Recurrence In Prostate Cancer Patients Research Articles

Quantitative 3T multiparametric MRI of benign and malignant prostatic tissue in patients with and without local recurrent prostate cancer after external-beam radiation therapy.

BackgroundPost‐radiotherapy locally recurrent prostate cancer (PCa) patients are candidates for focal salvage treatment. Multiparametric MRI (mp‐MRI) is attractive for tumor localization. However, radiotherapy‐induced tissue changes complicate image interpretation. To develop focal salvage strategies, accurate tumor localization and distinction from benign tissue is necessary.PurposeTo quantitatively characterize radio‐recurrent tumor and benign radiation‐induced changes using mp‐MRI, and investigate which sequences optimize the distinction between tumor and benign surroundings.Study TypeProspective case–control.SubjectsThirty‐three patients with biochemical failure after external‐beam radiotherapy (cases), 35 patients without post‐radiotherapy recurrent disease (controls), and 13 patients with primary PCa (untreated).Field Strength/Sequences3T; quantitative mp‐MRI: T2‐mapping, ADC, and Ktrans and kep maps.AssessmentQuantitative image‐analysis of prostatic regions, within and between cases, controls, and untreated patients.Statistical TestsWithin‐groups: nonparametric Friedman analysis of variance with post‐hoc Wilcoxon signed‐rank tests; between‐groups: Mann–Whitney tests. All with Bonferroni corrections. Generalized linear mixed modeling to ascertain the contribution of each map and location to tumor likelihood.ResultsBenign imaging values were comparable between cases and controls (P = 0.15 for ADC in the central gland up to 0.91 for kep in the peripheral zone), both with similarly high peri‐urethral Ktrans and kep values (min−1) (median [range]: Ktrans = 0.22 [0.14–0.43] and 0.22 [0.14–0.36], P = 0.60, kep = 0.43 [0.24–0.57] and 0.48 [0.32–0.67], P = 0.05). After radiotherapy, benign central gland values were significantly decreased for all maps (P ≤ 0.001) as well as T2, Ktrans, and kep of benign peripheral zone (all with P ≤ 0.002). All imaging maps distinguished recurrent tumor from benign peripheral zone, but only ADC, Ktrans, and kep were able to distinguish it from benign central gland. Recurrent tumor and peri‐urethral Ktrans values were not significantly different (P = 0.81), but kep values were (P < 0.001). Combining all quantitative maps and voxel location resulted in an optimal distinction between tumor and benign voxels.Data ConclusionMp‐MRI can distinguish recurrent tumor from benign tissue. Level of Evidence: 2 Technical Efficacy Stage: 2J. Magn. Reson. Imaging 2019;50:269–278.

Quantitative 3-T multi-parametric MRI and step-section pathology of recurrent prostate cancer patients after radiation therapy

ObjectivesDiagnosis of radio-recurrent prostate cancer using multi-parametric MRI (mp-MRI) can be challenging due to the presence of radiation effects. We aim to characterize imaging of prostate tissue after radiation therapy (RT), using histopathology as ground truth, and to investigate the visibility of tumor lesions on mp-MRI.MethodsTumor delineated histopathology slides from salvage radical prostatectomy patients, primarily treated with RT, were registered to MRI. Median T2-weighted, ADC, Ktrans, and kep values in tumor and other regions were calculated. Two radiologists independently performed mp-MRI-based tumor delineations which were compared with the true pathological extent. General linear mixed-effect modeling was used to establish the contribution of each imaging modality and combinations thereof in distinguishing tumor and benign voxels.ResultsNineteen of the 21 included patients had tumor in the available histopathology slides. Recurrence was predominantly multifocal with large tumor foci seen after external beam radiotherapy, whereas these were small and sparse after low-dose-rate brachytherapy. MRI-based delineations missed small foci and slightly underestimated tumor extent. The combination of T2-weighted, ADC, Ktrans, and kep had the best performance in distinguishing tumor and benign voxels.ConclusionsUsing high-resolution histopathology delineations, the real tumor extent and size were found to be underestimated on MRI. mp-MRI obtained the best performance in identifying tumor voxels. Appropriate margins around the visible tumor-suspected region should be included when designing focal salvage strategies. Recurrent tumor delineation guidelines are warranted.Key Points• Compared to the use of individual sequences, multi-parametric MRI obtained the best performance in distinguishing recurrent tumor from benign voxels.• Delineations based on mp-MRI miss smaller foci and slightly underestimate tumor volume of local recurrent prostate cancer.• Focal salvage strategies should include appropriate margins around the visible tumor.

