pre-RT Prostate-specific Antigen Research Articles

Hypofractionated radiation therapy combined with androgen deprivation therapy for high-risk localized prostate cancer.

This study aimed to analyse the treatment outcomes of moderately hypofractionated radiation therapy (RT) combined with androgen deprivation therapy (ADT) and the prognostic implications of prostate-specific antigen (PSA) kinetics in high-risk localized prostate cancer. The medical records of 140 patients who underwent definitive RT (70 Gy in 28 fractions) combined with ADT were retrospectively reviewed. ADT consists of a gonadotropin-releasing hormone agonist and an anti-androgen. Clinical outcomes included the biochemical failure rate (BFR), clinical failure rate (CFR), overall survival (OS) and prostate cancer-specific survival (PCSS). The BFR and CFR were stratified by the PSA nadir and the time to the PSA nadir, respectively. Acute and late genitourinary and gastrointestinal adverse events were also recorded. The 5-year BFR, CFR, OS and PCSS rates were 9.8%, 4.5%, 90.2% and 98.7%, respectively. Ninety-five (67.9%) patients achieved a PSA nadir of 0.01 ng/mL. Patients with a PSA nadir >0.01 ng/mL had a significantly higher BFR and CFR (BFR, P = 0.001; CFR, P = 0.027), even after adjusting for other prognostic factors [per 0.1 ng/mL; BFR, hazard ratio (HR) 4.440, P < 0.001; CFR, HR 4.338, P = 0.001]. However, the time to the PSA nadir and pre-RT PSA were not significantly associated with the BFR and CFR. Six patients (4.3%) reported grade 3 late adverse events, mostly haematuria and haematochezia. Definitive RT with moderate hypofractionation combined with long-term ADT showed good efficacy for high-risk localized prostate cancer. The lowest PSA nadir was significantly associated with a low recurrence rate, indicating the importance of PSA follow-up.

Prostate-specific membrane antigen-based imaging for stereotactic irradiation of low-volume progressive prostate cancer: a single-center experience.

Prostate-specific membrane antigen (PSMA) is a transmembrane protein that may be expressed on the surface of prostate cancer (PC) cells. It enables a more sensitive and specific diagnosis PC, compared to conventional anatomical imaging. The integration of PSMA-based imaging in the personalized radiotherapy of PC patients and the evaluation of its impact on target volume definition if stereotactic body radiotherapy (SBRT) is planned for locally recurrent or oligometastatic disease. The data from 363 examinations were analyzed retrospectively. Inclusion criteria were histologically verified PC and clinical data suggesting local recurrence or distant metastasis. Whole-body 99mTc-PSMA-I&S single-photon emission computed tomography (SPECT)/CT or 18F-JK-PSMA-7 positron emission tomography/computer tomography (PET/CT) was carried out, and the evaluation of the scans and biological tumor volume contouring was performed at the Department of Nuclear Medicine. The target volume delineation on topometric CT (TCT) scan was performed at the Department of Oncotherapy. The comparison of the two volumes was performed by image fusion and registration. From 363 PSMA isotope-based examinations, 84 lesions of 64 patients were treated with SBRT. In 50 patients, 70 lesions were examined for intermodality comparison. The target volume defined by the PSMA density was significantly smaller than the tumor size defined by the TCT scan: GTVCT (gross tumor volume on the TCT), 27.58 ± 46.07 cm3; BTVPSMA (biological target volume on the PSMA-based examination), 16.14 ± 29.87 cm3. During geometrical analyses, the Dice similarity coefficient (DSC) was 0.56 ± 0.20 (0.07-0.85). Prostate-specific antigen (PSA) control was performed to evaluate the response: mean pre-radiotherapy (pre-RT) PSA was 16.98 ng/ml ( ± SD: 33.81), and post-RT PSA at 3 months after SBRT was 11.19 ng/ml ( ± SD: 32.85). Three-month post-therapy PSMA-based imaging was performed in 14 cases, in which we observed a decrease or cessation of isotope uptake. Conventional imaging control was performed in 42 cases (65.6% of all cases): 22 (52.4%) complete remissions, 14 (33.3%) partial remissions, four (9.5%) stable diseases, and two (4.8%) progressive diseases were described. PSMA-based imaging is a promising diagnostic method for specifying the stage and detecting the low-volume progression. Our results suggest that PSMA-based hybrid imaging can influence treatment decisions and target volume delineation for SBRT.

Dose-Volume Histogram Parameters and Quality of Life in Patients with Prostate Cancer Treated with Surgery and High-Dose Volumetric-Intensity-Modulated Arc Therapy to the Prostate Bed.

