Early Salvage Radiotherapy Research Articles

First Postprostatectomy Ultrasensitive Prostate-specific Antigen Predicts Survival in Patients with High-risk Prostate Cancer Pathology

BackgroundUltrasensitive prostate-specific antigen (uPSA) has untapped potential for optimizing management following radical prostatectomy (RP) in terms of facilitating early salvage, minimizing overtreatment, and identifying those at risk of occult systemic disease. ObjectiveTo test first postoperative uPSA for prediction of outcome in patients with adverse pathology after RP. Design, setting, and participantsPatients with extraprostatic extension and/or a positive margin who did not receive immediate adjuvant therapy. Outcome measurements and statistical analysisFirst uPSA was measured at 3 mo after RP. The study endpoints were biochemical relapse (BCR), defined as PSA ≥0.2ng/ml, bone metastasis–free survival (BMFS), prostate cancer–specific survival (PCSS), overall survival (OS), and salvage radiation therapy (SRT) success. Outcome results were compared using the Kaplan-Meier method and multivariate analysis (MVA). Results and limitationsThe cohort consisted of 269 RP patients from 1991–2015 with median follow-up of 77 mo. Sensitivity analysis identified first postoperative uPSA of ≥0.03ng/ml as the optimal threshold for predicting BCR. First postoperative uPSA ≥0.03 versus <0.03ng/ml was associated with worse 5-yr BCR (86%, 95% confidence interval [CI] 71–93% vs 39%, 95% CI 25–51%; p<0.00001), 10-yr BMFS (75%, 95% CI 62–92% vs 95%, 95% CI 88–100%; p=0.0001), 10-yr PCSS (84%, 95% CI 73–96% vs 100%, 95% CI 100–100%; p=0.005), and 10-yr OS (81%, 95% CI 70–93% vs 98%, 95% CI 94–100%; p=0.009). On MVA, first postoperative uPSA ≥0.03ng/ml was an independent predictor of BCR (hazard ratio [HR] 9.4, 95% CI 5.8–15.4; p<0.00001) and the only predictor for BMFS (HR 9.7, 95% CI 2.1–44.6; p=0.0034), PCSS (HR 13.5, 95% CI 1.7–107.9; p=0.014), and OS (HR 5.0, 95% CI 1.4–18.3; p=0.014). Following SRT, first postoperative uPSA ≥0.03ng/ml independently predicted worse BMFS (HR 5.9, 95% CI 1.3–26.9; p=0.021), PCSS (HR 6.9, 95% CI 0.9–55.8; p=0.07), and OS (4.5, 95% CI 1.0–20.1; p=0.057). Limitations include the retrospective design and potential selection bias. ConclusionsFirst postoperative uPSA ≥0.03ng/ml independently predicts BCR, BMFS, PCSS, and OS better than traditional risk factors. SRT alone may be insufficient for patients with high-risk disease when first postoperative uPSA is ≥0.03ng/ml. Patient summaryWhen the first postprostatectomy ultrasensitive prostate-specific antigen level is ≥0.03ng/ml, patients are at higher risk of recurrent and occult prostate cancer. They should be considered for early salvage radiotherapy, possibly with hormone therapy.

Postoperative adjuvant and very early salvage radiotherapy after prostatectomy in high-risk prostate cancer patients can improve specific and overall survival

Adjuvant radiotherapy (ART) for biochemical relapse (BR) after radical prostatectomy (RP) showed increased disease-free survival (DFS) in three previous randomized trials. Retrospective phase II trials evaluated if early salvage RT (ESRT) is equivalent to ART. Our study aims to compare ART and ESRT to salvage RT. We compared RP plus ART and ESRT versus SRT. Indication for RT was made by PSA determination after RP: ART when PSA ≤ 0.2ng/ml, ESRT when PSA ≤ 0.3 after PSA rise from 0.0 to SRT PSA ≥ 0.3. The cause of death of each patients was analyzed, DFS, cause-specific survival (CSS) overall survival (OS) and metastasis-free survival (MFS) in relation to RT intention. Between 1993 and 2008, 204 patients with a median age of 65years (44-75) were treated. The median follow-up was 160months (28.1-273.3). At diagnosis, 89.7% had localized clinical stages and 90.2% had Gleason (G) ≤ 7. The median PSA was 10 (range 4-101). The postoperative G was ≥ 7 in 66.2%; 56.4% had ≥ 2 positive margins; 29.4% received ART, 20% ESRT and 59.3% SRT. The DFS for ART, ESRT and SRT was 74, 56 and 39% with significant differences between the three groups (p < 0.001). ART + ESRT were combined versus SRT; for the DFS, the significant differences (p < 0.001) remained 67% versus 39%. Positive margins, pT3 and pre-RT PSA were significant factors on multivariate analysis. The CSS in the ART + ESRT group was 92 vs. 78% in the SRT group (p < 0.05). OS was 69% in ART + ESRT vs. 57% in SRT (p < 0.05). MFS was 82.7% in ART + ESRT vs. 67.4% in SRT. In this study the ART + ESRT presented benefits versus SRT in DFS, CSS, OS and MFS.

