Salvage Radiotherapy In Patients Research Articles

High-Grade Late Urinary Toxicity Following Salvage Radiotherapy After Radical Prostatectomy: A Retrospective Cohort Study

Purpose: To find out the incidence and predictors for late high-grade genitourinary (GU) toxicity following salvage radiotherapy (SRT), we investigated the consecutive patients who were treated with SRT after radical prostatectomy.Materials and Methods: Patients who underwent SRT for biochemical recurrence after radical prostatectomy were reviewed. The incidence of GU toxicity was assessed and risk factors for grade ≥2 and ≥3 GU toxicity were evaluated. The STROBE (STrengthening the Reporting of OBservational studies in Epidemiology) guided the reporting of this study.Results: Among the total of 217 patients, 88 patients (40.5%) showed late grade ≥2 GU toxicity. The incidence of late grade ≥3 GU toxicity was 11.5%. The presence of grade ≥2 baseline GU dysfunction (hazard ratio [HR], 6.097; 95% confidence interval [CI], 3.280–11.333; p<0.001) and short interval (<1 year) from surgery to SRT (HR, 1.994; 95% CI, 1.182–3.365; p=0.01) were associated with late grade ≥2 GU toxicity. A short interval from surgery to SRT was an independent predictor of late grade ≥3 GU toxicity (HR, 2.975; 95% CI, 1.135–7.794; p=0.027).Conclusions: The incidence of late high-grade GU toxicity was not uncommon after SRT. Thus, care should be taken when we consider SRT in patients with baseline urinary dysfunction and a short interval from surgery to SRT, to determine an optimal treatment strategy with balancing quality of life and oncologic outcome of patients.

Salvage Radiotherapy for Relapsed Prostate Cancer after Radical Prostatectomy Is Associated with Normal Life Expectancy

In patients with prostate cancer (PCa), salvage radiotherapy (SRT) for biochemical progression (BP) after radical prostatectomy (RP) improves PCa-specific survival. However, no prospective randomized trials have compared the effect of SRT with untreated patients. In this analysis of 151 patients who received SRT for post-RP BP, we compared their overall survival (OS) with virtual, age-matched controls (n = 151,000) retrieved from government life tables. We also investigated the risk factors associated with BP and OS and compared the prostate-specific antigen (PSA) doubling times (DTs) before and after SRT for patients with BP. The median follow-up was 9.3 years for BP and 17.4 years for OS. The risk factors significantly affecting BP were Gleason score (p < 0.001), pre-SRT PSA (p = 0.003), and negative surgical margins (p = 0.003). None of these risk factors were associated with OS. In 93 patients with BP after SRT, the median PSADT was significantly prolonged compared with pre-SRT values (3.7 vs. 8.3 months, p < 0.001). The OS did not differ between patients and controls (p = 0.112), and life expectancy was similar, likely due to the survival benefit of SRT. The prolonged PSADT after SRT further supports the beneficial role of SRT in this patient population. However, subsequent treatments were not systematically recorded, which may have affected the results.

The prognostic significance of a negative PSMA-PET scan prior to salvage radiotherapy following radical prostatectomy

AimThe optimal management for early recurrent prostate cancer following radical prostatectomy (RP) in patients with negative prostate-specific membrane antigen positron-emission tomography (PSMA-PET) scan is an ongoing subject of debate. The aim of this study was to evaluate the outcome of salvage radiotherapy (SRT) in patients with biochemical recurrence with negative PSMA PET finding.MethodsThis retrospective, multicenter (11 centers, 5 countries) analysis included patients who underwent SRT following biochemical recurrence (BR) of PC after RP without evidence of disease on PSMA-PET staging. Biochemical recurrence-free survival (bRFS), metastatic-free survival (MFS) and overall survival (OS) were assessed using Kaplan-Meier method. Multivariable Cox proportional hazards regression assessed predefined predictors of survival outcomes.ResultsThree hundred patients were included, 253 (84.3%) received SRT to the prostate bed only, 46 (15.3%) additional elective pelvic nodal irradiation, respectively. Only 41 patients (13.7%) received concomitant androgen deprivation therapy (ADT). Median follow-up after SRT was 33 months (IQR: 20–46 months). Three-year bRFS, MFS, and OS following SRT were 73.9%, 87.8%, and 99.1%, respectively. Three-year bRFS was 77.5% and 48.3% for patients with PSA levels before PSMA-PET ≤ 0.5 ng/ml and > 0.5 ng/ml, respectively. Using univariate analysis, the International Society of Urological Pathology (ISUP) grade > 2 (p = 0.006), metastatic pelvic lymph nodes at surgery (p = 0.032), seminal vesicle involvement (p < 0.001), pre-SRT PSA level of > 0.5 ng/ml (p = 0.004), and lack of concomitant ADT (p = 0.023) were significantly associated with worse bRFS. On multivariate Cox proportional hazards, seminal vesicle infiltration (p = 0.007), ISUP score >2 (p = 0.048), and pre SRT PSA level > 0.5 ng/ml (p = 0.013) remained significantly associated with worse bRFS.ConclusionFavorable bRFS after SRT in patients with BR and negative PSMA-PET following RP was achieved. These data support the usage of early SRT for patients with negative PSMA-PET findings.

