Salvage Radiotherapy For Prostate Cancer Research Articles

Comparative outcomes between adjuvant and salvage radiotherapy in prostate cancer after minimally invasive radical prostatectomy

Objective: Radical prostatectomy (RP) is the standard treatment in clinically localized prostate cancer. However, the timing of postoperative radiotherapy (RT) in patients with adverse pathologic features or PSA persistence remains controversial. The objective of this study is to compare the survival outcomes and treatment complications between adjuvant radiotherapy (aRT) and salvage radiotherapy (sRT) in patients after minimally invasive RP. Materials and Methods: This retrospective study reviewed the clinical data in patients who underwent minimally invasive RP in our institution between January 2012 and April 2021. The patients were divided into three groups: no RT, aRT, and sRT. Patient demographic data, pathological reports, RTOG/EORTC toxicity scores, functional outcomes, and survival outcomes were compared between aRT and sRT groups. Results: A total of 487 patients were included in the study. One-hundred and thirty-three patients (27.3%) received postoperative RT. The pathological stage and positive margin rate were significantly higher in the aRT group. Five-year ADT-free survival (78.8% vs 80%, p = 0.68), 5-year metastasis-free survival (80.2% vs 92.2%, p = 0.38), and 5-year overall survival (97.1% vs 100%, p = 0.68) were no different between groups. There were no significant differences in continence, potency, genitourinary or gastrointestinal toxicities between groups. Conclusions: Timing of postoperative RT does not affect survival. Functional outcomes and radiation toxicity were comparable between patients undergoing aRT and sRT.

Is the Addition of Pelvic Nodal Irradiation Beneficial in Postoperative Salvage Radiotherapy for Prostate Cancer?

Is the Addition of Pelvic Nodal Irradiation Beneficial in Postoperative Salvage Radiotherapy for Prostate Cancer?

Lesion segmentation on 18F-fluciclovine PET/CT images using deep learning.

A novel radiotracer, 18F-fluciclovine (anti-3-18F-FACBC), has been demonstrated to be associated with significantly improved survival when it is used in PET/CT imaging to guide postprostatectomy salvage radiotherapy for prostate cancer. We aimed to investigate the feasibility of using a deep learning method to automatically detect and segment lesions on 18F-fluciclovine PET/CT images. We retrospectively identified 84 patients who are enrolled in Arm B of the Emory Molecular Prostate Imaging for Radiotherapy Enhancement (EMPIRE-1) trial. All 84 patients had prostate adenocarcinoma and underwent prostatectomy and 18F-fluciclovine PET/CT imaging with lesions identified and delineated by physicians. Three different neural networks with increasing levels of complexity (U-net, Cascaded U-net, and a cascaded detection segmentation network) were trained and tested on the 84 patients with a fivefold cross-validation strategy and a hold-out test, using manual contours as the ground truth. We also investigated using both PET and CT or using PET only as input to the neural network. Dice similarity coefficient (DSC), 95th percentile Hausdorff distance (HD95), center-of-mass distance (CMD), and volume difference (VD) were used to quantify the quality of segmentation results against ground truth contours provided by physicians. All three deep learning methods were able to detect 144/155 lesions and 153/155 lesions successfully when PET+CT and PET only, respectively, served as input. Quantitative results demonstrated that the neural network with the best performance was able to segment lesions with an average DSC of 0.68 ± 0.15 and HD95 of 4 ± 2mm. The center of mass of the segmented contours deviated from physician contours by approximately 2mm on average, and the volume difference was less than 1 cc. The novel network proposed by us achieves the best performance compared to current networks. The addition of CT as input to the neural network contributed to more cases of failure (DSC = 0), and among those cases of DSC > 0, it was shown to produce no statistically significant difference with the use of only PET as input for our proposed method. Quantitative results demonstrated the feasibility of the deep learning methods in automatically segmenting lesions on 18F-fluciclovine PET/CT images. This indicates the great potential of 18F-fluciclovine PET/CT combined with deep learning for providing a second check in identifying lesions as well as saving time and effort for physicians in contouring.

Immunohistochemistry-Based Biomarkers and Impact on Outcomes Following Salvage Radiotherapy for Prostate Cancer.