Prostate bed radiotherapy (RT) is a major affecter of patients' long-term quality of life (QoL). To ensure the best possible outcome of these patients, dose constraints are key for optimal RT planning and delivery. However, establishing refined dose constraints requires access to patient-level data. Therefore, we aimed to provide such data on the relationship between OAR and gastrointestinal (GI) as well as genitourinary (GU) QoL outcomes of a homogenous patient cohort who received dose-intensified post-operative RT to the prostate bed. Furthermore, we aimed to conduct an exploratory analysis of the resulting data. Patients who were treated with prostate bed RT between 2010 and 2020 were inquired about their QoL based on the Expanded Prostate Cancer Index Composite (EPIC). Those (n = 99) who received volumetric arc therapy (VMAT) of at least 70 Gy to the prostate bed were included. Dose-volume histogram (DVH) parameters were gathered and correlated with the EPIC scores. The median age at the time of prostate bed RT was 68.9 years, and patients were inquired about their QoL in the median 2.3 years after RT. The median pre-RT prostate-specific antigen (PSA) serum level was 0.35 ng/mL. The median duration between surgery and RT was 1.5 years. The median prescribed dose to the prostate bed was 72 Gy. A total of 61.6% received prostate bed RT only. For the bladder, the highest level of statistical correlation (p < 0.01) was seen for V10-20Gy, Dmean and Dmedian with urinary QoL. For bladder wall, the highest level of statistically significant correlation (p < 0.01) was seen for V5-25Gy, Dmean and Dmedian with urinary QoL. Penile bulb V70Gy was statistically significantly correlated with sexual QoL (p < 0.05). A larger rectal volume was significantly correlated with improved bowel QoL (p < 0.05). Sigmoid and urethral DVH parameters as well as the surgical approach were not statistically significantly correlated with QoL. Specific dose constraints for bladder volumes receiving low doses seem desirable for the further optimization of prostate bed RT. This may be particularly relevant in the context of the aspiration of establishing focal RT of prostate cancer and its local recurrences. Our comprehensive dataset may aid future researchers in achieving these goals.

The impact of salvage radiotherapy initiation at PSA ≤ 0.5 ng/mlon metastasis-free survival in patients with relapsed prostate cancer following prostatectomy.

Salvage radiation therapy (SRT) is indicated for biochemical failure after radical prostatectomy. Prior data have shown that initiation of SRT at lower PSA levels improves subsequent biochemical control, yet given the long natural history of prostate cancer questions remain regarding optimal timing of SRT. We analyzed the impact of prostate specific antigen (PSA) level at time of salvage radiotherapy with regard to both biochemical relapse-free (bRFS) as well as metastasis-free survival (MFS) in patients with biochemically recurrent prostate cancer. Using prospective institutional tumor registry data, univariate and multivariable-adjusted Cox proportional hazards models were constructed to assess association between outcomes and clinical and pathologic prognostic features, including pre-SRT PSA, interval from prostatectomy to SRT, androgen deprivation therapy (ADT), and adverse pathologic features. We identified 397 patients who received salvage RT between 1985 and 2016: 187 (45.8%) received SRT initiated when pre-RT PSA was ≤0.5 ng/ml; 212 (52.0%) patients had pre-SRT PSA > 0.5 ng/ml. Independent of pathologic risk status and ADT use, pre-SRT PSA ≤ 0.5 ng/mlwas the most significant predictor of bRFS (HR 0.39, 95% CI [0.27, 0.56]) as well as MFS (HR = 0.58, 95% CI [0.37, 0.91]). Seminal vesicle invasion was also associated with shorter interval to biochemical failure, HR = 1.79, 95% CI [1.07, 2.98], and eventual metastases, HR = 2.07, 95% CI [1.14, 3.740]. Initiation of salvage RT while PSA levels remain ≤0.5 ng/ml was associated with improved MFS. Consideration for salvage RT initiation while PSA levels remain low is warranted to minimize risk of future prostate cancer metastasis.

The effectiveness of high-dose-rate brachytherapy with external beam radiotherapy for clinically locally advanced and node-positive prostate cancer: long-term results of a retrospective study.

No standard treatment exists for locally advanced prostate cancer (PC). This study evaluated the long-term treatment outcomes and toxicity in patients with clinically locally advanced and/or lymph node (LN)-positive PC who underwent high-dose-rate brachytherapy (HDR-BT) with external beam radiotherapy (EBRT). The treatment outcomes and toxicities of 152 patients with PC who underwent HDR-BT with EBRT and had at least 2years of observation were examined. The treatment dose was 19- and 13-Gy HDR-BT in two and single fractions, respectively, both combined with external irradiation of 46Gy in 23 fractions. Long-term androgen deprivation therapy (ADT) for patients harboring very high-risk tumors was used in combination. The median observation period was 59.7 (24.4-182.1) months. The 5-year prostate cancer-specific and recurrence-free (RFS) survival rates were 99.0% and 91.8%, respectively, with only two PC mortalities. When 5-year RFS was examined for each parameter, RFS was significantly lower in pre-radiotherapy (pre-RT) prostate-specific antigen (PSA) > 0.5ng/mL (77.1%; p = 0.008), and presence of LN metastasis (68.1%; p = 0.017). Multivariable analysis demonstrated that pre-RT PSA (HR, 4.68; 95% CI, 1.39-15.67; p = 0.012) and presence of LN metastasis (HR, 4.70; 95% CI, 1.24-17.74; p = 0.022) were independent recurrence predictors. The 5-year cumulative incidence rate of grade ≥ 2 toxicities in genitourinary and gastrointestinal tracts were 15.4% and 1.3%, respectively. HDR-BT combined with EBRT and long-term ADT shows promising disease control and tolerant toxicities for clinically locally advanced and LN-positive PC.

