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We present the first case of salvage radiotherapy based on the results of 18F-FACBC PET/CT performed for a PSA relapse after radical prostatectomy. The patients underwent 11CCholine PET/CT and multiparametric MRI that were negative while 18F-FACBC PET/CT visualized a suspected local relapse confirmed by transrectal ultrasound-guided biopsy. No distant relapse was detected. Thus the patient was submitted to salvage radiotherapy in the prostatic fossa. After 20 months of follow-up, the PSA was undetectable and 18F-FACBC PET/CT was negative. Salvage radiotherapy after surgery, provided that it is administered at the earliest evidence of the biochemical relapse, may improve cancer control and favourably influence the course of disease as well as the adjuvant approach. New imaging techniques may increase the efficacy of the salvage radiotherapy thus helping in the selection of the patients. Preliminary clinical reports showed an improvement in the detection rate of 20-40% of 18F-FACBC in comparison with 11C-Choline for the detection of disease relapse after radical prostatecomy, rendering the 18F-FACBC the potential radiotracer of the future for prostate cancer.

Objectives One-third of patients with positive surgical margins after radical prostatectomy develop recurrent disease. The distinction between pT2 with positive margins and pT3a can be difficult. Aim of the present study was to assess the impact of positive surgical margins on biochemical relapse after radical prostatectomy, adjusted for pathological stage and Gleason score. Methods We retrospectively evaluated 837 consecutive patients who underwent radical prostatectomy for organ-confined or locally-advanced prostate cancer. Exclusion criteria were: presence of node or distant metastases, neo-adjuvant or adjuvant therapy, and unavailability of full data regarding pathological stage and margin status. A single dedicated genitourinary pathologist evaluated all the specimens. The Kaplan- Meier method and univariable and multivariable Cox regressions were applied for survival analyses. Results The median follow up was 54.0 ± 35.0 months. Margin status, prostate-specific antigen and Gleason score significantly predicted biochemical relapse in the pT2 group at multivariable analysis, whereas only pathological stage and pathological Gleason score were significant predictors of recurrence in pT3a patients. There were no significant differences in biochemical disease-free survival among pT2 with positive margins patients and pT3a patients (with or without positive surgical margins). Pathological Gleason score was the only significant predictor of biochemical relapse in patients with negative and positive margins, regardless of the pathological stage. Conclusions pT2 patients with positive surgical margins and pT3a (with or without positive margins) seem to have similar biochemical disease-free survival. Positive margins and pathological stage might be insufficient clinical predictors. Gleason score remains the most reliable prognostic factor. [ABSTRACT FROM AUTHOR]

Purpose: The aims of the study were (a) to evaluate the diagnostic role, by means of positive detection rate (PDR), of 18F-choline (CH) positron emission tomography (PET)/CT in patients with prostate cancer treated with radiotherapy, with curative intent, and suspicion of relapse during follow-up, (b) to correlate the PDR with trigger prostate-specific antigen (PSA), (c) to investigate the possible influence of androgen deprivation therapy (ADT) at the time of scan on PDR and (d) to assess distribution of metastatic spread. Methods: 18F-CH PET/CT exams from 46 consecutive patients (mean age 71.3 years, range 51–84 years) with prostate cancer (mean Gleason score 6.4, range 5–8) previously treated by definitive radiotherapy and with suspicion of relapse with negative or inconclusive conventional imaging were retrospectively evaluated. Of the 46 patients, 12 were treated with brachytherapy and 34 with external beam radiation therapy. Twenty-three patients were under ADT at the time of the examination. Trigger PSA was measured within 1 month before the exam (mean value 6.5 ng/ml, range 1.1–49.4 ng/ml). Patients were subdivided into four groups according to their PSA level: 1.0 < PSA ≤ 2.0 ng/ml (11 patients), 2.0 < PSA ≤ 4.0 ng/ml (16 patients), 4.0 < PSA ≤ 6.0 ng/ml (9 patients) and PSA > 6.0 ng/ml (10 patients). Correlation between ADT and PDR was investigated as well as between PSA and distribution of metastatic spread. Results: The overall PDR of 18F-CH PET/CT was 80.4 % (37/46 patients), increasing with the increase of trigger PSA. PDR of 18F-CH PET/CT is not influenced by ADT ( p = 0.710) even if PET performed under ADT demonstrated an overall higher PDR (82.6 %). The majority of the patients (59 %, 22/37 patients) showed local relapse only, confined to the prostatic bed; 22 % of the PET/CT-positive patients (8/37 patients) showed distant relapse only (bone localizations in all of them), while the remaining 19 % (7/37 patients) showed both local and distant (lymph node and bone) spread. Conclusion: 18F-CH PET/CT showed a high overall detection rate (80 %), proportional to the trigger PSA (both for local and distant relapse) not influenced by ADT. 18F-CH PET/CT is proposed as a first-line imaging procedure in restaging prostate cancer patients primarily treated with radiotherapy. [ABSTRACT FROM AUTHOR]