Salvage radiation therapy (SRT) is a mainstay of treatment for prostate cancer patients who experience biochemical relapse following radical prostatectomy. We sought to characterize the prognostic impact of previously identified deleterious molecular phenotypes-loss of PTEN, ERG expression, and p53 mutation- upon survival in patients undergoing SRT. We analyzed an institutional database of 320 patients treated with SRT for whom prostatectomy tissue was available; tissue microarrays (TMAs) were constructed and used for genetically validated immunohistochemistry assays for PTEN, ERG, and p53. Chi-squared and Mann-Whitney's tests were used to assess association between molecular expression and clinical risk factors for adverse survival. Uni- and multivariate Cox-proportional hazards models were constructed to determine effects on biochemical (bRFS) and metastasis-free survival (MFS), calculated from end of SRT to event. Loss of PTEN (n = 123, 50%) and ERG expression (n = 118, 39.1%) were common, while p53 overexpression (signifying TP53 missense mutation) was less common (n = 21, 6.6%). On univariate Cox regression, loss of PTEN portended worse bRFS [HR 1.86; 95% CI 1.36-2.57] and MFS [HR 1.89; 1.21-2.94], with homogeneous loss associated with particularly worse MFS [HR 2.47; 1.54-3.95]. Similarly, p53 overexpression predicted worse bRFS [HR 1.95; 1.14-3.32] and MFS [HR 2.79; 1.50-5.19]. ERG expression was associated with only worse MFS [HR 1.6; 1.03-2.48]. On multivariate analysis adjusting for known prognostic features (grade, nodal involvement, pathologic stage, androgen deprivation therapy (ADT), and PSA velocity), homogeneous PTEN loss remained predictive of adverse bRFS [HR 1.73; 1.06-2.82] and MFS [HR 2.35; 1.04-5.34]. PTEN loss identified by immunohistochemistry is an independent adverse prognostic factor for both biochemical and metastasis-free survival in prostate cancer patients treated with SRT. Although clinically validated RNA expression assays also exist which are prognostic for outcomes following SRT, stromal contamination in bulk RNA could mask "loss" signals specific to tumor cells, such as PTEN. Further work is necessary to determine the optimal approach to treating patients with poor molecular prognostic features in a salvage setting.

Randomized phase II trial of MRI-guided salvage radiotherapy for prostate cancer in 4 weeks versus 2 weeks (SHORTER)

BackgroundUltra-hypofractionated image-guided stereotactic body radiotherapy (SBRT) is increasingly used for definitive treatment of localized prostate cancer. Magnetic resonance imaging-guided radiotherapy (MRgRT) facilitates improved visualization, real-time tracking of targets and/or organs-at-risk (OAR), and capacity for adaptive planning which may translate to improved targeting and reduced toxicity to surrounding tissues. Given promising results from NRG-GU003 comparing conventional and moderate hypofractionation in the post-operative setting, there is growing interest in exploring ultra-hypofractionated post-operative regimens. It remains unclear whether this can be done safely and whether MRgRT may help mitigate potential toxicity. SHORTER (NCT04422132) is a phase II randomized trial prospectively evaluating whether salvage MRgRT delivered in 5 fractions versus 20 fractions is non-inferior with respect to gastrointestinal (GI) and genitourinary (GU) toxicities at 2-years post-treatment.MethodsA total of 136 patients will be randomized in a 1:1 ratio to salvage MRgRT in 5 fractions or 20 fractions using permuted block randomization. Patients will be stratified according to baseline Expanded Prostate Cancer Index Composite (EPIC) bowel and urinary domain scores as well as nodal treatment and androgen deprivation therapy (ADT). Patients undergoing 5 fractions will receive a total of 32.5 Gy over 2 weeks and patients undergoing 20 fractions will receive a total of 55 Gy over 4 weeks, with or without nodal coverage (25.5 Gy over 2 weeks and 42 Gy over 4 weeks) and ADT as per the investigator’s discretion. The co-primary endpoints are change scores in the bowel and the urinary domains of the EPIC. The change scores will reflect the 2-year score minus the pre-treatment (baseline) score. The secondary endpoints include safety endpoints, including change in GI and GU symptoms at 3, 6, 12 and 60 months from completion of treatment, and efficacy endpoints, including time to progression, prostate cancer specific survival and overall survival.DiscussionThe SHORTER trial is the first randomized phase II trial comparing toxicity of ultra-hypofractionated and hypofractionated MRgRT in the salvage setting. The primary hypothesis is that salvage MRgRT delivered in 5 fractions will not significantly increase GI and GU toxicities when compared to salvage MRgRT delivered in 20 fractions.Trial registrationClinicalTrials.gov Identifier: NCT04422132. Date of registration: June 9, 2020.