Timing of Early Salvage Therapy for Patients With Biochemical Relapse of Prostate Carcinoma.

Between 25% and 33% of patients after radical prostatectomy experience a relapse of the disease. The risk of relapse increases in patients with risk factors up to 50%-80%. For a long time, adjuvant radiotherapy has been considered the standard of care. Four large prospective trials, that compared adjuvant and salvage radiotherapy in patients with biochemical relapse, showed the superiority of the adjuvant approach in biochemical and local relapse-free survival, but no consistent benefit in long-term endpoints (i.e., metastasis-free survival, overall survival, or carcinoma-specific survival) at the expense of increased urinary and bowel toxicity. Three large international studies comparing adjuvant and salvage radiotherapy paved the way toward early salvage radiotherapy. However, the optimal threshold of the PSA level (range of 0.2-0.5ng/mL) for initiating early salvage radiotherapy remains unresolved and still poses a challenge in everyday clinical practice when balancing the need for early radiotherapy and the associated toxicity. Imprecise stratification of biochemical relaps patients according to the risk of clinical relapse drives efforts to find additional molecular biomarkers that would improve the timing of the salvage therapy.

Radiotherapy of patients with regional recurrence of prostate cancer after radical prostatectomy

Background. Salvage radiation therapy is the “gold standard” of treatment for patients with recurrent prostate cancer after radical prostatectomy. However, the results of the effectiveness of salvage radiation therapy in patients with regional recurrences are significantly lower than in patients with local one of prostate cancer, and, as a rule, the progression of the disease more often continues lymphogenic, affecting the next barrier of lymph outflow – retroperitoneal lymph nodes.Aim. To develop a new more effective radical method of salvage radiation therapy in patients with regional relapses of prostate cancer after radical prostatectomy.Materials and methods. The radiotherapy department of the N. N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russia has developed a new method of hypofractionation salvage radiation therapy of patients with regional recurrences of prostate cancer after radical prostatectomy, which includes treatment not only to regional recurrences, the bed of prostate and regional lymph nodes of the pelvis, but also and prophylactic radiation treatment to retroperitoneal lymph nodes.Results. 25 patients were treated with prophylactic radiation treatment to retroperitoneal lymph nodes from 2018 to 2021. The median follow-up of patients was 19 (7–22) months. In all patients, radiotherapy was performed in combination with hormone therapy with analogues of luteinizing hormone releasing hormone with a median duration of administration of 8 (6–10) months. All patients were treated without interruption according to the previously planned dosimetric treatment plans. At the end of the course of radiation therapy, none of the patients had any pronounced negative effects of the III–IV degree (according to the RTOG /EORTC scale). The 1-year local and biochemical control of the disease were 100 and 88 %, respectively.Conclusions. Initial data assessing the safety of the newly developed salvage radiation therapy technique in hypofractionation mode with additional prophylactic of retroperitoneal lymph nodes demonstrate good tolerability. However, further study and randomized phase III clinical trial are required to determine clinical efficacy.

Clinical outcomes of salvage radiotherapy in patients with supraclavicular lymph node metastases after esophagectomy.

To evaluate the clinical outcomes of salvage radiotherapy in patients with supraclavicular lymph node (SCLN) metastases after esophagectomy. After initial esophagectomy (R0 resection), clinical outcomes in patients with esophageal squamous cell carcinoma with SCLN metastases during follow-up were retrospectively analyzed. A total of 114 patients were split into two groups: the salvage radiotherapy (SR) (n=89) and the control (NSR) (without salvage radiotherapy, n=25). The overall survival rates of 1 year, 3 years and 5 years were 81.6%, 31.4% and 8.6%, accordingly. The 1-year and 3-year survival after SCLN metastases (SASM) rates were 40.2% and 14.5%, respectively; the median SASM time was 10 months. In the SR group, the SASM rates of 1-year and 3-year were 48.1% and 18.9%, compared to 12.0% and 0% in the NSR group (p<0.001). Patients in the SR group who received combined radiochemotherapy experienced 1-year and 3-year SASM rates of 62.6% and 33.4%, compared to 41.9% and 16.5% with single radiotherapy (p<0.001). The salvage radiation dose revealed that the 1-year and 3-year SASM rates turned out to be 56.5% and 23.4% in group of ≥60 Gy, and 29.2% and 7.5% in group of <60 Gy (p<0.001). According to multivariate analysis, combined visceral metastases (CVM), combined mediastinal failure (CMF), salvage radiotherapy, salvage radiation dose and salvage treatment method possibly were identified as important prognostic variables. After propensity score matching (PSM), the above results were similar to those before PSM, except for that only salvage radiotherapy is possibly independent prognostic variables for survival after SCLN metastases in multivariate analysis. It is possible that salvage radiotherapy can increase the survival rate of patients who receive SCLN metastases following esophagectomy.