Prognostic factors in postoperative radiotherapy for prostate cancer - tertiary center experience.

BackgroundThe aim of the study was to analyse the prognostic factors in postoperative prostate cancer irradiation and develop a nomogram for disease-free survival (DFS).Patients and methodsThis retrospective study included 236 consecutive prostate cancer patients who had radical prostatectomy followed by radiotherapy (RT) at a single tertiary institution between 2009 and 2014. The main outcome was DFS analysed through uni- and multivariable analysis, Kaplan-Meier curves, log-rank testing, recursive partitioning analysis, and nomogram development.ResultsThe median follow up was 62.3 (interquartile range [IQR] 38.1–79) months. The independent clinical factors associated with increased risk of recurrence or progression in the multivariate analysis (MVA) were prostate-specific antigen (PSA) level before RT, pT3 characteristic, and local failure as salvage indication. The value of PSA nadir had a significant impact on the risk of biochemical failure. Biochemical control and DFS were significantly different depending on treatment indication (p < 0.0001). The recursive partitioning analysis highlighted the importance of the PSA level before RT, Gleason Grade Group, PSA nadir, and local failure as a treatment indication. Finally, the nomogram for DFS was developed and is available online at https://apps.konsta.com.pl/app/prostate-salvage-dfs/.ConclusionsThe Pre-RT PSA level, pT3 characteristic and local failure as salvage indication are pivotal prognostic factors associated with increased risk of recurrence or progression. The Gleason grade group of 4–5 and PSA nadir value allow for further risk stratification. The treatment outcomes in postoperative prostate cancer irradiation are significantly different depending on treatment indication. An online nomogram comprising of both pre-treatment and current data was developed allowing for visualization of changes in prognosis depending on clinical data.

A prospective study of the effect of testosterone escape on preradiotherapy prostate-specific antigen kinetics in prostate cancer patients undergoing neoadjuvant androgen deprivation therapy.

Introduction:Prostate-specific antigen (PSA) kinetic patterns during neoadjuvant androgen deprivation therapy have been shown to predict unfavorable long-term outcomes.Objective:To investigate the effect of testosterone escape (TE) on these kinetic patterns, as this had not been previously reported.Methods:There were 50 consecutive prostate cancer patients who received 6 months of triptorelin prior to definitive radiotherapy (RT). Testosterone and PSA levels were measured at baseline and every 6 weeks. Clinical factors were tested for their ability to predict for TE and unfavorable PSA kinetic patterns. The effects of TE, at both 1.7 and 0.7 nmol/L levels, were analyzed.Results:TE occurred in at least one reading for 14% and 34% of the patients at the 1.7 and 0.7 nmol/L levels, respectively. No baseline factors predicted TE. The median PSA halving time was 25 days and the median pre-RT PSA level was 0.55 ng/mL. The only factor significantly associated with a higher pre-RT PSA level was a higher baseline PSA level. The only factor that significantly predicted a longer PSA halving time was TE at the 1.7 nmol/L level.Conclusions:TE and higher baseline PSA levels may adversely affect PSA kinetics and other outcomes for patients undergoing neoadjuvant hormone therapy prior to radiotherapy. Studies investigating the tailoring of neoadjuvant therapy by extending the duration in those patients with a higher baseline PSA level or by the addition of anti-androgens in those demonstrating TE, should be considered.

Sensitivity of CE-MRI in detecting local recurrence after radical prostatectomy.

The aim of our study was to evaluate the sensitivity of contrast-enhanced magnetic resonance (CE-MR) with phased array coil in the diagnosis of local recurrence in patients with prostate cancer after radical prostatectomy and referred for salvage radiotherapy (SRT). This retrospective study included 73 patients treated with SRT after radical prostatectomy in the period between September 2006 and November 2017. All patients performed a CE-MRI with phased array coil before the start of SRT. A total of 213 patients treated at the ASST Grande Ospedale Metropolitano Niguarda in the period between September 2006 and November 2017 with SRT after radical prostatectomy were reviewed. Seventy-three patients with a CE-MRI with phased array coil of the pelvis before the start of SRT were included in the present study. At imaging review, recurrence local recurrent disease was diagnosed in 48 of 73 patients. By considering as reference standard the decrease in prostate-specific antigen (PSA) value after radiotherapy, we defined: 41 true positive (patients with MRI evidence of local recurrence and PSA value decreasing after SRT), 7 false positive (patients with MRI evidence of local recurrence without biochemical response after SRT), 3 true negative (patients without MRI evidence of local recurrence and stable or increased PSA value after SRT) and 22 false negative (patients without MRI evidence of local recurrence and PSA value decreasing after SRT) cases. The sensitivity values were calculated in relation to the PSA value before the start of treatment, obtaining a value of 74% for PSA above 0.2ng/mL. The sensitivity of CE-MRI in local recurrence detection after radical prostatectomy increases with increasing PSA values. CE-MRI with phased array coil can detect local recurrences after radical prostatectomy with a good sensitivity in patients with pre-RT PSA value above 0.2ng/mL.

