Local Recurrence Of Prostate Cancer Research Articles

PSOR09 Presentation Time: 12:10 PM: Initial Clinical Outcomes of a Phase II Trial of Focal Salvage LDR Brachytherapy for Local Recurrence of Prostate Cancer after External Beam Radiation Therapy

PSOR09 Presentation Time: 12:10 PM: Initial Clinical Outcomes of a Phase II Trial of Focal Salvage LDR Brachytherapy for Local Recurrence of Prostate Cancer after External Beam Radiation Therapy

Cryotherapy versus radical prostatectomy as a salvage treatment for radio-recurrent prostate cancer.

The aim of this study is to compare outcomes of SRP (salvage radical prostatectomy) with SCAP (salvage cryoablation of the prostate) in local radio-recurrent PCa (prostate cancer) patients. A retrospective analysis of a multicentric European Society of Uro-technology (ESUT) database was performed. Data on patients with local recurrent PCa after radiotherapy who underwent salvage treatment were collected. Patients and their respective disease characteristics, perioperative complications as well as oncological outcomes were then described. The treatment success rate was defined as PSA nadir < 0,4 ng/ml. Any complications were graded according to the modified Clavien system. A descriptive and comparative analysis was performed using SPSS software. 25 patients underwent SRP and 71 patients received SCAP. The mean follow-up was 24 months. The median PSA level before initial treatment was 8.3 (range 7-127) ng/ml. The success rates of SRP and SCAP were largely comparable (88% (22 patients) vs. 67.7% (48 patients), respectively, p = 0.216). The mean serum PSA levels at 12 months after salvage treatment were 1.2 ± 0.2 ng/mL vs. 0.25 ± 0.5 ng/mL, p > 0.05). During the follow-up period, only 3 (12%) patients in the SRP group had PSA recurrence compared with 21 patients (29.6%) in the SCAP group. The 5-year BRFS was similar (51,6% and 48,2%, p = 0,08) for SRP and SCAP respectively. The 5-year overall survival rate was 91.7%, and 89,7% (p = 0.669) and the 5-year cancer-specific survival was 91.7%, and 97,1% (p = 0.077), after SRP and SCAP respectively. No difference was found regarding the complications. Both SRP and SCAP should be considered as valid treatment options for patients with local recurrence of PCa after radiotherapy. SCAP has a potentially lower risk of morbidity and acceptable intermediate-term oncological efficacy, but a longer follow up and a higher number of patients is ideally needed to draw any long-term conclusions regarding the oncological data.

MRI accuracy for recurrence after partial gland ablation with HIFU for localized prostate cancer. A systematic review and meta-analysis.

Prostate cancer remains the most frequently diagnosed cancer among men. High-Intensity Focused Ultrasound (HIFU) has emerged as a thermal ablative technique for partial-gland-ablation (PGA), aiming to minimize collateral damage while maximizing tumor control. Monitoring after HIFU PGA relies on serial PSA testing, multiparametric-MRI, and biopsies. The diagnostic accuracy of MRI for clinically-significant cancer(csPCa) recurrence is challenging. This systematic review and meta-analysis aim to evaluate the accuracy of MRI in detecting early recurrence of localized prostate cancer following HIFU PGA. Adhering to PRISMA guidelines, a comprehensive literature search was conducted until May 8th 2024 using MEDLINE and Scopus. The inclusion criteria encompassed randomized controlled trials and cohort studies involving men diagnosed with localized prostate cancer who had as primary treatment HIFU PGA. The primary outcome measures included the sensitivity, specificity, positive-predictive value (PPV), and negative-predictive value (NPV) of MRI for csPCa(ISUP ≥ 2) based on biopsy results. We pooled data from studies with sufficient csPCa and csPCa-free patients (≥5) post HIFU for statistical analysis. Fifteen studies meet the inclusion criteria, encompassing 1093 patients and 12 studies were eligible for meta-analysis. MRI sensitivity in detecting clinically-significant prostate cancer (csPCa) recurrence post HIFU PGA varied widely (0-89%), with a pooled sensitivity of 0.52 (95% CI:0.36-0.68). Specificity ranged from 44% to 100%, with a pooled specificity of 0.81 (95% CI:0.68-0.91). The pooled NPV was 0.82 (95% CI:0.72-0.90), and the pooled PPV was 0.50 (95% CI:0.35-0.65). Three studies reported in-field diagnostic performance with sensitivities ranging from 0.42 to 0.80 and specificities from 0.45 to 0.97. MRI accuracy for clinically-significant recurrence after partial gland ablation with HIFU for localized prostate cancer shows low diagnostic performance in the treated lobe with pooled sensitivity of 0.52 (95% CI:0.36-0.68) and specificity of 0.81 (95% CI:0.68-0.91). Limits of this review include the low number of studies reporting about site of recurrence in or out of the treated lobe.