Discord Among Radiation Oncologists and Urologists in the Postoperative Management of High-Risk Prostate Cancer.

To query specialty-specific differences regarding postoperative radiotherapy (RT) for high-risk prostate cancer. Electronic mail survey of radiation oncologists (ROs) and urologists. We sought to maximize absolute response number to capture contemporary practice ethos. The outcome of interest was association between response and specialty. Training level/expertise, practice setting, percentage of consultation caseload consisting of high-risk prostate cancer, and nationality were set as effect modifiers for multivariate logistic regression. In total, 846 ROs and 407 urologists responded. ROs were more likely to prefer adjuvant radiotherapy (ART). ART or early salvage radiotherapy (SRT, with early SRT defined as that delivered at prostate-specific antigen<0.2), whereas urologists were more likely to prefer early or delayed SRT (P<0.0001). ROs were more likely to prefer lower PSA thresholds for initiating SRT (P<0.0001), and more likely to recommend ART in the setting of adverse pathologic features or node-positive disease (P<0.0001). Significantly more ROs would recommend concurrent androgen deprivation therapy or pelvic nodal RT in the setting of node-positive or Gleason score 8 to 10 disease (P<0.0001). Specialty-specific differences were readily elucidated with respect to timing and indications for ART and SRT, as well as for indications for androgen deprivation therapy and nodal RT. These differences are likely to create a sense of dissonance for patients, which may in turn explain the underutilization of postoperative RT in general practice.

MP22-03 UTILIZATION OF SALVAGE RADIATION THERAPY FOR BIOCHEMICAL RECURRENCE AFTER RADICAL PROSTATECTOMY

You have accessJournal of UrologyProstate Cancer: Localized: Radiation Therapy1 Apr 2018MP22-03 UTILIZATION OF SALVAGE RADIATION THERAPY FOR BIOCHEMICAL RECURRENCE AFTER RADICAL PROSTATECTOMY Scott Hawken, Daniel E Spratt, Ji Qi, Susan M Linsell, Michael L Cher, Kurshid R Ghani, David C Miller, James E Montie, Todd M Morgan, and for the Michigan Urological Surgery Improvement Collaborative Scott HawkenScott Hawken More articles by this author , Daniel E SprattDaniel E Spratt More articles by this author , Ji QiJi Qi More articles by this author , Susan M LinsellSusan M Linsell More articles by this author , Michael L CherMichael L Cher More articles by this author , Kurshid R GhaniKurshid R Ghani More articles by this author , David C MillerDavid C Miller More articles by this author , James E MontieJames E Montie More articles by this author , Todd M MorganTodd M Morgan More articles by this author , and for the Michigan Urological Surgery Improvement Collaborativefor the Michigan Urological Surgery Improvement Collaborative More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.714AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES For men with biochemical recurrence after radical prostatectomy (RP), salvage radiation therapy (SRT), especially ″early″ SRT (PSA ≤0.5 ng/mL), is a potentially curative option. However, its utilization in clinical practice is not well defined. We sought to determine factors associated with SRT utilization as well as the variation in administration across diverse urology practices. METHODS Patients with localized prostate cancer (PCa) undergoing RP at 27 practices participating in the Statewide Michigan Urological Surgery Improvement Collaborative (MUSIC) between 2012-2016 were prospectively followed. Eligible patients for this study had at least 1 post-RP PSA ≥0.1 ng/ml. SRT utilization along with clinical and pathologic patient characteristics were examined, including PSA, pathologic stage, grade, margin status, race, Charlson comorbidity index, age, and insurance type. Associations with SRT use were analyzed using logistical regression modeling. RESULTS Of 1017 eligible patients with a detectable PSA, only 29.7% underwent SRT; 16.7%, 5.2%, 3.3%, and 4.5% of patients underwent SRT at PSA levels of 0.1 to <0.5, 0.5 to <1.0, 1.0 to <2.0, and ≥2.0 ng/mL, respectively. After adjusting for patient and practice level factors, higher maximum post-RP PSA, positive surgical margins, higher T-stage, and higher grade group were all associated with receipt of SRT (all p<0.05). Even after adjusting for patient and tumor characteristics, there remained significant variation in the adjusted rate of SRT utilization across practices sites, ranging from 3.5% (95% CI 0.5-15%) to 74% (95% CI 35-94%, p<0.001). Practices were grouped into tertiles based on SRT utilization, and those practices that utilized SRT more frequently overall were more likely to administer SRT across all patient-based predictors of SRT utilization (Figure). CONCLUSIONS Of men with a detectable PSA post-RP, one in six received early SRT, with significant variation in practice-level SRT utilization which can′t be explained by patient factors alone. Factors suggesting higher risk disease were predictors of SRT administration. These data support the potential to expand the use of SRT, particularly among low utilization sites. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e272 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Scott Hawken More articles by this author Daniel E Spratt More articles by this author Ji Qi More articles by this author Susan M Linsell More articles by this author Michael L Cher More articles by this author Kurshid R Ghani More articles by this author David C Miller More articles by this author James E Montie More articles by this author Todd M Morgan More articles by this author for the Michigan Urological Surgery Improvement Collaborative More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