BACKGROUND. The objective of this study was to report the rates of disease-free survival (DFS), cause-specific survival (CSS), and overall survival after low-dose-rate (LDR) prostate brachytherapy (PB). METHODS. Data from 1006 consecutive patients with prostate cancer who received LDR-PB and underwent implantation on or before October 23, 2003 were extracted from a prospective database on November 11, 2011. The selected patients had low-risk (58%) or intermediate-risk (42%) disease according to National Comprehensive Cancer Network criteria. The Phoenix threshold was used to define biochemical relapse. Sixty-five percent of patients received 3 months of neoadjuvant androgen-deprivation therapy (ADT) and 3 months of concomitant ADT. Univariate and multivariate analyses are reported in relation to patient, tumor, and treatment variables. RESULTS. The median follow-up was 7.5 years. By using Fine and Gray competing risks analysis, the 5-year and 10-year actuarial DFS rates were 96.7% (95% confidence interval, 95.2%-97.7%) and 94.1% (95% confidence interval, 92%-95.6%), respectively. When applied to the whole cohort, none of the usual prognostic variables, including dose metrics, were correlated with DFS. However, in both univariate and multivariate models, increasing dose was the only covariate that correlated with improved DFS for the subset of men (N = 348) who did not receive ADT ( P = .043). The actuarial 10-year CSS rate was 99.1% (95% confidence interval, 97.3%-99.7%). The overall survival rate was 93.8% at 5 years (95% confidence interval, 92%-95.1%) and 83.5% at 10 years (95% confidence interval, 79.8%-86.6%). Only age at implantation ( P = .0001) was correlated with overall survival in multivariate analysis. CONCLUSIONS. In a consecutive cohort of 1006 men with National Comprehensive Cancer Network low-risk and intermediate-risk prostate cancer, the actuarial rate of recurrent disease after LDR-PB was approximately 3% at 5 years and 6% at 10 years. Cancer 2013. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND: Success rates with salvage radiotherapy (SRT) in men who have a postprostatectomy biochemical relapse are suboptimal. One treatment-intensification strategy includes elective irradiation of the pelvic lymph nodes with whole pelvis radiotherapy (WPRT). METHODS: An inter-institutional retrospective cohort study compared outcomes for patients who received SRT at 2 separate academic institutions with disparate treatment paradigms: almost exclusively favoring WPRT (n = 112) versus limiting treatment to the prostate bed (PBRT) (n = 135). Patients were excluded if they had lymph node involvement or if they received androgen-deprivation therapy. The Cox proportional hazards model was used to adjust for potential confounders. RESULTS: In total, 247 patients were analyzed with a median follow-up of 4 years. The pre-SRT prostate-specific antigen (PSA) level (adjusted hazard ratio [HR], 1.58; P < .0001) and a Gleason score of 8 to 10 (adjusted HR, 3.21; P < .0001) were identified as independent predictors of increased risk of biochemical PSA progression after SRT. However, WPRT was not independently associated with biochemical progression-free survival in the multivariate model (adjusted HR, 0.79; P = .20). Neither low-risk patients nor high-risk patients (defined a priori by a preoperative PSA level ≥20 ng/mL, a pathologic Gleason score between 8 and 10, or pathologic T3 tumor classification) benefited from WPRT. Overall survival was similar between treatment groups. When restricting the analysis to patients with pre-SRT PSA levels ≥0.4 ng/mL (n = 139), WPRT was independently associated with a 53% reduction in the risk of biochemical progression (adjusted HR, 0.47; P = .031). CONCLUSIONS: WPRT did not improve outcomes among the entire group but was independently associated with improved biochemical control among patients with pre-SRT PSA levels ≥0.4 ng/mL. Cancer 2013. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

Abstract: Permanent seeds brachytherapy is a standard in the treatment of localized prostate cancer. Follow-up of patients treated with brachytherapy relies on monitoring the concentration of PSA. It is supposed to decrease steadily to a nadir after several years. This decrease could be disrupted by transient and benign elevation of the marker, sometimes mimicking genuine biochemical relapses, sources of anxiety for patients or even unnecessary tests. While the precise mechanisms of this phenomenon are poorly understood, their characteristics have been, however, extensively studied. This work aims to make an update on the current state of knowledge. [Copyright &y& Elsevier]

Objectives: The aim of the present study was external validation to determine whether the Cancer of the Prostate Risk Assessment (CAPRA) score predicts biochemical relapse (BCR) after radical prostatectomy (RP) in Japanese patients. Methods: From 1995 to 2008, 503 Japanese patients undergoing RP for clinically localized prostate cancer were included in the validation cohort. The BCR-free rate was estimated using the Kaplan-Meier method. Performance of the CAPRA score was assessed using Cox proportional hazards regression models, concordance index (c-index) and calibration plots. Results: Unlike the results in the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) cohort, the BCR-free rate and the hazard ratio for CAPRA score 4 were inversely better than those for CAPRA scores 2 and 3 in Japanese patients. The c-index of the CAPRA score was 0.673. The calibration plot demonstrated that the CAPRA score was generally well calibrated. Conclusions: In Japanese patients, the CAPRA score can predict BCR after RP only to some degree. Although our c-index is comparable with the c-index of 0.66 in the original CaPSURE cohort, it is lower than the c-indices reported in other validation cohorts, which range from 0.68 to 0.81. The CAPRA score may not predict BCR after RP in Japanese patients as accurately as it did in Western patients. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

If a mathematical model is to be used in the diagnosis, treatment, or prognosis of a disease, it must describe the inherent quantitative dynamics of the state. An ideal candidate disease is prostate cancer owing to the fact that it is characterized by an excellent biomarker, prostate-specific antigen (PSA), and also by a predictable response to treatment in the form of androgen suppression therapy. Despite a high initial response rate, the cancer will often relapse to a state of androgen independence which no longer responds to manipulations of the hormonal environment. In this paper, we present relevant background information and a quantitative mathematical model that potentially can be used in the optimal management of patients to cope with biochemical relapse as indicated by a rising PSA. [ABSTRACT FROM PUBLISHER]

