsy based on the studied PSA trends, and finally to assess the prostatic histopathology in cases of persistently high PSA levels after 6 weeks. Materials and Methods: This was an observational follow-up study including 41 patients diagnosed with CUR due to prostatic etiology, matching the inclusion and exclusion criteria. On presentation, serum PSA levels were recorded. Retention was relieved by either per urethral catheterization or suprapubic catheterization. PSA levels were recorded after 24 hours, 1 week, 3 weeks, and 6 weeks and PSA trends were noted. Prostatic biopsy was advised for only those subjects in whom PSA did not attain the baseline value of 4 ng/mL within 6 weeks. The histopathological report of the biopsy was followed in each patient for studying its association with PSA trends. Results: Mean PSA at the time of presentation was 17.92 ng/mL. PSA trends showed that in the majority of the patients “Suspected benign group” (80.49%, n = 33), PSA returned to <4 ng/mL within 6 weeks of catheterization. Six patients, the “Borderline group” (14.63%), showed a downtrend in their PSA trends but could not attain baseline value. PSA trends in only two patients, the “Suspected malignant group” (4.87%), showed a comparative constant or an uptrend. All patients in the “Suspected benign group” and a majority of the “Borderline group” patients (83.33%) had a histopathologically confirmed benign prostatic pathology. Out of the two highly suspected malignant cases, only one patient (50%) had carcinoma prostate on final histopathology. Conclusion: PSA rises mainly in carcinoma prostate, but it falsely rises in all urinary retentions. The relationship between AUR and PSA had been studied in detail as evident from the past literature but needs to be established in patients with CUR. A period of 4 to 6 weeks can be safely employed for waiting for PSA to fall back to normal in CUR. A biopsy is required only for patients in which PSA is constantly high to rule out carcinoma prostate.

Correlative Analysis of Vitamin D and Omega-3 Fatty Acid Intake in Men on Active Surveillance for Prostate Cancer

ObjectiveTo investigate the influence of targeted serum vitamin-D level and omega-6:3 fatty-acid ratio on prostate-specific antigen (PSA) level in men with prostate cancer managed with active surveillance by providing a nutritional intervention and vitamin supplementation. MethodsSixty-eight patients with biopsy-proven National Comprehensive Cancer Network very-low or low-risk prostate cancer were enrolled in the prostate cancer nutrition and genetics clinic at the Cleveland Clinic from July 2013-December 2019. Patients adhered to a specific dietary regimen devoid of animal-based products and foods containing omega-6 polyunsaturated fatty acids (PUFAs). The supplement regimen consisted of: Omega-3 PUFAs 720mg (3/day); curcumin 2000 mg/day; vitamin D3 dose titrated to achieve serum level of 60 ng/ml; and vitamin B-complex 1000 mg (4 times weekly). Patients underwent periodic monitoring of PSA, serum vitamin D, and PUFA levels and had frequent follow-up with the nutritionist which included a food frequency questionnaire. Interval prostate biopsy was performed as clinically indicated and/or at 9 months. ResultsThe mean and 95% confidence interval of PSA slope and Vitamin D serum levels slope were 0.11 (0-0.25) ng/mL/month and 4.65 (3.09-5.98) ng/mL/month, respectively. Patients with higher initial vitamin D levels were twice as likely to have a downward PSA trend (OR = 2.04, 95% confidence interval 1.04-4.01, P = .04). Fifty-five patients underwent follow-up biopsy, all showing no progression of disease. Three patients had loose bowel movements that required omega-3 and or curcumin dose adjustments. ConclusionIntensive nutritional intervention with Vitamin D and Omega-3 PUFA supplementation may benefit men on active surveillance for prostate cancer and further studies are warranted.