Patterns of Recurrence After Salvage Radiotherapy Encompassing Pelvic Lymphatics in Men with High-risk Prostate Cancer.

The efficacy of adjuvant or salvage radiation to the regional lymph node area has not been fully investigated in high-risk prostate cancer patients; instead, radiotherapy is limited to the prostate fossa. The present study aimed to assess patterns of recurrence in prostate cancer patients with biochemical failure (BCF) who were treated with whole-pelvic salvage radiotherapy (SRT) following radical prostatectomy. The clinical data from 196 high-risk prostate cancer patients who received SRT for BCF after radical prostatectomy were reviewed. BCF after SRT was detected in 80 patients, and 59 patients underwent imaging studies. Twenty four recurrences in 16 patients were identified, including 13 bone metastases, 6 vesicourethral anastomosis site recurrences, and 5 lymph node recurrences (one simultaneous with vesicourethral anastomosis). Regarding the treatment field, no in-field nodal recurrence was observed, whereas 4 out-of-field and 1 edge-of-field recurrences were detected. Locoregional recurrence was most common at the anastomosis site. Most nodal recurrences were located outside the pelvis, suggesting that elective pelvic nodal irradiation should be recommended in a selected patient population.

Metastases-yield and Prostate-specific Antigen Kinetics Following Salvage Lymph Node Dissection for Prostate Cancer: A Comparison Between Conventional Surgical Approach and Prostate-specific Membrane Antigen-radioguided Surgery

The first results on 99mTechnetium prostate-specific membrane antigen-radioguided surgery (99mTc-PSMA- RGS) showed promising outcome. Here, we sought to evaluate if this targeted molecular surgical approach might be more effective than conventional salvage lymph node dissection (sLND). We prospectively analysed 42 consecutive patients who underwent sLND based on preoperative 68Gallium (68Ga)-PSMA-positron emission tomography (PET) imaging between 2015 and 2018. In 29 patients, the dissection field was based solely 68Ga-PSMA-PET imaging (conventional surgical approach [CSA]), whereas 13 patients underwent 99mTc-PSMA-RGS. Preoperative characteristics of both groups were similar. Final pathology revealed no metastases in nine CSA patients (31%), whereas all visible lesions on preoperative 68Ga-PSMA-PET were removed in patients who underwent RGS. A PSA decline in general, >50% and >90% within 6 wk was seen in 50%, 29%, and 7% versus 100%, 92%, and 53% in CSA versus RGS groups, respectively (all p<0.01). This is the first comparison of conventional and PSMA-radioguided approach with regards to short-term efficacy of sLND. Although long-term outcome needs to be awaited, RGS offers promising results. Patient summaryWe compared two surgical approaches for lymph node dissection in lymph node only recurrent prostate cancer patients. The radioguided approach was superior in removing the affected lymph nodes, resulting in a more pronounced prostate-specific antigen decline.