Purpose: This study attempts to improve our understanding of the role of salvage radiotherapy (SRT) in patients with prostate-specific antigen (PSA) relapse after radical prostatectomy with regard to biochemical control, rate of distant metastasis, and survival. Methods and Materials: We performed a retrospective analysis of 96 men treated with conformal prostate bed SRT (median, 64.8 Gy) at a single institution (median follow-up, 70 months). The majority had intermediate- or high-risk prostate cancer. Fifty-four percent underwent a resection with positive margins (R1 resection). The median time interval between surgery and SRT was 22 months. Results: After SRT, 66% of patients reached a PSA nadir of less than 0.2 ng/mL. However, the 5-year biochemical no evidence of disease rate was 35%. Seminal vesicle involvement was predictive for a significantly lower biochemical no evidence of disease rate. All patients with a preoperative PSA level greater than 50 ng/mL relapsed biochemically within 2 years. The 5-year distant metastasis rate was 18%, the 5-year prostate cancer–specific survival rate was 90%, and the 5-year overall survival rate was 88%. Significantly more distant metastases developed in patients with a PSA nadir greater than 0.05 ng/mL after SRT, and they had significantly inferior prostate cancer–specific and overall survival rates. Resection status (R1 vs. R0) was not predictive for any of the endpoints. Conclusions: Men with postoperative PSA relapse can undergo salvage treatment by prostate bed radiotherapy, but durable PSA control is maintained only in about one-third of the patients. Despite a high biochemical failure rate after SRT, prostate cancer–specific survival does not decrease rapidly. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate genitourinary (GU) and gastrointestinal (GI) morbidity and biochemical control of disease in patients with localized prostate adenocarcinoma treated with escalating doses per fraction of high-dose rate brachytherapy alone. Methods and Materials: A total of 197 patients were treated with 34 Gy in four fractions, 36 Gy in four fractions, 31.5 Gy in three fractions, or 26 Gy in two fractions. Median follow-up times were 60, 54, 36, and 6 months, respectively. Results: Incidence of early Grade ≥ 3 GU morbidity was 3% to 7%, and Grade 4 was 0% to 4%. During the first 12 weeks, the highest mean International Prostate Symptom Score (IPSS) value was 14, and between 6 months and 5 years it was 8. Grade 3 or 4 early GI morbidity was not observed. The 3-year actuarial rate of Grade 3 GU was 3% to 16%, and was 3% to 7% for strictures requiring surgery (4-year rate). An incidence of 1% Grade 3 GI events was seen at 3 years. Late Grade 4 GU or GI events were not observed. At 3 years, 99% of patients with intermediate-risk and 91% with high-risk disease were free of biochemical relapse (log-rank p = 0.02). Conclusions: There was no significant difference in urinary and rectal morbidity between schedules. Biochemical control of disease in patients with intermediate and high risk of relapse was good. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To compare freedom from biochemical failure (FFBF) of French Polynesian (FP) and Native European (NE) prostate cancer patients after definitive conformal radiotherapy (RT). Patients and methods: Data were reviewed from medical records of 152 consecutive patients (46 FP and 106 NE) with clinically localised prostate cancer treated with definitive RT. Neoadjuvant androgen deprivation therapy (ADT) was used in 22% of cases. Definition for biochemical failure was a rise by 2ng/mL or more above the nadir prostate-specific antigen (PSA) level. The median follow-up was 34months. Results: In comparison to NE patients, FP patients were younger (p =0.002) with a higher low-risk proportion (p =0.06). Probability of 5-year FFBF was 77% in the NE cohort and 58.0% in the FP cohort (p =0.017). Univariate analysis showed that FP ethnicity was associated with worse prognosis in high-risk tumours (p =0.004). Cox multivariate analysis showed that factors associated with FFBF were risk category (p <0.017), and FP origin (p =0.03), independently of ADT and radiation dose. Conclusion: FP ethnicity was an independent prognostic factor for biochemical relapse after definitive conformal RT for prostate cancer. [Copyright &y& Elsevier]