Evaluación del papel de la PET/TC con [68Ga]Ga-PSMA I&T en la evaluación de la respuesta a la terapia con docetaxel en pacientes con cáncer de próstata resistente a la castración

ObjectiveThere have been only few studies investigating the role of PSMA ligands in the therapy response assessment of metastasized castration resistant prostate cancer (mCRPC) cases. In this study we aimed at evaluating the capability of 68Ga- prostate-specific membrane antigen (PSMA) I&T positron emission tomography/computerized tomography (PET/CT) in the assessment of therapeutic response in patients under docetaxel therapy for prostate cancer (PCa). Material and methodsThe clinical records of all mCRPC patients treated with docetaxel and referred to our department for 68Ga-PSMA I&T PET/CT imaging were retrospectively analysed. Sixteen patients (mean age 69 years, range 52–82 years) with castration-resistant prostate cancer patients receiving palliative docetaxel therapy and had undergone 68Ga-PSMA I&T PET/CT scan were included in the study. 68Ga-PSMA I&T PET/CT imaging was done and prostate specific antigen (PSA) levels were measured at baseline before administration of docetaxel (PET1) and after at least 3 cycles (range 4–12) of chemotherapy (PET2). Patient-based as well as lesion-based comparison of PET2 findings with PET1 findings were done. ResultsThe change (decrease) observed in lymph node and prostate gland/prostatic bed SUVmax values after treatment compared to pretreatment was found to be statistically significant (P=.033).3/16 patients (19%) were classified as progressive disease (PD), 4/16 (25%) as stable disease (SD), 9/16 (56%) as partial remission (PR) radiologically. An increasing PSA trend (IT) was observed in 4 patients (25%) and a decreasing PSA trend (DT) in 3 patients (18%). Nine patients showed a PSA response of ≥ 50% (56%). Of the 4 patients showing SD, 3 had IT, 3 had BR. Of the 9 patients who showed PR on PET studies, 8 patients showed BR and 1 patient showed DT. ConclusionImaging with 68Ga-PSMA PET/CT showed great concordance with biochemical response evaluation in terms of PSA levels, especially in patients showing good response to therapy. 68Ga-PSMA PET/CT was also successful in identifying progressive disease in patients showing paradoxical decline in PSA levels.

Association between prostate-specific antigen change over time and prostate cancer recurrence risk: A joint model.

Background:Prostate specific antigen (PSA) is an important biomarker to monitor patients after treated with radiation therapy (RT). The aim of this study is to evaluate the relationship between the PSA data and prostate cancer recurrence using the joint modeling.Methods:This historical cohort study was performed on 422 prostate cancer patients. Inclusion criteria included: patients with localized prostate cancer referring to Cancer Institute in Tehran (Iran) from 2007 to 2012, and under radiation therapy. Joint model has two components or sub-models. We showed the results by parameter estimating the longitudinal sub-model and survival sub-model. EM algorithm, Newton-Gauss and Gauss-Hermit law were used for final model parameters. R software version 3.2 was used for statistical analysis.Results:In this study, considering the inclusion and exclusion criteria, out of 422 patients, the data on 314 cases were selected for analysis and the main result of joint model was obtained. PSA directly and significantly was associated with recurrence risk, therefore increasing 2.6 ml/lit PSA (one unit in transformed PSA) increases 39% recurrence risk (95% CI for RR: 1.09-1.77). Also, slope of PSA trend has significant association with prostate cancer recurrence risk (95% CI for RR: 1.05-1.41).Conclusion:This study showed a significant relationship between PSA, and its slope with the recurrence risk by joint model, with regard to the pathological, demographic and clinical features in the Iranian population.

Assessment of the role of Ga-68 PSMA I&T PET/CT in response evaluation to docetaxel therapy in castration resistant prostate cancer patients