EP-1597: Dose-escalation for early salvage radiotherapy in prostate cancer improves bDFS

EP-1597: Dose-escalation for early salvage radiotherapy in prostate cancer improves bDFS

Who benefits most from early salvage radiation therapy after prostatectomy?

We are grateful for the opportunity to provide commentary on the recent work by Fossati et al ., entitled “Impact of Early Salvage Radiation Therapy in Patients with Persistently Elevated or Rising Prostate-specific Antigen After Radical Prostatectomy” (1). The optimal post-operative management of patients with prostate cancer who undergo radical prostatectomy (RP) is unclear. In general, there are two strategies for approaching radiotherapy. Adjuvant radiation therapy (ART) typically refers to post-operative radiation in the setting of high risk pathologic features but with an undetectable post-prostatectomy PSA, where the presence of residual prostate cancer is suspected but unknown. In this setting, radiation is typically delivered within a few months of surgery once there has been adequate recovery of urinary function. In contrast, salvage radiation therapy (SRT) refers to post-operative radiation in the setting of a rising or persistently detectable PSA, indicative of active prostate cancer and may be delivered several years after the initial RP (2). However, it is important to note that these definitions lack consensus.

Optimal timing of post-prostatectomy radiotherapy for prostate cancer with high-risk pathologic features: A multi-institutional analysis.

24 Background: The use of radical prostatectomy (RP) as initial treatment of high-risk/locally-advanced prostate cancer is increasing but patients (pts) with adverse pathologic features such as positive surgical margins or T3 disease have up to 70% recurrence risk. These high-risk pts may be managed with adjuvant radiotherapy (ART) or early salvage radiotherapy (ESRT). The optimal timing of post-operative radiotherapy is unclear. Methods: Individual data from 1566 consecutive pts with pT2N0M0/R1 or pT3N0M0/R0-1 disease who underwent post-prostatectomy ART or ESRT (1987-2013) at 10 academic centers were pooled. Post-irradiation freedom from biochemical failure (FFBF), freedom from distant metastases (FFDM), prostate-cancer specific survival (PCSS), and overall survival (OS) were compared using Kaplan-Meier and multivariate competing-risks regression (MVA) analyses. Propensity score (PS) matching was used to account for covariates potentially associated with treatment allocation. All outcomes were measured from the date of surgery to address lead time bias. Results: After PS-matching, median follow-up after surgery was 66 vs. 73 months for the ART and ESRT groups, respectively, and baseline characteristics were well-matched. ART was associated with higher FFBF (12-yr: 69% vs. 43%; log-rank P &lt; 0.0001), FFDM (12-yr: 95% vs. 85%; log-rank P = 0.03), PCSS (12-yr: 99% vs. 94%; log-rank P = 0.048), and OS (12-yr: 91% vs. 79%; log-rank P = 0.01). ART, lower Gleason score, lower T-stage, nodal irradiation, and postoperative androgen deprivation therapy were favorable prognostic features on MVA for BF. Sensitivity analysis demonstrated that the decreased risk of BF associated with ART remained significant unless more than 56% of ART pts were cured by surgery alone. This threshold is greater than the estimated 12-yr FFBF of 46% after RP alone as determined by a contemporary nomogram. Conclusions: To the best of our knowledge, this represents the largest multi-institutional study to date comparing ART to ESRT. ART was associated with reduced biochemical recurrence, distant metastases, and death compared to ESRT for high-risk pts, pending prospective validation.