PO50 Presentation Time: 10:00 AM: Long-Term Results of Salvage High Dose-Rate Brachytherapy with or without Pelvic External Beam Radiotherapy in Patients with Palpable Local Recurrence of Prostate Cancer After Radical Prostatectomy

<h3>Purpose</h3> This study aims to evaluate the long term outcomes and toxicities in patients with clinically apparent, gross local recurrence of prostate cancer after radical prostatectomy, treated with salvage high dose-rate brachytherapy (HDR-BT) with or without pelvic external beam radiotherapy (EBRT). <h3>Materials and Methods</h3> Retrospective chart review was performed to identify patients with clinically apparent, gross local recurrence of prostate cancer after radical prostatectomy who underwent salvage HDR-BT at a single institution between 2002 and 2020. HDR-BT regimens included 950 cGy x 2 (N=4), 1500 cGy x 1 (N=2), 950 cGy x 4 (N=1), and 800 cGy x 2 (N=1). Pelvic EBRT was allowed at the discretion of the treating physician. Treatment and clinical characteristics were obtained for each patient, and outcome and toxicity data were collected. Toxicity was graded according to Common Toxicity criteria for Adverse Events Version 5.0. Descriptive analysis was performed. <h3>Results</h3> A total of 8 patients were included in analysis with a median follow-up of 49 months (range: 9 to 223 months). Five (63%) patients presented with a biochemical recurrence, and 3 patients (38%) presented with symptoms including hematuria and urinary obstruction. Seven patients underwent TRUS-guided biopsy which confirmed recurrent adenocarcinoma. The remaining patient underwent a PSMA PET/CT scan revealing a PET-avid soft tissue lesion in the prostate bed, but declined biopsy and proceeded with treatment without pathologic confirmation. Median age at time of salvage brachytherapy was 68 years (range: 59 to 85 years). Median time from prostatectomy to salvage HDR-BT was 95 months (range: 19 to 207 months). Median PSA at time of HDR brachytherapy was 2.32 ng/ml (range: undetectable on ADT to 13 ng/ml). Median lesion size was 2.5 cm (range: 1 to 3.6 cm). Six patients (75%) received adjuvant pelvic EBRT, 45-50 Gy in 25 fractions. Seven out of 8 patients received ADT after salvage brachytherapy for a median duration of 12 months (range: 8 to 24 months). The remaining patient did not receive ADT due to cardiac comorbidities. Seven out of 8 patients were alive at last follow-up. There have been no locoregional recurrences. Three patients developed distant metastatic disease. One patient, who had negative conventional staging scans 3 months prior to brachytherapy, was found to have distant metastatic disease only 2 months after salvage brachytherapy and died due to metastatic prostate cancer 9 months after HDR-BT. The other 2 patients developed distant metastases at 14 and 27 months after brachytherapy. One patient developed late grade 3 urinary incontinence requiring artificial urinary sphincter (AUS) placement 18 months after brachytherapy. This patient had the largest tumor size, 3.6 cm in longest dimension, and received pelvic EBRT in addition to HDR-BT. He is now more than 10 years out from HDR-BT with undetectable PSA and doing well with his AUS. There were no other grade 2 or higher genitourinary or gastrointestinal toxicities. <h3>Conclusions</h3> This study demonstrates the long-term safety and efficacy of salvage HDR brachytherapy in the setting of clinically apparent local recurrence of prostate cancer after radical prostatectomy, with durable locoregional control and acceptable rates of toxicity. HDR-BT should be further explored as an option for dose-escalated salvage radiotherapy in patients with gross local recurrences after radical prostatectomy.