Prostatectomy Bed Image-guided Dose-escalated Salvage Radiotherapy (SPIDER): An International Multicenter Retrospective Study

BackgroundManagement of macroscopic local recurrence (MLR) after radical prostatectomy is a challenging situation with no standardized approach. ObjectiveThe objective of our study was to assess the efficacy and safety of functional image-guided salvage radiotherapy (SRT) in patients with MLR in the prostate bed. Design, setting, and participantsIn this international multicenter retrospective study across 16 European centers, eligible patients were initially treated by radical prostatectomy (RP) with or without pelvic lymph node dissection for localized or locally advanced adenocarcinoma of the prostate. Outcome measurements and statistical analysisProstate-specific antigen (PSA) measured 4 wk after RP was <0.1 ng/ml. All patients presented a biochemical relapse after RP defined by an increase in PSA level of ≥0.2 ng/ml on two successive measures. Only patients with an MLR lesion in the prostatectomy bed visualized on functional imaging (multiparametric magnetic resonance imaging, positron emission tomography/computed tomography [PET/CT] choline, or PET/CT prostate-specific membrane antigen) were eligible. Patients with lymph node, bone, or visceral dissemination at restaging imaging (CT and/or bone scintigraphy and/or magnetic resonance imaging and/or PET) were excluded. Dose escalation was defined as a dose of >66 Gy prescribed to the prostate bed or to MLR. Toxicities were classified using the Common Terminology Criteria for Adverse Events scale, version 4.03. The primary endpoint was progression-free survival (PFS). Secondary outcomes were metastasis-free survival (MPFS), biochemical progression-free survival, and overall survival. Genitourinary (GU) and gastrointestinal (GI) toxicities were analyzed. Results and limitationsBetween January 2000 and December 2019, 310 patients received at least one dose escalation on MLR and 25 patients did not receive any dose escalation. The median PSA level before SRT was 0.63 ng/ml (interquartile range [IQR], 0.27–1.7). The median follow-up was 54 mo (IQR, 50–56). Five-year PFS and MPFS were 70% (95% confidence interval [CI]: [64; 75]) and 84% (95% CI: [78; 88]), respectively. Grade ≥2 GU and GI late toxicities were observed in 43 (12%) and 11 (3%) patients, respectively. When the prescribed dose on the MLR lesion was ≥72 Gy, an improvement in 5-yr PFS was found for patients received at least one dose escalation (73% [95% CI: 65–79]) vs 60% [95% CI: 48; 70]; p = 0.03). ConclusionsIn this contemporary study integrating functional imaging data, we found potential efficacy of SRT with dose escalation ≥72 Gy for patients with MLR in the prostate bed and with an acceptable toxicity profile. Prospective data exploring this MLR dose escalation strategy are awaited. Patient summaryIn this report, we looked at the outcomes from salvage radiotherapy for prostate cancer and macroscopic relapse in a large European population. We found that outcomes varied with prostate-specific antigen at relapse, Gleason score, and dose escalation. We found potential efficacy of salvage radiotherapy with dose escalation for macroscopic relapse in the prostate bed, with an acceptable toxicity profile.

Randomized trial of MRI-guided salvage radiotherapy for prostate cancer in 4 weeks vs. 2 weeks (SHORTER).

