Unfavorable Intermediate-risk Disease Research Articles

High-volume prostate biopsy core involvement is not associated with an increased risk of cancer recurrence following 5-fraction stereotactic body radiation therapy monotherapy

PurposePercentage of positive cores involved on a systemic prostate biopsy has been established as a risk factor for adverse oncologic outcomes and is a National Comprehensive Cancer Network (NCCN) independent parameter for unfavorable intermediate-risk disease. Most data from a radiation standpoint was published in an era of conventional fractionation. We explore whether the higher biological dose delivered with SBRT can mitigate this risk factor.MethodsA large single institutional database was interrogated to identify all patients diagnosed with localized prostate cancer (PCa) treated with 5-fraction SBRT without ADT. Pathology results were reviewed to determine detailed core involvement as well as Gleason score (GS). High-volume biopsy core involvement was defined as ≥ 50%. Weighted Gleason core involvement was reviewed, giving higher weight to higher-grade cancer. The PSA kinetics and oncologic outcomes were analyzed for association with core involvement.ResultsFrom 2009 to 2018, 1590 patients were identified who underwent SBRT for localized PCa. High-volume core involvement was a relatively rare event observed in 19% of our cohort, which was observed more in patients with small prostates (p < 0.0001) and/or intermediate-risk disease (p = 0.005). Higher PSA nadir was observed in those patients with low-volume core involvement within the intermediate-risk cohort (p = 0.004), which was confirmed when core involvement was analyzed as a continuous variable weighted by Gleason score (p = 0.049). High-volume core involvement was not associated with biochemical progression (p = 0.234).ConclusionsWith a median follow-up of over 4 years, biochemical progression was not associated with pretreatment high-volume core involvement for patients treated with 5-fraction SBRT alone. In the era of prostate SBRT and MRI-directed prostate biopsies, the use of high-volume core involvement as an independent predictor of unfavorable intermediate risk disease should be revisited.

Intensity modulated radiation therapy with stereotactic body radiation therapy boost for unfavorable prostate cancer: five-year outcomes

PurposeIntensity-modulated radiation therapy (IMRT) with brachytherapy boost for unfavorable prostate cancer has been shown to improve biochemical relapse-free survival compared to IMRT alone. Stereotactic body radiation therapy (SBRT) is a less-invasive alternative to brachytherapy. Early outcomes utilizing SBRT boost suggest low rates of high-grade toxicity with a maintained patient-reported quality of life. Here, we report the 5-year progression-free survival (PFS) and prostate cancer-specific survival (PCSS) of patients treated with IMRT plus SBRT boost.Materials and methodsBetween 2008 and 2020, 255 patients with unfavorable prostate cancer were treated with robotic SBRT (19.5 Gy in three fractions) followed by fiducial-guided IMRT (45–50.4 Gy) according to an institutional protocol. For the first year, the patient’s PSA level was monitored every 3 months, biannually for 2 years, and annually thereafter. Failure was defined as nadir + 2 ng/mL or a rising PSA with imaging suggestive of recurrence. Detection of recurrence also included digital rectal examination and imaging studies, such as MRI, CT, PET/CT, and/or bone scans. PFS and PCSS were calculated using the Kaplan–Meier method.ResultsThe median follow-up period was 71 months. According to the NCCN risk classification, 5% (13/255) of the patients had favorable intermediate-risk disease, 23% (57/255) had unfavorable intermediate-risk disease, 40% (102/255) had high-risk disease, and 32% (83/255) had very high-risk disease. Androgen deprivation therapy was administered to 80% (204/255) of the patients. Elective pelvic lymph node IMRT was performed in 28 (10%) patients. The PFS for all patients at 5 years was 81% (favorable intermediate risk, 91%; unfavorable intermediate risk, 89%; high-risk, 78%; and very-high risk, 72%). The PCSS for all patients at 5 years was 97% (favorable intermediate risk, 100%; unfavorable intermediate risk, 100%; high risk, 100%; and very high risk, 89%).ConclusionThe incidence of failure following IMRT plus SBRT for unfavorable prostate cancer remains low at 5 years.