Machine Learning for the Prediction of Distant Metastases Following Postprostatectomy Salvage Radiation Therapy

<h3>Purpose/Objective(s)</h3> Salvage radiotherapy (SRT) is the only curative option for patients with biochemical recurrence (BCR) following radical prostatectomy (RP). Tendulkar's nomogram was developed to predict outcomes following SRT in patients with a median pre-SRT PSA of 0.5 ng/mL. We aim to externally validate Tendulkar's nomogram and provide an updated tool for the prediction of distant metastasis (DM) in a contemporary cohort of patients with lower pre-SRT PSA. <h3>Materials/Methods</h3> Patients were included from two academic institutions, treated between 1989 and 2019, with RP followed by SRT for either persistent or increasing PSA. A gradient boosted tree was trained on data from one institution (n=2,529) and tested on another (n=566). For baseline comparison, we also evaluated Tendulkar's nomogram. Models were evaluated in terms of their time-dependent area under the curve (AUC) of the receiver operator curve (ROC). <h3>Results</h3> Median age was 64 years. 1,422 (469%) patients were pT2, 1,047 (33.8%) pT3a, and 626 (20.2%) ≥pT3b. Most patients (78.48%) had a surgical Gleason score (GS) of 7 and 10.6% had GS ≥8. Almost one-third (30%) had positive surgical margins and 12.6% had persistent PSA post-RP. Median pre-SRT PSA was 0.27 ng/mL. 208 (6.7%) patients received androgen deprivation therapy with SRT. Median RT dose was 66.6 Gy. Median follow up from SRT was 4.6 years. Distant metastasis occurred in 9% of patients at 5 years, and 12.5% at 10 years. On the test dataset, our model showed AUCs of 0.72 (CI: 0.63 – 0.81) and 0.74 (0.65 – 0.83) for the prediction of DM development at 5-and 10-years compared to 0.57 (0.49 – 0.66) and 0.66 (0.55 – 0.78) for Tendulkar' nomogram. The improvement in the prediction of DM development at 5 years showed statistical significance (p <0.05), whereas this improvement was nonsignificant for the prediction of DM development at 10 years. <h3>Conclusion</h3> We provide an updated tool with improved prediction of distant metastases for patients with BCR after RP treated with SRT in modern practice.

Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography–based Lymph Node Atlas for Salvage Radiotherapy in Patients with Recurrent Prostate Cancer: A Validation of the New NRG Oncology 2020 guideline

BackgroundApproximately 20–40% of patients with prostate cancer (PC) who undergo radical prostatectomy (RP) experience relapse, with the majority of these cases developing pelvic lymph node (LN) metastases. Taking new data from the prostate-specific membrane antigen (PSMA) positron emission tomography (PET) era into account, the Radiation Therapy Oncology Group (RTOG) 2009 contouring guideline for the pelvic LNs from 2009 was updated by the NRG Oncology group in 2020 (NRG 2020). ObjectiveTo evaluate and validate the updated NRG 2020 guideline with our established LN atlas. Design, setting, and participantsWe screened 1653 PSMA PET/computed tomography (CT) data sets for patients with biochemical relapse who underwent a PET scan between November 2012 and November 2017. After screening, we developed an LN atlas using data from 233 patients. Outcome measurements and statistical analysisWe evaluated LN overlap (OL) with the RTOG 2009 and NRG 2020 contouring guidelines. OL was defined as within (>90%), partly within (10–90%), or outside (<10%). Results and limitationsIn comparison to the RTOG 2009 guideline, 403 (52%), 134 (17%), and 241 (31%) of the LNs were not, were partly, or were fully covered within the overall group, respectively. By contrast, using the NRG 2020 guideline, 302 (39%), 190 (24%), and 286 (37%) of the LNs were not, were partly, or were fully covered, respectively (p < 0.001). Limitations include the retrospective design with missing data and no histopathological confirmation of the PET results. ConclusionsThe updated NRG 2020 contouring guideline improves coverage of the pelvic LNs in patients undergoing salvage radiation therapy. However, PET/CT should be considered whenever possible to ensure coverage of untypical LN spread. Patient summaryWe compared the 2009 and 2020 guidelines on the radiation area for the pelvis for patients with recurrent prostate cancer that has spread to lymph nodes. The newer guideline provides better coverage of pelvic lymph nodes than the older one and is useful in planning radiation therapy. However, a scan of the pelvis using the newest technique should be considered for individual patients to ensure coverage of untypical lymph nodes.

PO-1422 Hypofractionated salvage radiotherapy in patients with biochemical recurrence of prostate cancer

PO-1422 Hypofractionated salvage radiotherapy in patients with biochemical recurrence of prostate cancer

Moderately hypofractionated salvage radiotherapy in patients with biochemical recurrence of prostate cancer after prostatectomy: long-term results and comparative analysis of two schedules.

