Salvage Androgen Deprivation Therapy Research Articles

PSMA PET/CT SUVmax as a prognostic biomarker in patients with metachronous metastatic hormone-sensitive prostate cancer (mHSPC).

Metastatic hormone-sensitive prostate cancer (mHSPC) is treatment-resistant and generally considered incurable. The development of prostate-specific membrane antigen positron emission-computed tomography (PSMA PET/CT) has generated immense expectations due to its diagnostic accuracy in prostate cancer (PCa). PSMA expression of the primary tumor, quantified by SUVmax, is a predictor of oncological outcomes. The role of PSMA-PET/CT SUVmax in metachronous mHSPC treated with ADT plus second-generation antiandrogens (ARSI) is unknown. The main aim of this study was to evaluate 68Ga-PSMA-11expression (SUVmax) as a potential prognostic biomarker in patients with metachronous mHSPC treated with ADT and first or second-generation antiandrogens. A second aim was to determine the association between PSMA SUVmax and PSA response to hormone therapy. Patients diagnosed with metachronous mHSPC between July 2017 and February 2023 who developed biochemical recurrence following radical surgery (with or without salvage radiotherapy and/or ADT) or external radiation therapy (with or without ADT) were included. All patients underwent 68Ga-PSMA-11 PET/CT imaging and the SUVmax value was determined for all measurable locations. The SUVmax value was used for the semiquantitative analysis. The Wilcoxon method was used to compare responders (PSA reduction ≥ 50%) to non-responders (PSA reduction < 50%). The SUVmax value and hormone therapy were evaluated as independent variables relative to the PSA response rate or PSA reduction using the linear regression method. A mixed-effects model (ANOVA) was used for the comparisons. A total of 82 patients were included. Median follow-up was 11.7 months. On the linear regression analysis, patients with a high SUVmax treated with ADT + ARSI showed a greater PSA response (p = 0.034) than those treated with ADT + first-generation antiandrogens. In the mixed-effects model, SUVmax was significant (p = 0.041). On the univariate analysis, PSA at recurrence (HR, 3.2; 95% CI: 1.07-13.6; p = 0.078) and the number of metastases (HR, 4.77; 95% CI 1.1-26.1: p = 0.002) were associated with the type of hormone therapy administered. PSMA-PET/CT SUVmax is a prognostic biomarker that can be used to predict a PSA response to ADT + ARSI in patients with metachronous mHSPC. However, these findings need to be confirmed in larger prospective studies.

Stereotactic Body Radiation Therapy for Clinically Localized Prostate Cancer in Men With Hip Prostheses: A Cautionary Note.

Stereotactic body radiation therapy (SBRT) has been established as a safe and effective treatment for prostate cancer. SBRT requires high accuracy to reduce treatment margins. Metal hip prostheses create artifacts that distort pelvic imaging and potentially decrease the accuracy of target/organ at risk (OAR) identification and radiation dose calculations. Data on the safety and efficacy of SBRT after hip replacement is limited. This single-institution study sought to evaluate the safety and local control following SBRT for prostate cancer in men with hip replacements. 23 patients treated with localized prostate cancer and a history of pre-treatment hip replacement, treated with SBRT from 2007 to 2017 at MedStar Georgetown University Hospital were included in this retrospective analysis. Treatment was administered with the CyberKnife® (Accuray Incorporated, Sunnyvale, CA) at doses of 35 Gy or 36.25 Gy in 5 fractions. The targets and OARs were identified and contoured by a single experienced Radiation Oncologist (SPC).The adequacy of the CT and T2W MRI images for treatment planning was assessed with a three-point scale (good, adequate, or suboptimal).During treatment planning, care was taken to avoid treatment beams that directly traversed the hip prosthesis. Toxicities were recorded and scored using the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v.4.0). Local recurrence was confirmed by magnetic resonance imaging and/or prostate biopsy. The median follow-up was seven years. The patients were elderly (median age = 71 years) with a high rate of comorbidities (Charlson Comorbidity Index > 2 in 25%). Four patients had bilateral hip replacements. The majority of patients were low to intermediate risk per the D'Amico classification. Around 13% received upfront ADT. In total, 13 patients were treated with 35 Gy, and 10 were treated with 36.25 Gy.The rates of late > Grade 3 GU toxicity and> Grade 2 GI toxicity were 8.6% and 4.3%, respectively. There were no Grade 4 or 5 toxicities.Six patients (26%) developed a local recurrence at a median time of 7.5 years. Of these six patients, four had unilateral hip replacements and two had bilateral.Three underwent salvage cryotherapy and three received salvage ADT. In the general population, high-grade toxicities and local recurrences are uncommon following prostate SBRT.However, in this cohort of patients with prior hip replacements, prostate SBRT had higher than expected rates of late toxicity and local recurrence. In the opinion of the authors, such patients should be counseled regarding an elevated risk of late toxicity and local recurrence with prostate SBRT. With its ultrasound guidance, brachytherapy would have the advantage of circumventing the need for MRI/CT-based imaging and thus may represent a preferable radiation alternative in this patient population. If these patients are treated with SBRT, they should be monitored closely for local recurrence so early salvage can be performed. We hopethat recent advances in metal artifact reduction techniques and dose-calculation algorithms will improve future outcomes.

Salvage Androgen Deprivation Therapy as Potential Treatment for Recurrence after Robot-Assisted Radical Prostatectomy.