Introduction. RP (radical prostatectomy) technique continues the major treatment option for men with potential cure and life expectancy exceeding 10 years. The aim of the study is to assess the impact of PSM on BR (biochemical relapse), to identify PSM risk factors, to clarify the factors involved in BR in the absence of PSM. Material and methods. Consultation of 171 medical-records from patients submitted to RRP (radical retropubic prostatectomy) between January/2000-December/2005. Mean-age: 64 yr. Mean - PSA (positive surgical margin): 11.88 ng/ml. Clinical staging: 67.8% cT1, 32.2% cT2. GS: ⩽6 (66.1%), =7 (21.1%), 8-10 (12.3%). PS: pT0 1.2%, pT2 50.3%, pT3a 36.3%, pT3b 12.9%, pT4 0.6%. pathological Gleason score: ⩽6 39.2%, =7 40.9%, 8-10 19.3%. RB definition was PSA ⩾0.2 ng/ml. Adjusted Odds-Ratios with 95% confidence intervals (CI) were estimated through univariate logistic regression. Results. There were PSM in 46 specimens, 28 had single PSM and 18 multiple PSM (⩾2). BR occurred in 57 patients (33.3%), with an average time after surgery of 23.5 months - 26 patients had PSM and 31 had not. Statistical significant results for BR in variables PSA, PS and PSM. Quadruples if PSM (p <0.0001), triples in single PSM (p = 0.01) and is 6x higher in multiple PSM (p = 0.001). Regarding factors that influence the presence of PSM, only PS ⩾pT3a reach statistical significance (p <0.0001). Patients with BR but without PSM (54.38%), variables statistically significant were: initial PSA >10, (p = 0.029) and pathological Gleason score ⩾8 with a risk nearly 4x higher than pathological Gleason score ⩽6 (p = 0.027). Conclusions. Statistical risk analysis concluded that the presence of PSM in RRP is strongly influenced by PS ⩾pT3a. The presence of PSM and their number increase significantly the risk of BR compared to other factors. In the absence of PSM, the factors that seem to be crucial and with greater impact on BR are initial PSA>10 and pathological Gleason score ⩾8. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: The British Columbia Cancer Agency has been performing iodine-125 prostate brachytherapy since 1998, initially using loose seeds and phasing into the exclusive use of RAPIDStrand (RS) (Oncura Inc., Plymouth Meeting, PA) by November 2000. The aim of this study was to investigate rates of biochemical no evidence of disease (bNED) in patients treated with loose seeds compared with RS from this population-based cohort. Methods and materials: Between July 1998 and February 2006, 1500 implants were performed (327 loose and 1173 RS). Biochemical failure is reported using the Phoenix definition and prostate-specific antigen (PSA) >0.4ng/mL at ≥48 months postimplant. Actuarial estimates were calculated by the Kaplan–Meier method. Analysis was repeated with the first 100 loose and stranded implants excluded to assess the learning curve effect. Log-rank test was used to evaluate differences in bNED. Variables showing association with bNED were included in a multivariate model. Results: There was no difference between loose and stranded seeds. Estimated rate of bNED was 93.5% (95% confidence interval [CI], 90.6–96.4) at 7 years for patients treated with loose seeds and 94.0% (95% CI, 91.8–96.2) for patients treated with RS according to Phoenix definition (p =0.846). Using the PSA >0.4ng/mL definition, estimated rates were 91.3% (95% CI, 88.0–94.6) and 91.9% (95% CI, 89.7–94.1) for loose and stranded seeds, respectively (p =0.871). Exclusion of the first 100 loose and stranded implants also revealed no difference in bNED. Conclusion: This study of 1500 patients treated with iodine-125 brachytherapy demonstrates no difference in bNED between loose and stranded seeds, using either Phoenix or PSA >0.4ng/mL definitions of biochemical failure. [Copyright &y& Elsevier]

Hypoxia inducible factor-1 alpha (HIF-1α) is known as an important transcription factor in endocrine tumours. It is elevated in hypoxic tumour microenvironment, increasing angiogenesis and enabling tumour cells to enter the circulation. We therefore hypothesised that patients with advanced prostate cancer disease have high tumoural HIF-1α xpression and worse disease specific survival. Aim of this study was to assess expression of HIF-1α in prostate cancer specimens taken before and after castrate resistance to address its cellular location and to examine if this is associated with clinicopathological features and clinical outcome of the particular prostate cancer cohort. 50 pairs of hormone naive and castrate resistant prostate cancer specimens were analysed employing tissue microarray technology. Immunohistochemistry was performed using an antibody to HIF-1α. HIF-1α expression was observed in both, cytoplasm and nucleus. Cytoplasmic HIF-1α expression correlated positively with metastases at diagnosis (p=0.005), whereas nuclear HIF-1α expression correlated with metastases at relapse (p=0.041). Cytoplasmic and nuclear HIF-1α expression did not change from hormone naive to hormone castrate resistant tumours. No significant association was observed in this study between tumoural HIF-1α expression, biochemical relapse and patient survival. HIF-1α was associated with the presence of metastases at time of diagnosis and time of relapse. HIF-1α is likely to play a role in progressive prostate cancer. [ABSTRACT FROM AUTHOR]

C-reactive protein (CRP) is an acute phase protein implicated in the progression of cancer. A positive correlation between tumour stage and plasma CRP levels was demonstrated in prostate cancer, indicating a relationship between raised CRP levels and more aggressive disease, suggesting a role for inflammatory response in tumour progression. Aim of this study was to assess the tumoural presence and cellular location of CRP and establish if these are linked to clincopathological features of the cohort and patient survival. Tissue microarray technology was employed to analyse 50 matched pairs of hormone sensitive and refractory prostate cancers. Immunohistochemistry was performed using antibody to CRP. CRP was assessed using the weighted histoscore method. CRP presence was observed in the cytoplasm and nucleus of selected tumours. Cytoplasmic CRP correlated positively with metastases at diagnosis (P=0.039), whereas nuclear CRP presence correlated with metastases at relapse (P=0.006). A trend towards an increase in cytoplasmic and nuclear CRP presence from hormone sensitive to hormone refractory tumours was noticed. No significant association between tumoural CRP presence, time to biochemical relapse or disease-specific survival was observed. Tumoural CRP is likely to have a role in progression of prostate cancer, as it is associated with increased presence of metastases at the time of diagnosis and time of relapse. A larger powered study is necessary to establish if CRP presence is associated with disease-specific survival. [ABSTRACT FROM AUTHOR]