Differential Use of Radiotherapy Fractionation Regimens in Prostate Cancer

Technical advances in treatment of prostate cancer and a better understanding of prostate cancer biology have allowed for hypofractionated treatment courses using a higher dose per fraction. Use of ultrahypofractionated stereotactic body radiotherapy (SBRT) has also been characterized. To characterize US national trends of different RT fractionation schemes across risk groups of prostate cancer. This retrospective cohort study used data collected by the National Cancer Database (NCDB) to characterize the fractionation regimens used for 302 035 patients diagnosed as having prostate cancer from January 1, 2004, to December 31, 2020, who underwent definitive RT. The analysis was performed between February 1 and April 30, 2023. Stereotactic body RT or ultrahypofractionation, defined as 5 or fewer fractions of external beam RT (EBRT), moderate hypofractionation, defined as 20 to 28 fractions of EBRT, or conventional fractionation, defined as all remaining EBRT fractionation schemes. Temporal trends and clinical and sociodemographic factors associated with SBRT, moderate hypofractionation, and conventional fractionation use. A total of 302 035 men receiving EBRT for localized prostate cancer between 2004 and 2020 were identified (40.1% aged 60-69 years). Black patients comprised 17.6% of this cohort; White patients, 77.9%; and other races and ethnicities, 4.5%. Patients with low-risk disease comprised 17.5% of the cohort; favorable intermediate-risk disease, 23.5%; unfavorable intermediate-risk disease, 23.9%; and high-risk disease, 35.1%. Treatment consisted of conventional fractionation for 81.2%, moderate hypofractionation for 12.9%, and SBRT for 6.0%. The rate of increase over time in patients receiving SBRT compared with conventional fractionation was higher (adjusted odds ratio [AOR] for 2005 vs 2004, 3.18 [95% CI, 2.04-4.94; P < .001]; AOR for 2020 vs 2004, 264.69 [95% CI, 179.33-390.68; P < .001]) than the rate of increase in patients receiving moderate hypofractionation compared with conventional fractionation (AOR for 2005 vs 2004, 1.05 [95% CI, 0.98-1.12; P = .19]; AOR for 2020 vs 2004, 4.41 [95% CI, 4.15-4.69; P < .001]). Compared with White patients, Black patients were less likely to receive SBRT compared with conventional fractionation or moderate hypofractionation (AOR for conventional fractionation, 0.84 [95% CI, 0.80-0.89; P < .001]; AOR for moderate hypofractionation, 0.77 [95% CI, 0.72-0.81; P < .001]). Compared with 2019, patients treated with all fractionation regimens declined in 2020 by 24.4%. In this hospital-based cohort study of patients with prostate cancer treated with definitive EBRT, use of moderate hypofractionation and SBRT regimens for definitive prostate cancer treatment has increased from 2004 to 2020. Despite this increasing trend, findings suggest potential health care disparities for Black patients receiving EBRT for localized prostate cancer. The number of patients treated with EBRT in the year 2020 decreased, coinciding with official onset of the COVID-19 pandemic in March 2020.

Androgen Deprivation Therapy Use among Intermediate Risk Prostate Cancer Patients Undergoing Radiation Therapy across a Statewide Radiation Oncology Quality Consortium

For men with intermediate (INT) risk prostate cancer, the addition of androgen deprivation therapy (ADT) reduces risk of PSA failure, distant metastasis, and cancer-related mortality. Moreover, the relative reduction in cancer-related adverse outcomes with ADT use appears consistent across all INT risk subgroups. The absolute benefit of ADT, however, varies by baseline risk. In contemporary practice, it is unknown which clinical factors are most strongly associated with intended ADT use. Therefore, we sought to identify such factors within the diverse practices of the Michigan Radiation Oncology Quality Consortium (MROQC). Patients with localized prostate cancer undergoing definitive radiation therapy were enrolled from 6/9/20 to 11/4/22 (n = 599). Standardized patient, physician, and physicist forms were used to collect baseline and follow-up information. Intended ADT use, defined by the treating physician, was prospectively collected and is the primary outcome of this analysis. Univariable (UVA) and multivariable analyses (MVA) associations with patient (age, race, comorbidities), tumor (T stage, Gleason, percent cores positive, and PSA), and practice-related (academic vs private) factors were performed. In addition, advanced modality testing (PET, MRI, and genomic classifiers) was available as of March 2021, and subgroup analysis were performed where appropriate. A total 351 patients across 26 centers were enrolled with INT risk disease. ADT use was intended for 46% of men (n = 162/351) which differed by men with NCCN favorable INT (21%, n = 22/105) vs unfavorable INT risk disease (57%, n = 140/246), p<0.001. Sixty two percent (n = 100/162) had an intended ADT duration of 4-6 months and 21% (n = 34/162) had ≥12 months. Older age was associated with ADT use (70 vs 67, p < 0.01); there were no significant differences by race or comorbidities number. MVA showed Gleason 4+3 (OR 4.61 [2.91 - 7.42]) and > = 50% positive cores (2.56 [1.52 - 4.37]) were significantly associated with ADT use. No significant differences were noted based on practice setting. Pelvic MRI was obtained for 71% of men (n = 197/279), genomic classifiers in 47% (n = 130/279), and PET in 2% (n = 6/282). In the subset with MRI (n = 197), adverse features (ECE, SVI, or equivocal LNs) were associated with intended ADT use (OR 3.0 [1.4 - 7.1]) after adjustment for NCCN favorable/unfavorable INT risk classification. Within a state-wide consortium, intended ADT use for intermediate prostate cancer is most strongly associated with Gleason score, ≥50% positive cores, NCCN unfavorable intermediate risk classification, and adverse features on MRI. Nearly half of men had genomic classifier testing underscoring the importance ongoing trials such as NRG/GU 010.

Acute toxicity and quality of life in prostate cancer patients treated with definitive hypofractionated pelvic radiation therapy: a single-center report.