830P - Synthetic DNA immunotherapy in biochemically relapsed prostate cancer

Background: INO-5150 (PSA and PSMA) +/- INO-9012 (IL-12), a synthetic DNA immunotherapy, was assessed for safety, immunogenicity and efficacy in biochemically recurrent prostate cancer patients (pts). Methods: Phase I, open-label, multi-center study in the US included pts with rising PSA after surgery and/or RT, PSA doubling time (PSADT) >3 months (mos), testosterone >150 ng/dL and no concurrent ADT. Safety, immunogenicity and efficacy (PSA kinetics, PFS) were evaluated in 4 treatment arms of 15 pts each. Arms A: 2mg INO-5150, B: 8.5 mg INO-5150, C: 2mg INO-5150 + 1mg INO-9012 and D: 8.5mg INO-5150 + 1mg INO-9012. Pts received 4 IM doses of vaccine followed by electroporation on day 0, wks 3, 12 and 24 and were followed for 72 wks. Results: 50/61 (82%) pts completed all visits and treatments were well tolerated with no safety concerns. Median PFS for overall population [N = 61, baseline (D0) PSADT range (mos) 1.5-217.1, median 9.8] and for a subset of pts with D0 PSADT ≤12mos (N = 36) has not yet been reached (FU 3-19 mos). 86% of pts with D0 PSADT ≤12 mos were progression free through 19mos FU. 27 out of 36 (75%) pts with D0 PSADT≤ 12 mos had disease stabilization at wks 27 evidenced by significant improvement in log2PSA change over time (slope) and PSADT from D0 (Slope=0.19 declined to 0.1, PSADT=5.3 improved to 10.1 mos, p = <0.0001). This effect was maintained at wk 72 (Slope=0.09, PSADT=10.6, p = <0.0001). Immunogenicity was observed in 77% (47/61) of pts by multiple immunologic assessments. Patient immunogenicity to INO-5150 as determined by CD38 and Perforin + CD8 T cell immune reactivity correlated with attenuated % PSA rise compared to pts without reactivity (p = 0.05, n = 50). Conclusions: INO-5150 +/- INO-9012 was safe, well tolerated and immunogenic. Clinical efficacy was observed in the patients with D0 PSADT≤ 12 mos as evidenced by a significant dampening of log2PSA change over time and increased PSADT up to 72 weeks FU. Additional genomic analyses are ongoing to further elucidate the correlation of immunologic efficacy and clinical benefit. (NCT02514213). Clinical trial identification: FDA IND number 15870. Legal entity responsible for the study: Inovio Pharmaceuticals, Inc. Funding: Inovio Pharmaceuticals, Inc. Disclosure: N. Shore: Consulting or advisory role for multiple pharmaceutical companies. E.I. Heath: Consulting or advisory role and honoraria or funding received for multiple pharmaceutical companies. H. Cheng, Y. Whang: Funding received from multiple pharmaceutical companies. K. Bhatt, M. Morrow, T. McMullan, K. Kraynyak, J. Lee, B. Sacchetta, L. Liu, S. Rosencranz, I. Csiki, M.L. Bagarazzi: Employee of the pharmaceutical company sponsoring this research trial. S.T. Tagawa, R. Tutrone, J. Garcia, W. Kelly: Consulting or advisory role and funding received from multiple pharmaceutical companies. All other authors have declared no conflicts of interest.

Abstract A45: Preliminary results of a phase 1 clinical trial of a PSA, IL-2, GM-CSF containing prostate cancer vaccine in PSA defined biochemical recurrent prostate cancer patients

Abstract Immunotherapy for cancer has had two main approaches that have led to clinical applications. The first is stimulating immune responses to tumor cells with cytokines or cellular immunotherapy and the second is blocking tumor immune evasion and the associated inhibition of T-cell activation with antibodies to the CTLA-4 receptor, PD-1 receptor or PD-L1. We have taken a different approach and have developed therapeutic cancer vaccines that are a combination of tumor antigens (proteins overexpressed by tumors) with biological adjuvants (the cytokines IL-2 and GM-CSF). This study is a Phase 1a/1b clinical trial of a PSA/IL-2/GM-CSF vaccine in recurrent prostate cancer in hormone-naïve and hormone-independent patients. Major inclusion criteria include adenocarcinoma of the prostate, rising serum PSA and no measurable disease. Phase 1a examines the rate of dose limiting adverse events (DLAEs) in an initial course of 6 vaccinations (“induction vaccination”). The patients will receive intradermal injections of the PSA/IL-2/GM-CSF vaccine at weeks 1, 2, 3, 7, 11 and 15. Enrollment of the twenty patients in the Phase 1a has been completed. To date, 14 patients in the Phase 1a portion of the trial have received all 6 vaccines. Twelve of the 15 patients who have received vaccines have increased immune responses to PSA in a lymphocyte blastogenesis assay by week 19. After 6 vaccines, 9 of 14 patients had an increase in the doubling time of their serum PSA, suggesting a slowing of the progression of the cancer. Median follow up after the first vaccine is 33 months. None of the patients vaccinated in the Phase 1a portion have had a DLAE. Citation Format: Jonathan F. Head, Gregory A. Daniels, Michelle McKinney, Weg Ongkeko, Kyoko Sakamoto, Jessica Wang-Rodriguez. Preliminary results of a phase 1 clinical trial of a PSA, IL-2, GM-CSF containing prostate cancer vaccine in PSA defined biochemical recurrent prostate cancer patients [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2017 Oct 1-4; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2018;6(9 Suppl):Abstract nr A45.