Contrasting Circulating Tumor Cells and Free Circulating DNA Responses in Men Treated for Prostate Cancer after Primary Versus Salvage Radiotherapy

Purpose: To investigate the relationships between circulating tumor cells (CTCs), free circulating DNA (fcDNA) and biochemical response in prostate cancer patients treated primarily versus salvage radiotherapy (RT). Methods and Materials: Blood was collected prospectively from patients, enrolled in two institutional Phase II trials for primary and salvage RT. Three blood samples were collected at: (i) prior to treatment [RT or androgen deprivation therapy (ADT)], (ii) last week of RT, and (iii) three months post-RT. CTCs were quantified in 31 samples from 12 primary patients and 30 samples from 12 salvage patients; fcDNA were analyzed in 11 primary (28 samples) and 5 (9 samples) salvage patients. CTCs were visualized by immunofluorescence after microfilter capture and fcDNA was quantified using real-time Polymerase chain reaction (PCR). CTCs and fcDNA were correlated with early biochemical response by subdividing patients into early favorable and unfavorable response at 3 months after RT. Results: For those treated primarily, there was a direct correlation with CTC counts and prostate specific antigen (PSA) pre-RT that changed to a reciprocal relationship 3 months post-RT. CTCs increased significantly (p=0.03) at 3 months after primary RT in the biochemical favorable patients, while no significant association was observed for fcDNA. Correspondingly, post-RT fcDNA levels were inversely related to CTC counts. In salvage patients, the number of CTCs was related to pre-RT PSA, but it was not correlated to RT response. In post-RT series, a significant direct correlation was observed between CTCs and PSA. Conclusion: Our preliminary studies suggest that RT affects CTC counts, which are thus associated with prostate cancer biochemical response. A larger cohort with longer follow-up will be needed to establish the association with more recognized treatment endpoints.

Prostate-Specific Antigen After Neoadjuvant Androgen Suppression in Prostate Cancer Patients Receiving Short-Term Androgen Suppression and External Beam Radiation Therapy: Pooled Analysis of Four NRG Oncology Radiation Therapy Oncology Group Randomized Clinical Trials

To validate whether prostate-specific antigen (PSA) level after neoadjuvant androgen suppression (neoAS) is associated with long-term outcome after neoAS and external beam radiation therapy (RT) with concurrent short-term androgen suppression (AS) in patients with prostate cancer. This study included 2404 patients. The patients were treated with neoAS before RT and concurrent AS (without post-RT AS) and were pooled from NRG Oncology/RTOG trials 9202, 9408, 9413, and 9910. Multivariable models were used to test associations between the prespecified dichotomized post-neoAS, pre-RT PSA level (≤0.1 vs>0.1ng/mL) groupings, and clinical outcomes. The median follow-up for surviving patients was 9.4years. The median post-neoAS, pre-RT PSA level was 0.3ng/mL, with 32% of patients having levels ≤0.1ng/mL. Race, Gleason score, tumor stage, node stage, pretreatment PSA level, and duration of neoAS were associated with the groups of patients with PSA levels ≤0.1 and>0.1ng/mL. In univariate analyses, post-neoAS, pre-RT PSA level >0.1ng/mL was associated with increased risks of biochemical failure (hazard ratio [HR], 2.04; P<.0001); local failure (HR, 2.51; P<.0001); distant metastases (HR, 1.73; P=.0006); cause-specific mortality (HR, 2.36; P<.0001); and all-cause mortality (HR, 1.24; P=.005). In multivariable models that also included baseline and treatment variables, post-neoAS, pre-RT PSA level >0.1ng/mL was independently associated with increased risk of biochemical failure (HR, 2.00; P<.0001); local failure (HR, 2.33; P<.0001); and cause-specific mortality (HR, 1.75; P=.03). Patients with a PSA level >0.1ng/mL after neoAS and before the start of RT had less favorable clinical outcomes than patients whose PSA level was ≤0.1ng/mL. The role of post-neoAS, pre-RT PSA level relative to PSA levels obtained along the continuum of medical care is not presently defined but could be tested in future clinical trials.