The objective was to report acute toxicity and quality of life in prostate cancer patients treated with definitive hypofractionated pelvic radiation therapy. Patients were designated candidates for hypofractionated pelvic radiation therapy if biopsy or imaging studies evidenced unfavorable intermediate-risk, high-risk or node-positive disease. Patients were treated using a regimen of 44 Gy to the nodal areas and simultaneous integrated boost of 60 Gy to the prostate in 20 fractions with CBCT-based imaging and volumetric arc therapy (VMAT). Patient data was obtained retrospectively; acute gastrointestinal (GI) and genitourinary (GU) toxicity was classified per Common Terminology Criteria for Adverse Events (CTCAE) v5.0 and obtained from clinical records. Quality of life was surveyed via phone call using the European Organization for Research and Treatment of Cancer (EORTC) questionnaire QLQ-PR25. 78 patients were treated between May and December 2021. 83.33% of patients had high-risk disease, 16.67% had intermediate-risk disease, and 34.62% patients had node-positive disease. Median follow-up was 10.6 months. No patients presented acute grade >3 GI toxicity, and one patient presented grade 3 GU toxicity. 25.64% patients presented acute G2 GI toxicity and 17.95% patients presented acute G2 GU toxicity. 60.26% of patients responded to the EORTC-PR25 questionnaire. Mean scores for symptom scales were 11.26, 4.96 and 9.57 for Urinary Symptoms, Bowel Symptoms and Hormonal Treatment-Related Symptoms; mean scores for Sexual Activity and Functioning were 19.86 and 31.08, respectively. Definitive hypofractionated pelvic radiation therapy has an acceptable acute toxicity and QoL profile in this series of patients, although longer follow-up is needed to properly evaluate short and long-term toxicity. Further follow-up and patient recruitment is ongoing.

MP77-15 INCREASED RISK OF BIOCHEMICAL RECURRENCE AFTER RADICAL PROSTATECTOMY IN THE ACTIVE SURVEILLANCE ERA

You have accessJournal of UrologyCME1 Apr 2023MP77-15 INCREASED RISK OF BIOCHEMICAL RECURRENCE AFTER RADICAL PROSTATECTOMY IN THE ACTIVE SURVEILLANCE ERA Sanjay Das, Michael Luu, Stephen Freedland, and Timothy Daskivich Sanjay DasSanjay Das More articles by this author , Michael LuuMichael Luu More articles by this author , Stephen FreedlandStephen Freedland More articles by this author , and Timothy DaskivichTimothy Daskivich More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003351.15AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: In the active surveillance (AS) era, radical prostatectomy (RP) has become more often used for intermediate- and high-risk disease and less for low-risk disease. AS/conservative management became the most common treatment for low-risk disease in the VA in 2010. However, the impact of this shift on risk of biochemical recurrence (BCR) after RP is unknown. We sought to determine how risk of BCR has changed before and after 2010 and to provide contemporary projections for BCR by tumor risk. METHODS: We sampled men who underwent RP for clinically localized disease between 2000 and 2017 from the VA SEARCH database. Kaplan Meier analysis was used to calculate incidence of BCR before and after 2010 overall and across tumor risk subgroups. Multivariable Cox proportional hazard regression analysis including an interaction term between epoch and tumor risk was used to compare risk of BCR before and after 2010 overall and across tumor risk subgroups. RESULTS: Of 5,648 patients, 3,276 (58%) underwent RP in 2010 or prior and 2,372 (42%) after 2010. Of those who underwent RP in 2010 or prior, 1,266 (39%), 503 (15%), 655 (20%), and 712 (22%) had low-, favorable intermediate-, unfavorable intermediate-, and high-risk disease, respectively, compared with 335 (14%), 488 (21%), 768 (32%), and 749 (32%) among those who underwent RP after 2010 (p<0.001). The 7-year risk of BCR in the post-2010 was 43%, compared with 33% in the pre-2010 era (HR 1.15, 95%CI 1.04–1.28). In a multivariable Cox model adjusting for tumor risk, there was a significant interaction between tumor risk and epoch in predicting BCR (p<0.001). Men with favorable intermediate risk (HR 0.71, 95%CI 0.53–0.96) and unfavorable intermediate risk disease (HR 0.74, 95%CI 0.61–0.90) had a lower risk of BCR in the post-2010 era. Men with high-risk disease (HR 1.24, 95%CI 1.06–1.45) had higher risk of BCR in the post-2010 (vs. pre-2010) era. The 5-year risk of BCR in the pre- vs. post-2010 eras were 17% vs. 15%, 23% vs. 20%, 40% vs. 33%, and 46% vs. 52% for low, favorable intermediate, unfavorable intermediate, and high-risk disease, respectively. CONCLUSIONS: Trends toward using RP for higher risk disease have increased the 7-year risk of BCR from 33% to 43% in the pre- vs. post-AS eras, primarily driven by increased risk of BCR in high-risk patients. Source of Funding: This research was supported by Cedars-Sinai Cancer at Cedars-Sinai Medical Center through the Biostatistics Core Voucher Program. Dr. Das was supported by the Patient Centered Outcomes in Urologic and Gynecologic Cancers (PCORT: UroGynCan) © 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 Sanjay Das More articles by this author Michael Luu More articles by this author Stephen Freedland More articles by this author Timothy Daskivich More articles by this author Expand All Advertisement PDF downloadLoading ...