Comparison Between Adjuvant and Early-Salvage Postprostatectomy Radiotherapy for Prostate Cancer With Adverse Pathological Features

Prostate cancer with adverse pathological features (ie, pT3 and/or positive margins) after prostatectomy may be managed with adjuvant radiotherapy (ART) or surveillance followed by early-salvage radiotherapy (ESRT) for biochemical recurrence. The optimal timing of postoperative radiotherapy is unclear. To compare the clinical outcomes of postoperative ART and ESRT administered to patients with prostate cancer with adverse pathological features. This multi-institutional, propensity score-matched cohort study involved 1566 consecutive patients who underwent postprostatectomy ART or ESRT at 10 US academic medical centers between January 1, 1987, and December 31, 2013. Propensity score 1-to-1 matching was used to account for covariates potentially associated with treatment selection. Data were collected from January 1 to September 30, 2016. Data analysis was conducted from October 1, 2016, to October 21, 2017. Freedom from postirradiation biochemical failure, freedom from distant metastases, and overall survival. All outcomes were measured from date of surgery to address lead-time bias. Of 1566 patients, 1195 with prostate-specific antigen levels of 0.1 to 0.5 ng/mL received ESRT and 371 patients with prostate-specific antigen levels lower than 0.1 ng/mL received ART. The median age (interquartile range) was 60 (55-65) years. After propensity score matching, the median (interquartile range) follow-up after surgery was similar between the ESRT and ART groups (73.3 [44.9-106.6] months vs 65.8 [40-107] months; P = .22). Adjuvant RT, compared with ESRT, was associated with higher freedom from biochemical failure (12-year actuarial rates: 69% [95% CI, 60%-76%] vs 43% [95% CI, 35%-51%]; effect size, 26%), freedom from distant metastases (95% [95% CI, 90%-97%] vs 85% [95% CI, 76%-90%]; effect size, 10%), and overall survival (91% [95% CI, 84%-95%] vs 79% [95% CI, 69%-86%]; effect size, 12%). Adjuvant RT, lower Gleason score and T stage, nodal irradiation, and postoperative androgen deprivation therapy were favorable prognostic features on multivariate analysis for biochemical failure. Sensitivity analysis demonstrated that the decreased risk of biochemical failure associated with ART remained significant unless more than 56% of patients in the ART group were cured by surgery alone. This threshold is greater than the estimated 12-year freedom from biochemical failure rate of 33% to 52% after radical prostatectomy alone, as determined by a contemporary dynamic nomogram. Adjuvant RT, compared with ESRT, was associated with reduced biochemical recurrence, distant metastases, and death for high-risk patients, pending prospective validation. These findings suggest that a greater proportion of patients with prostate cancer who have adverse pathological features may benefit from postprostatectomy ART rather than surveillance followed by ESRT.

Image-guided, whole-pelvic, intensity-modulated radiotherapy for biochemical recurrence following radical prostatectomy in high-risk prostate cancer patients.