Local salvage therapies in patients with radio-recurrent prostate cancer following external beam radiotherapy: a systematic review and meta-analysis.

To date, radio-recurrent prostate cancer (PCa) ranks as the fourth most common urological malignancy when considering the number of men with localized PCa who undergo radiation treatment and subsequently experience a biochemical recurrence. This systematic review aimed to summarize available evidence about the outcomes of local salvage strategies in patients with local PCa recurrence following primary external-beam radiation therapy (EBRT). We conducted a comprehensive bibliographic search on MEDLINE, Scopus, and Web of Science Core Collection databases in October 2023 to identify studies published in the last 20 years evaluating outcomes of local salvage procedures in patients with locally radio-recurrent PCa following EBRT. The meta-analysis was performed using ProMeta 3 software when two or more studies reported the same outcome. The effect size (ES) was estimated using rates reported with its 95% confidence interval (CI). Overall, 28 studies (6 prospective and 22 retrospective) including 1544 patients were included in the review. Two-year recurrence-free survival (RFS) was 84.0% (95% CI: 67.0-93.0%), 69.0% (95% CI: 42.0-87.0%), 58.0% (95% CI: 43.0-71.0%), and 45% (95% CI: 38.0-52.0%), for patients undergoing brachytherapy (BT), EBRT, Cryotherapy and High-Intensity Focused Ultrasound (HIFU), respectively. After salvage prostatectomy, RFS ranged from 75% to 78.5% at a median follow-up ranging from 18 to 35 months. Estimates for severe gastrointestinal toxicity were 2%, 3%, 3%, 4%, and 11% following cryotherapy, BT, HIFU, EBRT, and salvage radical prostatectomy, respectively. In patients who underwent EBRT as primary treatment, prostate salvage re-irradiation through BT or EBRT represents the modality providing the best balance between efficacy and safety. Unfortunately, due to the low level of evidence, strong recommendations regarding the choice of any of these techniques cannot be made.

Local Recurrence of Postoperative Prostate Cancer, Treatment and Toxicity with Stereotactic Body Radiotherapy (SBRT): A Case Report

Background: Prostate cancer remains a major health concern worldwide, and postoperative recurrences are a significant challenge in its treatment. Various treatment modalities have been studied, but consensus on optimal strategies has not yet been established. This case report examines the feasibility and toxicity of stereotactic body radiation therapy (SBRT) as a therapeutic option for postoperative recurrences of prostate cancer. Case presentation: A 68-year-old man with a history of prostate cancer, initially treated with radical prostatectomy, who presented biochemical recurrence. Diagnostic imaging revealed a 9 mm nodule in the prostate bed, which was treated by SBRT guided by ultrasound visualization. The patient tolerated the treatment well, experiencing minimal genitourinary and gastrointestinal discomfort. Discussion: Multiple treatment alternatives exist for post-prostatectomy recurrence. Retrospective studies have suggested the efficacy of SBRT, although they lack robust empirical evidence. Recent investigations have highlighted the safety profile of SBRT, emphasizing the need for further exploration, particularly in image-guided radiotherapy. Conclusion: SBRT guided by ultrasound visualization emerges as a promising option for ablative treatment of postprostatectomy recurrence, offering a favorable safety profile and encouraging oncologic outcomes. Further research is needed to further clarify its role in salvage radiotherapy for localized recurrences.

Salvage low-dose-rate brachytherapy for locally recurrent prostate cancer after definitive irradiation

PurposeThe optimal management of locally recurrent prostate cancer after definitive irradiation is still unclear but local salvage treatments are gaining interest. A retrospective, single-institution analysis of clinical outcomes and treatment-related toxicity after salvage I-125 low-dose-rate (LDR) brachytherapy (BT) for locally-recurrent prostate cancer was conducted in a Comprehensive Cancer Center. Patients and methodsA total of 94 patients treated with salvage LDR-BT between 2006 and 2021 were included. The target volume was either the whole-gland +/- a boost on the GTV, the hemigland, or only the GTV. The prescribed dose ranged from 90 to 145 Gy. Toxicity was graded by Common Terminology Criteria for Adverse Events (CTCAE) v5.0. ResultsMedian follow-up was 34 months. Initial radiotherapy was external beam radiotherapy in 73 patients (78 %) with a median dose of 76 Gy and I-125 BT in 21 patients (22 %) with a prescribed dose of 145 Gy. Median PSA at salvage was 3.75 ng/ml with a median interval between first and salvage irradiation of 9.4 years. Salvage brachytherapy was associated with androgen deprivation therapy for 32 % of the patients. Only 4 % of the patients were castrate-resistant. Failure free survival was 82 % at 2 years and 66 % at 3 years. The only factors associated with failure-free survival on multivariate analysis were hormonosensitivity at relapse and European Association of Urology (EAU) prognostic group. Late grade 3 urinary and rectal toxicities occurred in 12 % and 1 % of the patients respectively.No significant difference in toxicity or efficacy was observed between the three implant volume groups. ConclusionThe efficacy and toxicity results are consistent with those in the LDR group of the MASTER meta-analysis. Salvage BT confirms to be an effective and safe option for locally recurrent prostate cancer. A focal approach could be interesting to reduce late severe toxicities, especially urinary.