MP38-01 PATIENT-LEVEL VALIDATION OF LIFE EXPECTANCY CUTOFFS FOR TRIAGE OF AGGRESSIVE TREATMENT BY TUMOR RISK USING TARGETED CROWDSOURCING

You have accessJournal of UrologyCME1 Apr 2023MP38-01 PATIENT-LEVEL VALIDATION OF LIFE EXPECTANCY CUTOFFS FOR TRIAGE OF AGGRESSIVE TREATMENT BY TUMOR RISK USING TARGETED CROWDSOURCING John M. Masterson, Michael Luu, Rebecca Gale, Brennan Spiegel, Stephen J. Freedland, and Timothy J. Daskivich John M. MastersonJohn M. Masterson More articles by this author , Michael LuuMichael Luu More articles by this author , Rebecca GaleRebecca Gale More articles by this author , Brennan SpiegelBrennan Spiegel More articles by this author , Stephen J. FreedlandStephen J. Freedland More articles by this author , and Timothy J. DaskivichTimothy J. Daskivich More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003276.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Life expectancy (LE) thresholds for triage of treatment vs conservative management (CM) in prostate cancer (PC) guidelines are based on expert opinion. However, patient opinion of when to defer treatment based on LE is lacking. We crowdsourced a conjoint analysis to define at which LE men are more likely to choose against treatment. METHODS: We used targeted crowdsourcing to query 2,046 men sociodemographically reflecting a US PC population based on SEER. We asked subjects to complete a conjoint analysis exercise in which they chose between treatment versus CM considering 4 tradeoffs: tumor risk, risk of erectile dysfunction, risk of urinary incontinence, risk of irritative urinary symptoms. Subjects were asked to consider LE throughout, which was calculated using the validated Prostate Cancer Comorbidity Index. Multinomial logistic regression defined the LE at which men were more likely to choose no treatment overall and in subgroups of tumor risk. RESULTS: We found an interaction between LE and treatment, indicating the odds of treatment vs CM choice is dependent on LE (p<0.001). The predicted probability of treatment decreased 15% with every 5 years of decreasing LE (OR 0.85, 95% CI .82-.89, p <0.001). Across all tumor risk levels, men were more likely to choose CM at a LE threshold <10 years (OR<1, p<0.05) (Figure 1). For low-, favorable intermediate-, unfavorable intermediate-, and high-risk cancers, men were more likely to choose CM at LE thresholds of <15, <10, <9, and <7 years, respectively. NCCN guidelines recommend CM overall at LE thresholds of £10 and <5–10 years for favorable and unfavorable intermediate-risk disease, and <5 years for high-risk disease (Figure 2). CONCLUSIONS: Patient preferences for LE cutoffs for when to consider CM align well with current guidelines recommendations, except for low-risk disease, for which patients are likely to consider conservative management even at LE <15 years, rather than <10. Guidelines should take patient preferences into account when recommending thresholds for CM. Source of Funding: none © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e523 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information John M. Masterson More articles by this author Michael Luu More articles by this author Rebecca Gale More articles by this author Brennan Spiegel More articles by this author Stephen J. Freedland More articles by this author Timothy J. Daskivich More articles by this author Expand All Advertisement PDF downloadLoading ...

A Contemporary Report of Low-Dose-Rate Brachytherapy for Prostate Cancer Using MRI for Risk Stratification: Disease Outcomes and Patient-Reported Quality of Life.

We examined a prospective consecutive cohort of low dose rate (LDR) brachytherapy for prostate cancer to evaluate the efficacy of monotherapy for unfavorable-intermediate risk (UIR) disease, and explore factors associated with toxicity and quality of life (QOL). 149 men with prostate cancer, including 114 staged with MRI, received Iodine-125 brachytherapy alone (144-145 Gy) or following external beam radiation therapy (110 Gy; EBRT). Patient-reported QOL was assessed by the Expanded Prostate Index Composite (EPIC) survey, and genitourinary (GU) and gastrointestinal (GI) toxicity were prospectively recorded (CTC v4.0). Global QOL scores were assessed for decline greater than the minimum clinically important difference (MCID). Univariate analysis (UVA) was performed, with 30-day post-implant dosimetry covariates stratified into quartiles. Median follow-up was 63 mo. Men with NCCN low (n = 42) or favorable-intermediate risk (n = 37) disease were treated with brachytherapy alone, while most with high-risk disease had combined EBRT (n = 17 of 18). Men with UIR disease (n = 52) were selected for monotherapy (n = 42) based on clinical factors and MRI findings. Freedom from biochemical failure-7 yr was 98%. Of 37 men with MRI treated with monotherapy for UIR disease, all 36 men without extraprostatic extension were controlled. Late Grade 2+/3+ toxicity occurred in 55/3% for GU and 8/2% for GI, respectively. Fifty men were sexually active at baseline and had 2 yr sexual data; 37 (74%) remained active at 2 yr. Global scores for urinary incontinence (UC), urinary irritation/obstruction (UIO), bowel function, and sexual function (SF) showed decreases greater than the MCID (p < 0.05) in UC at 2 mo, UIO at 2 and 6 mo, and SF at 2-24 mo, and >5 yr. Analysis did not reveal any significant associations with any examined rectal or urethral dosimetry for late toxicity or QOL. Disease outcomes and patient-reported QOL support LDR brachytherapy, including monotherapy for UIR disease.