ObjectiveThere have been only few studies investigating the role of PSMA ligands in the therapy response assessment of metastasized castration resistant prostate cancer (mCRPC) cases. In this study we aimed at evaluating the capability of 68Ga- prostate-specific membrane antigen (PSMA) -I&T positron emission tomography/computerized tomography (PET/CT) in the assessment of therapeutic response in patients under docetaxel therapy for prostate cancer (PCa). Material and methodsThe clinical records of all mCRPC patients treated with docetaxel and referred to our department for 68Ga-PSMA I&T PET/CT imaging were retrospectively analysed. Sixteen patients (mean age 69 years, range 52–82 years) with castration-resistant prostate cancer patients receiving palliative docetaxel therapy and had undergone 68Ga-PSMA I&T PET/CT scan were included in the study. 68Ga-PSMA I&T PET/CT imaging was done and prostate specific antigen (PSA) levels were measured at baseline before administration of docetaxel (PET1) and after at least 3 cycles (range 4–12) of chemotherapy (PET2). Patient-based as well as lesion-based comparison of PET2 findings with PET1 findings were done. ResultsThe change (decrease) observed in lymph node and prostate gland/prostatic bed SUVmax values after treatment compared to pretreatment was found to be statistically significant (p=0.033).3/16 patients (19%) were classified as progressive disease (PD), 4/16 (25%) as stable disease (SD), 9/16 (56%) as partial remission (PR) radiologically. An increasing PSA trend (IT) was observed in 4 patients (25%) and a decreasing PSA trend (DT) in 3 patients (18%). Nine patients showed a PSA response of ≥50% (56%). Of the 4 patients showing SD, 3 had IT, 3 had BR. Of the 9 patients who showed PR on PET studies, 8 patients showed BR and 1 patient showed DT. ConclusionImaging with 68Ga-PSMA PET/CT showed great concordance with biochemical response evaluation in terms of PSA levels, especially in patients showing good response to therapy. 68Ga-PSMA PET/CT was also successful in identifying progressive disease in patients showing paradoxical decline in PSA levels.

Retrospective review of 11C-choline detected thoracic lesions in prostate cancer.

325 Background: Prostate cancer recurrence is detected by serum measurements of prostate specific antigen (PSA). Upon PSA elevation, locating sites of recurrence is important to guiding treatment and affecting patient outcomes. The imaging modalities in current practice have varying sensitivities and specificities and often miss early recurrent disease. 11C-choline positron emission tomography (11C-PET) may be able to detect occult disease and guide treatment decisions earlier in the clinical course. We assessed a case series of patients who underwent 11C-PET imaging and were identified to have thoracic disease to estimate the benefit of detection with this modality. Methods: Clinical records were retrospectively reviewed of seventy patients from thoracic oncology teams at Mayo Clinic in Rochester, Minnesota. Patients who had thoracic +/- extra-thoracic metastases on 11C-PET imaging were followed, noting changes in treatment and PSA trends to look for biochemical recurrence of disease. Results: Seventy patients with thoracic metastases discovered on 11C-PET imaging were initially identified. Median time to choline-avid disease from original diagnosis was 82 (IQR: 40-129) months with a median PSA at time of choline of 7.4 (IQR: 3.1-15.7). 11C-PET findings showed 28 patients with metastases limited to the thorax and 42 patients with thoracic and extra-thoracic metastases. After 11C-PET imaging, 1 patient underwent localized therapy only (radiation and surgery), 44 patients underwent systemic therapy only (chemotherapy or hormonal therapy), 19 patients underwent both localized (cryotherapy, radiation, or surgery) and systemic therapy, 3 patients underwent no further treatment, and 3 patients were lost to follow up. After a median follow-up of 36.5 (IQR: 13-52) months, 30 patients had no recurrence and 20 had evidence of biochemical recurrence. For those who underwent local therapy (N=21), 11 had no recurrence of disease. Conclusions: Choline-based imaging may earlier identify metastatic disease that is amenable to local therapy. Further studies are needed to validate the effectiveness of 11C-PET in identifying early, responsive metastatic prostate cancer and its utility in affecting patient outcomes.

Prostate-Specific Antigen Trends Predict the Probability of Prostate Cancer in a Very Large U.S. Veterans Affairs Cohort

If prostate-specific antigen (PSA) trends help identify elevated prostate cancer (PCa) risk, they might provide early warning of progressing cancer for further evaluation and justify annual testing. Our objective was to determine whether PSA trends predict PCa likelihood. A biopsy cohort of 361,657 men was obtained from a Veterans Affairs database (1999–2012). PSA trends were estimated for the 310,458 men with at least 2 PSA tests prior to biopsy. Cancer tumors may grow exponentially with cells doubling periodically. We hypothesized that PSA from prostate cancer grows exponentially above a no cancer baseline. We estimated PSA trends on that basis along with five descriptive variables: last PSA before biopsy, growth rate in PSA from cancer above a baseline, PSA variability around the trend, number of PSA tests, and time span of tests. PSA variability is a new variable that measures percentage deviations of PSA tests from estimated trends with 0% variability for a smoothly increasing trend. Logistic regression models were used to estimate relationships between the probability of PCa at biopsy and the trend variables and age. All five PSA trend variables and age were significant predictors of prostate cancer at biopsy (p < 0.0001). An overall logistic regression model achieved an AUC of 0.67 for men with at least 4 tests over at least 3 years, which was a substantial improvement over a single PSA (AUC 0.58). High probability of PCa was associated with low PSA variability (smooth trends), high PSA, high growth rate, many tests over a long time-span and older age. For example, at 4.0 PSA the probability of cancer is 32% for 1 PSA test and increases to 68% for 8 tests over 7 years with smooth, fast growth (0% variability and 50% exponential growth). Our results show that smooth, fast exponential growth in PSA above a baseline predicts an increased probability of PCa. The probability increases as smooth (low variability) trends are observed for more tests over a longer time span, which makes annual testing worth considering. Worrisome PSA trends might be used to trigger further evaluation and continued monitoring of the trends—even at low PSA levels.