BackgroundThe optimal field size of salvage radiotherapy (SRT) for biochemical recurrence, particularly for patients with high-risk prostate cancer, remains undefined. This retrospective analysis was performed to investigate oncological outcomes as well as treatment-related toxicity following salvage intensity-modulated radiotherapy (IMRT) to the whole pelvis and to compare the results with other studies implementing a small field size of the prostate bed.MethodsThe medical records of 170 patients with high-risk prostate cancer who received SRT for biochemical recurrence following prostatectomy were reviewed. Whole-pelvic IMRT was administered with a median dose of 66 Gy in 30 fractions. To improve treatment accuracy, an endorectal balloon device and daily cone-beam computed tomography were utilized. Androgen-deprivation therapy combined with SRT was administered to 97 (57.1%) patients.ResultsEventually, 68 (40.0%) patients showed biochemical progression (BCP) after SRT. With a median follow-up period of 56 months, the 5-year BCP-free survival was 38.6%. The overall and cause-specific survival rates were 90.9% and 96.7%, respectively. Regarding BCP-free survival analysis, pathological T stage, persistent prostate-specific antigen (PSA) elevation after prostatectomy, and preSRT PSA level were significant prognostic factors on univariate analysis. On multivariate analysis, pathological T stage and preSRT PSA value retained their significance. Acute and late grade-3 genitourinary toxicities were observed in one (0.6%) and five (2.9%) patients, respectively. One patient each developed acute and late grade-3 gastrointestinal toxicity.ConclusionSRT to whole pelvis using IMRT and image guidance is as safe as SRT to the prostate bed, but its efficacy should be confirmed in ongoing randomized trials. PreSRT PSA was the only controllable prognostic factor, suggesting the benefit of early SRT.

Prostate cancer: Utility of ADT during early salvage radiotherapy.

Prostate cancer: Utility of ADT during early salvage radiotherapy.

Re: Impact of Early Salvage Radiation Therapy in Patients with Persistently Elevated or Rising Prostate-specific Antigen After Radical Prostatectomy

Re: Impact of Early Salvage Radiation Therapy in Patients with Persistently Elevated or Rising Prostate-specific Antigen After Radical Prostatectomy

Use of Concomitant Androgen Deprivation Therapy in Patients Treated with Early Salvage Radiotherapy for Biochemical Recurrence After Radical Prostatectomy: Long-term Results from a Large, Multi-institutional Series

BackgroundHormonal manipulation concomitant to salvage radiotherapy (SRT) given for biochemical recurrence (BCR) after radical prostatectomy (RP) improved outcomes in two randomized trials. However, neither of these studies focused on men treated at low prostate-specific antigen (PSA) levels. ObjectiveTo test if the impact of androgen deprivation therapy (ADT) on metastasis in patients undergoing early SRT varies according to prostate cancer (PCa) features. Design, setting, and participantsA total of 525 patients received SRT at PSA levels ≤2ng/ml. Outcome measurements and statistical analysesMultivariable Cox regression analyses assessed factors associated with metastasis. We tested the hypothesis that the impact of ADT varied according to the risk of metastasis. An interaction with groups (concomitant ADT vs no ADT) and the probability of distant metastasis according to a newly developed model was tested. A nonparametric curve explored the relationship between the risk of metastasis and 10-yr metastasis rates according to ADT. Results and limitationsMedian PSA and radiotherapy dose were 0.42ng/ml and 66Gy, respectively. Overall, 178 (34%) patients received ADT. At a median follow-up of 104 mo, 71 patients experienced metastasis. Grade group ≥4 (hazard ratio [HR]: 1.66; 95% confidence interval [CI]: 1.01–3.30), pT3b/4 (HR: 2.61; 95% CI: 1.51–4.52), and dose (HR: 0.82; 95% CI: 0.76–0.89) were associated with metastasis. The impact of ADT differed according to the risk of metastasis calculated using a multivariable model (p=0.01). This was confirmed when considering patients treated with early SRT (p=0.046), where ADT was associated with a reduction in the rate of metastasis only in eSRT; patients with more aggressive characteristics (ie, pT3b/4 and grade group ≥4, or pT3b/4 and PSA at eSRT ≥0.4ng/ml). ConclusionsThe beneficial effect of ADT concomitant to eSRT varied significantly according to disease characteristics, such that only men with more aggressive PCa features benefit from ADT in the eSRT setting for BCR after RP. Patient summaryThe oncological benefits of concomitant androgen deprivation therapy (ADT) in patients undergoing salvage radiotherapy (SRT) vary according to pathological characteristics. Only patients with more aggressive disease characteristics seemed to benefit from the use of hormonal manipulation at the time of early SRT. Conversely, the potential side effects of ADT could be spared in patients with low prostate-specific antigen levels and favorable pathological features.

Functional and oncological outcomes of salvage external beam radiotherapy following robot-assisted radical prostatectomy in a Canadian cohort.