The efficacy of intermittent androgen deprivation therapy (ADT) for biochemical recurrence (BCR) after robot-assisted radical prostatectomy (RARP) is unknown, and its usefulness in Japanese practice needs to be investigated. We conducted a retrospective analysis of 85 patients who underwent RARP and were selected for intermittent ADT for postoperative recurrence at Kanazawa University Hospital between 2009 and 2019. Intermittent ADT was administered for 2 years. If prostate-specific antigen levels increased post-treatment, intermittent ADT was reinitiated. The median follow-up period was 47 months. The 73 patients had completed the initial course of ADT, and 12 were under initial ADT. The 5-year castration-resistant prostate-cancer-free survival rates, cancer-specific survival, and overall survival were 92.7%, 98.3%, and 94.7%, respectively. A subgroup analysis of 69 patients who completed intermittent ADT was conducted to evaluate the BCR rate following initial ADT. The 5-year BCR-free survival rate was 53.2%. Multivariate analysis identified testosterone ≤ 0.03 ng/mL during ADT as the sole predictor of BCR after ADT. Salvage intermittent ADT may be an effective treatment option for BCR after RARP. In addition, it would be useful to confirm strong testosterone suppression as a criterion for transition to intermittent therapy.

Effects of Radiation Doses on Clinical Recurrence in Patients with Biochemically Recurrent Prostate Cancer after Prostatectomy.

Salvage radiotherapy (SRT) to the prostate bed is the only curative treatment for patients with biochemical recurrence (BCR) after radical prostatectomy (RP). Although several systematic reviews indicated that a dose escalation in the range of 60-70 Gy improved biochemical control, the effects of radiation doses on clinical relapse after SRT remain unclear. Our aim was to investigate the relationship between radiation doses and clinical relapse-free survival (cRFS) after SRT. We identified 295 eligible patients receiving SRT for biochemically recurrent prostate cancer after RP between 2005 and 2018 at 15 institutions. Sixteen patients (5%) received short-term (< 6 months) androgen deprivation therapy (ADT) following RP and/or concurrently with SRT. SRT was delivered to the prostate and seminal vesicle bed using photon beams at a median (range) dose of 66 Gy (61-85) in 1.8-3.0 Gy fractions. The primary outcome was cRFS. Clinical relapse was identified on radiological imaging and/or biopsy and included local recurrence, lymph node metastasis, and distant metastasis. In all analyses, doses were recalculated as an equivalent dose in 2-Gy fractions (EQD2) with α/β = 1.5 Gy. Clinical RFS between the EQD2 ≥ 66 Gy (n = 229) and EQD2 < 66 Gy (n = 66) groups were compared using the Log-rank test, followed by univariate and multivariate Cox regression analyses and a subgroup analysis. The median follow-up duration was 73 months. Among patients with BCR (n = 119), 79 of 96 (82%) in the EQD2 ≥ 66 Gy group and 21 of 23 (91%) in the EQD2 < 66 Gy group received second salvage ADT (p = 0.36). Among all patients (n = 295), clinical relapse was identified in 22 (7%) patients after SRT. Six-year biochemical relapse-free survival (bRFS), cRFS, cancer-specific survival (CSS), and overall survival (OS) rates were 58%, 93%, 98%, and 94%, respectively. Six-year cRFS rates were 94% (95% confidence interval [CI], 90-97) in the EQD2 ≥ 66 Gy group and 87% (95% CI, 75-93) in the EQD2 < 66 Gy group (p = 0.020). The multivariate analysis revealed that EQD2 < 66 Gy, Gleason score ≥ 8, seminal vesicle involvement, and PSA at BCR ≥ 0.5 ng/ml correlated with clinical relapse (p = 0.0016, 0.014, 0.011, and 0.027, respectively). The subgroup analysis showed the consistent benefit of EQD2 ≥ 66 Gy in patients across most subgroups including PSA at BCR after RP, extracapsular extension, and age at SRT. This large multi-institutional observational study demonstrated that a higher SRT dose (EQD2 ≥ 66 Gy) resulted in superior cRFS. The present result supports the dose recommendations in the 2023 National Comprehensive Cancer Network guidelines (64-72 Gy) even in terms of clinical relapse. Prospective trial is warranted to investigate an upper threshold for optimal SRT dose.

Impact of Testosterone Recovery on Clinical Outcomes of Patients Treated with Salvage Radiotherapy and Androgen Suppression: A Secondary Analysis of the NRG/RTOG 0534 Sport Phase 3 Trial