Association of prostate-specific antigen (PSA) trajectories with risk for metastasis and mortality in non-metastatic castration-resistant prostate cancer (nmCRPC).

27 Background: Currently there is insufficient guidance for the management of nmCRPC. This study assessed patient risk of developing metastases and death based on their PSA levels over time. Methods: This was a retrospective study using the Optum electronic health record database (1/1/2007 – 4/30/2016) in men ≥18 years. nmCRPC was defined as a PC diagnosis, 2 rising PSA levels ≥1 week apart, testosterone &lt; 50 ng/dL (post-PC diagnosis), and no ICD-9/10 code or therapy indicating metastasis. Patients were required to have ≥1 PSA record per 3-month period for 9 months following nmCRPC diagnosis. Group Based Trajectory Modeling (GBTM) was used to group patients based on similar PSA trends over 9 months. The association of these PSA groups with metastasis/mortality risk was measured using multivariate Cox proportional hazard regression models. An overall trend for metastasis and mortality across the groups was also tested. Results: From a total of 729 patients included, 4 distinct groups were identified: Group 1 (49% of patients), 2 (32%), 3 (14%) and 4 (5%). Group 1 had the lowest PSA (7 ng/mL) at nmCRPC diagnosis and steady PSA during the 9-month follow-up. In contrast, Groups 2, 3 and 4 had higher PSA at nmCRPC diagnosis (17, 61, 513 ng/mL respectively) and rising PSA during follow-up. There was a trend of increasing metastasis and mortality risk (p &lt; 0.001 for both trends) with the higher PSA groups. For metastasis, Hazard Ratios (HRs) and 95% confidence intervals (CIs) were 1.7 (1.3-2.2), 3.5 (2.5-5.0), 1.8 (0.7-4.7) in Groups 2, 3 and 4, respectively, vs. Group 1. For mortality, HRs (95% CIs) were 1.9 (1.4-2.5), 2.6 (1.8-3.7), 4.5 (2.4-8.4) in Groups 2, 3 and 4, respectively, vs. Group 1. Metastasis-free survival (MFS) independently predicted mortality risk. Patients developing metastasis within 1 year had 4.4-fold greater risk for mortality (95% CI = 2.2-8.8) than those who remained MFS at year 3. Conclusions: A large proportion of nmCRPC patients with PSA increases during the follow-up period had significantly increased risk for metastasis and mortality, with MFS predicting mortality risk. Periodic measurement of PSA may better inform management of nmCRPC.

Refined Analysis of Prostate-specific Antigen Kinetics to Predict Prostate Cancer Active Surveillance Outcomes