Purpose: Primary androgen deprivation therapy (PADT) is an important treatment modality for men with localized or locally advanced prostate cancer and without bone metastasis. There is, however, a lack of data on the biochemical relapse (BR) outcomes in these patients. Here, we studied the outcome of a contemporary series of men treated by PADT and investigated predictive risk factors for BR. Methods: One hundred and fifty-five patients treated by PADT formed the initial study cohort, and BR outcomes in this group were reviewed. The outcomes of men with bone scan negative disease were specifically analysed. The predictive value of a panel of clinical risk factors for BR was evaluated using univariate and multivariate analysis. The results were further validated in a separate cohort of patients without bone metastasis from a second institution ( n = 84). Results: Median follow-up was 70 months. In the first study cohort, 109/155 men (70%) had bone scan negative disease. In these patients, only 45% developed BR during the follow-up period with only 28% relapsing within 5 years of initiating PADT. Key-independent factors predicting BR were a high PSA nadir ( p = 0.001) and a shorter time to nadir ( p < 0.001). A nadir of ≤0.1 ng/ml and time to nadir of >24 months specifically identified men with a very good outcome from PADT. In a second-independent cohort, very similar overall and 5-year BR rates were observed in men without bone metastasis (39 and 35%, respectively). PSA nadir thresholds identified in the first cohort were again able to define a good prognostic group in this re-test cohort ( p = 0.005 and p = 0.01, respectively). Conclusion: Men treated by PADT and without bone metastasis can have very durable responses to PADT with the majority remaining BR free at 5 years. PSA nadir and time to nadir are key predictors of a good outcome in this group. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to evaluate the potential usefulness of whole-body C-choline PET/CT in the re-staging of prostate cancer (PC) patients previously treated with radical prostatectomy (RP), who presented a mild increase of prostate-specific antigen (PSA) <1.5 ng/ml (early biochemical relapse) during follow-up (FU). Methods: We evaluated 102 consecutive patients (mean age = 68 years, range = 54-82 years) previously treated with RP and who presented during FU a mild increase of trigger PSA serum levels <1.5 ng/ml: mean 0.86 ± 0.40 ng/ml (range 0.2-1.5) and median 0.93 ng/ml (range 0.67-1.10). In this patient series C-choline PET/CT was used as the first imaging examination at the time of the detection of a mild serum PSA increase <1.5 ng/ml. C-Choline PET/CT was performed following standard procedures in our centre. At the time of PET/CT, 86 patients were not receiving any pharmacologic treatment, while 16 were under anti-androgenic therapy. Positive PET findings were validated by: (a) transrectal ultrasound (TRUS)-guided biopsy in cases of local recurrence, (b) surgical lymphadenectomy, (c) other imaging procedures or (d) FU lasting for at least 12 months. Univariate and multivariate analyses were used to evaluate the following variables: age, TNM staging, Gleason score, time from RP to the biochemical relapse, anti-androgen therapy at the time of C-choline PET/CT scan, trigger PSA value and PSA kinetics, i.e. PSA doubling time (PSAdt) and PSA velocity (PSAvel), in order to assess the significant predictive factors related to the findings of a positive C-choline PET/CT scan. Results: Overall, C-choline PET/CT showed positive findings in 29 of 102 patients (28% of cases). In detail, C-choline PET/CT detected: local relapse in 7 patients, bone metastases in 13 patients (4 single and 9 multiple) and lymph node metastases in 9 patients (6 single and 3 multiple). Positive PET findings were validated by: (a) TRUS-guided biopsy in 7 patients with local recurrence, (b) surgery and lymphadenectomy in 3 patients, (c) other targeted imaging procedures (MR or bone scan) in 5 patients and (d) clinical FU lasting a minimum of 12 months and including also a contrast-enhanced CT (CECT), an MR, a bone scan and a repeated C-choline PET/CT in 14 patients. Age, time to biochemical relapse (TTR), initial T staging, Gleason score and trigger PSA were not statistically significant in predicting a positive C-choline PET/CT scan both at univariate and multivariate analysis. Instead, PSA kinetics (PSAdt and PSAvel), N status and anti-androgenic therapy at the time of PET scan were statistically significant predictive factors at univariate analysis. Of note, only PSAdt and initial N status were found to be significant and independent predictive factors at multivariate analysis. The mean PSAdt in PET-positive patients was 4.34 months (SD 2.82) while in PET-negative patients it was 13.30 months (SD 9.75) ( p = 0.0001). The optimal threshold for PSAdt established by receiver-operating characteristic (ROC) analysis was 7.25 months (AUC 0.85; 95% confidence interval 0.77-0.91) providing 93% sensitivity, 74% specificity, 60% positive predictive value and 96% negative predictive value. Conclusion: In our study, C-choline PET/CT was able to detect recurrent disease in 28% of the patients with mild biochemical relapse characterized by very low trigger PSA levels (PSA <1.5 ng/ml). Very interestingly C-choline PET/CT detected distant unexpected metastases in 21% of the patients. At multivariate statistical analysis only PSAdt and node status were shown to be significant and independent predictive factors for positive C-choline PET/CT. Therefore, C-choline could be suggested to be performed early during initial biochemical relapse in patients presenting with fast PSA kinetics. The early detection of the site of recurrence could lead to a prompt instauration of the most appropriate treatment, i.e. local surgery or radiation treatment vs systemic treatment. In this view, one of the main advantages should be the avoidance of unnecessary local radiotherapy in those patients showing distant metastasis at C-choline PET/CT. [ABSTRACT FROM AUTHOR]