TPS400 Background: The objective of this randomized clinical trial is to demonstrate that 2 weeks (5 fractions) of real-time MRI-guided radiotherapy (RT) with an MR Linac does not significantly increase patient-reported GI and GU symptoms compared to 4 weeks (20 fractions) of RT 2 years after treatment completion. Methods: Key Eligibility Criteria: Inclusion Criteria 1. Men aged &gt; 18 with histologically confirmed prostate cancer after prostatectomy with detectable PSA. 2. KPS &gt; 70. 3. Patients with no evidence of distant metastatic disease on PET/CT/MRI/bone scan&lt; 180 days prior to enrollment. 4. Ability to receive MRI-guided radiotherapy. 5. Ability to complete the Expanded Prostate Cancer Index Composite (EPIC) questionnaire. Exclusion Criteria 1. Prior history of receiving pelvic RT. 2. Patient with history of IBD. 3. History of bladder neck or urethral stricture. Study Design/Endpoints: This is a randomized phase II non-inferiority trial comparing 5 fractions of ultrahypofractionated RT (32.5 Gy total with optional PSMA/MRI boost to 40 Gy) versus 20 fractions of hypofractionated RT (55 Gy total with optional PSMA/MRI boost to 60 Gy) in the post-operative setting for prostate cancer. Subjects will be stratified based on pre-specified stratification factors and randomized 1:1 to receive 5 or 20 fractions using permuted block randomization. The primary endpoint is the change in patient-reported GI and GU symptoms as measured by EPIC at 2 years from end of treatment. Secondary endpoints will include both the safety endpoints including change in GI and GU symptoms at 3, 6, 12 and 60 months from end of treatment, and multiple efficacy endpoints including time to progression, prostate cancer specific survival and overall survival. Sample Size: The sample size is calculated based on a non-inferiority design. The non-inferiority margins are set to be a change score of 6 points for the GI symptoms and 5 points for the GU symptoms. The standard deviations of the change scores are assumed to be 13.2 for the GI symptoms and 10.5 for the GU symptoms based on estimates generated in RTOG 0415 trial. This level of change in scores are deemed as clinically meaningful. For example, 6 points of change score for GI symptoms corresponds to two symptoms worsening by 1 level (i.e., loose stools and frequency of bowel movements change from “no problem” to “very small problem”) or one of the symptoms worsening by 2 levels (i.e., loose stool change from “no problem” to “small problem”). A sample size of 122 with 61 in each arm will ensure 80% power for GI endpoint and 83% power for GU endpoint to detect non-inferiority using a one-sided two-sample t-test at the significance level of 0.05. Adjusting for a projected 10% EPIC/non-compliance rate, 136 patients (68 per arm) will be randomized. Stratification Factors: Patients will be stratified according to baseline EPIC bowel and urinary domain scores and use of nodal treatment and ADT. Enrollment: 91 patients. Clinical trial information: NCT04422132 .

Oncologic outcomes of postoperative adjuvant versus salvage radiotherapy in prostate cancer.

The aim of this study was to compare the long-term oncological results of patients with the diagnosis of prostate cancer who underwent open radical retropubic prostatectomy (RRP) and subsequent adjuvant (ART) or salvage radiotherapy (SRT). A total of 145 patients underwent open RRP for prostate cancer and subsequent ART or SRT postoperatively between 2010 and 2019. ART (n = 56) is defined as the group of patients with prostate-specific antigen (PSA) <0.2 ng/mL or with positive lymph nodes without PSA increase who received radiotherapy within the first 6 months of urinary continence. SRT (n = 89) is defined as the group of patients with PSA >0.2 ng/mL who received RT before PSA amounted to 0.5 ng/mL. Statistically no significant difference was found between groups in terms of age, prostate volume, final pathology Gleason scores, lymphadenectomy, duration of androgen deprivation therapy (ADT), time to relapse after radiotherapy, development of biochemical recurrence and disease progression. Extraprostatic extension, seminal vesicle invasion and surgical margin positivity were significantly higher in the ART group. No difference was found between the groups in terms of biochemical recurrence-free survival, while cancer-specific survival and overall survival rates were significantly higher in the SRT group. It was found that cancer-specific and overall survival was better in the SRT group. It will be more appropriate to follow-up until the recurrence and then to perform SRT after the relapse in the postoperative period.

Bladder Volumes Matter: Clinical Significance of Bladder Filling in Salvage Radiotherapy for Prostate Cancer

<h3>Purpose/Objective(s)</h3> Salvage radiotherapy (SRT) is the only curative option for recurrent prostate cancer after radical prostatectomy. Urinary bladder is the major organ at risk in this setting. Different bladder filling protocols are used to reduce radiation dose to the bladder and thus limit genitourinary (GU) side effects. However, constant bladder volume is hard to maintain throughout the treatment course. A pronounced inter-fractional variation in bladder volume is a well-recognized problem in SRT. The purpose of this study was to investigate if there is a relationship between actual bladder volumes measured on daily cone-beam computer tomography (CBCT) images and GU adverse effects. <h3>Materials/Methods</h3> Consecutive patients treated with SRT at Karolinska university hospital, Sweden, in 2019-2020 (n=126) were included. Patients received either 35 × 2 Gy (n=103) or 35 × 2.2 Gy and/or pelvic lymph node irradiation (n=23) with IMRT (n=82) or four-field box-technique (n=44). All patients were treated with image-guided radiotherapy (IGRT) including daily cone-beam CT (CBCT). Bladder volumes were graded (visual analogue scale) on CBCT images (n=4410) at each treatment fraction. Internal validation of bladder volume measurements was performed in 22 patients by manually delineating bladders on daily CBCTs (n=770). Clinician-reported outcome (ClinRO) and patient-reported outcome measures (PROM) were available in 103 (83%) and 80 (66%) cases, respectively, ClinRO and PROM combined in 68 (54%) patients. Baseline bladder volumes, within-patient volume variation as well as average of 35 CBCT bladder volumes for the entire treatment course were compared between groups of patients with and without GU adverse events during 12 months of follow-up. <h3>Results</h3> Manually delineated and visually graded bladder volumes were strongly correlated (r=0.869, p<0.001). ClinRO and PROM were significantly associated (Chi-square =33.1, p<0.001). A repeated-measures ANOVA determined that mean bladder volumes did not differ across 35 CBCT measurements (p=0.16). Average actual bladder volumes were significantly smaller than baseline volumes (Wilcoxon S-R test Z=-2.68, p<0.007). Bladder volumes were significantly smaller in patients with GU adverse events compared to asymptomatic patients, measured with both ClinRO (p=0.006) and PROM (p=0.003). <h3>Conclusion</h3> In conclusion, our detailed analysis indicates that patients with GU adverse effects had significantly smaller bladder volumes during SRT. Clinical use of bladder filling protocol to increase bladder size during SRT is thus justified.