Reproducibility of standardized uptake values of same-day randomized 68Ga-PSMA-11 PET/CT and PET/MR scans in recurrent prostate cancer patients.

Positron emission tomography in association with magnetic resonance imaging (PET/MR) and 68Ga-PSMA-11 has shown superior detection in recurrent prostate cancer patients as compared to PET/computed tomography (PET/CT). There are, however, several technological differences between PET/CT and PET/MR systems which affect the PET image quality. The objective of this study was to assess the reproducibility of PET/CT and PET/MR SUV's in recurrent prostate cancer patients. We randomized the patients regarding the order of the PET/CT and PET/MR scans to reduce the influence of tracer uptake as a function of time. Thirty patients, all with biochemical recurrence after radical prostatectomy, underwent whole-body PET/CT and PET/MR scans after intravenous injection of a single dose of 68Ga-PSMA-11. Fifteen patients underwent PET/CT first and 15 patients underwent PET/MR first. Volumes of interest on tumor lesions were outlined and maximum standardized uptake value (SUVmax) corrected for lean body mass was calculated. Correlation and agreement between scans were assessed by generalized linear mixed-effects models and Bland-Altman analysis. The association between SUV, patient characteristics and imaging parameters was assessed. Eighteen of the 30 evaluated patients had at least one positive lesion, giving an overall detection rate of 60%. In total, there were 34 visible lesions: 5 local recurrences, 22 lymph node metastases and 7 bone metastases. One group acquired PET/CT and PET/MR at median time points of 63.0 and 159.0min, while the other group acquired PET/MR and PET/CT at median time points of 92.0 and 149.0min. SUVmax between scans was linearly correlated, described by the equation Y(PET/CT SUVmax) = 0.75 + 1.00 × (PET/MR SUVmax), on average 20% higher on PET/CT than on PET/MR. SUV associated significantly only with type of lesion, scan time post-injection and acquisition time per bed position. SUVmax from PET/CT and PET/MR are linearly correlated, on average 20% higher on PET/CT than on PET/MR and should, therefore, not be used interchangeably in patient follow-up.

Abstract LB-021: Combination of quantitative histomorphometry with NFκB/p65 nuclear localization is better predictor of biochemical recurrence in prostate cancer patients

Abstract Clinical management decisions in prostate cancer are often based on risk determination with major uncertainty since limited tools are available to understand the risk of disease progression and guide the treatment decision process. Computer-aided quantitative histomorphometric analysis has emerged as a powerful computing tool to identify, characterize, and quantitate histologic features of tissues beyond human visual capabilities. Several quantitative features can be assessed, such as precise numeric measurements pertaining to the spatial arrangement and architecture of nuclei, shapes of nests and nuclei, and nuclear texture. This technology has proven to be useful for the detection of cancer in tissue sections and also for predicting tumor biology and clinical outcome in cancer patients. Utilizing a combination of synergistic strategy of quantitative histomorphometry and biomarker expression of NF-κB/p65 from prostate tissue specimens, we sought to fuse structural and functional information from morphological and molecular markers to better characterize disease progression improving prediction of biochemical recurrence (BCR). Here we utilized radical prostatectomy specimens (n=23) for feature extraction from 15 patients without BCR and 8 patients who experienced BCR (PSA &amp;gt; 0.2 ng/ml) within two years of surgery. Digitized H&amp;E slides were annotated for a representative cancerous region, glands were automatically segmented, and 216 features of gland architecture, shape, and orientation disorder were extracted. Nuclei were automatically segmented from NF-κB/p65 stained slides. Based on digitally calculated stain optical density, every nuclei pixel was classified as either negative or weakly, moderately, or strongly positive for NF-κB/p65 staining. We first used the H&amp;E features alone in leave-one-out cross validation with a naive Bayes classifier, using the top two features by t-test in every fold, to obtain a recurrence probability for each patient. We repeated that experiment with the NF-κB/p65 features. We then multiplied together patients' posterior class probabilities from each model for a final probability. In every fold a probability threshold was identified from the training set to classify patients as BCR or non-BCR. Our results demonstrate that the three most predictive H&amp;E features were all gland orientation disorder features. The top NF-κB/p65 feature was percentage of nuclei pixels positive for staining. Accuracy predicted was 78% with H&amp;E features alone, 74% with NF-κB/p65 features alone, and 87% in the aggregate model. Taken together, our results demonstrate that fusing nuclei NF-κB/p65 and gland morphology information allows for functional and morphologic characterization of prostate cancer, potentially allowing for improved risk characterization and prognosis prediction in prostate cancer patients. Citation Format: Patrick Leo, Eswar Shankar, Robin Elliott, Andrew Janowczyk, Nafiseh Janaki, Gregory T. MacLennan, Anant Madabhushi, Sanjay Gupta. Combination of quantitative histomorphometry with NFκB/p65 nuclear localization is better predictor of biochemical recurrence in prostate cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-021.