Testosterone (T) kinetics and its relationship with clinical outcomes has not been studied in trials using salvage radiotherapy and androgen deprivation therapy (ADT). We performed a secondary analysis of the NRG Oncology/RTOG 0534 SPPORT trial, which compared prostate bed radiotherapy (PBRT) (arm 1), PBRT + short-term androgen deprivation therapy (ADT) (arm 2), or PBRT + pelvic lymph node radiotherapy (PLNRT) + short-term ADT (arm 3). We assessed longitudinal serum T levels and the impact of testosterone recovery (TR) on clinical outcomes. ADT was given for 4-6 months in arms 2 and 3, starting 2 months prior to radiotherapy. The trial excluded patients with baseline T < 40% of the lower limit of normal. TR was defined in 3 ways: 1) return to non-castrate level (>50 ng/dL), 2) return to normal level (>300 ng/dL), and 3) return to baseline level. Time to TR was estimated using cumulative incidence and death without an event considered a competing risk. Unadjusted and adjusted hazard ratios and 95% confidence intervals (CIs) were calculated using Cox proportional hazards model. Freedom from progression (FFP) was defined as biochemical failure according to the Phoenix definition (PSA ≥2 ng/mL over the nadir PSA), clinical failure (local, regional, or distant), or death from any cause. A total of 1699 patients with T at baseline and at least 1 follow-up assessment were included. The median age was 64 years (IQR 59 - 69), 12.8% were black, 14.9% had diabetes, and 54.1% were former or current smokers. Median baseline T in arms 1, 2 and 3 was 320 ng/dL (IQR 239 - 424), 319 ng/dL (IQR 237 - 438) and 330 ng/dL (IQR 252 - 446), respectively. At 6 months, median T in arms 1, 2 and 3 was 290 ng/dL (IQR 210 - 390), 190.4 ng/dL (IQR 66 - 296) and 191 ng/dL (IQR 40.5 - 313). At 2 years, in arms 2 and 3, TR to non-castrate, normal and baseline levels were 95%, 55% and 23%, respectively. At 5 years, in arms 2 and 3, TR to non-castrate, normal and baseline levels were 98%, 73% and 42%, respectively. FFP was superior in arms 2 and 3 vs. arm 1 in patients with TR by all three definitions. In patients with recovered T to normal levels by 2 years (n = 904), the 5-year FFP rates were 71.8% (95% CI 66.9-76.6) in arm 1, 77.2% (72.1-82.2) in arm 2, and 86.3% (82.3-90.3) in arm 3 (arm 2 vs arm 1: HR 0.74, 95% CI 0.56-0.98, p = 0.034; arm 3 vs arm 1: HR 0.54, 95% CI 0.40-0.72, p<.0001). This work represents the largest study of T kinetics in patients treated with salvage radiation and ADT. Approximately half of patients did not normalize their T levels by 2 years. Our data validate an incremental and meaningful FFP benefit of adding short-term ADT and PLNRT to PBRT independent of T recovery.

Health-Related Quality of Life at Five Years for a Randomized Trial of Tri-Modality Therapy with I-125 Brachytherapy, External Beam Radiation Therapy, and Short- vs. Long-Term Androgen Deprivation Therapy for High-Risk Localized Prostate Cancer (TRIP)

To describe the patient-reported health-related quality of life (HR-QoL) outcomes at five years for a multicenter randomized trial of tri-modality therapy with iodine-125 brachytherapy, external beam radiation therapy (EBRT), and short- versus long-term androgen deprivation therapy (ADT) for high-risk localized prostate cancer (TRIP/TRIGU0907). A total of 332 men with high-risk prostate cancer were randomized to either 6 months of ADT (n = 165) or 30 months of ADT (n = 167) in conjunction with combined modality radiation therapy. For the HR-QoL assessment, general HR-QoL and disease-specific HR-QoL were measured using the Japanese version of the Medical Outcomes Study 8-items Short-Form Health Survey (SF-8) and the Expanded Prostate Cancer Index Composite (EPIC). Patient-reported outcome questionnaires were filled out before ADT initiation, and five years after. Scores were reported as mean with the standard deviation. QoL end points were assessed as the change between pre and post treatment using paired student t-test. Changes in the International Prostate Symptom Scores (IPSS) score, including total score and subscores, were also evaluated. The study was powered according to the primary endpoint of biochemical progression free survival with HR-QoL as a secondary endpoint. In addition, recovery of testosterone level (300ng/dL or higher) was calculated as the cumulative incidence curve and compared between arms by log-rank test. The cumulative incidence of biochemical progression, and salvage ADT treatment were not different between the arms. Mean domain scores at baseline were well balanced between the two arms in all HR-QoL. There were no differences in the SF-8 assessment and the total and subscore EPIC assessments between the arms. The average sexual function score was lower in short arm versus long arm; 16.24 versus 20.24 at baseline, but not different at five years, 9.96 versus 7.78 (p = 0.164). There were no significant differences between the arms for the total and subscore IPSS. Significantly higher percentage of patients, 71.7% in the short arm recovered to a normal testosterone level at 6 years after the initiation of ADT compared to 43.2% in long arm (p<0.0001). At five years after ADT initiation, there were no significant differences in all score changes between the two arms with general HR-QoL and disease-specific HR-QoL. Most of HR-QoL returned to baseline level, and sexual function scores were low from baseline in this population. Two-years' adjuvant ADT did not affect HR-QoL at five years, although it significantly retarded testosterone recovery compared to 6 months of hormone therapy.

Biochemical recurrence after salvage prostate bed radiotherapy captured on PSMA-PET: Patient characteristics and distribution of recurrent disease.