Objective. The presence of a tertiary Gleason grade (TGG) pattern 4 or 5 in radical prostatectomy (RP) specimens has been reported with adverse pathology and a higher biochemical relapse rate after RP. This study investigated the impact of a TGG pattern 4 or 5 on biochemical and pathological outcome in men operated with RP. Material and methods. The study reviewed 151 consecutive cases treated at the hospital between 1985 and 2006; 148 were included in the study. All prostatectomy specimens were re-examined by a genitourinary pathologist and among others parameters the presence of TGG pattern 4 or 5 was recorded. The hospital files were examined retrospectively for clinical follow-up data. Prostate-specific antigen (PSA) relapse was defined as two subsequent rising measurements above 0.20 ng/ml. The influence of a TGG pattern 4 or 5 on prognosis was assessed in a Cox proportional hazards regression model controlling for pathological stage, surgical margin (SM) status, seminal vesicle invasion (SVI) and extraprostatic extension (EPE). Results. Fifty-six patients (38%) experienced PSA relapse during follow-up. Twenty-one patients (58%) with a TGG pattern 4 or 5 had a biochemical relapse compared with 35 patients (31%) without TGG pattern 4 or 5. In the Cox regression model, TGG pattern 4 or 5 was an independent predictor of biochemical failure ( p = 0.020). Conclusions. In patients undergoing RP the presence of a TGG pattern 4 or 5 is an independent predictor for biochemical relapse. Consequently, the RP specimens should routinely be investigated for TGG pattern 4 or 5. [ABSTRACT FROM AUTHOR]

The biochemical relapse of prostate cancer is diagnostically challenging but of high clinical impact for subsequent patient treatment. PET/CT with radiolabeled PSMA ligands outperforms conventional diagnostic methods in the detection of tumor recurrence. Several radiopharmaceuticals were and are available for use. The aim of this study was to investigate whether the routinely applied [68Ga]Ga-PSMA ligands PSMA-617, -I&T and -11 (HBED-CC) differ in physiological and pathological distribution, or in tumor detection rate. A retrospective evaluation of 190 patients (39 patients received PSMA-617, 68 patients PSMA-I&T and 83 patients PSMA-11) showed significant differences in tracer accumulation within all organs examined. The low retention within the compartments blood pool, bone and muscle tissue is a theoretical advantage of PSMA-11. Evaluation of tumor lesion uptake and detection rate did not reveal superiority of one of the three radiopharmaceuticals, neither in the whole population, nor in particularly challenging subgroups like patients with very low PSA levels. We conclude that all three [68Ga]Ga-PSMA ligands are equally feasible in this clinically important scenario, and may replace each other in case of unavailability or production restrictions. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To assess the efficacy of granulocyte macrophage colony-stimulating factor (GM-CSF) in combination with thalidomide on prostate-specific antigen (PSA) reduction in hormone-naïve prostate carcinoma (HNPC) patients with rising PSA levels after definitive local treatment. Materials and methods: HNPC patients (n = 21) with evidence of progression demonstrated by 3 consecutive rises in PSA and no evidence of radiographic involvement were treated on a chronic dosing schedule with GM-CSF. Patients received 250 μg/m2 (maximum 500 μg) 3 times a wk by subcutaneous injection, with injections at least 24 h apart. Thalidomide administration began concurrently with an initial dose of 100 mg daily for 7 consecutive days. During wk 2 to 4, the dose was escalated every 7 d by 100 mg per individual tolerance to a maximum of 400 mg. The maximum tolerated dose of thalidomide was continued without interruption. PSA, testosterone, and routine laboratory parameters were measured every 6 wk. Results: One patient was not evaluable because of noncompliance. For the 20 evaluable patients, baseline PSA levels ranged from 1.3 to 61.0 ng/ml. Nineteen patients left the study at 3.0 to 33.3 mo, secondary to individual tolerance, progressive disease, or development of a second primary tumor. One patient continues to receive therapy at 33.8 mo. Two patients did not respond to the therapy. For the 18 patients who did respond, the median reduction in PSA level was 59% (range 26%–89%), and the median duration of response was 11 mo (range 4.5–36). Grades 1–2 toxicity included peripheral neuropathy, fatigue, skin rash, and constipation. One patient had deep-vein thrombosis/pulmonary embolism. Conclusions: GM-CSF plus thalidomide can be administered successfully with encouraging antitumor activity and reversible toxicity. This may represent an alternative to hormonal therapy. [Copyright &y& Elsevier]

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The patient population with a rising prostate specific antigen (PSA) post-therapy with no evidence of disease on standard imaging studies currently represents the second largest group of prostate cancer patients. Little information is still available regarding the specificity and sensitivity of positron emission tomography (PET) tracers in the assessment of early biochemical recurrence. Ideally, PET imaging would allow one to accurately discriminate between local vs nodal vs distant relapse, thus enabling appropriate selection of patients for salvage local therapy. The vast majority of studies show a relatively poor yield of positive scans with PSA values <4 ng ml−1. So far, no tracer has been shown to be able to detect local recurrence within the clinically useful 1 ng ml−1 PSA threshold, clearly limiting the use of PET imaging in the post-surgical setting. Preliminary evidence, however, suggests that 11C-choline PET may be useful in selecting out patients with early biochemical relapse (PSA <2 ng ml−1) who have pelvic nodal oligometastasis potentially amenable to local treatment. The role of PET imaging in prostate cancer is gradually evolving but still remains within the experimental realm. Well-conducted studies comparing the merits of different tracers are needed.Prostate Cancer and Prostatic Diseases (2008) 11, 121–128; doi:10.1038/sj.pcan.4501028; published online 8 January 2008 [ABSTRACT FROM AUTHOR]