Salvage prostate intensity modulated radiation therapy after cryotherapy failure

Cryotherapy is an ablative therapy that can be used to treat localized prostate cancer. In case of recurrence, treatment options are not well-defined, and their outcomes are unknown. We therefore collected all patients treated with radiotherapy after cryotherapy for prostate cancer recurrence in Nantes (France) between 2012 and 2019. We identified ten patients. After a median follow-up of 5 years, two patients presented late grade 3 toxicities; one patient presented a grade 3 rectal hemorrhage, and one had a grade 3 hematuria. Two patients relapsed at 61 and 62 months, and three patients died of other causes. Radiotherapy to treat local prostate cancer recurrence after cryotherapy seems feasible and effective in local control. These results do not allow us to recommend this technique in current practice but are encouraging for the conduct of prospective trials.

Assessing the effectiveness of MRI, 18F-fluciclovine PET, SUVmax, and PSA in detecting local recurrence of prostate cancer after prostatectomy.

The primary objective of this study was to evaluate the discriminatory utility of magnetic resonance imaging (MRI), 18F-fluciclovine positron emission tomography (PET), maximum standardized uptake value (SUVmax), prostate-specific antigen (PSA), and combinations of these diagnostic modalities for detecting local prostate cancer recurrence in the setting of rising PSA after radical prostatectomy. Patients were characterised for clinical features such as Gleason score, PSA at surgery, PSA at follow-up, follow-up MRI result, follow-up PET result, follow-up SUVmax, and follow-up disease status. The utility of diagnostic parameters for detecting disease recurrence at the prostatectomy bed was assessed using receiver operating characteristics (ROC) analysis to determine the area under the curve (AUC) for each model. Sensitivity, specificity, and positive/negative predictive values were also calculated. Optimal cut-off points for continuous variables were determined based on maximum Youden's J statistics. The study found that MRI had the highest concordance (96%), sensitivity (100%), specificity (91%), positive predictive value (93%), and negative predictive value (100%) among the diagnostic modalities. The AUC for MRI was 0.9545, indicating a high discriminatory ability for detecting prostate cancer local recurrence. When combined, PET and SUVmax (cut-off value of 2.85) showed an improved performance compared to using them individually, with an AUC of 0.8925. The analysis suggests that MRI is the most effective imaging modality for detecting local prostate cancer recurrence, with 18F-fluciclovine PET and SUVmax also showing promising combined results. PSA has moderate discriminatory utility at follow-up but can still provide valuable information in detecting prostate cancer recurrence. Further research and recent references are needed to support these findings.

Diagnostic efficacy and interobserver agreement among readers with variable experience of the Prostate Imaging for Recurrence Reporting system with whole-mount histology after androgen deprivation therapy as a reference.

The Prostate Imaging for Recurrence Reporting (PI-RR) system was recently proposed to assess the local recurrence of prostate cancer (PCa), but its exact performance for the prostate after radiotherapy or radical prostatectomy is difficult to determine. We aimed to evaluate the diagnostic performance and interreader agreement of this system using whole-mount histology of the prostate after androgen deprivation therapy (ADT) as the standard of reference. In total, 119 patients with PCa post-ADT underwent multiparametric magnetic resonance imaging (mp-MRI) before prostatectomy. Three radiologists analyzed the MRI images independently, scoring imaging findings according to PI-RR. Spearman correlation was performed to assess the relationship between the percentage of sectors with residual cancer and PI-RR score. The diagnostic performance for detection of residual cancer was assessed on a per-sector basis. The chi-squared test was used to compare the cancer detection rate (CDR) among readers. Overall and pairwise interreader agreement in assigning PI-RR categories and residual cancer sectors with a score ≥3 or ≥4 were evaluated with the Cohen kappa coefficient. Histology revealed 209 sectors with residual cancer. The percentage of pathologically positive sectors increased with the increase in PI-RR score for all readers. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) at a cutoff of score 3 ranged from 74.2% to 83.7%, 86.4% to 92.7%, 51.3% to 64.3%, and 95.4% to 96.9%, respectively, and at a cutoff of score 4, they ranged from 47.4% to 56.5%, 97.9% to 98.6%, 82.5% to 85.3%, and 91.6% to 92.9%, respectively. There was no significant difference among the CDR of readers. In PI-RR categories and detection of residual cancer sectors, overall interreader agreement was moderate for all readers, but agreement was higher between the more experienced readers (moderate to substantial) than between the more and less experienced readers (fair to moderate). MRI scoring with the PI-RR assessment provided accurate evaluation of PCa after ADT, but readers' experience influenced interreader agreement and cancer diagnosis.