e17088 Background: The SPPORT trial demonstrated that salvage whole pelvic radiotherapy (sWPRT) after radical prostatectomy (RP) reduced prostate cancer progression compared to salvage prostate bed radiotherapy (sPBRT), at the expense of greater toxicity. To identify pts most appropriate for sWPRT, we studied the incidence of and risk factors associated with radiologic relapse after sPBRT on 18F-DCFPyL PET, a sensitive new imaging modality. Methods: We analyzed 538 18F-DCFPyL PET/CTs performed at our large academic institution and screened for pts who had biochemical recurrence (BCR), defined as PSA &gt; 0.2 ng/mL, after receiving sPBRT for persistent or recurrent PSA. Risk factors including pathologic T stage (pT), pathologic Gleason score (pGS), seminal vesicle invasion (SVI), positive margins, perineural invasion (PNI), PSA at RP (PSA1), prior to RT (PSA2), and at time of scan (PSA3), and PSA doubling time after sPBRT (PSADT) were obtained. Associations between risk factors and radiographic relapse were quantified with logistic regression, with a p &lt; 0.05 defined as significant. Results: 38 pts with BCR after sPBRT were identified. Median values were: pt age = 69.5 years (interquartile range 64 – 74), PSA1 = 7.83 ng/mL (4.7 – 11.5), PSA2 = 0.26 (0.1 – 0.8), PSA3 = 0.71 (0.5 – 2.2), PSA DT = 9.8 (5.3 – 18.2). Pt characteristics were: pT (pT2, 46% of pts; pT3a/b, 54%), pGS ( &lt; 7, 11%; 3+4, 32%; 4+3, 39%; &gt; 7, 18%), 19% w/ SVI, 68% w/ positive margins, 93% w/ PNI and 80% (of evaluable pts) w/ high-risk decipher score. 42% of pts received salvage ADT with sPBRT. 68% of pts had detectable disease on 18F-DCFPyL PET. Radiologic relapse in pelvic LNs was present in 47% of all pts, and 32% of pts had relapse only in the pelvic nodes. 26% of pts had distant metastases (DM) on imaging. Only 13% of pts had DM without pelvic LN involvement. Between pts with pelvic LN only relapse (n = 12) and pts without radiographic disease (n = 12), age, pT, pGS, SVI, margins, ADT, PSA1-3 and PSADT did not differ on univariate or multivariate analyses. On the univariate analysis between pts with DM (n = 10) and without DM (n = 28), only PSA3 (p &lt; 0.05) was associated with radiographic relapse, and pT trended toward a negative association (p&lt; 0.10) with DM. Only PSA3 (p &lt; 0.10) trended toward association with DM in a multivariate analysis using age, pT, margins, ADT, and PSA2-3. Conclusions: Pts with biochemical relapse after sPBRT had frequent high-risk pathology. Aside from PSA3, no risk factors were predictive of detectable pelvic nodal or DM disease. However, most pts with detectable disease had pelvic LN involvement, suggesting that a substantial portion of these high-risk pts may have benefited from whole-pelvic RT. Further data on risk factors will help inform selection of pts appropriate for salvage whole pelvic RT.

MP77-16 MANAGEMENT OF BIOCHEMICAL RECURRENCE AND INCIDENT METASTATIC DISEASE AFTER RADICAL PROSTATECTOMY FOR PROSTATE CANCER

You have accessJournal of UrologyCME1 Apr 2023MP77-16 MANAGEMENT OF BIOCHEMICAL RECURRENCE AND INCIDENT METASTATIC DISEASE AFTER RADICAL PROSTATECTOMY FOR PROSTATE CANCER Ted Skolarus, Kristian Stensland, Daniel Herr, David Elliott, Jennifer Burns, Jordan Sparks, Chris Shin, Alexander Zaslavsky, Alexander Tsodikov, and Megan Caram Ted SkolarusTed Skolarus More articles by this author , Kristian StenslandKristian Stensland More articles by this author , Daniel HerrDaniel Herr More articles by this author , David ElliottDavid Elliott More articles by this author , Jennifer BurnsJennifer Burns More articles by this author , Jordan SparksJordan Sparks More articles by this author , Chris ShinChris Shin More articles by this author , Alexander ZaslavskyAlexander Zaslavsky More articles by this author , Alexander TsodikovAlexander Tsodikov More articles by this author , and Megan CaramMegan Caram More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003351.16AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Prostate cancer recurrence after surgery often presents as asymptomatic, biochemically recurrent, non-metastatic castration-sensitive disease. The extent to which the use and timing of ADT in this setting is associated with progression to metastatic disease is largely unknown. For these reasons, we conducted a population-based study to examine associations between biochemical recurrence management and progression along the castration cascade. METHODS: We used national electronic health record, cancer registry, administrative, pharmacy, and laboratory data to conduct a retrospective cohort study of men undergoing radical prostatectomy for localized prostate cancer from 2005 through 2015 in the Veterans Health Administration. We followed men through 2019 for biochemical recurrence, defined as PSA ≥0.2 ng/mL, and incident metastatic disease, identified using a validated natural language processing algorithm. We used multivariable regression to examine associations between metastatic disease and patient, disease, and salvage management approaches including ADT. RESULTS: We identified 8,558 men with biochemical recurrence after radical prostatectomy. Most patients were managed with observation and/or salvage radiation therapy (70%). Metastatic disease occurred in 14% and on univariate analysis was associated with decreased time to biochemical recurrence (15.5 months, metastatic vs. 19.2 months non-metastatic), younger age at recurrence, positive surgical margins, higher pathologic stage and PSA at diagnosis (all p<0.01). Salvage ADT was used in 30% of patients with recurrence, mostly among men who remained non-metastatic (65%). Pre-ADT PSA was higher among men with metastatic disease (4.1 ng/mL metastatic vs. 0.9 ng/mL non-metastatic, p<0.001), as was castration-resistant drug use (48.2% metastatic vs. 4.5% non-metastatic, p<0.001). Salvage ADT was highly associated with metastatic disease in this observational study (adjusted odds ratio 6.04, 95% CI 4.68-7.81). CONCLUSIONS: Management of biochemically recurrent disease after radical prostatectomy varied widely, including the use and timing of ADT. We found metastatic disease occurred in about 1 in 7 men with recurrence and was associated with traditional risk factors. While most salvage ADT was for non-metastatic disease, the extent to which castration use in observational data reflects disease severity or incites castration-resistance and metastatic disease warrants further study. Source of Funding: NCI R01 CA242559 © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1108 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ted Skolarus More articles by this author Kristian Stensland More articles by this author Daniel Herr More articles by this author David Elliott More articles by this author Jennifer Burns More articles by this author Jordan Sparks More articles by this author Chris Shin More articles by this author Alexander Zaslavsky More articles by this author Alexander Tsodikov More articles by this author Megan Caram More articles by this author Expand All Advertisement PDF downloadLoading ...