Abstract CT061: Interim results of a phase Ia clinical trial of a PSA, IL-2, GM-CSF containing prostate cancer therapeutic vaccine in PSA defined biochemical recurrent prostate cancer patients

Abstract While progress has occurred in both cellular and immune checkpoint therapy, the benefit of therapeutic cancer vaccines has been difficult to demonstrate. Prostate cancer may be an exception with the modest activity of sipuleucel-T. We have developed a potentially lower cost and easy to administer therapeutic vaccine with the combination of tumor antigen (PSA) and biologic adjuvants (IL-2 and GM-CSF). This study is a Phase 1a clinical trial of a PSA/IL-2/GM-CSF vaccine in 20 biochemically recurrent hormone-naïve and hormone-independent prostate cancer patients. Major inclusion criteria include adenocarcinoma of the prostate, rising serum PSA and no measurable disease. Phase 1a examines the rate of serious adverse events (SAEs) and dose limiting adverse events (DLAEs) in an initial course of 6 vaccinations (“induction vaccination”). Twenty patients enrolled and nineteen patients completed all six intradermal injections (one patient received 5 vaccines, missed week 11 vaccine) of the PSA/IL-2/GM-CSF vaccine at weeks 1, 2, 3, 7, 11 and 15. None of the patients vaccinated in the Phase 1a portion had a SAE or DLAE with the most common AE relating to grade 1 injection site reactions. Fifteen of the 18 patients who received vaccines had immune responses to PSA as demonstrated in a lymphocyte blastogenesis assay by week 31. Interestingly, after vaccination 14 of 20 patients had an increase in the doubling time of their serum PSA, suggesting a slowing of the growth of the prostate cancer. Four of 20 patients have progressed (3 PSA progression and 1 radiological progression) at 31 weeks follow-up. Citation Format: Jonathan F. Head, Gregory A. Daniels, Michelle A. McKinney, Weg M. Ongkeko, Kyoko Sakamoto, Jessica Wang-Rodriguez. Interim results of a phase Ia clinical trial of a PSA, IL-2, GM-CSF containing prostate cancer therapeutic vaccine in PSA defined biochemical recurrent prostate cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT061.

PV-0622: Impact and efficacy of 68GA-PSMA PET/CT in recurrent prostate cancer patients with PSA &lt; 0.5 ng/ml

PV-0622: Impact and efficacy of 68GA-PSMA PET/CT in recurrent prostate cancer patients with PSA &lt; 0.5 ng/ml

Tumour-associated macrophages in prostate biopsy determined by automated image analysis are an independent prognostic marker for biochemical recurrence in prostate cancer patients

Tumour-associated macrophages in prostate biopsy determined by automated image analysis are an independent prognostic marker for biochemical recurrence in prostate cancer patients

A microRNA-based signature predicting immune-related toxicity (iRAEs) to pembrolizumab in prostate cancer patients.