The Prognostic Value of the Size and the Sub-Site of the Local Failure at DCE-MRI before Salvage Radiotherapy for Prostate Cancer

<h3>Purpose/Objective(s)</h3> To investigate predictors of biochemical failure after salvage radiotherapy (sRT) in the context of a presumed local failure at dynamic contrast-enhancement-magnetic resonance imaging (DCE-MRI) post radical prostatectomy (RP). <h3>Materials/Methods</h3> All patients referred for sRT at our Institution with a biochemical failure after RP have been consistently offered restaging with both PET/CT and multiparametric MRI since January 2014. Those with a presumed local failure at DCE-MRI as well as no regional/distant disease at PET/CT (either choline and/or PSMA) were selected for the present study. Exclusion criteria were history of androgen deprivation (AD) before sRT and positive nodes at RP. All patients underwent 3T DCE-MRI without endorectal coil and the lesion(s) transferred to the planning CT after co-registration. sRT consisted in 73.5 Gy to the presumed local lesion and 66-69 Gy to the prostatic bed in 30 fxs. Pelvic nodes (PN) were covered to 54 Gy/30 fxs in selected patients. The endpoint of the study was the development of a biochemical failure after sRT defined as a 0.2 ng/ml PSA rise above the nadir. Various covariates (age, pre-RP PSA, pT and pN stages at RP, margins status at RP, ISUP grade group, time from RP to sRT, PSA doubling time, PSA detectability after RP, PSA at sRT, the location, number and volume of the detected recurrence(s), AD use, PN coverage, EUA risk category) were investigated at univariate analysis (UVA) on the time to biochemical failure (bNED-survival). Covariates with a p value <0.2 at UVA were entered a Cox proportional hazards regression analysis. <h3>Results</h3> Up to June 2020, 146 patients satisfying all selection criteria have been treated with sRT. Median (IQR) PSA at sRT was 0.60 ng/ml (0.38-1.05 ng/ml) and only 17 patients (11.6%) received AD along with sRT. A total of 168 local lesions have been detected, 92 (54.8%), 40 (23.8%) and 36 (21.4%) at the vesicourethral anastomosis (VUA), the bladder neck and the retrovesical space, respectively. At the median (IQR) follow-up of 48.1 months (31.3-60.6 months), 22 biochemical failures have been observed for a 4-yr bNED survival of 84.4% (95%CI: 77.9-90.9%). On UVA, bNED-survival after sRT was significantly more likely for patients with VUA-only lesions (VUA-only vs others, HR=0.307, 95%CI: 0.120-0.784, p=0.014) and with smaller lesions (for every cc, HR: 1.071, 95%CI: 1.025-1.119, p=0.002). These associations remained significant (p< 0.01) on multivariate analysis as well. For patients with VUA-only disease or with lesions smaller than 0.5cc, 4-yr bNED survival rates were 90.7% (95%CI: 83.4-98.0%) and 90.6% (95%CI: 83.9-97.3%), respectively. The 46 patients with both favorable features had a 4-yr bNED rate of 94.6% (95%CI: 87.3-100%). <h3>Conclusion</h3> These data support local restaging with DCE-MRI before sRT in the setting of a biochemical failure after RP. Patients with VUA-only and/or small volume lesions have an excellent outcome after dose-escalated sRT.