Hypofractionation in salvage radiotherapy (HSRT) for biochemical recurrence of prostatic cancer after prostatectomy is a debated issue and at present, it should be considered purely investigational because of the lack of evidence supporting its use. In this study, we report the outcomes of patients presenting with biochemical recurrence after radical prostatectomy who received HSRT. The additional aim of this study is to compare two moderately HSRT schedules. Patients treated to prostate bed with daily Image Guided-VMAT and a total dose of 65 Gy/26 fractions (Group A) or 66 Gy/30 fractions (Group B) were included in the study. Inclusion criteria were: pN0/pNx, pre-HSRT PSA ≥0.2 ng/ml and ≤1 ng/ml, no evidence of pelvic/extrapelvic disease at restaging, no pelvic irradiation or dose boost on macroscopic local recurrence, no neoadjuvant/concomitant Androgen Deprivation Therapy (ADT), follow-up ≥36 months, and available pre/post HSRT data. Genitourinary (GU) and gastrointestinal (GI) toxicities, early and late, were assessed using CTCAE Vers. 5.0. One hundred patients were retrospectively identified to 50 in each group. Median follow-up was 59 months. All patients completed the prescribed HSRT. 5-year biochemical failure-free survival, local control, distant relapse-free survival, and ADT- free survival were 52.1%, 85.9%, 63.7%, and 73.2%, respectively. No significant differences in these outcomes were found between the two groups. On multivariate analysis, a hypofractionation schedule was not associated with any outcome, but ISUP score ≥ 4 and pre-HSRT PSA were associated with worse biochemical failure-free survival while only ISUP score ≥ 4 was associated with worse distant relapse-free survival. No Grade 3 GU/GI acute event was reported; 6 (6%) and 2 (2%) patients experienced late Grade ≥ 2 GU and GI events, respectively. No difference was found between the two groups neither in acute nor in late GU/GI toxicities. Our findings demonstrate that HSRT is feasible, effective, and safe. Our analysis did not show any significant difference between the two hypofractionated schedules. Further studies and randomized controlled trials are required in order to confirm these results and to identify the optimal hypofractionated schedule in the salvage setting.

Comparison of hypofractionation and standard fractionation for post-prostatectomy salvage radiotherapy in patients with persistent PSA: single institution experience

BackgroundHypofractionated post-prostatectomy radiotherapy is emerging practice, however with no randomized evidence so far to support it’s use. Additionally, patients with persistent PSA after prostatectomy may have aggressive disease and respond less well on standard salvage treatment. Herein we report outcomes for conventionally fractionated (CFR) and hypofractionated radiotherapy (HFR) in patients with persistent postprostatectomy PSA who received salvage radiotherapy to prostate bed.MethodsSingle institution retrospective chart review was performed after Institutional Review Board approval. Between May 2012 and December 2016, 147 patients received salvage postprostatectomy radiotherapy. PSA failure-free and metastasis-free survival were calculated using Kaplan–Meier method. Cox regression analysis was performed to test association of fractionation regimen and other clinical factors with treatment outcomes. Early and late toxicity was assessed using Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.ResultsSixty-nine patients who had persistent PSA (≥ 0.1 ng/mL) after prostatectomy were identified. Median follow-up was 67 months (95% CI 58–106 months, range, 8–106 months). Thirty-six patients (52.2%) received CFR, 66 Gy in 33 fractions, 2 Gy per fraction, and 33 patients (47.8%) received HFR, 52.5 Gy in 20 fractions, 2.63 Gy per fraction. Forty-seven (68%) patients received androgen deprivation therapy (ADT). 5-year PSA failure- and metastasis-free survival rate was 56.9% and 76.9%, respectively. Thirty patients (43%) experienced biochemical failure after salvage radiotherapy and 16 patients (23%) experienced metastatic relapse. Nine patients (13%) developed metastatic castration-resistant disease and died of advanced prostate cancer. Median PSA failure-free survival was 72 months (95% CI; 41–72 months), while median metastasis-free survival was not reached. Patients in HFR group were more likely to experience shorter PSA failure-free survival when compared to CFR group (HR 2.2; 95% CI 1.0–4.6, p = 0.04). On univariate analysis, factors significantly associated with PSA failure-free survival were radiotherapy schedule (CFR vs HFR, HR 2.2, 95% CI 1.0–4.6, p = 0.04), first postoperative PSA (HR 1.02, 95% CI 1.0–1.04, p = 0.03), and concomitant ADT (HR 3.3, 95% CI 1.2–8.6, p = 0.02). On multivariate analysis, factors significantly associated with PSA failure-free survival were radiotherapy schedule (HR 3.04, 95% CI 1.37–6.74, p = 0.006) and concomitant ADT (HR 4.41, 95% CI 1.6–12.12, p = 0.004). On univariate analysis, factors significantly associated with metastasis-free survival were the first postoperative PSA (HR 1.07, 95% CI 1.03–1.12, p = 0.002), seminal vesicle involvement (HR 3.48, 95% CI 1.26–9.6,p = 0.02), extracapsular extension (HR 7.02, 95% CI 1.96–25.07, p = 0.003), and surgical margin status (HR 2.86, 95% CI 1.03–7.97, p = 0.04). The first postoperative PSA (HR 1.04, 95% CI 1.00–1.08, p = 0.02) and extracapsular extension (HR 4.24, 95% CI 1.08–16.55, p = 0.04) remained significantly associated with metastasis-free survival on multivariate analysis.Three patients in CFR arm (8%) experienced late genitourinary grade 3 toxicity.ConclusionsIn our experience, commonly used hypofractionated radiotherapy regimen was associated with lower biochemical control compared to standard fractionation in patients with persistent PSA receiving salvage radiotherapy. Reason for this might be lower biological dose in HFR compared to CFR group. However, this observation is limited due to baseline imbalances in ADT use, ADT duration and Grade Group distribution between two radiotherapy cohorts. In patients with persistent PSA post-prostatectomy, the first postoperative PSA is an independent risk factor for treatment failure. Additional studies are needed to corroborate our observations.