269 Background: The need to predict immune-related adverse events (iRAEs) for patients receiving checkpoint inhibitors is a pressing issue, with up to 25-30% Grade 2 or higher toxicity with single agent therapy, regardless of cancer type. Our group is studying a novel class of inherited mutations that disrupt the normal regulatory process of microRNAs as they function to control the genome. We have previously applied a panel of these mutations to predict iRAEs in melanoma and NSCLC patients receiving anti-PD1/anti-PDL1 therapy. We hypothesize that our mutations will predict iRAEs across cancer types. Here we have investigated their ability to predict iRAEs in a cohort of recurrent or advanced prostate cancer patients receiving Pembrolizumab (Pembro). Methods: We previously trained several statistical classifiers on a set of 86 melanoma and NSCLC patients evaluated for iRAEs. Subjects were classified as experiencing high toxicity (grade 2 or more) versus low toxicity (less than 2). We next tested the performance of the identified biomarkers on a set of 40 prospectively-treated prostate cancer patients who had received at least three cycles of Pembro, 200mg every 3 weeks. Samples were collected via cheek swab and germ-line DNA was isolated for testing. Predictive models of high-grade toxicity were based on 49 common markers between training and test samples. Classifiers were built comparing: classification trees, LASSO-regularized logistic regression, and random forests. All models were tuned at training using leave-one-out cross validation. The final extrapolation test errors were estimated on the prostate cohort as validation data not used in training. Results: Within the melanoma and NSCLC training sample we estimate toxicity with 71% accuracy (85% sensitivity, 43% specificity). We found that our biomarker panel when applied to prostate cancer patients extrapolates quite well, where our biomarkers predict toxicity with 68% accuracy (82% sensitivity, 38% specificity). Conclusions: We have identified a panel of microRNA-based, germ-line biomarkers which predict the risk of iRAEs. This panel appears to predict iRAEs across cancer types, including prostate cancer.

Predictors of biochemical recurrence of prostate cancer

Aim. To study the role of postoperative parameters in predicting the probability of development of biochemical recurrence in patients with prostate cancer with low pre-operative risk of its progression. Methods. 95 patients who underwent radical prostatectomy, were included in the study, the average age being 59.5±0.7 (44-76) years. The average levels of total and free prostate-specific antigen were 5.8±0.2 (1.71-9.9) and 1.03±0.07 (0.2-3.6) ng/ml respectively. Biochemical recurrence was defined as the level of prostate-specific antigen higher than 0.2 ng/ml after radical prostatectomy. Results. 8 (8.4%) patients during the follow-up period were diagnosed with biochemical recurrence. The average period to biochemical recurrence development was 45.8±6.7 (24-84) months. Pathomorphological examination revealed presence of tumor cells at surgical margin in 18 (18.9%) cases. Biochemical recurrence was diagnosed in 5 out of 77 (6.5%) patients with negative surgical margins and in 3 out of 18 (1.7%) patients with positive surgical margins. In our study, no correlation between the state of surgical margin and biochemical recurrence development was revealed (χ2=1.958; р=0.162). In the study group postoperative Gleason score was not prognostically significant as well (р=0.294). The average tumor volume in resected material was 11.8±1.0% (1-55%) of prostate volume (мм3). Extraprostatic extension was diagnosed in 10 (10.5%) cases. Results of univariate dispersion analysis of postoperative parameters revealed prognostic significance of tumor volume in removed specimen (р=0.007) and extracapsular extension (р=0.027). Conclusion. In our study we determined that tumor volume and extracapsular extention are independent risk factors for biochemical recurrence in prostate cancer patients with low pre-operative risk of disease progression.

Interobserver variation in target volume for salvage radiotherapy in recurrent prostate cancer patients after radical prostatectomy using CT versus combined CT and MRI: a multicenter study (KROG 13-11).

PurposeTo investigate interobserver variation in target volume delineations for prostate cancer salvage radiotherapy using planning computed tomography (CT) versus combined planning CT and magnetic resonance imaging (MRI).Materials and MethodsTen radiation oncologists independently delineated a target volume on the planning CT scans of five cases with different pathological status after radical prostatectomy. Two weeks later, this was repeated with the addition of planning MRI. The volumes obtained with CT only and combined CT and MRI were compared, and the effect of the addition of planning MRI on interobserver variability was assessed.ResultsThere were large differences in clinical target volume (CTV) delineated by each observer, regardless of the addition of planning MRI (9.44–139.27 cm3 in CT only and 7.77–122.83 cm3 in CT plus MRI) and no significant differences in the mean and standard deviation of CTV. However, there were decreases in mean volume and standard deviation as a result of using the planning MRI.ConclusionThis study showed substantial interobserver variation in target volume delineation for salvage radiotherapy. The combination of planning MRI with CT tended to decrease the target volume and the variation.

11C-Choline PET/CT based Helical Tomotherapy as Treatment Approach for Bone Metastases in Recurrent Prostate Cancer Patients.