Nadir prostate-specific antigen after salvage cryotherapy as a potential prognostic factor for oncologic outcomes.

To report oncologic outcomes of patients undergoing salvage cryotherapy (SCT) for local recurrence of prostate cancer (PCa) and to establish a nadir PSA (nPSA) value that best defines long-term oncologic success. Retrospective study of men who underwent SCT for local recurrence of PCa between 2008 and 2020. SCT was performed in men with biochemical recurrence (BCR), after primary treatment and with biopsy-proven PCa local recurrence. Survival analysis with Kaplan-Meier and Cox models was performed. We determined the optimal cutoff nPSA value after SCT that best classifies patients depending on prognosis. Seventy-seven men who underwent SCT were included. Survival analysis showed a 5-year biochemical recurrence-free survival (BRFS), androgen deprivation therapy-free survival (AFS), and metastasis-free survival (MFS) after SCT of 48.4%, 62% and 81.3% respectively. On multivariable analysis for perioperative variables associated with BCR, initial ISUP, pre-SCT PSA, pre-SCT prostate volume and post-SCT nPSA emerged as variables associated with BCR. The cutoff analysis revealed an nPSA < 0.5ng/ml to be the optimal threshold that best defines success after SCT. 5-year BRFS for patients achieving an nPSA < 0.5 vs nPSA ≥ 0.5 was 64% and 9.5% respectively (p < 0.001). 5-year AFS for men with nPSA < 0.5 vs ≥ 0.5 was 81.2% and 12.2% (p < 0.001). Improved 5-year MFS for patients who achieved nPSA < 0.5 was also obtained (89.6% vs 60%, p = 0.003). SCT is a feasible rescue alternative for the local recurrence of PCa. Achieving an nPSA < 0.5ng/ml after SCT is associated with higher long-term BRFS, AFS and MFS rates.

A Phase 1 Trial of Salvage Stereotactic Body Radiation Therapy for Radiorecurrent Prostate Cancer After Brachytherapy

NCT03253744 is a phase 1 trial with the primary objective to identify the maximum tolerated dose (MTD) of salvage stereotactic body radiation therapy (SBRT) in patients with local prostate cancer recurrence after brachytherapy. Additional objectives included biochemical control and imaging response. This trial was initially designed to test 3 therapeutic dose levels (DLs): 40 Gy (DL1), 42.5 Gy (DL2), and 45 Gy (DL3) in 5 fractions. Intensity modulation was used to deliver the prescription dose to the magnetic resonance imaging and prostate-specific membrane antigen-based positron emission tomography imaging-defined gross tumor volume while simultaneously delivering 30 Gy to an elective volume defined by the prostate gland. This phase 1 trial followed a 3+3 design with a 3-patient expansion at the MTD. Toxicities were scored until trial completion at 2 years post-SBRT using Common Terminology Criteria for Adverse Events version 5.0. Escalation was halted if 2 dose limiting toxicities occurred, defined as any persistent (>4 days) grade 3 toxicity occurring within the first 3 weeks after SBRT or any grade ≥3 genitourinary (GU) or grade 4 gastrointestinal toxicity thereafter. Between August 2018 and January 2023, 9 patients underwent salvage SBRT and were observed for a median of 22 months (Q1-Q3, 20-43 months). No grade 3 to 5 adverse events related to study treatment were observed; thus, no dose limiting toxicities occurred during the observation period. Escalation was halted by amendment given excellent biochemical control in DL1 and DL2 in the setting of a high incidence of clinically significant late grade 2 GU toxicity. Therefore, the MTD was considered 42.5 Gy in 5 fractions (DL2). One- and 2-year biochemical progression-free survival were 100% and 86%, representing a single patient in the trial cohort with biochemical failure (prostate-specific antigen [PSA] nadir + 2.0) at 20 months posttreatment. The MTD of salvage SBRT for the treatment of intraprostatic radiorecurrence after brachytherapy was 42.5 Gy in 5 fractions producing an 86% 2-year biochemical progression-free survival rate, with 1 poststudy failure at 20 months. The most frequent clinically significant toxicity was late grade 2 GU toxicity.