Prognostic Value of the Intermediate-risk Feature in Men with Favorable Intermediate-risk Prostate Cancer: Implications for Active Surveillance

BackgroundGuidelines suggest that active surveillance (AS) may be considered for select patients with favorable intermediate-risk (fIR) prostate cancer. ObjectiveTo compare the outcomes between fIR prostate cancer patients included by Gleason score (GS) or prostate-specific antigen (PSA). Most patients are classified with fIR disease due to either a 3 + 4 = 7 GS (fIR-GS) or a PSA level of 10–20 ng/ml (fIR-PSA). Previous research suggests that inclusion by GS 7 may be associated with worse outcomes. Design, setting, and participantsWe conducted a retrospective cohort study of US veterans diagnosed with fIR prostate cancer from 2001 to 2015. Outcome measurements and statistical analysisWe compared the incidence of metastatic disease, prostate cancer–specific mortality (PCSM), all-cause mortality (ACM), and receipt of definitive treatment between fIR-PSA and fIR-GS patients managed with AS. Outcomes were compared with those of a previously published cohort of patients with unfavorable intermediate-risk disease using cumulative incidence function and Gray’s test for statistical significance. Results and limitationsThe cohort included 663 men; 404 had fIR-GS (61%) and 249 fIR-PSA (39%). There was no evidence of difference in the incidence of metastatic disease (8.6% vs 5.8%, p = 0.77), receipt of definitive treatment (77.6% vs 81.5%, p = 0.43), PCSM (5.7% vs 2.5%, p = 0.274), and ACM (16.8% vs 19.1%, p = 0.14) between the fIR-PSA and fIR-GS groups at 10 yr. On multivariate regression, unfavorable intermediate-risk disease was associated with higher rates of metastatic disease, PCSM, and ACM. Limitations included varying surveillance protocols. ConclusionsThere is no evidence of difference in oncological and survival outcomes between men with fIR-PSA and fIR-GS prostate cancer undergoing AS. Thus, presence of GS 7 disease alone should not exclude patients from consideration of AS. Shared decision-making should be utilized to optimize management for each patient. Patient summaryIn this report, we compared the outcomes of men with favorable intermediate-risk prostate cancer in the Veterans Health Administration. We found no significant difference between survival and oncological outcomes.

Multimodality Therapies for Localized Prostate Cancer.

Multimodality therapy including radical prostatectomy, radiation therapy, and hormone therapy are frequently deployed in the management of localized prostate cancer. We sought to perform a critical appraisal of the most contemporary literature focusing on the multimodality management of localized prostate cancer. Men who are ideal candidates for multimodality therapy include those with unfavorable intermediate-risk disease, high-risk disease, and very high-risk disease. Enhancements in both systemic agents (including second-generation antiandrogens) as well as localized therapies (such as stereotactic body radiotherapy and brachytherapy) are refining the optimal balance between the use of systemic and local therapies for localized prostate cancer. Genomic predictors are emerging as critical tools for more precisely allocating treatment intensification with multimodality therapies as well as treatment de-intensification. Close collaboration among medical oncologists, surgeons, and radiation oncologists will be critical for coordinating evidence-based multimodality therapies when clearly indicated and for supporting shared decision-making in areas where the evidence is mixed.

Friday, June 17, 20229:00 AM - 10:00 AM PP01 Presentation Time: 9:00 AM: Propensity-Matched Analysis of High-Dose-Rate Brachytherapy in Intermediate Risk Prostate Cancer: Monotherapy or Boost?