Strategy for PSA progression in patients undergoing salvage radiation for biochemical recurrence after radical prostatectomy.

The treatment strategy for prostate-specific antigen (PSA) progression in patients who receive salvage radiation therapy (RT) for biochemical recurrence (BCR) after radical prostatectomy (RP) is salvage androgen deprivation therapy (ADT). However, its optimal timing is highly controversial. The study sample consisted of 77 men who underwent RP, received salvage RT against BCR, and underwent salvage ADT for PSA progression. The endpoint of this study was development to castration-resistant prostate cancer (CRPC), from the start of salvage RT. Themedian follow-uptime was 9.5years, and 20 patients experienced CRPC. The multivariable analysis identified PSA-doubling time (PSA-DT) ≤ 12months (hazard ratio, 3.5) and seminal vesicle invasion (SVI) (hazard ratio, 4.4) as independent risk factors. We defined the high-risk and low-risk groups as those with one or two risk factors and no risk factors, respectively. In the high-risk group, a significant difference in time to CRPC was observed between patients who received salvage ADT at PSA ≤ 1.0ng/mL (n = 8) and at > 1.0ng/mL (n = 27) (10-year non-CRPC rate: 100.0% vs. 46.3%, respectively). In contrast, in the low-risk group, no significant difference in CRPC-free survival was observed between patients who received salvage ADT at PSA ≤ 1.0ng/mL (n = 14) and at > 1.0ng/mL (n = 28) (10-year non-CRPC rate: 86.4% vs. 80.8%, respectively). In high-risk patients (PSA-DT ≤ 12months and/or SVI), salvage ADT for PSA progression after salvage RT should be started before the PSA levels exceed 1.0ng/mL.

Comparative Outcomes of Robotic Radical Prostatectomy in Patients with Locally Advanced Prostate Cancer.

The effectiveness of radical prostatectomy alone for locally advanced prostate cancer is controversial owing to an increased complication rate and treatment-related morbidity. With technical advances and refinements in surgical techniques, robotic-assisted radical prostatectomy (RARP) has improved the outcomes of patients with locally advanced prostate cancer. RARP therefore plays a role in the treatment of locally advanced prostate cancer. In this study, we enrolled a total of 76 patients with pathologic stage pT3a, pT3b, pT4, or pN1. All patients were followed from surgery to June 2022, and their characteristics, perioperative outcomes, complications, adjuvant therapies and outcomes were analyzed. The median age of the patients was 69 years, and the initial PSA level was 20.5 (IQR 10.8-31.6) ng/mL. The median operative time was 205 (IQR 182-241) minutes. Sixty-six patients (86.8%) regained continence within 1 year, and the continence rate within 3 years of follow-up was 90.8% (69 patients). The overall survival rate was 100%. Twenty-two patients had BCR, of whom 13 received salvage androgen deprivation therapy (ADT), 2 received salvage external beam radiation therapy (EBRT) alone, and 7 received combined ADT and EBRT. No patient had disease progression to castration-resistant prostate cancer during a median 36 months of follow-up after salvage therapy. Our results suggest that RARP can also decrease tumor burden and allow for accurate and precise pathological staging with the need for subsequent treatment. Therefore, we recommend that RARP represents a well-standardized, safe, and oncologically effective option for patients with locally advanced prostate cancer.

PP49 Financing The Line Of Care In The First Biochemical Relapse Of Prostate Cancer After [68Ga] PSMA PET- CT

IntroductionIt is estimated that prostate cancer will reach 66 thousand by the triennium 2020-2022 according to the National Cancer Institute (INCA). After initial diagnosis and staging the patient may undergo radical prostatectomy and/or curative radiotherapy. In patients with biochemical relapse (PSA &gt;0.2 ng/ml) initially treated with radical prostatectomy, salvage external radiotherapy is indicated. The [68Ga] Prostate Specific Membrane Antigen Positron Emission Tomography-Computed Tomography (PSMA PET-CT) scan is mainly used for localization of prostate cancer in the setting of first biochemical recurrence and can significantly influence the clinical management of the patient.MethodsThe overall objective of this work is to perform a treatment cost analysis for patients in first biochemical recurrence of prostate cancer after curative radical prostatectomy and after performing [68Ga] PSMA PET-CT from the perspective of the Brazilian Health System (SUS). A decision tree was constructed through consultation with experts to outline the patient’s entire treatment. Values per modelled therapeutic procedure were surveyed in two different scenarios, with and without [68Ga] PSMA PET-CT. The average treatment in scenario 1 was stereotaxic radiation therapy (SBRT), and rescue radiotherapy and androgen deprivation therapy (ADT). In scenario 2, it was salvage radiotherapy and ADT. The reimbursement table was prepared from data collected by SUS system. Variations were analyzed using a sensitivity study. Total average values included: individual procedure, according to medical management (up to 3 years) and population percentage with and without [68Ga] PSMA PET-CT.ResultsValues were calculated in Brazilian currency (BRL) for each procedure. The total amount calculated for scenario 1 was BRL 264,965,465.00 (USD 55,642,747.65) and for scenario 2 was BRL 123,585,612.72 (USD 26,162,978.67).ConclusionsThe reimbursement of line of care adopted after [68Ga] PSMA PET-CT is an important information to expand access to the Brazilian population. It shows an increased cost with [68Ga] PSMA PET-CT adoption. A prospective study should be considered with high follow up.