Effect of Salvage Radiotherapy and Endocrine Therapy on Patients with Biochemical Recurrence After Prostate Cancer Operation- a Meta‑Analysis.

Context:Several studies reported the application of androgen deprivation therapy and radiotherapy in patients with biochemical recurrence after prostate cancer operation.Objective:To perform a systematic review and meta-analysis evaluating of endocrine therapy and radiotherapy in patients with biochemical recurrence after prostate cancer surgery. The primary end point was biochemical progression-free survival (bPFS). Secondary end point was overall survival (OS).Methods:A systematic review of PubMed/Medline, Embase, and Cochrane databases to identify relevant studies published in English up to March 2020. Twelve studies were selected for inclusion.Results:There were 11 studies included in the present study. Including two randomized controlled trials and nine cohort studies. The meta-analysis shows a significant bPFS benefit from androgen deprivation therapy and radiotherapy in patients with biochemical recurrence after prostate cancer operation. (hazard ratio [HR]: 0.57; 95% confidence interval CI, 0.52–0.63; p < .001). For patients with GS < 7 and low-risk patients, combined treatment can have a benefit for BPFs (HR: 0.53; 95% CI, 0.37–0.76; HR: 0.58; 95% CI, 0.36–0.93). Androgen deprivation therapy and radiotherapy in patients with biochemical recurrence was associated with a slightly OS improvement (HR: 0.73; 95% CI, 0.57–0.93; p = 0.01).Conclusions:Compared with salvage radiotherapy alone, This meta-analysis shows a significant bPFS benefit from endocrine therapy combined with salvage radiotherapy in patients with biochemical recurrence after prostate cancer operation. And benefit more for high-risk groups. However, there was no significant benefit in group GS ≥ 8. It shows a slightly OS benefit from endocrine therapy combined with salvage radiotherapy in patients with biochemical recurrence.

Validation of the European association of urology biochemical recurrence risk groups after radical prostatectomy in an Asian cohort and suggestions for refinement

BackgroundTo validate the prognostic utility of the novel European Urology Association (EAU) biochemical recurrence (BCR) risk groups in an Asian cohort and to determine whether refinement is necessary. MethodsTwo cohorts of men who experienced BCR after radical prostatectomy between 1998 and 2014 were employed. The Cox model was used to validate and model the probability of metastasis and death after BCR. Data from 817 men from the first cohort were used to develop a modified model and external validation was performed on 344 men from the second cohort. ResultsDistant metastasis-free survival and cancer-specific survival from the time of BCR were significantly higher in patients with a low EAU BCR risk (prostate-specific antigen doubling time [PSADT] >1 year and pathologic Gleason score [pGS] ≤7) than in high EAU BCR risk patients (PSADT ≤1 year or pGS 8–10). In the high EAU BCR risk group, survival outcomes and efficacy of early salvage radiotherapy in patients with PSADT 6–12 months and pGS ≤7 were similar to those in the low EAU BCR risk group. The C-index, which predicts metastatic progression and cancer-specific death, improved after PSADT cutoff point was modified to 6 months, and was validated externally. ConclusionEAU BCR risk stratification reliably identified patients at increased risk of metastasis and cancer-specific mortality in the present cohort. Modification of the PSADT cutoff point may help to optimize the predictive performance and utility of the EAU BCR risk groups in clinical practice.