We sought to determine the impact of salvage radio-therapy (SRT) on oncological and functional outcomes of patients with prostate cancer after biochemical recurrence (BCR) following robot-assisted radical prostatectomy (RARP). Data of 70 patients with prostate cancer treated with SRT after developing BCR were retrospectively analyzed from a prospectively collected RARP database of 740 men. Oncological (prostate-specific antigen [PSA]) and functional (pads/day, International Prostate Symptom Score [IPSS], and Sexual Health Inventory for Men [SHIM]) outcomes were reported at six, 12, and 24 months after RT and adjusted for pre-SRT status. Men who underwent SRT had a mean age, PSA, and time from radical prostatectomy (RP) to RT of 61.8 years (60.1-63.6), 0.5 ng/ml (0.2-0.8), and 458 days (307-747), respectively. Freedom from biochemical failure (FFBF) post-SRT, defined as a PSA nadir <0.2 ng/mL, was observed in 89%, 93%, and 81%, at six, 12, and 24 months, respectively. Undetectable PSA was observed in 14%, 35%, and 40% at the same time points, respectively. There was no significant difference in urinary continence post-SRT (p=0.56). Rate of strict continence (0 pads/day) was 71% at 24 months compared to 78% pre-SRT. Mean IPSS at six, 12, and 24 months was 3.4, 3.6, and 3.6, respectively compared to pre-RT score of 3.3 (p=0.61). The mean SHIM score pre-SRT was comparable at all time points following treatment (p=0.86). In this unique Canadian experience, it appears that early SRT is highly effective for the treatment of BCR following RARP with little impact on urinary continence and potency outcomes.

Long-term Outcome of Prostate Cancer Patients Who Exhibit Biochemical Failure Despite Salvage Radiation Therapy After Radical Prostatectomy.

Salvage radiation therapy (SRT) is an effective treatment for recurrent prostate cancer (PCa) after radical prostatectomy. We report the long-term outcome of men who developed biochemical recurrence (BCR) after SRT and were treated >14 years ago. In total, 61 patients treated with SRT from 1992 to 2000 at our institution were identified. Survival was calculated by Kaplan-Meier method. Log-rank test and Cox regression were used to determine significance of clinical parameters. The median follow-up was 126 months (interquartile range, 66-167 mo). Thirty-four (56%) had prostate-specific antigen (PSA) failure after SRT. At 10 years, overall survival (OS) was 67%, freedom from PSA failure (FFPF) was 33%, prostate cancer-specific survival (PCSS) was 84%, and distant metastases-free survival (DMFS) was 84%. Pathologic T-stage, Gleason score, seminal vesicle involvement, and pre-SRT PSA were associated with FFPF. For patients who failed SRT, the median time to BCR after SRT was 30 mo. A total of 19 (68%) received androgen deprivation therapy. The median OS was 13.6 years. At 10 years from time of BCR, OS was 59%, PCSS was 73%, DMFS was 75%, and castration-resistant-free survival was 70%. Early SRT failure correlated with significantly decreased DMFS and PCSS. Ten-year DMFS from SRT was 43% (BCR≤1 y) versus 91% (BCR>1 y). Extended follow-up demonstrates that despite SRT failure, PCSS remains high in select patients. Early failure (≤1 y after SRT) predicted for significantly worse outcome and may represent a subgroup with more aggressive disease that may be considered for further prospective clinical studies.

Use of the Electronic Medical Record to Facilitate Intervention for Patients With Rising Prostate-Specific Antigen Values After Radical Prostatectomy: A Feasibility Study.

Salvage radiotherapy (SRT) is the standard of care offered when postprostatectomy prostate-specific antigen (PSA) levels are ≥ 0.2 ng/mL. However, emerging evidence suggests that early SRT (ie, SRT delivered at PSA values < 0.2 ng/mL, but generally ≥ 0.05 ng/mL) improves oncologic outcomes. We evaluated the feasibility of improving referral rates for discussion of early SRT by using a dynamic registry that identifies through the electronic medical record patients with rising postprostatectomy PSA levels. We developed an iteratively updated registry that identifies patients who fall within two postoperative PSA strata: ≥ 0.05 to < 0.1 ng/mL and ≥ 0.1 to < 0.2 ng/mL. We compared referral rates to radiation oncology during a 3-year period before use of this registry with those during a 1-year period after promotion of the registry in multidisciplinary tumor board settings. Before promotion of the registry, referral rates for patients with PSA values ≥ 0.05 to < 0.1 ng/mL and ≥ 0.1 to < 0.2 ng/mL were 35% and 65%, respectively. After promotion of the registry, referral rates within each stratum increased significantly to 82% and 94%, respectively ( P < .05 for both by Fisher's exact test). The overall rate of referral for patients with PSA values ≥ 0.05 to < 0.2 ng/mL rose from 48% to 90% ( P < .001). The creation of a registry of patients with rising postprostatectomy PSA values can facilitate increased referral rates for early SRT without burdening providers with a clinical support tool embedded within the EMR itself. This is true even in the case of already high baseline rates of referral for early SRT. The changes reported herein most likely reflect a Hawthorne effect wherein the ability to track referrals rather than a direct function of the registry influenced practice patterns. Nonetheless, the registry provided an integral framework to allow for tracking.