BackgroundFor men on active surveillance for prostate cancer, utility of prostate-specific antigen (PSA) kinetics (PSAk) in predicting pathologic reclassification remains controversial. ObjectiveTo develop prediction methods for utilizing serial PSA and evaluate frequency of collection. Design, setting, and participantsData were collected from men enrolled in the multicenter Canary Prostate Active Surveillance Study, for whom PSA data were measured and biopsies performed on prespecified schedules. We developed a PSAk parameter based on a linear mixed-effect model (LMEM) that accounted for serial PSA levels. Outcome measurements and statistical analysisThe association of diagnostic PSA and/or PSAk with time to reclassification (increase in cancer grade and/or volume) was evaluated using multivariable Cox proportional hazards models. Results and limitationsA total of 851 men met the study criteria; 255 (30%) had a reclassification event within 5 yr. Median follow-up was 3.7 yr. After adjusting for prostate size, time since diagnosis, biopsy parameters, and diagnostic PSA, PSAk was a significant predictor of reclassification (hazard ratio for each 0.10 increase in PSAk=1.6 [95% confidence interval 1.2–2.1, p<0.001]). The PSAk model improved stratification of risk prediction for the top and bottom deciles of risk over a model without PSAk. Model performance was essentially identical using PSA data measured every 6 mo to those measured every 3 mo. The major limitation is the reliability of reclassification as an end point, although it drives most treatment decisions. ConclusionsPSAk calculated using an LMEM statistically significantly predicts biopsy reclassification. Models that use repeat PSA measurements outperform a model incorporating only diagnostic PSA. Model performance is similar using PSA assessed every 3 or 6 mo. If validated, these results should inform optimal incorporation of PSA trends into active surveillance protocols and risk calculators. Patient summaryIn this report, we looked at whether repeat prostate-specific antigen (PSA) measurements, or PSA kinetics, improve prediction of biopsy outcomes in men using active surveillance to manage localized prostate cancer. We found that in a large multicenter active surveillance cohort, PSA kinetics improves the prediction of surveillance biopsy outcome.

PD56-09 PSA TRENDS FOLLOWING PRIMARY FOCAL CRYOSURGERY FOR EARLY STAGE PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Localized: Ablative Therapy II1 Apr 2017PD56-09 PSA TRENDS FOLLOWING PRIMARY FOCAL CRYOSURGERY FOR EARLY STAGE PROSTATE CANCER Michael Kongnyuy, Shahidul Islam, Daniel Halpern, Kaitlin Kosinski, Jose Salcedo, Jeffrey Schiff, Anthony Corcoran, and Aaron Katz Michael KongnyuyMichael Kongnyuy More articles by this author , Shahidul IslamShahidul Islam More articles by this author , Daniel HalpernDaniel Halpern More articles by this author , Kaitlin KosinskiKaitlin Kosinski More articles by this author , Jose SalcedoJose Salcedo More articles by this author , Jeffrey SchiffJeffrey Schiff More articles by this author , Anthony CorcoranAnthony Corcoran More articles by this author , and Aaron KatzAaron Katz More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2598AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Determination of biochemical (BCR) recurrence in patients who undergo primary focal cryosurgery (PFC) for organ confined prostate cancer (PCa) is controversial. We aim to evaluate prostate specific antigen (PSA) trends in post PFC patients. METHODS A single-center retrospective review of patients from our IRB-approved database who underwent PFC was performed. Patients were followed with serial PSAs and BCR was determined using the Phoenix (PD: PSA nadir + 2 ng/ml) and Stuttgart (SD: PSA nadir + 1.2 ng/ml) definitions. PSA bounce was assessed using 2 different definitions (B1: increase in PSA of 0.4 in first 6 months and any drop thereafter, B2: increase in PSA of ≥0.2 above nadir and then a drop to/below nadir) Age, prostate volume, D′Amico risk, Gleason score, PSA variables and kinetics overtime were assessed between those who experienced BCR versus not. Various PSA permutations were analyzed. RESULTS 123 (94.6%) consecutive patients who had >1 PSA follow-up values were included in our analysis. Median (range) age and follow-up time was 66 (48-82) years and 19 (6.3-68.6) months respectively. 11 (8.9%, 7B1; 4B2) patients experienced PSA bounce and a median percent drop in first post-PFC PSA of 80.0 (0.0-98.7) was not associated with BCR, p=0.301. PSA values in both groups increased over time but the rate of change was significantly higher in patients who experienced BCR compared to those who did not [median PSA velocity: 0.1 vs 0.04, p=0.003]. Other PSA variables associated with experiencing BCR were higher pre-PFC PSA (7.2 vs 5.4 ng/ml, p=0.003) and higher PSA nadir (1.3 vs 1 ng/ml, p=0.012). CONCLUSIONS Higher PSA velocity, nadir and pre-PFC PSA may help raise suspicion for BCR. In the future with validation, these variables could serve as the components of PFC-specific BCR criteria. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e1119 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Michael Kongnyuy More articles by this author Shahidul Islam More articles by this author Daniel Halpern More articles by this author Kaitlin Kosinski More articles by this author Jose Salcedo More articles by this author Jeffrey Schiff More articles by this author Anthony Corcoran More articles by this author Aaron Katz More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Estimation of the optimal regime in treatment of prostate cancer recurrence from observational data using flexible weighting models.