To evaluate the efficacy of 11C-choline PET/CT (CHO-PET/CT) based helical tomotherapy (HTT) as a therapeutic approach for bone metastases in recurrent prostate cancer (PCa) patients. This retrospective study includes 20 PCa patients (median age: 67; range: 51-80 years) presenting biochemical relapse after primary treatment who underwent CHO-PET/CT based HTT on positive bone metastases from December 2007 to June 2014. The effectiveness of HTT has been assessed with biochemical response at 3/6/12 months, biochemical relapse free survival (bRFS) and overall survival (OS) at 2 years. Toxicity has also been considered and assessed according to Common Terminology Criteria for Adverse Events (CTCAE). All patients presented a relapse at the time of CHO-PET/CT at bone level. In addition 15/20 (75%) also at lymph nodes (LNs) level (total lesions= 54). All patients underwent HTT on bone metastases and 19/20 concomitantly on prostatic bed and LNs. The median follow-up from CHO-PET/CT was 2 years (range: 1-7 years). At 3 months after the beginning of HTT treatment complete or partial biochemical response occurred in 79% of patients, at 6 months in 82% and at 12 months in 63% of patients. bRFS and OS at 2 years were 50% and 55% of patients, respectively. Patients presented mostly grade 1 or 2 toxicity according to CTCAE. The only grade 3 late toxicity has been observed in one patient. CHO-PET/CT based HTT is a suitable therapeutic approach in patients with recurrent PCa presenting bone metastases with a medium-low toxicity.

Impact of dose intensified salvage radiation therapy on urinary continence recovery after radical prostatectomy: Results of the randomized trial SAKK 09/10

IntroductionAdjuvant radiation therapy (aRT) after radical prostatectomy (RP) is associated with impaired urinary continence recovery as compared to surveillance. Less is known regarding the effect of salvage radiation therapy (sRT) dose intensification on continence outcomes. Materials and methodsUrinary continence recovery was investigated within a multicentre randomized trial in biochemically recurrent prostate cancer patients who received either 64 Gy (32 fractions) or 70 Gy (35 fractions) sRT. Incontinence was assessed using Common Toxicity Criteria for Adverse Events v4.0 at baseline, at the end of sRT and 3 months afterward. Quality of life (QoL) was assessed with the EORTC QoL questionnaires C30 and PR25 at baseline and 3 months after completion of sRT. A total of 344 patients were evaluable. ResultsAt baseline 233 (68%) of patients were fully continent and 14% in both arms became incontinent three months after treatment. Of the remaining 111 (32%) patients being incontinent at baseline, continence recovery was achieved 3 months after sRT by 44% vs. 41% with 64 vs. 70 Gy, respectively (p = 0.8). This analysis is limited by its short follow-up. ConclusionsDose intensification of sRT had no impact on early urinary continence recovery or prevalence of de novo incontinence.

Combination of Androgen Deprivation Therapy and Salvage Radiotherapy versus Salvage Radiotherapy Alone for Recurrent Prostate Cancer after Radical Prostatectomy

Introduction: To assess the value of androgen deprivation therapy (ADT) on salvage radiotherapy (RT) in post-prostatectomy recurrent prostate cancer patients, we compared the oncologic outcomes between patients receiving RT + ADT and those receiving RT alone. Materials and Methods: We reviewed the records of patients diagnosed with prostate cancer between 1995 and 2011, including 93 patients who underwent salvage RT and 69 patients who underwent salvage RT + ADT. The ADT-free duration after withdrawal was calculated to verify testosterone recovery. Results: Presalvage prostate serum antigen (PSA) was the only significantly different characteristic between the 2 groups (p < 0.001). The ADT-free duration was greater than 6 months in >80% of patients. Presalvage PSA ≥0.6 ng/mL, pathologic stage ≥T3b, and RT + ADT were significantly associated with biochemical progression after salvage treatment. RT + ADT reduced biochemical progression in patients with seminal vesicle invasion or presalvage PSA ≥0.6 ng/mL (p = 0.001) compared to RT alone; biochemical progression-free probability was unchanged in seminal vesicle noninvasive prostate cancer patients with presalvage PSA <0.6 ng/mL (p = 0.541). Conclusions: RT + ADT reduced the risk of biochemical progression after salvage treatment in patients with seminal vesicle invasion or presalvage PSA ≥0.6 ng/mL, but had no effect in patients with seminal vesicle noninvasive disease and presalvage PSA <0.6 ng/mL.