268P - Image-guided, whole-pelvic, intensity-modulated radiotherapy for biochemical recurrence following radical prostatectomy in high-risk prostate cancer patients

Background: The optimal field size of salvage radiotherapy (SRT) for biochemical recurrence, particularly for patients with high-risk prostate cancer, remains undefined. This retrospective analysis was performed to investigate oncological outcomes as well as treatment-related toxicity following salvage intensity-modulated radiotherapy (IMRT) to the whole pelvis and to compare the results with other studies implementing a small field size of the prostate bed. Methods: The medical records of 170 patients with high-risk prostate cancer who received SRT for biochemical recurrence following prostatectomy were reviewed. Whole-pelvic IMRT was administered with a median dose of 66 Gy in 30 fractions. To improve treatment accuracy, an endorectal balloon device and daily cone-beam computed tomography were utilized. Androgen-deprivation therapy combined with SRT was administered to 97 (57.1%) patients. Results: Eventually, 68 (40.0%) patients showed biochemical progression (BCP) after SRT. With a median follow-up period of 56 months, the 5-year BCP-free survival was 38.6%. The overall and cause-specific survival rates were 90.9% and 96.7%, respectively. Regarding BCP-free survival analysis, pathological T stage, persistent prostate-specific antigen (PSA) elevation after prostatectomy, and preSRT PSA level were significant prognostic factors on univariate analysis. On multivariate analysis, pathological T stage and preSRT PSA value retained their significance. Acute and late grade-3 genitourinary toxicities were observed in one (0.6%) and five (2.9%) patients, respectively. One patient each developed acute and late grade-3 gastrointestinal toxicity. Conclusions: SRT to whole pelvis using IMRT and image guidance is as safe as SRT to the prostate bed, but its efficacy should be confirmed in ongoing randomized trials. PreSRT PSA was the only controllable prognostic factor, suggesting the benefit of early SRT. Legal entity responsible for the study: IRB of Asan Medical Center Funding: None Disclosure: The author has declared no conflicts of interest.

Multi-institutional Outcomes of Postprostatectomy Adjuvant Versus Early Salvage Radiation Therapy in Prostate Cancer Patients With Adverse Pathologic Features

Multi-institutional Outcomes of Postprostatectomy Adjuvant Versus Early Salvage Radiation Therapy in Prostate Cancer Patients With Adverse Pathologic Features

Post-prostatectomy radiotherapy adversely affects urinary continence irrespective of radiotherapy regime.

To investigate the influence of different postoperative radiotherapy (RT) regimes on post-prostatectomy continence and QoL. Men after prostatectomy (RP) and RT were assigned in adjuvant (ART), early salvage (ESRT) and salvage radiotherapy (SRT) groups depending on time of initiation, indication and pre-RT-PSA (≤/>0.5ng/ml). Continence and QoL outcomes were evaluated by validated questionnaire. Statistical analysis included students t test, Chi square, Fisher's test, ROC- and McNemar-Bowker-Analyses. The mean follow-up was 5.1years. 33.5, 38.2 and 28.3% received ART, ESRT and SRT, respectively. Mean time to RT was 0.3 (±0.4), 1.8 (±2.5) and 3.3 (±3.6) years respectively. Differences in age at RP (p=0.54) and RT (p=0.47) between groups were not significant. Mean-RT-dose was similar (p=0.70). Differences in continence distribution between groups before (p=0.56) and after RT (p=0.38) were not significant. No significant differences were observed for frequency (p=0.58) or amount (p=0.88) of urine loss, impact on QoL (p=0.13) and ICIQ-SF scores (p=0.69) between groups. Even though no significant difference in post-RT-continence (p=0.89) was observed in the direct comparison between groups, a significant worsening of long-term continence was observed in all groups (p<0.001). We found no cutoff and no time-point after RP at which this negative effect of RT on continence became insignificant (AUC=0.474). A subgroup with apparent local recurrence showed no differences for ICIQ-SF-score (p=0.155), QoL (0.077), incontinence grade (p=0.387), frequency (p=0.182) and amount (p=0.415) of urine loss. Proportionally more men in this subgroup remembered deterioration of continence after RT (p=0.029). Postoperative RT adversely affects long-term continence; this negative effect is irrespective of time of initiation or indication for RT. These results suggest a need for innovative strategies of prostate cancer therapy with lasting oncological, functional and QoL outcomes.