Phase III Trial of Dose Escalated Radiation Therapy and Standard Androgen Deprivation Therapy (ADT) vs. Dose Escalated Radiation Therapy and Enhanced ADT with TAK-700 for Men with High-Risk Prostate Cancer (NRG Oncology/RTOG 1115)

<h3>Purpose/Objective(s)</h3> RTOG 1115 was a randomized phase III trial evaluating the addition of orteronel (TAK-700), a novel CYP17A1 inhibitor, to dose escalated radiation plus ADT in men with high risk, localized prostate cancer. Originally designed to evaluate overall survival, the trial was halted early due to discontinuation of orteronel development in prostate cancer. We report here the initial primary endpoint analysis. <h3>Materials/Methods</h3> The study was designed to enroll 900 men with high-risk prostate cancer (Gleason 9-10, PSA > 20, or clinical stage T2 or higher with Gleason ≥ 8). Ultimately, 238 patients were enrolled (May 2012-Sept 2014), and randomized 1:1 to receive standard therapy (Arm A), or standard therapy plus two years of twice daily orteronel (Arm B). Radiation therapy entailed dose-escalated external beam radiation (EBRT) to the prostate and pelvis to 45 Gy in 25 fractions, followed by a boost to 79.2 Gy using EBRT or either HDR or LDR. The analysis plan was reframed around detecting a reduction in rate of a composite biochemical failure endpoint (Phoenix biochemical failure, local/regional or distant disease, or salvage ADT). With 238 patients enrolled and followed, the study would have 70% power to detect a 40% decrease in the composite failure primary endpoint after 70 events had occurred. <h3>Results</h3> 231 patients were evaluable for efficacy and toxicity, 115 in Arm A and 116 in Arm B, and median follow up was 6.2 years. Grade 3 adverse events were observed in 35% and 60% of men in Arm A and B, respectively, with most common being urinary or gastrointestinal disturbance. Time to grade 3 adverse event was significantly faster in Arm B (log rank P value < 0.001). There were four deaths due to adverse events, three of which were in Arm A, and all were deemed unlikely related to treatment. Notably, only 29% of men in Arm B received 80% or more of the planned dose of orteronel due to a variety of factors that impacted drug tolerability. With respect to the primary outcome, patients did well overall with 6-year failure rates of 22.5% and 16.1%, respectively, in Arms A and B (hazard ratio [HR] 0.83, 95% CI 0.47-1.48). By Phoenix definition, PSA failure was only 18.4% and 12.1% in Arms A and B through 6 years. Distant failure occurred in 10.0% and 4.0% of patients (HR 0.71, 95% CI 0.29-1.75). Quality of life outcomes will be reported separately. While all efficacy trends favored the experimental arm, due to the small number of patients and events none of the differences between arms achieved statistical significance. <h3>Conclusion</h3> The addition of orteronel to dose escalated RT and ADT did not result in statistically significant improvement in efficacy outcomes, although results were limited by early termination of accrual and impaired drug tolerability. Intensification of hormonal therapy with better tolerated novel agents remains an appealing strategy for the treatment of high-risk localized prostate cancer.

Salvage focal brachytherapy in castration-resistant prostate cancer with neuroendocrine differentiation after radiation therapy.

IntroductionTreatment strategy for castration‐resistant prostate cancer with neuroendocrine differentiation after radiation therapy has not been established.Case presentationWe described a case of castration‐resistant prostate cancer with neuroendocrine differentiation after initial external beam radiotherapy followed by salvage androgen deprivation therapy. Magnetic resonance imaging detected recurrence of a suspicious lesion in the left lobe of the prostate, although the prostate‐specific antigen level was <0.2 ng/mL. Transperineal prostate saturation needle biopsy detected adenocarcinoma with neuroendocrine differentiation. The patient underwent salvage focal brachytherapy and had a prostate‐specific antigen progression‐free survival of 20 months with no obvious adverse events. No recurrence has been detected on magnetic resonance imaging for 18 months.ConclusionSalvage focal brachytherapy for prostate cancer after external beam radiotherapy can be one of the treatment strategies for local recurrence of castration‐resistant prostate cancer with neuroendocrine differentiation.

Outcomes following radical prostatectomy or external beam radiation for veterans with Gleason 9 and 10 prostate cancer.

BackgroundThe optimal upfront treatment modality for patients with nonmetastatic Gleason Score 9 and 10 prostate cancer (GS 9–10 PCa) is unknown.MethodsWe conducted a retrospective cohort study of patients in the Veterans Health Administration (VHA) with GS 9–10 PCa treated with radical prostatectomy (RP) or external beam radiation therapy with androgen deprivation therapy (EBRT+ADT) from 1/2000 to 12/2010. Outcomes included overall survival (OS), distant metastasis‐free survival (DMFS), and salvage/adjuvant therapy‐free survival (SAFS), as assessed by Kaplan–Meier analysis.ResultsWe identified 1220 veterans with GS 9–10 PCa; 335 were treated with RP, and 885 were treated with EBRT+ADT. With a median follow‐up of 9.9 years, propensity score‐matched analyses demonstrated that RP had superior 10‐year OS (70.8% [RP] vs. 61.2% [EBRT+ADT], p < 0.001), 10‐year DMFS rates were similar between RP (76.7%) and EBRT+ADT (81.0%), and 10‐year SAFS rates were lower for RP vs EBRT + ADT (35.2% [RP] vs. 75.2% [EBRT+ADT], p < 0.001). The receipt of salvage ADT was higher with upfront RP (51.9% vs. 26.1%, p < 0.001), despite receipt of adjuvant/salvage EBRT in 41.8% of RP patients. Among patients treated with RP, there were no differences in outcomes by race. However, higher survival rates were noted among Black patients treated with EBRT+ADT compared with White patients.ConclusionsThis analysis demonstrated higher 10‐year OS rates among men treated with upfront RP versus EBRT+ADT, though missing confounders and similar DMFS rates suggest the long‐term cause‐specific OS rates may be similar. We also highlight real‐world outcomes of a diverse patient population in the VHA and improved outcomes for Black patients receiving EBRT+ADT.