OBJECTIVE To determine the biological effects of imatinib mesylate (STI-571, Gleevec®; Novartis Pharmaceuticals, Inc., East Hanover, NJ, USA), as measured by prostate-specific antigen (PSA) kinetics in men with biochemical relapse of prostate cancer after definitive local therapy. PATIENTS AND METHODS Men with prostate cancer, who had had definitive local therapy, with nonmetastatic recurrent disease as manifested by a rising PSA level, were enrolled on this phase II trial. Men received 400 mg of imatinib mesylate orally twice daily and continuously until disease progression or unacceptable toxicity. The PSA level was measured monthly. RESULTS In all, 20 men with biochemically relapsed prostate cancer were treated. The median pretreatment PSA level was 5.4 ng/mL. Of the 19 evaluable men, one achieved a ≥ 50% reduction in PSA level and two had decreases of <50%. For the 16 men in whom the on-treatment PSA doubling time (PSADT) could be calculated (those with increasing PSA level) the median PSADT did not increase significantly (5.8 vs 7.2 months, P = 0.64). Eleven of 20 men discontinued therapy due to toxicity and the trial was stopped early due to toxicity. CONCLUSIONS Based on the lack of PSA modulation and pronounced toxicities leading to early closure of this trial, further study of single-agent imatinib mesylate at this dose (400 mg twice daily) cannot be recommended in this patient population. [ABSTRACT FROM AUTHOR]

Purpose: To determine the false call (FC) rate for prostate-specific antigen (PSA) relapse according to nine different PSA relapse definitions after a PSA fluctuation (bounce) has occurred after external beam radiation therapy (EBRT) or brachytherapy, with or without adjuvant androgen deprivation therapy. Methods and Materials: An analysis of a prospective database of 2030 patients was conducted. Prostate-specific antigen relapse was scored according to the American Society for Therapeutic Radiology and Oncology (ASTRO), Vancouver, threshold + n, and nadir + n definitions for the complete data set and then compared against a truncated data set, with data subsequent to the height of the bounce deleted. The FC rate was calculated for each definition. Results: The bounce rate, with this very liberal definition of bounce, was 58% with EBRT and 84% with brachytherapy. The FC rate was lowest with nadir + 2 and + 3 definitions (2.2% and 1.6%, respectively) and greatest with low-threshold and ASTRO definitions (32% and 18%, respectively). The ASTRO definition was particularly susceptible to FC when androgen deprivation therapy was used with radiation (24%). Discussion: New definitions of biochemical non-evidence of disease that are more robust than the ASTRO definition have been identified. Those with the least FC rates are the nadir + 2 and nadir + 3 definitions, both of which are being considered to replace the ASTRO definition by the 2005 meeting of the Radiation Therapy Oncology Group–ASTRO consensus panel. [Copyright &y& Elsevier]

Purpose: To investigate whether prostate-specific antigen PSA doubling time (PSADT) is constant in men with biochemical prostate cancer relapse after external beam radiotherapy (EBRT). Methods and Materials: A total of 513 men treated radically with EBRT, with or without androgen ablation (AA), between 1993 and 2000, developed biochemical relapse. The slope of the ln (PSA) vs. time graph is calculated for the first two values after PSA nadir (first slope), the last two recorded PSAs (last slope), and all values excluding the first and final PSA (mid slope). Differences in these slopes were compared statistically with subgroup analysis for AA and secondary intervention. Results: For men treated with EBRT and AA first slope was faster than either mid slope (p = 0.031) or last slope (p < 0.001). Men treated with EBRT alone had no change in PSADT over time unless they subsequently received secondary intervention. This group had a more rapid last slope compared with mid slope (p < 0.001). Conclusions: PSA initially rises more rapidly after AA cessation, probably because of testosterone recovery. A subgroup of patients, who received secondary intervention after treatment with radiotherapy alone, showed a change in PSADT, to a faster velocity. This greater than constant exponential PSA growth is presumably the catalyst for secondary intervention. Otherwise, PSADT did not change during prostate cancer biochemical relapse. [Copyright &y& Elsevier]

Our understanding of the screening, prevention and treatment of early prostate cancer is improving. This is a result of new data from clinical trials and the incorporation of efficacy measures based on risk assessment and quality of life (QoL). This review aims to examine completed and ongoing clinical trials that address issues in early prostate cancer, including screening, prevention, treatment, and QoL. Prostate-specific antigen (PSA) testing has a crucial and evolving role in detecting primary prostate cancer, evaluating prevention interventions and assessing the effectiveness of treatment. Questions remain about the optimal PSA parameters appropriate for primary screening and for diagnosing relapse. Emerging and established data provide evidence that early intervention with hormone therapy, either as immediate or adjuvant therapy, delays progression in prostate cancer patients with intermediate or poor prognosis. The impact of therapeutic modality on QoL has become better characterized, as QoL instruments have been developed, validated and applied. [Copyright &y& Elsevier]

Introduction: Prostate cancer (PCa) is the second most prevalent neoplasm among men in the world. Its treatment has a wide spectrum of alternatives and variables, ranging from active surveillance through radio and/or brachytherapy, to surgery., Objective: The present work aimed to identify the predictive factors for biochemical recurrence and to evaluate the toxicity of the treatment using the association of external beam radiation therapy (EBRT) with high dose rate brachytherapy (HDR-BT) applied in the treatment of patients with prostate cancer., Methods: Longitudinal retrospective study, using a prospectively collected database between 2005 and 2014 of 186 consecutive patients records with a diagnosis of low, intermediate, or high-risk prostate cancer treated with EBRT combined with HDR-BT, in a single medical institution located in the city of Campinas, SP, Brazil (Radium Institute). PSA increase over 2 ng/ml above the nadir PSA was considered as biochemical recurrence, following the definition of the Phoenix Consensus. Continuous and clinically relevant categorical variables (age, initial PSA, delivered dose in EBRT, number of implants, number of positive cores in transrectal biopsy, use of hormone blockade, Gleason score, TNM staging, post treatment PSA and PSA Nadir) were evaluated with absolute (n) and percentage (%) values using multiple logistic regression and validated our previously described optimal PSA nadir as predictor of biochemical recurrence., Results: Post treatment PSA was the only independent predictor of biochemical recurrence, P<0.0001. The lower the PSA nadir the lower the biochemical recurrence risk (P=0.0009). PSA nadir >1 was the best cutoff (P=0.018) determinant of biochemical recurrence. The incidence of grade 3 late toxicity to the genitourinary tract was 0.6%, and there were no cases of severe complications to the gastrointestinal tract., Conclusion: External Beam Radiation Therapy conjugated to Brachytherapy in the treatment of Prostate Cancer has demonstrated low biochemical recurrence rates, mainly when PSA nadir <1, with low toxicity into both GU and GI tracts., Competing Interests: None., (AJCEU Copyright © 2022.)