Salvage high-dose rate brachytherapy for local recurrence of prostate cancer after radical prostatectomy

Background. The current need for optimization of salvage treatment methods is dictated by the growing expansion of indications for radical prostatectomy in many centers in the developed countries of the world.Aim. To evaluate the effectiveness, toxicity, and technical characteristics of high-dose rate brachytherapy in treatment of local prostate cancer (PCa) recurrences after radical prostatectomy.Materials and methods. Between January 2015 and December 2020, salvage high-dose rate brachytherapy was performed in 17 patients at the Russian Scientific Center of Roentgenology and Radiology for local recurrence of PCa after radical prostatectomy. All patients underwent multiparametric magnetic resonance imaging of the pelvis at the stage of primary diagnosis in order to determine macroscopic tissue component in the prostate bed area. To rule out regional and distant metastases, all patients underwent positron emission tomography with 18F- or 68Ga-labeled prostate-specific membrane antigen. All patients included in the study underwent perineal biopsy of the prostate bed and seminal vesicles.Results. Median follow-up in the treatment group was 35.7 (24–54) months. Overall survival was 100 %. Prostatespecific antigen-specific survival was 88.2 %. There were no local recurrences of PCa in the treatment group. In patients with local PCa recurrence, significant predictors of treatment failure were the presence of clinically extremely high risk of progression at initial diagnosis (p = 0.003), development of biochemical relapse up to 24 months after main treatment (p = 0.001), and increased blood level of prostate-specific antigen above 10 ng/mL during registration of biochemical relapse (p = 0.002).Conclusion. High-dose rate brachytherapy is a safe and effective salvage treatment for local recurrence of PCa after radical prostatectomy. In addition to the brachytherapy technique, the diagnostic stage is also of great importance providing visualization of the exact location of tumor recurrence.

Multiparametric magnetic resonance imaging in diagnosis of local prostate cancer recurrence after radiation therapy and radical prostatectomy: a unified PI-RR reporting system

Multiparametric magnetic resonance imaging (mpMRI) has an indisputable advantage in diagnosis of local recurrences of prostate cancer (PCa). Even though mpMRI has been shown to be very informative for detection of local PCa recurrences, high variability in its application and interpretation remains. Experts from the European Society for Urogenital Radiology (ESUR), the Imaging Committee of the European Association of Urology (ESUI), and several members of the PI-RADS committee developed a unified report system called Prostate Imaging Recurrence Reporting (PI-RR) to measure the risk of local recurrence of PCa in men who have had radical prostatectomy and radiation therapy and are being followed up. The principles of mpMRI that form the basis of PI-RR are well known and are stated in the PI-RADS v.2.1 guidelines, which have proven their diagnostic efficiency. The PI-RR system has the potential to become an important tool for improving communication between specialists involved in the process of PCa diagnosis and treatment, for optimizing treatment strategy in patients with local PCa recurrence, and for improving survival rates in patients with PCa after specialized anticancer treatment.

Nonsurgical salvage options for locally recurrent prostate cancer after primary definitive radiotherapy: a systematic review and meta-analysis.

To conduct a meta-analysis to provide the latest evidence of nonsurgical local salvage options in the first-line radiotherapy (RT) failure setting for localized prostate cancer patients. Recurrence of localized prostate cancer after primary RT remains a clinical challenge. There is no consensus on optimal nonsurgical local salvage therapies, which mainly consist of cryotherapy (CRYO), high-intensity focused ultrasound (HIFU), high/low-dose-rate brachytherapy (HDR/LDR), and stereotactic body radiotherapy (SBRT). Our study was performed following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The authors systematically searched PubMed, Web of Science, Cochrane Library, and ClinicalTrials.gov up to September 2023 to identify potentially relevant studies. The risk of bias was assessed using the European Association of Urology (EAU) items. Biochemical recurrence-free survival (bRFS) and genitourinary/gastrointestinal toxicities were the outcomes of interest. Pooled rates with 95% CIs were evaluated. A total of 99 studies comprising 8440 patients were included. The pooled rate of 1-year biochemical control (BC) was highest for LDR (0.88, 95% CI: 0.72-0.95) and lowest for SBRT (0.68, 95% CI: 0.49-0.83). The pooled rate of 5-year BC was highest for CRYO (0.52, 95% CI: 0.33-0.69) and lowest for HDR (0.23, 95% CI: 0.08-0.51). HIFU presented the worst outcome of grade ≥3 genitourinary toxicities (GU3), with a rate of 0.22 (95% CI: 0.12-0.3). Conversely, CRYO (0.09, 95% CI: 0.04-0.14), HDR (0.05, 95% CI: 0.02-0.07), LDR (0.10, 95% CI: 0.06-0.14), and SBRT (0.06, 95% CI: 0.03-0.09) presented low rates of GU3. All subgroups induced a quite low incidence of grade ≥3 gastrointestinal toxicities (GI3). Nonsurgical salvage therapies are promising modalities for prostate cancer in the local radiorecurrence setting. Based on the preliminary evidence from this study, CRYO and SBRT might present a relatively steady efficacy of BC with acceptable treatment-related toxicities.