Nandrolone-Induced Tumor Progression in Hormone-Sensitive Prostate Cancer.

Hormone-sensitive prostate cancer responds favorably to testosterone suppression induced by GnRH analogs or antagonists. This effect may theoretically be countered by anabolic steroids. We describe a patient of a recurrent hormone-sensitive prostate cancer who was on salvage androgen deprivation therapy with degarelix and developed rapid progression after over-the-counter nandrolone injections.

Performance of a Genomic Classifier (GC) Within a Phase 3 Randomized Trial of Dose Escalated Salvage Radiotherapy (SRT) After Radical Prostatectomy (RP)

Presalvage PSA is an important prognostic and a predictive factor for salvage radiotherapy (SRT) and androgen deprivation therapy (ADT) post-prostatectomy. GC can independently prognosticate prostate cancer outcomes and may help individualize treatment intervention. Herein, we assessed the role of the GC in patients treated within a contemporary phase 3 trial.The SAKK 09/10 trial (NCT01272050) is an open-label, multicenter, randomized phase 3 trial performed in 24 centers in Switzerland, Germany, and Belgium. Patients with biochemical progression (PSA > 0.1 to 2 ng/mL at randomization) were randomized to 64 Gy vs 70 Gy to the prostate bed. No patients received ADT or pelvic nodal radiotherapy. A pre-specified statistical plan was developed to assess the impact of the GC on clinical outcomes. GC score range is 0 to 1, with locked cut points of < 0.45, 0.45-0.6, > 0.6 for low, intermediate, and high, respectively. In this sub-analysis, the primary endpoint was freedom from biochemical progression (FFBP) according to PSA at randomization (≤0.5 vs > 0.5, a trial stratification variable). Cox multivariable analysis (MVA) adjusting for age, T-category, Gleason score, persistent PSA after RP, and randomization arm were performed. Secondary endpoints included clinical progression-free survival (CPFS) and time to salvage ADT.Of 233 patients with tissue available, 1 was ineligible and 6 failed QC. The remaining 226 were included for analysis with a median follow-up of 6.3 years (IQR 6.0-7.2). High- vs. low/intermediate-GC had an HR of 2.22 (95% CI 1.37-3.58, P = 0.001) for FFBP, 2.29 (95% CI 1.32-3.98, P = 0.003) for CPFS, and 2.99 (95% CI 1.50-5.95, P = 0.002) for use of salvage ADT. In patients with PSA ≤0.5 ng/mL (165/226, 73%), the 5-year FFBP was 74% [95% CI 66-82] for low-intermediate GC compared to 59% [95% CI 43-74] in patients with high-GC. High-GC patients had 5-year FFBP of 13% [95% CI 0-32] when SRT was delivered at PSA > 0.5 ng/mL compared to 59% [95% CI 43-74] when PSA ≤0.5 ng/mL.In a contemporary phase 3 trial, patients with a high-GC were more than twice as likely than patients with low/intermediate-GC to experience biochemical and clinical progression and receive salvage ADT. High-GC patients who received SRT with PSA > 0.5 ng/mL had nearly 90% risk of recurrence by 5-years post-SRT. This data validates the clinical utility of the GC for tailoring treatment in the salvage setting.

HIGH RISK PROSTATE CANCER: COMPARISON OF RADICAL PROSTATECTOMY VERSUS RADIATION THERAPY: EXPERIENCE OF MILITARY HOSPITAL RABAT

Context: To date, there is no Level 1 evidence comparing the efficacy of radical prostatectomy and radiotherapy for patients with clinically-localized prostate cancer. Objective: to evaluate overall survival (OS) and relapse free survival of high risk prostate cancer (PCa) treated either with external beam radiotherapy (EBRT) associated with androgen deprivation therapy (ADT) or radical prostatectomy (RP) with adjuvant or salvage radiotherapy and ADT. Also, it is very interesting to compare different acute and late toxicity of the both approach. Materials and Methods: During a period of 10 years from April 2009 and December 2018, 149 patients with high-risk prostate cancer were admitted to the radiotherapy department of the Mohammed V military hospital in Rabat (HMIMV). Among these patients, 17 underwent surgery followed by EBRT and ADT: this is the experimental arm (Group I) and 34 patients who had benefited from treatment with EBRT with ADT were selected from the other patients by a 1: 2 matching method who will represent the reference group (Group II) to allow a comparison with the experimental arm with the minimum possible bias. Results: The overall survival (OS) at 5 and 10 years was 100 % in the both arms while relapse free survival at 5 years was 91,7 % and 93,1% respectively in group I and II and at 10 years 91,7% in the group multimodal approach and 88,9 % in the EBRT+ADT group without any significant difference. We note more toxicities in the surgical group with more urinary incontinence (p=0,001) and more erectile dysfunction. Conclusion: RP with adjuvant EBRT and EBRT+ADT provided similar long-term cancer control for patients with high-risk prostate cancer but with different toxicity profiles.