Prostate cancer patients are closely followed after the initial therapy and salvage treatment may be prescribed to prevent or delay cancer recurrence. The salvage treatment decision is usually made dynamically based on the patient's evolving history of disease status and other time-dependent clinical covariates. A multi-center prostate cancer observational study has provided us data on longitudinal prostate specific antigen (PSA) measurements, time-varying salvage treatment, and cancer recurrence time. These data enable us to estimate the best dynamic regime of salvage treatment, while accounting for the complicated confounding of time-varying covariates present in the data. A Random Forest based method is used to model the probability of regime adherence and inverse probability weights are used to account for the complexity of selection bias in regime adherence. The optimal regime is then identified by the largest restricted mean survival time. We conduct simulation studies with different PSA trends to mimic both simple and complex regime adherence mechanisms. The proposed method can efficiently accommodate complex and possibly unknown adherence mechanisms, and it is robust to cases where the proportional hazards assumption is violated. We apply the method to data collected from the observational study and estimate the best salvage treatment regime in managing the risk of prostate cancer recurrence.

Looking to possible predictive factors of primary resistance to abiraterone acetate (AA) and enzalutamide (ENZ) in pretreated patients (pts) with castration-resistant prostate cancer (CRPC).

248 Background: Abiraterone acetate (AA) and enzalutamide (ENZ) are new generation hormonal agents (NHA) which demonstrated a survival gain in patients (pts) with castration-resistant prostate cancer (CRPC) pre-treated with docetaxel. Although all patients eventually became resistant to these NHAs, some of them show primary resistance, defined as an early progression within the first 3 months, which leads to an early treatment interruption. In the present analysis we have tried to identify which factor, if any, may predict primary resistance to AA and ENZ. Methods: We evaluated a consecutive series of 57 pts, treated in our hospital in two successive named patient programs conducted in our hospital to allow pre-treated CRPC patients to receive NHAs before their approval in Italy: 26 received AA (1,000 mg po + prednisone 10 mg po daily) and 31 ENZ (160 mg po daily). For each pt we have recorded the pre- and post-NHA clinical history, the treatment details and outcomes. We have also assessed the ability of a series of 24 selected clinical factors to predict NHAs resistance, through a logistic regression analysis. Continuous variables were categorized by quartiles and chosen for the initial model after a univariate chi-square analysis. Results: Among the 24 factors, the presence of pain at baseline, high baseline lactate dehydrogenase levels and prostate-specific antigen (PSA) levels after one month of treatment were predictive of primary NHA resistance at the univariate analysis. However, only PSA levels were confirmed at the multivariate analysis [exp(beta) 0.115; p = 0.007], as patients failing to achieve a 50% or more reduction in baseline PSA levels, were more likely to show primary NHA resistance (48% vs. 15%). Conclusions: Our results suggest that PSA trend may represent a simple and rapid method of identifying patients with primary resistance to NHAs, so patients failing to achieve a 50% or more reduction within the first month of treatment should undergo intensive investigations, to verify whether they have primary resistance to NHAs. These data should be confirmed in a larger patient population.

Visceral Disease in Castration-resistant Prostate Cancer

Metastatic involvement of the viscera in men with advanced castration-resistant prostate cancer (CRPC) has been poorly characterised to date. In 359 CRPC patients treated between June 2003 and December 2011, the frequency of radiologically detected visceral metastases before death was 32%. Of the 92 patients with computed tomography performed within 3 mo of death, 49% had visceral metastases. Visceral metastases most commonly involved the liver (20%) and lung (13%). Median survival from diagnosis of visceral disease was 7.1 mo (95% confidence interval, 5.9–8.3). Survival was affected by the degree of bone involvement at detection of visceral disease, varying from 6.1 mo in men with more than six bone metastases to 18.2 mo in men with no bone metastases (p=0.001). Heterogeneity was noted in clinical phenotypes and prostate-specific antigen trends at development of visceral metastases. Visceral metastases are now more commonly detected in men with CRPC, likely due to the introduction of novel survival-prolonging treatments.