The practical clinical role of machine learning models with different algorithms in predicting prostate cancer local recurrence after radical prostatectomy

BackgroundThe detection of local recurrence for prostate cancer (PCa) patients following radical prostatectomy (RP) is challenging and can influence the treatment plan. Our aim was to construct and verify machine learning models with three different algorithms based on post-operative mpMRI for predicting local recurrence of PCa after RP and explore their potential clinical value compared with the Prostate Imaging for Recurrence Reporting (PI-RR) score of expert-level radiologists.MethodsA total of 176 patients were retrospectively enrolled and randomly divided into training (n = 123) and testing (n = 53) sets. The PI-RR assessments were performed by two expert-level radiologists with access to the operative histopathological and pre-surgical clinical results. The radiomics models to predict local recurrence were built by utilizing three different algorithms (i.e., support vector machine [SVM], linear discriminant analysis [LDA], and logistic regression-least absolute shrinkage and selection operator [LR-LASSO]). The combined model integrating radiomics features and PI-RR score was developed using the most effective classifier. The classification performances of the proposed models were assessed by receiver operating characteristic (ROC) curve analysis.ResultsThere were no significant differences between the training and testing sets concerning age, prostate-specific antigen (PSA), Gleason score, T-stage, seminal vesicle invasion (SVI), perineural invasion (PNI), and positive surgical margins (PSM). The radiomics model based on LR-LASSO exhibited superior performance than other radiomics models, with an AUC of 0.858 in the testing set; the PI-RR yielded an AUC of 0.833, and there was no significant difference between the best radiomics model and the PI-RR score. The combined model achieved the best predictive performance with an AUC of 0.924, and a significant difference was observed between the combined model and PI-RR score.ConclusionsOur radiomics model is an effective tool to predict PCa local recurrence after RP. By integrating radiomics features with the PI-RR score, our combined model exhibited significantly better predictive performance of local recurrence than expert-level radiologists’ PI-RR assessment.

Recurrent prostate cancer: combined role for MRI and PSMA-PET in 68Ga-PSMA-11 PET/MRI

ObjectivesTo investigate the specific strengths of MRI and PET components in 68Ga-PSMA-11 PET/MRI for staging of patients with biochemically recurrent prostate cancer (PCa).MethodsPatients with biochemical recurrence of PCa and contrast-enhanced whole-body 68Ga-PSMA-11 PET/MRI including a dedicated pelvic multiparametric MRI were included in this retrospective study. Imaging datasets of MRI and PET were evaluated separately regarding local PCa recurrence (Tr), pelvic lymph node metastases (N1), distant lymph node metastases (M1a), bone metastases (M1b), and soft tissue metastases (M1c) according to PROMISE version 1. Data evaluation was performed patient- and region-/lesion-based. Cox regression revealed a PSA of 1.69 ng/mL as a cut-off for subgroup analysis. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were evaluated for each image component. Differences in staging accuracy were assessed using the Wilcoxon and McNemar test.ResultsAltogether 102 patients (mean aged 68 ± 8 years, median PSA 1.33 ng/mL) were included. PCa was found in 70/102 (68%) patients. Accuracy of MRI in the detection of Tr, N1, M + , M1a, and M1b was 100%, 79%, 90%, 97%, and 95% for PSA < 1.69 ng/mL and 100%, 87%, 87%, 91%, and 96% for PSA > 1.69 ng/mL. Accuracy of 68Ga-PSMA-11 PET was 93%, 97%, 93%, 98%, and 100% for PSA < 1.69 ng/mL and 87%, 91%, 96%, 100%, and 96% for PSA > 1.69 ng/mL.ConclusionsCombined assessment of 68Ga-PSMA-11 PET/MRI improves tumor localization in men with biochemical recurrence. The MRI detected local recurrence of PCa more often whereas 68 Ga-PSMA-11 PET detected lymph node metastases more often, especially for PSA < 1.69 ng/mL.Clinical relevance statementThis study gives a scientific baseline to improve the understanding and reading of 68Ga-PSMA-11 PET/MRI imaging in patients with biochemically recurrent PCa by showing the specific strength of each imaging component.Key Points• Combining the individual modality strengths of 68Ga-PSMA-11 PET/MRI improves tumor localization in men with biochemical recurrence of prostate cancer.• MRI component of 68 Ga-PSMA-11 PET/MRI shows its strength in detecting local recurrence of prostate cancer, especially at PSA < 1.69 ng/mL.• 68 Ga-PSMA-11 PET component shows its strength in detecting local and distant lymph node metastases, especially at PSA < 1.69 ng/mL.