<h3>Purpose</h3> High-Dose-Rate Brachytherapy (HDR BT) either as monotherapy or boost has excellent reported prostate cancer control outcomes. Monotherapy is more commonly used for those with favorable risk features, while HDR tends to be combined with external beam radiotherapy (EBRT) for those with higher risk disease. Patients with intermediate risk prostate cancer (IR-PCa) can be managed either with monotherapy or boost. In the absence of randomized data, our objective is to compare biochemical response and oncological outcomes for patients with intermediate risk prostate cancer treated with either HDR as monotherapy or as a boost in combination with EBRT. <h3>Materials and Methods</h3> A propensity score matching analysis was performed of IR-PCa patients treated with either HDR monotherapy (27 Gy in 2 fractions), or HDR boost (15 Gy followed by EBRT; 37.5 Gy in 15 fractions delivered with Intensity modulated radiotherapy). The former patients were included in a prospective clinical trial whereas the latter were selected from a retrospective institutional database. Matching was based on age, baseline PSA, T stage, grade group, perineural invasion, and percentage of positive cores. No patient received androgen deprivation therapy. The primary outcome was biochemical disease-free survival (bDFS) defined as time from treatment to PSA nadir +2 or death. Secondary outcomes included PSA nadir and incidence of grade (G) ≥3 genitourinary (GU) and gastrointestinal (GI) toxicities measured using CTCAE v.4. A General Linear Mixed Model and Analysis of Covariance was used to investigate changes in PSA over time. <h3>Results</h3> A total of 132 patients were matched, 66 in each cohort with a median age of 66 years (range: 48-80). Median follow up was 59 months (interquartile range (IQR) 54, 62) for the HDR monotherapy cohort and 63 months (IQR 42, 81) for the boost BT group. They were well matched with a Propensity Score of 0.4615 and 0.4612, respectively. Thirty-eight percent of patients had unfavorable intermediate risk disease. Patients treated with monotherapy had slightly higher PSA in the first 4 years, Figure 1 (p=0.034), although by 5-years median PSA was 0.14 ng/ml (IQR 0.06, 0.34) with monotherapy and 0.15 ng/ml (IQR 0.07, 0.51) with boost. At 4 years, 24 (36%) monotherapy patients and 26 (44%) boost patients had PSA <0.2 ng/ml. Among all patients, 7% (10 of 132) experienced biochemical failure: six patients in the HDR monotherapy group and four in the boost group, resulting in 5-year bDFS of 93.5% and 93.3%, respectively. Favorable and Unfavorable IR-PCa had similar risk of recurrence. Late G3 GU toxicity occurred in 2 out of 66 boost patients and was not seen in the monotherapy patients. <h3>Conclusions</h3> Although limited by small sample size, we report high efficacy of HDR brachytherapy as either monotherapy or boost for all patients with intermediate risk disease. Boost patients had a lower PSA value in the first 4 years, although with a suggestion of greater G3 urinary toxicity.

PP06 Presentation Time: 9:50 AM: Biochemical Failure-Free Survival Rates After Brachytherapy with I-125, Pd-103, or Cs-131 for Intermediate-Risk Prostate Cancer: Phase II Trial

<h3>Background</h3> Iodine (I)-125 is traditionally used for low-dose-rate (LDR) brachytherapy for prostate cancer, but emerging data support the use of cesium (Cs)-131 or palladium (Pd)-103 as well. Although the safety and effectiveness of these three isotopes for intermediate risk prostate cancer have been established, the relative efficacy of each is unknown. <h3>Purpose</h3> To compare biochemical outcomes after I-125, Pd-103, or Cs-131 brachytherapy as definitive treatment for intermediate-risk prostate cancer. <h3>Materials and Methods</h3> This prospective phase II trial evaluated ultrasound-guided LDR brachytherapy monotherapy as definitive treatment for intermediate-risk prostate cancer at a single institution in 2006-2013. The choice of isotope and corresponding prescribed dose was made sequentially (starting with I-125, D=144 Gy; followed by Pd-103, D=125 Gy; then Cs-131, D=115 Gy. Patients had intermediate-risk disease (Gleason score [GS] 6 or 7 [3+4 or 4+3]), no evidence of nodal or metastatic disease, and no prior hormonal or radiation therapy. Follow-up visits were every 4 months for the first year after the implant, every 6 months for the next 5 years, and yearly thereafter, with prostate-specific antigen (PSA) levels measured at each visit. Biochemical failure (BCF) was defined per the Phoenix criteria as an increase in PSA value to nadir +2 ng/dL or radiologic or histologic evidence of recurrence with increasing PSA value. Patients were considered to have no evidence of disease (NED) if the PSA was <0.2 ng/dL at the specified time. Treatment efficacy was defined as time to BCF and the presence or absence of NED at a given time. Kaplan-Meier analysis was used to estimate BCF-free survival rates by isotope, with between-group differences assessed with log-rank tests. One-way analysis of variance was used to compare time to BCF between groups. Simple linear regression was used to determine the influence of isotope on achieving NED. <h3>Results</h3> Of the 300 patients in this trial (median age 64.9 years), 100 were treated with Cs-131, 98 with I-125, and 102 with Pd-103. Eleven patients (3.7%) had GS 6 disease, 236 (78.7%) had GS 7 (3+4) disease, and 53 (17.7%) had GS 7 (4+3) disease; 195 (65.0%) had favorable intermediate-risk, and 105 (35.0%) had unfavorable intermediate-risk disease. The median follow-up time was 8.7 years. During follow-up, 27 patients (9.0%) experienced BCF, 7 (7%) in the Cs-131 group, 13 (13.3%) in the I-125 group, and 7 (7.1%) in the Pd-103 group. Among those 27 patients with BCF, 10 (37.0%) received salvage therapy with surgery, brachytherapy, radiation therapy, or cryotherapy. The BCF-free survival rates were 93% for those treated with Cs-131, 86.7% for I-125, and 93.1% for Pd-103 (p=0.86) (Figure); the median time was not reached because of the short follow-up and the limited number of events. Follow-up data were available for 101 patients at 8.7 years; 100 patients (99%) had NED. Although 36 patients (12%) died during the study, only 1 death (0.3%) was related to prostate cancer. <h3>Conclusions</h3> No significant differences in efficacy were found among Cs-131, Pd-103, and I-125 for LDR brachytherapy monotherapy for intermediate-risk prostate cancer. The choice of isotope should be based on dosimetric advantages, estimated risk of toxicity, and quality-of-life profile. A larger randomized trial is needed to assess potential differences in efficacy among isotopes.