OC-0766 Response of local disease at magnetic resonance after salvage radiotherapy for prostate cancer

OC-0766 Response of local disease at magnetic resonance after salvage radiotherapy for prostate cancer

A prospective study assessing the pattern of response of local disease at DCE-MRI after salvage radiotherapy for prostate cancer

BackgroundTo assess the pattern of response of presumed local lesions at dynamic contrast enhancement magnetic resonance imaging (DCE-MRI) after salvage radiotherapy (sRT). MethodsThis is a prospective study conducted at a single Institution accruing patients with one or more local failures at DCE-MRI after radical prostatectomy between August 2017 and June 2020. Patients underwent exclusive sRT delivering 66–69 Gy and 73.5 Gy in 30 fractions to the whole prostatic fossa and to the local failure(s) seen at DCE-MRI, respectively.Patients were offered DCE-MRI at 3 months intervals after sRT until complete disappearance (CR) of the lesion(s) or up to a maximum of 4 revaluations. Results62 patients with 72 nodules were enrolled. All patients underwent the 1st revaluation, and 33 patients (53.2%) showed a CR. The median time to CR was 4.7 months. Four patients did not undergo further testing before achieving a CR and even considering these patients as no responses, the vast majority (87.1%, 95%CI: 78.5–94.4%) of lesions would have completely disappeared by 12 months from the end of sRT.The volume of the lesion at pre-sRT DCE-MRI was an independent predictor of CR at the 1st revaluation (OR: 0.076, 95%CI: 0.009–0.667; p = 0.020) along with time elapsed from sRT (OR: 3.399, 95% CI: 1.156–9.993, p = 0.026). ConclusionsThe present study documents the complete disappearance of the vast majority of local lesions after dose-escalated sRT though this requires several months after sRT; timing of CR is at least in part predictable based on the volume of the lesion.Trial registration: Clinicaltrials.gov NCT04703543, registered July 15 2020, retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04703543.

Management of osteomyelitis of the pubic symphysis following urinary fistula in patients with radiation-induced urethral strictures after prostate cancer treatment.

Osteomyelitis of the pubic symphysis is a rare condition often occurring in patients with radiation therapy-related urethral strictures after prostate cancer treatment. We retrospectively reviewed patients who presented with osteomyelitis of the pubic symphysis from November 2016 to September 2021. We investigated the factors leading to urosymphyseal fistulas, clinical presentation, radiological assessment, treatments, and outcomes. A total 4 cases were collected. All patients underwent surgery and adjuvant or salvage radiotherapy for prostate cancer. Subsequently, they developed stricture of the vesicourethral anastomosis which was initially treated conservatively. Symptoms of pubic bone osteomyelitis included pain in the pubic area, fever, difficulty walking, and recurrent urinary tract infections. In all cases, computed tomography and magnetic resonance imaging showed a urinary fistula arising from the vesicourethral anastomosis with the involvement of the pubic bone, and severe osteomyelitis. Due to the failure of conservative treatment, debridement of the pubic bone with cystectomy and ileal conduit was performed in 3 patients. One patient refused surgery and bilateral percutaneous nephrostomies were placed. Patients regained their original performance status 1 to 6 months after surgery. General recommendations for the best diagnostic and therapeutic approach to osteomyelitis of the pubic symphysis due to urosymphyseal fistula still do not exist. Conservative treatment often fails and a surgical approach with definitive urinary diversion may be required.

Results of salvage radiotherapy for prostate cancer after radical prostatectomy

The aim of the study. To evaluate the results of radiation therapy for recurrent prostate cancer after radical prostatectomy.Methods. The analysis of medical records data of 60 patients with recurrent prostate cancer after radical prostatectomy (RP) was performed.Results. Biochemical control was achieved in 55 (92.0%) patients, PSA progression – in 3 (5.0%) and generalization – in 2 (3.0%) patients. Grade I–II cystitis developed in 25 patients (42.0%), grade I–II rectitis – in 7 (11.0%), late hemorrhagic cystitis was noted in 4 (7.0%) patients, late hemorrhagic rectitis – in 2 (3.3%) ones.Сonclusions. Salvage radiation therapy for recurrent prostate cancer after radical prostatectomy is an important treatment method that allows to achieve biochemical control with acceptable toxicity.