Salvage Radiotherapy and Androgen-Deprivation Therapy for Local Recurrence of Prostate Cancer after Radical Prostatectomy

Актуальность. Пациенты с биохимическим рецидивом рака предстательной железы (РПЖ) после радикальной простатэктомии (РПЭ) представляют собой сложную и гетерогенную группу. Данная статья посвящена выбору лечебной тактики локального рецидива РПЖ после РПЭ.&#x0D; Цель. Оценить клиническую эффективность и проанализировать осложнения и качество жизни после проведения спасительной высокомощностной брахитерапии в монорежиме, дистанционной лучевой терапии и андроген-депривационной терапии локальных рецидивов РПЖ после РПЭ.&#x0D; Материал и методы. За период с января 2016 по декабрь 2020 в ФГБУ «РНЦРР» МЗ РФ пролечено 60 пациентов с локальным рецидивом РПЖ после РПЭ. Выделено 2 группы: в I группу вошло 30 пациентов, которым проведена сальважная дистанционная лучевая терапия (ДЛТ) в режиме классического фракционирования; II группе в рамках научного протокола 30 пациентам выполнено 2 фракции сальважной HDR-брахитерапии РОД 15 Гр до СОД 30 Гр. Дополнительно выделена 3 группа пациентов, которым проводилась андроген-депривационная терапия (АДТ) без облучения. Всем пациентам выполнено мпМРТ малого таза и ПЭТ-КТ с лигандами простатспецифического мембранного антигена (ПСМА), также 2 группе проведена биопсия ложа удалённой предстательной железы промежностным доступом. Проанализирована общая и биохимическая безрецидивная выживаемость, а также структура ранних и поздних лучевых осложнений.&#x0D; Результаты: Общая выживаемость составила 100%. Значения 1-летней, 2-летней и 3-летней безрецидивной выживаемости в группе спасительной ДЛТ составила 96,7 %, 83,3 % и 76,7 %, а в группе спасительной брахитерапии – 100%, 93,3 %, 89,4 %. При сравнительном анализе ПСА-специфической безрецидивной выживаемости отмечается тенденция к её увеличению в группе брахитерапии. (p = 0,075). Сальважная ДЛТ оказалась токсичнее СБТ-ВМД. Сравнительная оценка лучевых токсических реакций выявила более высокую частоту ранней генитоуринарной токсичности I степени , интестинальной I и II степени в группе сальважной ДЛТ, чем в группе сальважной брахитерапии, а также поздней гастроинтестинальной токсичности I и II степени.&#x0D; Выводы. При сравнении двух технологий спасительной лучевой терапии была показана эквивалентная эффективность с точки зрения 3-летней общей и ПСА-специфической безрецидивной выживаемости, однако, при этом технология спасительной высокодозной брахитерапии значительно снижала как раннюю, так и позднюю генитоуринарную и гастроинтестинальную токсичность, что статистически и клинически значимо влияло на качество жизни больных.

Initial Clinical Outcomes of a Phase II Trial of Focal Salvage LDR Brachytherapy for Local Recurrence of Prostate Cancer after External Beam Radiation Therapy.