Biochemical recurrence (BCR) is a clinical challenge in prostate cancer (PCa) patients, as recurrence localization guides subsequent therapies. The use of PET with prostate-specific membrane antigen (PSMA) provides better accuracy than conventional imaging practice. This prospective, multicenter, international study was performed to evaluate the diagnostic performance and clinical impact of PSMA PET/CT for evaluating BCR in PCa patients in a worldwide scenario. Methods: Patients were recruited from 17 centers in 15 countries. Inclusion criteria were histopathologically proven prostate adenocarcinoma, previous primary treatment, clinically established BCR, and negative conventional imaging (CT plus bone scintigraphy) and MRI results for patients with PSA levels of 4-10 ng/mL. All patients underwent PET/CT scanning with 68 Ga-PSMA-11. Images and data were centrally reviewed. Multivariate logistic regression analysis was applied to identify the independent predictors of PSMA-positive results. Variables were selected for this regression model on the basis of significant associations in the univariate analysis and previous clinical knowledge: Gleason score, the PSA level at the time of the PET scan, PSA doubling time, and primary treatment strategy. All patients were monitored for a minimum of 6 mo. Results: From a total of 1,004 patients, 77.7% were treated initially with radical prostatectomy and 22.3% were treated with radiotherapy. Overall, 65.1% had positive PSMA PET/CT results. PSMA PET/CT positivity was correlated with the Gleason score, PSA level at the time of the PET scan, PSA doubling time, and radiotherapy as the primary treatment ( P < 0.001). Treatment was modified on the basis of PSMA PET/CT results in 56.8% of patients. PSMA PET/CT positivity rates were consistent and not statistically different among countries with different incomes. Conclusion: This multicenter, international, prospective trial of PSMA PET/CT confirmed its capability for detecting local and metastatic recurrence in most PCa patients in the setting of BCR. PSMA PET/CT positivity was correlated with the Gleason score, PSA level at the time of the PET scan, PSA doubling time, and radiotherapy as the primary treatment. PSMA PET/CT results led to changes in therapeutic management in more than half of the cohort. The study demonstrated the reliability and worldwide feasibility of PSMA PET/CT in the workup of PCa patients with BCR., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

The biochemical relapse of prostate cancer is diagnostically challenging but of high clinical impact for subsequent patient treatment. PET/CT with radiolabeled PSMA ligands outperforms conventional diagnostic methods in the detection of tumor recurrence. Several radiopharmaceuticals were and are available for use. The aim of this study was to investigate whether the routinely applied [ 68 Ga]Ga-PSMA ligands PSMA-617, -I&T and -11 (HBED-CC) differ in physiological and pathological distribution, or in tumor detection rate. A retrospective evaluation of 190 patients (39 patients received PSMA-617, 68 patients PSMA-I&T and 83 patients PSMA-11) showed significant differences in tracer accumulation within all organs examined. The low retention within the compartments blood pool, bone and muscle tissue is a theoretical advantage of PSMA-11. Evaluation of tumor lesion uptake and detection rate did not reveal superiority of one of the three radiopharmaceuticals, neither in the whole population, nor in particularly challenging subgroups like patients with very low PSA levels. We conclude that all three [ 68 Ga]Ga-PSMA ligands are equally feasible in this clinically important scenario, and may replace each other in case of unavailability or production restrictions.

Abstract Purpose To evaluate predictive factors for PSA bounce after 125I permanent seed prostate brachytherapy and identify criteria that distinguish between benign bounces and biochemical relapses. Materials and methods Men treated with exclusive permanent 125I seed brachytherapy from November 1999, with at least a 36 months follow-up were included. Bounce was defined as an increase ≥ 0.2 ng/ml above the nadir, followed by a spontaneous return to the nadir. Biochemical failure (BF) was defined using the criteria of the Phoenix conference: nadir +2 ng/ml. Results 198 men were included. After a median follow-up of 63.9 months, 21 patients experienced a BF, and 35.9% had at least one bounce which occurred after a median period of 17 months after implantation (4-50). Bounce amplitude was 0.6 ng/ml (0.2-5.1), and duration was 13.6 months (4.0-44.9). In 12.5%, bounce magnitude exceeded the threshold defining BF. Age at the time of treatment and high PSA level assessed at 6 weeks were significantly correlated with bounce but not with BF. Bounce patients had a higher BF free survival than the others (100% versus 92%, p = 0,007). In case of PSA increase, PSA doubling time and velocity were not significantly different between bounce and BF patients. Bounces occurred significantly earlier than relapses and than nadir + 0.2 ng/ml in BF patients (17 vs 27.8 months, p < 0.0001). Conclusion High PSA value assessed 6 weeks after brachytherapy and young age were significantly associated to a higher risk of bounces but not to BF. Long delays between brachytherapy and PSA increase are more indicative of BF.