Post-Prostatectomy Radiotherapy in a Single Tertiary Institution: Outcomes Relating to Pre-Radiotherapy Prostate Specific Antigen

Objective: Timing of post-radical prostatectomy (RP) radiotherapy (RT) in patients with high risk prostate cancer continues to be debated. This is a retrospective review aiming to evaluate the influence of pre-RT prostate specific antigen (PSA) values on postprostatectomy RT outcomes in one Australian center. Method: Eligible patients were treated at the Royal Adelaide Hospital between January 2004 and December 2013, excluding those with nodal or distant metastatic disease pre-RT, or those who received neoadjuvant androgen deprivation therapy pre-RT. The primary endpoint of biochemical failure-free survival (bFFS) was defined as time from RP to date of biochemical failure (bF). Covariates of Gleason score, post-RP PSA, and pre-RT PSA were further analysed in relation to bFFS. Results: 103 of 122 patients underwent final analysis (8 were excluded for the above reasons; 11 had missing data). Median follow-up from RP was 60 months. Kaplan-Meier (KM) estimates of 1, 2, 3, 4 and 5-year survival probabilities were 93.5%, 83.4%, 82.4%, 76.6% and 71% respectively. There was no statistically significant correlation between bFFS and pathological T-stage (p=0.1), surgical margin involvement (p=0.7), or RT total dose (p=0.8). Analysis based on KM survival distributions and log-rank tests suggest that pathological Gleason score may have some influence on bFFS (p=0.04). Doubling the pre-RT PSA whilst holding all other factors and covariates constant, increases the hazard of bF at a particular time-point by approximately 19% on average. Conclusion: This single-institution retrospective study provides reasonable evidence for influence of pre-RT PSA on post-RP RT outcomes, arguing for earlier referral for RT.

Salvage radiotherapy for biochemical recurrence after radical prostatectomy: experience of a single center

Background: The purpose of this study was to report the outcomes and prognostic factors of patients who underwent salvage radiotherapy (SRT) for biochemical recurrence (BCR) following radical prostatectomy (RP) at a single center. Methods: We retrospectively reviewed 48 patients who underwent SRT for BCR after RP between January 2004 and December 2012. The Kaplan-Meier method and Cox proportional hazard regression models were used to evaluate the BCR-free survivals and the prognostic factors for BCR after SRT. Results: After a median follow-up of 68.7 months (range, 34.0–143.3 months). The BCR-free survival rates at 3 and 5 years for the 48 patients after SRT were 72.9% and 68.4%, respectively. Multivariate analysis showed that pre-RT PSA (prostate specific antigen) level >0.5 ng/mL, Gleason score at RP ≥8, and seminal vesicle invasion were significantly predictive of PSA relapse after SRT (HR: 23.29, 7.92, and 21.73). The BCR-free rate at 5 years in the pre-RT PSA level ≤0.5 and >0.5 ng/mL group was 83.4% and 52.2% (P=0.007), respectively. No grade 3 or worse acute adverse events were noted. Conclusions: SRT was an effective treatment for BCR following RP with tolerable toxicities. Lower pre-RT PSA value, low Gleason score, and non-seminal vesicle invasion were significant predictors of favorable biochemical outcomes. Our results supported the current recommendations that SRT should be initiated before PSA reaches 0.5 ng/mL.

Outcomes and toxicity of 313 prostate cancer patients receiving helical tomotherapy after radical prostatectomy

PurposeThere are limited long-term data on patients treated with image guided intensity modulated radiation therapy (IG-IMRT) for prostate cancer recurrence or high-risk disease features after radical prostatectomy. We report single-institution results for patients treated with IG-IMRT and identify variables associated with outcome. Methods and materialsThis is a retrospective chart review consisting of 313 consecutive patients who were treated with adjuvant or salvage IG-IMRT from 2004 to 2013. Cox proportional hazards analysis was used to identify factors related to survival and toxicity. Toxicity was graded using the Common Terminology Criteria for Adverse Events Version 4.0. ResultsThe median follow-up was 55 months (range, 6-131 months). The median pre-radiation therapy (RT) prostate-specific antigen (PSA) was 0.3 ng/mL (range, <0.01-55.4). The vast majority of patients (87%) received elective pelvic nodal irradiation (median dose: 45 Gy). Androgen deprivation therapy (ADT) was given to 39% of patients for a median of 9 months. Five-year biochemical progression-free survival and distant metastasis-free survival were 59% (95% confidence interval, 53%-66%) and 89% (95% confidence interval, 85%-93%), respectively. On multivariate analysis, higher pre-RT PSA (>0.2 ng/mL), biopsy Gleason score (≥7 [4+3]), and duration of ADT (>6 months) were significantly associated (P < .05) with biochemical progression-free survival. Actuarial late grade 3 genitourinary and gastrointestinal toxicities at 5 years were 10% and 2%, respectively. ConclusionOur results suggest that lower pre-RT PSA level and longer duration of ADT are associated with improved biochemical control. The incidence of late grade 3 gastrointestinal toxicity was low, but late grade 3 genitourinary toxicity was higher than anticipated.