To evaluate the clinical outcomes of focal salvage low dose rate brachytherapy (FSB) for biopsy proven local recurrence of prostate cancer after definitive external beam radiation therapy (EBRT). Patients with a Phoenix definition PSA recurrence (nadir + 2.0ng/dL) after definitive EBRT for localized prostate cancer and a negative metastatic work up were enrolled in a Phase II clinical trial. Patients first underwent MR-guided transperineal mapping biopsy of the prostate using a template grid. Patients with a pathologically confirmed recurrence underwent FSB using iodine-125 seeds to a prescription dose of 145 Gy. The brachytherapy planning target volume (PTV) was defined by the positions of the pathologically negative core biopsies adjacent to the positive core biopsies as recorded on the template grid during the biopsy procedure. An intraoperative treatment plan was then developed to cover the PTV with the 145 Gy isodose line. Follow up included assessment of genitourinary (GU) and gastrointestinal (GI) toxicities using Common Terminology Criteria for Adverse Events version 4.03 (CTCAEv4.03), patient reported outcomes using the International Prostate Symptom Score (IPSS) and Expanded Prostate Cancer Index-26 (EPIC-26) forms, and serial PSA blood draws. Ten patients underwent FSB. The median prior EBRT dose was 7805 cGy (interquartile range IQR 7560-7920) and the median time from completion of EBRT to FSB was 81 months (IQR 68-134). The median PSA prior to FSB was 3.2 ng/dL (IQR 2.3 - 4.5). The median follow up after FSB was 32 months (IQR 18-57). Eight patients were free of Phoenix definition PSA failure at last follow up. Of the two patients who experienced a PSA failure, one developed distant metastases 5 months after FSB and the other a biopsy proven seminal vesicle recurrence 3 years after FSB. The median change in post FSB IPSS score compared to the pre-FSB IPSS score was an increase of 1.5 (IQR -1.5 to 8) at 3 month follow up and an increase of 3.5 (IQR 0.5 to 5.5) at last follow up (≥1 year). The median change in post FSB EPIC-26 urinary domain score compared to the pre-FSB score was -1 (IQR -26 to +14.5) at 3 month follow up and +2 (IQR -12.5 to +14.5) at last follow up (≥1 year). The median change in post FSB EPIC-26 bowel domain score compared to the pre-FSB score was -2 (IQR -9.5 to 0.0) at 3 month follow up and 0 (IQR -6.0 to +3.0) at last follow up (≥1 year). No patients experienced post FSB Grade 3 or higher GU or GI toxicities. High dose FSB for a local recurrence of prostate cancer after EBRT can be delivered with good biochemical control and a favorable toxicity profile. Further clinical trial enrollment and longer follow up will be needed to better assess long term outcomes.

Salvage Cryoablation for Recurrent Prostate Cancer Following Primary External Beam Radiotherapy or Primary Cryotherapy: A Propensity Score Matched Analysis of Mid-term Oncologic and Functional Outcomes.

Local prostate cancer recurrence following radiotherapy (XRT) or cryoablation (CRYO) may be addressed with salvage cryotherapy (SCT), although little is known about how the primary treatment modality affects SCT results. Oncologic and functional outcomes of patients who underwent SCT after primary XRT (XRT-SCT) or cryoablation (CRYO-SCT)were studied. Data was collected using the Duke Prostate Cancer database and the Cryo On-Line Data (COLD) registry. The primary outcome was biochemical progression-free survival (BPFS). Urinary incontinence, rectourethral fistula, and erectile dysfunction were secondary outcomes. The Kaplan-Meier log-rank test and univariable/multivariable Cox proportional hazards (CPH) models were utilized to evaluate BPFS between groups. 419 XRT-SCT and 63 CRYO-SCT patients met inclusion criteria, that was reduced to 63 patients in each cohort after propensity matching. There was no difference in BPFS at 2 and 5 years both before (P=.5 and P=.7) and after matching (P=.6 and P=.3). On multivariable CPH, BPFS was comparable between treatment groups (CRYO-SCT, HR=1.1, [0.2-2.2]). On the same analysis, BPFS was lower in D'Amico high-risk (HR 3.2, P < .01) and intermediate-risk (HR 1.95, P < .05) categories compared to low-risk. There was no significant difference in functional outcomes between cohorts. Following primary cryotherapy, salvage cryoablation provides comparable intermediate oncological outcomes and functional outcomes compared to primary radiotherapy.

MRI-Guided Radiation Therapy for Prostate Cancer: The Next Frontier in Ultrahypofractionation.

Technological advances in MRI-guided radiation therapy (MRIgRT) have improved real-time visualization of the prostate and its surrounding structures over CT-guided radiation therapy. Seminal studies have demonstrated safe dose escalation achieved through ultrahypofractionation with MRIgRT due to planning target volume (PTV) margin reduction and treatment gating. On-table adaptation with MRI-based technologies can also incorporate real-time changes in target shape and volume and can reduce high doses of radiation to sensitive surrounding structures that may move into the treatment field. Ongoing clinical trials seek to refine ultrahypofractionated radiotherapy treatments for prostate cancer using MRIgRT. Though these studies have the potential to demonstrate improved biochemical control and reduced side effects, limitations concerning patient treatment times and operational workflows may preclude wide adoption of this technology outside of centers of excellence. In this review, we discuss the advantages and limitations of MRIgRT for prostate cancer, as well as clinical trials testing the efficacy and toxicity of ultrafractionation in patients with localized or post-prostatectomy recurrent prostate cancer.