Short-term ADT and Dose-escalated IMRT in Patients With Intermediate-risk Prostate Cancer: Benefit or Caution?

In the era of dose-escalated prostate radiation therapy (RT), the use of androgen deprivation therapy (ADT) is undefined for intermediate-risk (IR) prostate cancer. There is growing concern of the risk of ADT to be detrimental to quality of life. This single-institution retrospective analysis aimed to evaluate outcomes of IR patients treated with dose-escalated intensity modulated radiation therapy (IMRT) with or without concurrent/adjuvant short-term ADT. Data was collected from 260 consecutive patients treated with dose-escalated IMRT with daily image-guided RT for newly diagnosed IR prostate cancer. Biochemical recurrence-free survival (BCRFS), distant metastasis-free survival, prostate cancer-specific survival, and overall survival (OS) were calculated using Kaplan-Meier methodology. Median follow-up was 93 months. A total of 181 patients had unfavorable IR disease, and 36.2% (N=94) received ADT, with median ADT duration of 6 months. Seven-year BCRFS was 94.1% vs. 86.2% (P=0.067), for ADT and no ADT, respectively, and no difference in distant metastasis-free survival or prostate cancer-specific survival was observed. ADT was associated with significantly worse 7-year OS (80.0% vs. 91.3%, P=0.010). Analysis of the unfavorable IR cohort alone, showed similar results; 7-year BCRFS and 7-year OS in patients who received ADT versus no ADT were 93.7% vs. 85.9% (P=0.093), and 79.0% vs. 90.6% (P=0.019), respectively. In our 15-year experience treating IR prostate cancer with dose-escalated IMRT with daily image-guided RT, short-term concurrent ADT was associated with a statistically significant worse OS. Additional studies are needed to determine if ADT is beneficial or detrimental for patients with IR prostate cancer treated with dose-escalated radiation.

Metastasis and Mortality in Men With Low- and Intermediate-Risk Prostate Cancer on Active Surveillance.

Active surveillance (AS) is a safe treatment option for men with low-risk, localized prostate cancer. However, the safety of AS for patients with intermediate-risk prostate cancer remains unclear. We identified men with NCCN-classified low-risk and favorable and unfavorable intermediate-risk prostate cancer diagnosed between 2001 and 2015 and initially managed with AS in the Veterans Health Administration. We analyzed progression to definitive treatment, metastasis, prostate cancer-specific mortality (PCSM), and all-cause mortality using cumulative incidences and multivariable competing-risks regression. The cohort included 9,733 men, of whom 1,007 (10.3%) had intermediate-risk disease (773 [76.8%] favorable, 234 [23.2%] unfavorable), followed for a median of 7.6 years. The 10-year cumulative incidence of metastasis was significantly higher for patients with favorable (9.6%; 95% CI, 7.1%-12.5%; P<.001) and unfavorable intermediate-risk disease (19.2%; 95% CI, 13.4%-25.9%; P<.001) than for those with low-risk disease (1.5%; 95% CI, 1.2%-1.9%). The 10-year cumulative incidence of PCSM was also significantly higher for patients with favorable (3.7%; 95% CI, 2.3%-5.7%; P<.001) and unfavorable intermediate-risk disease (11.8%; 95% CI, 6.8%-18.4%; P<.001) than for those with low-risk disease (1.1%; 95% CI, 0.8%-1.4%). In multivariable competing-risks regression, favorable and unfavorable intermediate-risk patients had significantly increased risks of metastasis and PCSM compared with low-risk patients (all P<.001). Compared with low-risk patients, those with favorable and unfavorable intermediate-risk prostate cancer managed with AS are at increased risk of metastasis and PCSM. AS may be an appropriate option for carefully selected patients with favorable intermediate-risk prostate cancer, though identification of appropriate candidates and AS protocols should be tested in future prospective studies.