Prostate-specific antigen after salvage radiotherapy for postprostatectomy biochemical recurrence predicts long-term outcome including overall survival

Background: For patients with recurrent prostate cancer after radical prostatectomy (RP), salvage radiotherapy (SRT) is a second chance of cure. However, depending on risk factors, 40–70% of the patients experience further progression. With a focus on the pre- and post-SRT serum level of the prostate-specific antigen (PSA), we assessed the determinants of the long-term outcome after SRT.Patient and methods: Between 1997 and 2011, 464 patients received 3D-conformal SRT with median 66.6 Gy. The median PSA level before SRT was 0.31 ng/ml. In our retrospective analysis, post-SRT progression was defined as either a rising PSA >0.2 ng/ml above the nadir, or the application of anti-androgens or clinical recurrence. A PSA <0.1 ng/ml was termed undetectable. We analyzed the data with the Kaplan–Meier method (Logrank test) and multivariable Cox regression.Results: The median follow-up was 5.9 years. Overall, 178 patients had recurrence, 13 developed distant metastases and 30 died. Univariate, a pre-RP PSA <10 ng/ml, pathological stage pT <3, Gleason score <8, positive surgical margins, a pre-SRT PSA <0.2 ng/ml and a post-SRT PSA nadir <0.1 ng/ml correlated with fewer and later second recurrences. In a multivariable Cox model, pT, Gleason score, margin status and pre-SRT PSA were significant covariates of progression. If the post-SRT PSA response was included in the regression analysis, then a nadir ≥0.1 ng/ml was the strongest risk factor. Initiating SRT at a PSA <0.2 ng/ml correlated with a post-SRT PSA <0.1 ng/ml. Men who achieved an undetectable post-SRT PSA nadir also had lower rates of metastases and a better overall survival. However, there were too few events for Cox regression analysis of these two endpoints.Conclusions: Early SRT at a PSA <0.2 ng/ml correlates with re-achieving an undetectable PSA, which predicts improved freedom from progression and metastases and better overall survival.

Risk Factors for Disease Progression After Postprostatectomy Salvage Radiation: Long-term Results of a Single-institution Experience.

Salvage radiotherapy (SRT) has been successfully used for recurrent prostate cancer after radical prostatectomy; however, the optimal timing of SRT remains controversial. Our objective was to identify the risk factors for disease progression after SRT, with a focus on the pre-SRT prostate-specific antigen (PSA) levels in the modern era of PSA testing. We performed a retrospective review of 551 consecutive patients who had undergone postradical prostatectomy SRT for recurrent prostate cancer from 2000 to 2013. The exclusion criteria were hormonal therapy before or concurrent with SRT, adjuvant RT, distant metastases, and missing data. Disease progression was defined as a repeat PSA level of≥ 0.2 ng/mL greater than the post-SRT nadir, a continued increase in the PSA level despite SRT, initiation of systemic therapy, local recurrence, nodal failure, and/or distant metastases. Univariate and multivariable Cox regression analysis were performed to identify the predictors of disease progression. Secondarily, PSA kinetics were evaluated in the model and compared using the Akaike information criterion. Of the 551 patients, 307 underwent SRT, of whom 134 experienced subsequent disease progression. The median interval to recurrence was 6.03 years (95% confidence interval, 3.74-8.36 years). On multivariable analysis, Gleason score, Tstage, positive surgical margins, and pre-SRT PSA level were associated with progression; PSA kinetics did not independently predict for progression. When the pre-SRT PSA level was stratified (≤ 0.30, 0.31-0.50, 0.51-1.00, and > 1 ng/mL), incremental elevations were associated with an increased risk of disease progression. Multiple factors predict for progression after SRT. These risk factors could help identify those who would derive the greatest benefit from additional systemic treatment. The findings of the present study also support initiation of early SRT, irrespective of the PSA kinetics.