Clinical outcomes of salvage treatment in lymph node-positive prostate cancer patients after radical prostatectomy.

IntroductionThe optimal salvage treatment strategies for lymph node-positive (LNP) patients after radical surgery have not been clearly defined in prostate cancer with biochemical recurrence or persistence of elevated prostate-specific antigen (PSA). In this study, we compared the clinical outcomes of two different salvage treatments, androgen deprivation therapy (ADT) alone versus ADT with radiotherapy (RT). We also investigated prognostic factors that could support the use of ADT with RT in LNP prostate cancer.Materials and methodsWe retrospectively reviewed 94 LNP prostate cancer patients who underwent radical prostatectomy (RP) followed by salvage treatment between 2004 and 2018. Salvage treatments involved either ADT alone or ADT with RT according to the clinical judgment of the physician. We analyzed clinicopathological and treatment factors related to 2nd biochemical failure (2nd BCF), clinical progression (CP), and progression-free survival (PFS). The cumulative failure after salvage treatment was defined as including both 2nd BCF and CP.ResultsThe median duration of follow-up was 55 months (interquartile range, 35–97 months). Thirty-seven (39.4%) patients were treated with ADT alone, and 57 patients (60.6%) were treated with a combination of ADT with RT. During follow-up period, the incidence of failure after salvage treatment in the ADT alone group and the combined treatment group was 89.2% and 45.6%, respectively (HR, 22.4; 95% CI 5.43–92.1; P < 0.001). The combination of ADT with RT was associated with better 2nd BCF and PFS than ADT alone (P = 0.007 and P = 0.015, respectively). In multivariate analyses, number of positive LN ≥ 2 and PSA nadir ≥ 0.005 ng/ml after RP were associated with poor 2nd BCF, CP, and PFS after salvage treatment. Salvage by combined ADT plus RT showed better 2nd BCF and PFS than ADT alone. Specifically, patients with number of positive LN ≥ 2 or PSA nadir ≥ 0.005 ng/ml after RP showed better 2nd BCF (P = 0.004) or PFS (P = 0.011) when treated with ADT plus RT rather than ADT alone.ConclusionsIn patients with LNP prostate cancer, salvage ADT plus RT improved 2nd BCF and PFS compared to ADT alone. In particular, when the patients had more than two positive lymph nodes or PSA nadir ≥ 0.005 ng/ml after RP, ADT with RT seems to be a more beneficial salvage treatment resulting in better 2nd BCF and PFS.

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

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

Validation of the decipher genomic classifier (GC) in SAKK 09/10: A phase III randomized trial of dose-escalated salvage radiotherapy (SRT) after radical prostatectomy (RP).

5010 Background: GC has been shown to independently prognosticate outcomes in prostate cancer. Herein, we validate the GC in a European randomized phase III trial of dose escalated SRT after RP. Methods: SAKK 09/10 (NCT01272050) randomized 350 patients with biochemical recurrence after RP to 64Gy vs 70Gy. No patients received androgen deprivation therapy (ADT) or pelvic nodal radiotherapy. A pre-specified statistical plan was developed to assess the impact of the GC on clinical outcomes. RP samples were centrally reviewed for the highest-grade tumor and those passing quality control (QC) were run on a clinical-grade whole-transcriptome assay to obtain the GC score (0 to 1; &lt; 0.45, 0.45-0.6, &gt; 0.6 for low-, intermediate-, and high, respectively). The primary aim of this study was to validate the GC for the prediction of freedom from biochemical progression (FFBP) using Cox multivariable analysis (MVA) adjusting for age, T-category, Gleason score, persistent PSA after RP, PSA at randomization, and randomization arm. The secondary aims were to evaluate the association of GC with clinical progression-free survival (CPFS) and use of salvage ADT. Results: Of 233 patients with tissue available, 226 passed QC and were included for analysis. The final GC cohort was a representative sample of the overall cohort, with a median follow-up of 6.3 years (IQR 6.0-7.2). GC score (continuous per 0.1 unit, score 0-1) was independently associated with FFBP (HR 1.14 [95% CI 1.03-1.25], p = 0.009). Higher GC scores were independently associated with CPFS, use of salvage ADT, and rapid biochemical failure ( &lt; 18 months after SRT). High- vs. low/intermediate-GC showed a HR of 2.22 ([95% CI 1.37-3.58], p = 0.001) for FFBP, 2.29 ([95% CI 1.32-3.98], p = 0.003) for CPFS, and 2.99 ([95% CI 1.50-5.95], p = 0.002) for use of salvage ADT. Patients with high-GC had 5-year FFBP of 45% [95% CI 32-59] vs 71% [95% CI 64-78] in low-intermediate GC. Similar estimates for GC risk groups were observed in the 64Gy vs 70Gy in GC high (5-year FFBP of 51% [95% CI 32-70] vs 39% [95% CI 20-59]) and in low-intermediate GC (75% [95% CI 65-84] vs 69% [95% CI 59-78]). Conclusions: This study represents the first contemporary randomized controlled trial in patients with recurrent prostate cancer treated with early SRT without ADT that has validated the prognostic utility of the GC. Independent of standard clinicopathologic variables and radiotherapy dose, patients with a high-GC were more than twice as likely than a lower GC score to experience biochemical and clinical progression and receive salvage ADT. This data confirms the clinical value of Decipher GC for tailoring treatment in the postoperative salvage setting.