Dynamic contrast-enhanced MRI for automatic detection of foci of residual or recurrent disease after prostatectomy.

This study aimed to develop an automated procedure for identifying suspicious foci of residual/recurrent disease in the prostate bed using dynamic contrast-enhanced-MRI (DCE-MRI) in prostate cancer patients after prostatectomy. Data of 22patients presenting for salvage radiotherapy (RT) with an identified gross tumor volume (GTV) in the prostate bed were analyzed retrospectively. An unsupervised pattern recognition method was used to analyze DCE-MRI curves from the prostate bed. Data were represented as aproduct of anumber of signal-vs.-time patterns and their weights. The temporal pattern, characterized by fast wash-in and gradual wash-out, was considered the "tumor" pattern. The corresponding weights were thresholded based on the number (1, 1.5, 2, 2.5) of standard deviations away from the mean, denoted as DCE1.0,…, DCE2.5, and displayed on the T2-weighted MRI. The resultant four volumes were compared with the GTV and maximum pre-RT prostate-specific antigen (PSA) level. Pharmacokinetic modeling was also carried out. Principal component analysis determined 2-4significant patterns in patients' DCE-MRI. Analysis and display of the identified suspicious foci was performed in commercial software (MIM Corporation, Cleveland, OH, USA). In general, DCE1.0/DCE1.5 highlighted larger areas than GTV. DCE2.0 and GTV were significantly correlated (r= 0.60, p< 0.05). DCE2.0/DCA2.5 were also significantly correlated with PSA (r= 0.52, 0.67, p< 0.05). Ktrans for DCE2.5 was statistically higher than the GTV's Ktrans (p< 0.05), indicating that the automatic volume better captures areas of malignancy. Asoftware tool was developed for identification and visualization of the suspicious foci in DCE-MRI from post-prostatectomy patients and was integrated into the treatment planning system.

A Retrospective Feasibility Study of Salvage Pelvic Nodal Radiation in 6 Patients With Biochemical Failure Following Prostate Fossa Radiation: An Alternative to Androgen Deprivation Therapy (ADT).

To evaluate salvage pelvic nodal radiation as an alternative to androgen deprivation therapy (ADT) in patients with biochemical failure and lymph node recurrence following salvage prostate fossa radiation. Six patients with biochemical failure and lymph node recurrence following prostate fossa radiation were treated with salvage pelvic nodal radiation therapy. A gross target volume was contoured using Choline PET/CT, CT, or MRI imaging. The clinical target volume included pelvic nodes. Avoidance structures were created using isodose lines from previous prostate fossa radiation plans. Radiation was delivered using IMRT or VMAT techniques. Failure was defined as a confirmed rise of prostate-specific antigen (PSA) over 0.2 ng/mL. Four patients had presalvage PSA values <1 and 2 patients had PSAs >1. Dose to the clinical target volume was 54 to 60 Gy. The gross target volume dose was 60 to 73.6 Gy. One of the 2 patients with a high PSA received 6 months of concomitant ADT. Mean follow-up after RT for all patients was 24.9 months (range, 18.1 to 33.0 mo). All 5 patients with no ADT had significant PSA responses. PSA reduction was 80% (62% to 100%) of pre-RT PSA. At last follow-up, 2 patients with initial PSA<1 ng/mL remain free of biochemical progression at 33 and 20 months. Four patients have had PSA rise and meet criteria for failure. This included both patients with initial PSA values > 1. Duration of response before failure was 18.1 to 30.7 months. ADT for failure has been started in 1 patient. There was no grade ≥2 GI or GU toxicity. Salvage lymph node irradiation for patients with early biochemical recurrence and radiologic evidence of pelvic nodal metastases is well tolerated and associated with a durable biochemical response and may be an alternative to or may delay the need for ADT in some patients.

Salvage Radiation Therapy Dose Response for Biochemical Failure of Prostate Cancer After Prostatectomy—A Multi-Institutional Observational Study