The prognostic value, sensitivity, and specificity of multiparametric magnetic resonance imaging before salvage radiotherapy for prostate cancer

AimTo determine the operational characteristics of pelvic magnetic resonance imaging (MRI) prior to salvage radiation therapy (SRT) for biochemically recurrent prostate cancer following radical prostatectomy. Methods and materialsWe reviewed the medical records of 386 patients who underwent MRI prior to SRT. We assessed associations of pre-SRT MRI findings with biochemical recurrence (BCR), distant metastasis (DM), prostate cancer-specific mortality (PCSM), and salvage androgen deprivation therapy (ADT) use following SRT. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of MRI for detecting local recurrence were also calculated. ResultsPre-SRT MRI was positive for local recurrence in 216 patients (56%), indeterminate in 46 (12%), and negative in 124 (32%). On univariate analysis, BCR following SRT was significantly less likely for patients with positive (HR: 0.58, 95% CI: 0.42–0.8) or indeterminate (HR: 0.6: 0.36–1) MRI findings, compared to patients with negative imaging (p = 0.003). These associations remained significant on multivariate analysis (p < 0.05) and across pre-SRT PSA groups.For the entire cohort, the sensitivity of MRI for local recurrence was 61.0% (53.5–68.1%), specificity 60.0% (44.3–73.0%), PPV 86.1% (78.9–91.5%) and NPV 27.6% (19.0–37.5%). Sensitivity of MRI was better in men with higher pre-SRT PSA (80.0% for PSA > 1.0), and specificity was improved with lower pre-SRT PSA (73.9% for PSA 0.1–0.5). ConclusionsPositive or indeterminate MRI findings prior to SRT were associated with improved biochemical control following SRT, across PSA levels. The sensitivity and specificity of MRI for local recurrence were 61% and 58.7%, respectively.

18F-fluciclovine-PET/CT imaging versus conventional imaging alone to guide postprostatectomy salvage radiotherapy for prostate cancer (EMPIRE-1): a single centre, open-label, phase 2/3 randomised controlled trial

Molecular imaging is increasingly used to guide treatment decisions and planning in prostate cancer. We aimed to evaluate the role of 18F-fluciclovine-PET/CT in improving cancer control compared with conventional imaging (bone scan and either CT or MRI) alone for salvage postprostatectomy radiotherapy. In EMPIRE-1, a single-centre, open-label, phase 2/3 randomised controlled trial, patients with prostate cancer with detectable PSA after prostatectomy and negative conventional imaging (no extrapelvic or bone findings) were randomly assigned in a 1:1 ratio to radiotherapy directed by conventional imaging alone or to conventional imaging plus 18F-fluciclovine-PET/CT. Computer-generated randomisation was stratified by PSA concentration, adverse pathology indicators, and androgen deprivation therapy intent. In the 18F-fluciclovine-PET/CT group, radiotherapy decisions were rigidly determined by PET findings, which were also used for target delineation. The primary endpoint was 3 year event-free survival, with events defined as biochemical or clinical recurrence or progression, or initiation of systemic therapy, using univariate and multivariable analyses in patients who received radiotherapy. This trial is registered with ClinicalTrials.gov, NCT01666808 and is closed to new participants. From Sept 18, 2012, to March 4, 2019, 165 patients were randomly assigned, with median follow-up of 3·52 years (95% CI 2·98-3·95). PET findings resulted in four patients in the 18F-fluciclovine-PET/CT group having radiotherapy aborted; these patients were excluded from survival analyses. Median survival was not reached (95% CI 35·2-not reached; 33% of 81 patients had events) in the conventional imaging group compared with not reached (95% CI not reached-not reached; 20% of 76 patients) in the 18F-fluciclovine-PET/CT group, and 3 year event-free survival was 63·0% (95% CI 49·2-74·0) in the conventional imaging group versus 75·5% (95% CI 62·5-84·6) for 18F-fluciclovine-PET/CT (difference 12·5; 95% CI 4·3-20·8; p=0·0028). In adjusted analyses, study group (hazard ratio 2·04 [95% CI 1·06-3·93], p=0·0327) was significantly associated with event-free survival. Toxicity was similar in both study groups, with the most common adverse events being late urinary frequency or urgency (37 [46%] of 81 patients in the conventional imaging group and 31 [41%] of 76 in the PET group), and acute diarrhoea (11 [14%] in the conventional imaging group and 16 [21%] in the PET group). Inclusion of 18F-fluciclovine-PET into postprostatectomy radiotherapy decision making and planning significantly improved survival free from biochemical recurrence or persistence. Integration of novel PET radiotracers into radiotherapy decisions and planning for prostate cancer patients warrants further study. National Institutes of Health/National Cancer Institute, Blue Earth Diagnostics, and Winship Cancer Institute of Emory University.

P011 - Salvage radiotherapy for prostate cancer on relapse after radical prostatectomy - How important is an early start?

P011 - Salvage radiotherapy for prostate cancer on relapse after radical prostatectomy - How important is an early start?