Single Center Experience with Third-Generation Cryosurgery for Management of Organ-Confined Prostate Cancer: Critical Evaluation of Short-Term Outcomes, Complications, and Patient Quality of Life

Technical refinements such as improved ultrasonographic localization and the routine use of urethral warmers and small-gauge needle delivery systems have renewed interest in cryosurgical treatment as a minimally invasive option for selected patients with localized prostate cancer. Only three reports of quality of life (QoL) in prostate cryoablation exist, and none report on patients treated with third-generation cryoablative technology. We critically examine our initial series of consecutive patients at a single institution undergoing primary third-generation cryosurgical treatment of localized prostate cancer with respect to treatment outcome, morbidity profile, and QoL parameters. To our knowledge, this is the first QoL report on third-generation cryoablation of the prostate. We retrospectively review the records of 89 consecutive patients with median followup of 11 months (1-32) who have undergone third-generation cryosurgical ablation of the prostate as primary treatment for localized prostate cancer with intention to cure. Patients were risk stratified according to preprocedural parameters of prostate-specific antigen (PSA), clinical stage, and Gleason score. PSA trends were recorded and treatment effectiveness was observed using different definitions of biochemical failure. Charts were reviewed for postprocedure complications. Quality of life was measured prospectively using the University of California, Los Angeles, Prostate Cancer Index as well as American Urological Association symptom scores. We compare a percent of baseline score (%BS) for various domains between our series of patients treated with primary cryoablation with a series of patients undergoing brachytherapy for localized prostate cancer. Treatment success was defined by achievement of a PSA nadir of < or =0.1 ng/mL and by biochemical disease-free survival (BDFS) assessed with both a PSA threshold of < or =0.4 ng/dL over time and the American Society for Therapeutic Radiology and Oncology (ASTRO) definition of three consecutive rises in PSA. According to risk stratification, 86%, 81.5%, and 78% of low-, intermediate-, and high-risk patients, respectively, achieved a PSA nadir of < or =0.1 ng/mL. Overall, at 12 months follow-up, 94% of patients achieved BDFS using ASTRO criteria while 70% achieved BDFS using a PSA threshold of < or =0.4 ng/mL. With risk stratification, 74%, 70%, and 60% of low-, intermediate-, and high-risk patients, respectively, achieved BDFS defined by PSA threshold of < or =0.4 ng/mL. Complications were rare. The response rate for Health Related Quality of Life (HRQoL) questionnaires was 71% for cryoablation patients and 51% for brachytherapy patients. At 12 months follow-up, patients undergoing cryoablation on average achieved urinary and bowel domain scores comparable to baseline, but sexual domains remained well below baseline. When compared with a brachytherapy series with better baseline sexual function (P = 0.04) and urinary function (P = 0.03), cryotherapy patients experienced more negative impact on sexual function steadily for up to 12 months (P = 0.02). Urinary function was similar between the groups until 18 months, at which time cryoablation patients fared better (P = 0.01); this was sustained up to 24 months (P = 0.04). Treatment success with cryosurgery varies with definition; however, our results are comparable to other series with regard to short-term cancer control. Complication rates in this series of third-generation cryosurgical patients are low. QoL characteristics of third-generation cryoablation are similar to those described in second-generation cryoablation series. Compared with brachytherapy, cryotherapy results in less irritative and obstructive voiding symptoms in the early post-treatment period and may improve urinary function up to 24 months after treatment. In a small group of older patients with baseline erectile dysfunction undergoing cryoablation, sexual function returns to 20% of its baseline value with up to 12 months follow-up.