To determine whether a dose-response relationship exists for salvage radiation therapy (RT) of biochemical failure after prostatectomy for prostate cancer. Individual data from 1108 patients who underwent salvage RT at 10 academic centers were pooled. The cohort was enriched for selection criteria more likely associated with tumor recurrence in the prostate bed (margin positive and pre-RT prostate-specific antigen [PSA] level of ≤2.0ng/mL) and without the confounding of planned androgen suppression. The cumulative incidence of biochemical failure and distant metastasis over time was computed, and competing risks hazard regression models were used to investigate the association between potential predictors and these outcomes. The association of radiation dose with outcomes was the primary focus. With a 65.2-month follow-up duration, the 5- and 10-year estimates of freedom from post-RT biochemical failure (PSA level >0.2ng/mL and rising) was 63.5% and 49.8%, respectively, and the cumulative incidence of distant metastasis was 12.4% by 10years. A Gleason score of ≥7, higher pre-RT PSA level, extraprostatic tumor extension, and seminal vesicle invasion were associated with worse biochemical failure and distant metastasis outcomes. A salvage radiation dose of ≥66.0Gy was associated with a reduced cumulative incidence of biochemical failure, but not of distant metastasis. The use of salvage radiation doses of ≥66.0Gy are supported by evidence presented in the present multicenter pooled analysis of individual patient data. The observational reporting method, limited sample size, few distant metastasis events, modest follow-up duration, and elective use of salvage therapy might have diminished the opportunity to identify an association between the radiation dose and this endpoint.

Predicting the 5-Year Risk of Biochemical Relapse After Postprostatectomy Radiation Therapy in ≥PT2, pN0 Patients With a Comprehensive Tumor Control Probability Model

To fit the individual biochemical recurrence-free survival (bRFS) data from patients treated with postprostatectomy radiation therapy (RT) with a comprehensive tumor control probability (TCP) model. Considering pre-RT prostate-specific antigen (PSA) as a surrogate of the number of clonogens, bRFS may be expressed as a function of dose-per-fraction-dependent radiosensitivity (αeff), the number of clonogens for pre-RT PSA=1ng/mL (C), and the fraction of patients who relapse because of clonogens outside the treated volume (K), assumed to depend (linearly or exponentially) on pre-RT PSA and Gleason score (GS). Data from 894 node-negative, ≥pT2, pN0 hormone-naive patients treated with adjuvant (n=331) or salvage (n=563) intent were available: 5-year bRFS data were fitted grouping patients according to GS (<7:392,=7:383, >7:119). The median follow-up time, pre-RT PSA, and dose were 72months, 0.25ng/mL, and 66.6Gy (range 59.4-77.4Gy), respectively. The best-fit values were 0.23 to 0.26Gy(-1) and 10(7) for αeff and C for the model considering a linear dependence between K and PSA. Calibration plots showed good agreement between expected and observed incidences (slope: 0.90-0.93) and moderately high discriminative power (area under the curve [AUC]: 0.68-0.69). Cross-validation showed satisfactory results (average AUCs in the training/validation groups: 0.66-0.70). The resulting dose-effect curves strongly depend on pre-RT PSA and GS. bRFS rapidly decreases with PSA: the maximum obtainable bRFS (defined as 95% of the maximum) declined by about 2.7% and 4.5% for each increment of 0.1ng/mL for GS <7 and≥7, respectively. Individual data were fitted by a TCP model, and the resulting best-fit parameters were radiobiologically consistent. The model suggests that relapses frequently result from clonogens outside the irradiated volume, supporting the choice of lymph-node irradiation, systemic therapy, or both for specific subgroups (GS <7: PSA >0.8-1.0ng/mL; GS ≥7: PSA >0.3ng/mL). Early RT should be preferred over delayed RT; the detrimental effect of PSA increase can never be fully compensated by increasing the dose, especially for patients with GS ≥7.

Validation of a genomic classifier for prediction of metastasis following postoperative salvage radiation therapy.

4 Background: Management of patients with a postoperative rising prostate-specific antigen (PSA) level is complex. Additional local treatment such as salvage radiation therapy (SRT) may be sufficient for many patients but some may require concurrent systemic therapy in order to delay or prevent metastatic disease. As PSA recurrence on its own is a poor surrogate for metastatic disease we hypothesized that the Decipher genomic classifier (GC), a validated predictor of metastasis may be able to better distinguish those patients where additional therapy is beneficial from those where SRT on its own is likely sufficient. Methods: Genomic classifier (GC) scores were calculated from 170 prostate cancer patients, who received SRT at the Veteran Affairs Medical Center Durham, Thomas Jefferson University and Mayo Clinic, between 1990 and 2010. SRT was defined as administration of RT with Pre-RT PSA levels &gt; 0.2 ng/ml. GC and CAPRA-S scores were compared using survival c-index, competing-risks and Cox regression analysis for the prediction of metastasis. Results: Survival c-index for predicting metastasis 5 years post SRT was 0.85 (95% CI: 0.73-0.88) for GC and 0.63 (95% CI: 0.49-0.77) for CAPRA-S. The cumulative incidence of metastasis at 5 years post-SRT was 2.7%, 8.4%, and 33.1% for low, average, and high GC scores (p &lt; 0.001) and 16.9%, 2.3% and 17.2% for low, average and high CAPRA-S scores (p = 0.113). In univariable analysis only GC, extraprostatic extension, path GS and Pre-RT PSA were significant predictors of metastasis. In multivariable analyses with clinical risk factors or the CAPRA-S risk model, GC was the only independent predictor of metastasis with a HR of 1.63 (1.22-2.18, p &lt; 0.001) for a 10% unit increase in risk score. Conclusions: In patients treated with postoperative SRT for PSA recurrence, GC is a powerful predictor of metastasis. Patients with low Decipher have excellent prognosis with SRT and may avoid concurrent hormonal therapy. Patients with high Decipher risk are at highest risk for metastatic disease and SRT failure and may benefit from intensified systemic therapy.