PSA decay during salvage radiotherapy for prostate cancer as a predictor of disease outcome – 5 year follow-up of a prospective observational study

Background and purposeBiochemical recurrence after prostatectomy is commonly treated with salvage radiotherapy (SRT). In this prospective observational study we investigated the PSA decay rate, determined by predefined serial PSA measurements during SRT, as a predictor for treatment outcome. Materials and methodsBetween 2013 and 2016, 214 patients were included in the study. The prescribed dose to the prostate bed was 70 Gy in 35 fractions (7 weeks) without hormonal treatment. PSA was measured weekly during SRT. Assuming first order kinetics, a PSA decay-rate constant (k) was calculated for 196 eligible patients. The ability of k to predict disease progression was compared with known clinical prediction parameters using Cox regression, logistic regression and ROC analyses. Disease progression was defined as continuously rising PSA after SRT, PSA increase by ≥0.2 ng/ml above nadir after SRT, hormonal treatment or clinical progression. ResultsAfter a median follow up of 4.7 years the estimated failure-free survival at 5 years was 56%. The PSA decay-rate constant (k) was found to be the strongest predictor of disease progression in both uni-and multivariable analyses. ConclusionThe addition of k to established clinical variables significantly improves the possibility to predict treatment outcome after SRT and could be used to personalize future therapies.

Salvage Radiotherapy for Prostate Cancer

For patients experiencing biochemical recurrence in the absence of distant metastasis, salvage radiotherapy (SRT) with or without androgen deprivation therapy (ADT) is currently the only possible curative treatment option. Prostate-specific antigen (PSA) monitoring and the selected use of SRT has some advantages when compared with adjuvant radiotherapy. The most important one is avoidance of a potential overtreatment of patients who would never have disease progression, even in the presence of high-risk pathological features. The identification of a specific PSA cut-off seems to be incorrect. In patients with more adverse pathological features, early SRT administered at the very first sign of a PSA rise granted better disease control. Dose-intensified SRT is feasible and well tolerated with no significant difference in grade 2 or more acute and late toxicity. At least 66 Gy must be given in the salvage setting. ADT has a radio-sensitising effect on the radiotherapy by inhibiting the repair of DNA double-strand breaks. The use of ADT in the salvage setting results in a better oncological outcome. Hormonal therapy is associated with a decrease in quality of life and side-effects depending on the duration of hormone therapy. The oncological benefit of hormone therapy duration depends on their clinical and pathological characteristics. 68-Ga-prostate-specific membrane antigen positron emission tomography-computed tomography is the gold standard in staging prostate cancer patients with biochemical persistence or recurrence after radical prostatectomy. The implementation of 18F-labelled PSMA tracers can provide a further improvement.

Early and late toxicity profiles of patients receiving immediate postoperative radiotherapy versus salvage radiotherapy for prostate cancer after prostatectomy

The present study aims to evaluate both early and late toxicity profiles of patients receiving immediate postoperative radiotherapy (RT; adjuvant RT or additive RT) compared to salvage RT. We evaluated 253patients with prostate cancer treated with either immediate postoperative (adjuvant RT, n = 42; additive RT, n = 39) or salvage RT (n = 137). Thirty-five patients received salvage treatment but did not achieve apostoperative prostate specific antigen (PSA) level <0.1 ng/ml and thus were excluded from analysis. Asignificantly higher rate of early grade1/2 proctitis in the immediate postoperative RT group without additional pelvic RT was observed (p = 0.02). Patients in the immediate postoperative RT group without additional pelvic RT showed significantly more early urinary tract obstructions (p = 0.003). Toxicity rates of early (<3months) and late (3-6months) postoperative RT were similar (p > 0.05). Baseline recovery rate of erectile dysfunction was better in patients with immediate postoperative RT without additional pelvic RT (p = 0.02; hazard ratio (HR) = 2.22, 95%-confidence interval, 95%-CI: 1.12-4.37). Recovery rate of urinary incontinence showed no significant difference in all groups (p > 0.05). Patients receiving immediate postoperative RT (adjuvant or additive RT) without additional pelvic RT experience early gastrointestinal (GI) side effect proctitis and, as well as early genitourinary (GU) toxicity urinary tract obstruction more frequently than patients treated with salvage RT. Therefore, complete recovery after surgery is essential. However, we suggest basing the treatment decision on the patient's postoperative clinical condition and evaluation of any adverse risk factors, since many studies demonstrate aclear benefit for immediate postoperative RT (adjuvant or additive RT) in terms of oncological outcome.