Prostate‐specific antigen half‐life and pretreatment prostate‐specific antigen: Crucial predictors for prostate‐specific antigen trend in delayed‐combined androgen blockade therapy

To elucidate the crucial predictors for prostate-specific antigen (PSA) trends and determine the usage of anti-androgen treatment during delayed-combined androgen blockade (CAB) leading to a PSA level below 0.2 ng/mL. From January 2001 to December 2004, 105 prostate cancer patients were enrolled. Medical castration and anti-androgen treatment were used sequentially and termed delayed-CAB. The first goal was to maintain an undetectable PSA level. The nadir PSA was determined after medical castration only. Anti-androgen was given if a PSA level of more than 0.2 ng/mL was observed and the subsequent PSA response was assessed. All cases were divided into two groups based on whether the PSA was lower (n = 59) or higher (n = 46) than 0.2 ng/mL. An analysis of the difference between the two groups was calculated. The median of the initial PSA level in the lower group was lower than in the higher group with a 95% cut-off level of 40 ng/mL. The median PSA half-life in the lower group was also reduced with a 95% cut-off of 3.6 months. In a multivariate analysis, the pretreatment PSA level and the PSA half-life exhibited a significant correlation between the two groups. Anti-androgen treatment was given to 26 cases in the higher group. The PSA increased in one case, decreased to less than 0.2 ng/mL in 17 cases and remained over 0.2 ng/mL in eight cases. Both the PSA half-life and the pretreatment PSA level were useful markers for predicting the PSA trends to determine the optimal use of anti-androgen treatment during delayed-CAB.

Evaluation of postradiotherapy PSA patterns and correlation with 10-year disease free survival outcomes for prostate cancer

To describe the prostate-specific antigen (PSA) pattern profiles observed after external beam radiotherapy with and without short-term neoadjuvant androgen deprivation therapy (ST-ADT) and to report the association of established posttreatment PSA patterns with long-term disease-free survival outcomes. A total of 1,665 patients were treated with conformal external beam radiotherapy for clinically localized prostate cancer. Of 570 patients who had the requisite>10 consecutive PSA measurements for statistical analysis, 194 patients received a median of 3 months of ADT before radiotherapy and 376 were treated with radiotherapy alone. The median follow up was 103 months. In the group treated with ST-ADT, three distinct postradiotherapy PSA patterns were identified: a stable trend (44%), an increasing trend followed by stabilization of the PSA (25%), and an increasing trend (31%). Among the subgroup that demonstrated a rising and subsequent stabilizing patterns, PSA levels had gradually risen to a median value of 0.9 ng/mL after therapy, stabilized, and remained durably suppressed. The only identified trends among patients treated with external beam radiotherapy without ST-ADT were declining PSA levels followed by stable PSA trends or declining patterns followed by rising levels. Patients whose PSA levels stabilized after an initial rise or those with slowly rising PSA profiles had a lower incidence of distant metastasis compared to those with accelerated rises after therapy. For those treated with external beam radiotherapy in conjunction with ST-ADT, a significant percentage who develop a rising PSA after treatment are expected to manifest subsequent stabilization at plateaued levels of approximately 1.0 ng/mL, which can remain durably suppressed. The likelihood of distant metastasis in these patients is low despite the PSA stabilization at levels 1.0 ng/mL or higher and comparable to outcomes observed for those with lower nonrising PSA values.

The value of radiotherapy in treating recurrent prostate cancer after radical prostatectomy

Approximately 25-40% of men who undergo radical retropubic prostatectomy (RRP) for the treatment of clinically localized prostate cancer will experience biochemical recurrence. A rapid prostate-specific antigen (PSA) doubling time or high-grade disease are risk factors for progression to bone metastases and cancer-specific mortality. Salvage external-beam radiotherapy (EBRT) to the prostate fossa is the only curative therapy for patients with biochemical recurrence after RRP, but it is used relatively infrequently to treat recurrent prostate cancer because of a widespread perception that most patients have systemic recurrence, and its reported lack of efficacy for high-risk disease. However, in a large, multicenter study of patients who received salvage EBRT for a rising PSA level after RRP, a substantial proportion of patients with high-grade disease and/or a rapid PSA doubling time were observed to have a favorable outcome after salvage EBRT if it was administered at low PSA values. This suggests that salvage EBRT could provide long-term cancer control for patients at the highest risk of progression to bone metastases and cancer-specific mortality. A nomogram that predicts the 3-year progression-free probability after salvage EBRT has been developed to facilitate the selection of patients for this potentially curative therapy. In the absence of other curative therapies, all patients with recurrent prostate cancer should be considered for salvage EBRT, particularly those with positive surgical margins. To be successful, salvage EBRT should be administered at the earliest evidence of recurrent disease, once a rising PSA trend as been confirmed.

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.