A phase 2 trial of salvage radiation and concurrent weekly docetaxel after a rising prostate-specific antigen level after radical prostatectomy

Purpose/Objective(s)We sought to assess the utility of docetaxel administered concurrently with salvage radiation therapy (SRT) following postprostatectomy biochemical failure (BF). Methods and materialsMen with postprostatectomy BF were accrued on a single-arm phase 2 clinical trial. SRT doses ranged from 64.8 to 70.2 Gy and were delivered in 1.8-Gy fractions to the prostate bed alone as the clinical target volume with a +1-cm uniform planning target volume expansion. The primary endpoint was progression-free survival at 4 years compared with the Stephenson nomogram estimate. Kaplan-Meier methods were used to assess late toxicity, BF, and distant metastases. An unplanned matched-pair analysis was performed with 19 patients treated with SRT alone. ResultsNineteen men were accrued and treated. Median follow-up was 4.8 years. Median pre-RT prostate-specific antigen level was 0.7 ng/mL (interquartile range, 0.4-1.3 ng/mL). All 8 cycles of docetaxel were completed in 17 (89%) patients. Acute grade 1-4 toxicities were observed in 79%, 50%, 58%, and 11%, respectively. A total of 68% of acute grade 1 toxicities were related to fatigue, urinary, or bowel symptoms. For grade 2 toxicities, 76% were related to neutropenia, fatigue, or urinary symptoms. Acute grade 3 and 4 toxicities were most commonly neutropenia (84% and 100%, respectively). All late toxicities were grade 1 to 2 with 89% related to bowel or urinary function. Predicted 4-year progression-free survival was 39% and observed was 42% (90% confidence interval [CI], 24-60). Matched-pair analysis demonstrated no significant improvement in BF (P = .96, hazard ratio, 0.98; 90% CI, 0.4-2.3) or distant metastases (P = .09; hazard ratio, 0.3; 90% CI, 0.07-1.2), and no difference between late bowel (P = .60) or urinary toxicity (P = .41). ConclusionsDocetaxel can safely be administered concurrently with SRT without significantly impacting posttreatment toxicity. Neutropenia was the most significant acute toxicity. Given the small sample size, no clear clinical benefit was observed. Larger studies are needed to determine the efficacy of concurrent docetaxel in this setting.

Image Guided Hypofractionated Postprostatectomy Intensity Modulated Radiation Therapy for Prostate Cancer

Hypofractionated radiation therapy (RT) has promising long-term biochemical relapse-free survival (bRFS) with comparable toxicity for definitive treatment of prostate cancer. However, data reporting outcomes after adjuvant and salvage postprostatectomy hypofractionated RT are sparse. Therefore, we report the toxicity and clinical outcomes after postprostatectomy hypofractionated RT. From a prospectively maintained database, men receiving image guided hypofractionated intensity modulated RT (HIMRT) with 2.5-Gy fractions constituted our study population. Androgen deprivation therapy was used at the discretion of the radiation oncologist. Acute toxicities were graded according to the Common Terminology Criteria for Adverse Events version 4.0. Late toxicities were scored using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scale. Biochemical recurrence was defined as an increase of 0.1 in prostate-specific antigen (PSA) from posttreatment nadir or an increase in PSA despite treatment. The Kaplan-Meier method was used for the time-to-event outcomes. Between April 2008 and April 2012, 56 men received postoperative HIMRT. The median follow-up time was 48 months (range, 21-67 months). Thirty percent had pre-RT PSA <0.1; the median pre-RT detectable PSA was 0.32 ng/mL. The median RT dose was 65 Gy (range, 57.5-65 Gy). Ten patients received neoadjuvant and concurrent hormone therapy. Posttreatment acute urinary toxicity was limited. There was no acute grade 3 toxicity. Late genitourinary (GU) toxicity of any grade was noted in 52% of patients, 40% of whom had pre-RT urinary incontinence. The 4-year actuarial rate of late grade 3 GU toxicity (exclusively gross hematuria) was 28% (95% confidence interval [CI], 16%-41%). Most grade 3 GU toxicity resolved; only 7% had persistent grade ≥3 toxicity at the last follow-up visit. Fourteen patients experienced biochemical recurrence at a median of 20 months after radiation. The 4-year bPFS rate was 75% (95% CI, 63%-87%). The biochemical control in this series appears promising, although relatively short follow-up may lead to overestimation. Late grade 3 GU toxicity was higher than anticipated with hypofractionated radiation of 65 Gy to the prostate bed, although most resolved.