Is immediate adjuvant radiotherapy necessary for men with positive surgical margin after robotic-assisted radical prostatectomy?

Background: The role of immediate adjuvant radiotherapy (ART) in the management of positive surgical margin (PSM) following radical prostatectomy (RP) for low-grade prostate cancer (PCa) remains unclear. We aim to investigate our experience on survival outcome between immediate ART versus active surveillance in PSM groups after robotic-assisted RP (RaRP).Materials and Methods: The PSM cohort was divided into an adjuvant therapy group, consisting of immediate radiotherapy (RT) with or without androgen deprivation therapy (ADT) within six months after surgery, and observation group, consisting of close follow-up at the out-patient clinic. Salvage therapy was conducted using RT with/without ADT if biochemical recurrence (BCR) occurred (PSA level >0.2 ng/mL) during follow-up. 461 patients with PCa who underwent RaRP between December 2006 and June 2014 were included. Data of patients with PSM (n = 79) were extracted and followed up to June 2020. We aimed to compare the outcomes of immediate ART against observation or salvage RT in patients with PSM. Hence, we focused on those who had a PSA level <0.2 ng/mL after RaRP. Those with a PSA level >0.2 ng/mL were excluded.Results: No significant differences in age or preoperative PSA levels were observed after stratification to immediate ART and observation groups. Three patients (5.6%) received immediate ART with/without ADT. Another 51 patients received active surveillance, of which 18 (35.3%) received salvage ART with/without ADT due to BCR (PSA ≥0.2 ng/mL). There was no significant difference between immediate ART and observation groups in 5-year BCR-free survival (P = 0.072), local recurrence-free survival (P = 0.490), distant metastasis-free survival (P = 0.225), and overall survival (P = 0.517).Conclusion: Of the RaRP patients with PSM in the Asian population, we discovered that immediate ART following RaRP may not offer a significant advantage to active surveillance. Routine monitor of PSA levels had shown equally successful disease control. Salvage ART could be used on detection of BCR.

Outcome After 68Ga-PSMA-11 versus Choline PET-Based Salvage Radiotherapy in Patients with Biochemical Recurrence of Prostate Cancer: A Matched-Pair Analysis.

The purpose of this analysis was primarily to analyze biochemical-recurrence free survival (BRFS) after positron emission tomography (PET)-guided salvage radiotherapy (sRT) in a large cohort, and to further compare BRFS after PSMA vs. choline PET/ computer tomography (CT)-based sRT. This retrospective analysis is based on 421 patients referred for PSMA or choline PET/CT after radical prostatectomy due to biochemically recurrent or persistent disease. BRFS (PSA: 0.2 ng/mL) was defined as the study endpoint. Cox regression analyses were performed to assess the impact of different clinical parameters on BRFS. Additionally, propensity score matching was performed to adjust patient cohorts (PSMA vs. choline PET/CT-based sRT). The median follow-up time was 30 months. BRFS at three years after sRT was 58%. In the multivariate analysis, only PSA before PET imaging and PSA before sRT were significantly associated with BRFS (p < 0.05). After propensity score matching, 272 patients were further analyzed; there was no significant difference in three-year BRFS between patients with PSMA PET-based vs. choline PET-based sRT (55% vs. 63%, p = 0.197). The present analysis confirmed the overall high BRFS rates after PET-based sRT and the strong prognostic effect of PSA level prior to sRT. PSMA PET-based sRT did not have superior BRFS rates when compared with choline PET-based sRT.

Early salvage radiotherapy in patients with biochemical recurrence after radical prostatectomy: Its impact and optimal candidate.

We aimed to identify the optimal candidates for early salvage radiotherapy (SRT) among patients with biochemical recurrence (BCR) after radical prostatectomy (RP). This multi-institutional retrospective study included 371 patients treated using SRT after RP. The median (range) PSA level at BCR was 0.36 (0.10-2.00) ng/mL. The association between early SRT (ie, starting PSA level<0.50) and BCR after SRT was tested in each subgroup according to our own risk stratification. The median follow-up time was 51 months. By multivariate analysis, pT3b, Gleason score ≥ 8, negative surgical margins, PSA doubling time<6 months, and non-early SRT were associated with BCR after SRT. Patients were stratified by four risk factors other than non-early SRT: (1) low risk (0 risk factor), (2) intermediate risk (1 risk factor), and (3) high risk (≥2 risk factors). The BCR-free survival was higher in the early SRT group than the nonearly SRT group in the high-risk subgroup (P=0.020), whereas that was similar between two groups in the low-risk and intermediate-risk subgroups (P=.79 and .18, respectively). Multivariate analysis revealed that early SRT was beneficial for the high-risk subgroup (P=.032), whereas early SRT was not associated with improved outcomes in the low-risk and intermediate-risk subgroups (P=.92 and 1.0, respectively). This study suggested that early SRT seemed to contribute to better biochemical control for patients with more adverse features, whereas no benefit was observed in men with no adverse features.