15-Year BPFS, OS, and DMFS Outcomes of High-Dose-Rate Salvage Therapy for Locally Recurrent Prostate Cancer

HDR brachytherapy has been used extensively as a boost after external beam radiation therapy or as monotherapy in select patients, but is increasingly being tested as salvage treatment for locally recurrent prostate cancer. We report long-term results for salvage HDR brachytherapy in patients in a cohort of patients with recurrent disease. 34 patients (median age of 71 years at time of recurrence) treated between 1991 and 2014 were analyzed. Median recurrent PSA was 7.1 ng/mL, and there were 11, 12, and 11 patients in low-, intermediate-, and high-risk NCCN risk groups, respectively. The majority of patients (79.4%) were treated with radiation therapy (RT group) for their initial disease (median dose 68.2 Gy), while the rest received primary prostatectomy or cryotherapy (non-RT group). Median salvage HDR brachytherapy dose was 36 Gy (range 15-46) in 6 fractions (range 1-8). Sustained PSA nadir+2 (Phoenix definition) was used to define biochemical failure. Kaplan-Meier analyses were performed to determine 5-15 year rates of overall survival (OS), biochemical progression free survival (BPFS), distant metastasis free survival (DMFS), and cause specific survival. Results were also stratified according RT vs. non-RT as primary treatment. Median follow-up was 7.1 years (range 0.62-16.65). 20 patients (59%) were still living at the time of analysis. The 5-, 10- and 15-year OS rates were 89%, 59% and 17%, respectively. 12 patients (35%) developed distant metastases. The 5-, 10- and 15-year DMFS rates were 65%, 52% and 18%, respectively. Cause specific survival was 93.1% and 71.4% at 5 and 10 years, respectively. 13 patients (38%) developed biochemical failure at a median time to failure of 1.89 years. The 5- and 10-year BPFS rates were 56.1% and 28.1%. Outcomes were comparable between the primary RT and non-RT groups. Rates of G2 and G3 GU and GI toxicity were minimal and mainly based upon the baseline toxicity with which the patient presented for salvage brachytherapy. Our long-term data validates HDR salvage brachytherapy in recurrent prostate cancer patients as standard treatment option with excellent rates of disease control and overall survival with acceptable toxicity rates.

Salvage lymph node dissection after 68Ga-PSMA or 18F-FEC PET/CT for nodal recurrence in prostate cancer patients.

The management of patients with biochemical recurrence (BCR) after definitive treatment for prostate cancer remains controversial. Our aim was to determine survival rates and complications of salvage lymph node dissection (sLND) in patients with recurrent prostate cancer after radical prostatectomy, while evaluating biochemical response (BR) with two different positron emission tomography/computed tomography (PET/CT) tracers used for preoperative imaging. sLND was performed in 104 patients diagnosed with isolated nodal recurrence on either 18F-fluoroethylcholine (18F-FEC) or 68Ga-PSMA-HBED-CC (68Ga-PSMA) PET/CT. Surgical complications, BR, clinical recurrence (CR), and cancer-specific survival (CSS) were evaluated. Logistic regression was used to determine predictors of complete BR (cBR) and CR after sLND and survival rates were assessed. Median follow-up was 39.5 months. Median patient age and prostate-specific antigen (PSA) at sLND were 64 years and 4.1 ng/mL. Median number of lymph nodes (LNs) removed was 13; median number of positive LNs was 3 per patient. Rate of Clavien-Dindo Grade III complications was low (4.8%). 29.8% of patients developed cBR (PSA < 0.2 ng/mL), and 56.7% partial BR (PSA postoperative < PSA preoperative) after sLND. Patients with LN metastases diagnosed on 68Ga-PSMA PET/CT showed a higher rate of cBR compared to 18F-FEC PET/CT (45.7 vs. 21.7%, p = 0.040). PSA at sLND (p = 0.031) and choice of PET tracer (p = 0.048) were independent predictors of cBR. The 5-year BCR-free, CR-free and CSS rates were 6.2%, 26.0%, and 82.8%, respectively. While preoperative staging with 68Ga-PSMA seems superior, only a limited number of patients developed cBR after surgery. Most patients experienced BCR and CR during follow-up.

PE07 - The impact of adding sentinel node biopsy to extended pelvic lymph node dissection on the biochemical recurrence of prostate cancer patients treated with robot-assisted radical prostatectomy

PE07 - The impact of adding sentinel node biopsy to extended pelvic lymph node dissection on the biochemical recurrence of prostate cancer patients treated with robot-assisted radical prostatectomy