Salvage radiotherapy in patients affected by oligorecurrent pelvic nodal prostate cancer

Metastasis-directed therapy (MDT) is an investigational treatment option in patients with oligorecurrent prostate cancer (PCa). The aim of this retrospective study is to report oncologic outcome and toxicity of elective nodal radiotherapy (ENRT) in PCa patients affected by pelvic nodal oligorecurrence. 41 consecutive patients were treated with salvage radiotherapy. At biochemical recurrence after primary treatment, oligorecurrent disease was detected by positron emission tomography (PET) in 94% of the patients. Image-guided intensity modulated radiation therapy (IMRT) was delivered using tomotherapy. 83% of the patients received androgen deprivation therapy (ADT) in combination with ENRT. Survival analysis was performed with Kaplan-Meier method, log-rank test was used to analyze associations between survival end-points and clinical parameters. Multivariate analysis was performed using Cox proportional hazards regression models. Toxicity was registered according to Common Terminology Criteria for Adverse Events (CTCAE) v4.0. The median at follow-up was 33.6months. At 3years, overall survival (OS), cancer-specific survival (CSS), and biochemical progression-free survival (b-PFS) were 89%, 92%, and 53%, respectively. At univariate analysis, all survival end-points were correlated with the number of positive pelvic lymph nodes at oligorecurrence (≤ 3 vs > 3). Biochemical-PFS was correlated with PSA (p = 0.034) and PSA doubling time (p = 0.004) at oligorecurrence. At multivariate analysis, no independent variable was statistically significant. No patient experienced grade ≥ 2 late toxicity after radiotherapy. The number of metastatic lymph nodes and PSA doubling time seems to be important prognostic factors in the pelvic oligorecurrent setting. Salvage radiotherapy combined with short-course ADT might be a valid treatment strategy.

Adjuvant versus early salvage radiotherapy: outcome of patients with prostate cancer treated with postoperative radiotherapy after radical prostatectomy

BackgroundAdjuvant (ART) and salvage radiotherapy (SRT) are two common concepts to enhance biochemical relapse free survival (BCRFS) in patients with prostate cancer (PC). We analyzed differences in outcome between ART and SRT in patients with steep decline of PSA-levels after surgery to compare outcome.MethodsWe evaluated 253 patients treated with postoperative RT with a median age of 66 years (range 42–85 years) treated between 2004 and 2014. Patients with additive radiotherapy due to PSA persistence and patients in the SRT group, who did not achieve a postoperative PSA level <0.1 ng/mL were excluded. Hence, data of 179 patients was evaluated. We used propensity score matching to build homogenous groups. A Cox regression model was used to determine differences between treatment options. Median follow-up was 32.5 months (range 1.4–128.0 months).ResultsEarly SRT at PSA levels <0.3 ng/mL was associated with significant longer BCRFS than late SRT (HR: 0.32, 95%-CI: 0.14–0.75, p = 0.009). Multiple Cox regression showed pre-RT PSA level, tumor stage, and Gleason score as predictive factors for biochemical relapse. In the overall group, patients treated with either ART or early SRT showed no significant difference in BCRFS (HR: 0.17, 95%-CI: 0.02–1.44, p = 0.1). In patients with locally advanced PC (pT3/4) BCRFS was similar in both groups as well (HR: 0.21, 95%-CI:0.02–1.79, p = 0.15).ConclusionFor patients with PSA-triggered follow-up, close observation is essential and early initiation of local treatment at low PSA levels (<0.3 ng/mL) is beneficial. Our data suggest, that SRT administered at early PSA rise might be equieffective to postoperative ART in patients with locally advanced PC. However, the individual treatment decision must be based on any adverse risk factors and the patients’ postoperative clinical condition.Study registrationThe present work is approved by the Ethics Commission of the Technical University of Munich (TUM) and is registered with the project number 320/14.

Impact of Early Salvage Radiotherapy in Patients with Biochemical Recurrence after Radical Prostatectomy: Results of a Multi-institutional Retrospective Study

Impact of Early Salvage Radiotherapy in Patients with Biochemical Recurrence after Radical Prostatectomy: Results of a Multi-institutional Retrospective Study