Five- and seven-year outcomes for image-guided moderately accelerated hypofractionated proton therapy for prostate cancer

Background To report 5- and 7-year outcomes after image-guided moderately accelerated hypofractionated proton therapy (AHPT) for prostate cancer. Material and methods We reviewed the first 582 prostate cancer patients enrolled on prospective outcomes tracking trial and treated with double-scattered moderately AHPT between 2008 and 2015. 269 patients had low-risk (LR) and 313 had intermediate-risk (IR) disease, including 149 with favorable intermediate-risk (FIR) and 164 with unfavorable intermediate-risk (UIR) disease. LR patients received a median 70.0GyRBE (2.5GyRBE/fraction) and IR patients received a median of 72.5 GyRBE. Seventeen patients (UIR, n = 12) received androgen deprivation therapy (ADT) for a median of 6 months. Toxicities were graded per the CTCAE, v4.0, and patient-reported quality-of-life data were reviewed. Results Median follow-up was 8.0 years (0.9–12.2). The 5- and 7-year rates of freedom from biochemical progression (FFBP) overall and in the LR and IR subsets, respectively, were 96.8/95.2%, 98.8/98.8%, and 95.0/91.9%. For the FIR and UIR subsets, they were 97.2/95.2% and 93.1/88.8%. Actuarial 5- and 7-year rates of late CTCAE, v4.0, grade 2 gastrointestinal (GI), grade 3 GI, and grade 3 genitourinary (GU) toxicities were 9.9%/11.2%, 1.4/1.4% and 1.3/2.1%, respectively. No grade ≥4 GI or GU toxicities occurred. The mean (standard deviation, SD) IPSS and EPIC Composite bowel function and bother scores were 7 (SD = 5), 97 (SD = 7), and 94 (SD = 6), respectively at baseline, 7 (SD = 5), 92 (SD = 13), and 92 (SD = 9) at the 5-year follow-up, and 7 (SD = 5), 93 (SD = 12), and 92 (SD = 10) at the 7-year follow-up. Conclusion Image-guided AHPT 5- and 7-year outcomes show high efficacy, minimal physician-assessed toxicity, and excellent patient-reported outcomes in this cohort.

Assessing the Risk of Pathologic Lymph Node Involvement in Intermediate Risk Prostate Cancer

Most intermediate risk (IR) prostate cancer (PCa) patients are predicted to have low rates of pelvic lymph node (PLN) involvement. The standard of care for radiation therapy in IR disease includes radiation to the prostate only, with PLN irradiation typically reserved for high-risk disease. This treatment strategy represents a divergence from the surgical approach, wherein PLN dissections (PLND) are recommended by NCCN guidelines for men with 2% or higher risk of nodal metastasis-a threshold typically met by men with IR disease. We conducted an analysis of radical prostatectomy (RP) patients to assess the rates of pathologic nodal involvement in IR disease. We aimed to evaluate the correlation of the NCCN risk strata of favorable and unfavorable disease on nodal outcomes among IR men treated by radical prostatectomy (RP).This is a National Cancer Database (NCDB) analysis from 2004-2015 of IR PCa patients treated by RP. Baseline clinical and demographic data were collected, and men were stratified into favorable and unfavorable risk groups. Treatment information assessed included performance of PLND at the time of surgery, number of nodes dissected, and pathologic outcomes at RP. The primary outcome of interest was the rate of pathologic nodal involvement.A total of 295,819 patients were identified in NCDB with IR PCa who underwent RP. Using NCCN risk stratification criteria, 147,193 (49.8%) men were identified with favorable intermediate risk (FIR) disease and 148,626 (50.2%) with unfavorable intermediate risk (UIR) disease. 90,410 (61.4%) FIR patients underwent pelvic node dissection compared to 107,135 (72.1%) UIR patients. Of the 189,304 (64.0%) total men who underwent PLND, 1.9% had pathologically involved nodes, with a rate of 0.7% for FIR disease and 2.8% for UIR (P < 0.001). The median [IQR] number of nodes resected on pelvic node dissection was 3[2-4] and 5[3-7] for FIR and UIR, respectively (P < 0.0001). Initial PSA > 5, Gleason pattern 4 on biopsy, and UIR disease were associated with pathologic nodal involvement (P < 0.0001).NCCN-defined FIR and UIR strata are associated with risk of PLN disease. The low number of nodes assessed on PLND may have contributed to the low rates of pathologic nodal involvement in IR PCa patients seen in this large database analysis. Even so, the low rates of pathologic nodal disease in this IR cohort, especially in FIR patients, should be considered in conjunction with upcoming clinical trial data to inform the therapeutic approach to PLN management for all intermediate risk patients undergoing surgery or radiation.

4-Year PSA Response Rate as a Predictive Measure in Intermediate Risk Prostate Cancer Treated With Ablative Therapies: The Sprat Analysis

There is a lack of early predictive measures of outcome for patients with intermediate-risk prostate cancer (PCa) treated with stereotactic body radiotherapy (SBRT). We aim to explore 4-year PSA response rate (4yPSARR) as an early predictive measure.Individual patient data from 6 institutions for patients with intermediate-risk PCa treated with SBRT between 2006 and 2016 with a 4-year (42-54 months) PSA available were analyzed. Cumulative incidences of biochemical failure and metastasis were calculated using Nelson-Aalen estimates and overall survival was calculated using the Kaplan-Meier method. Biochemical failure-free survival was analyzed according to 4yPSARR with groups dichotomized based on PSA < 0.4 ng/mL or ≥ 0.4 ng/mL and compared using the log-rank test. Multivariable competing risk analysis was performed to predict for biochemical failure and development of metastasis.Six-hundred thirty-seven patients were included, including 424 (67%) with favorable and 213 (33%) with unfavorable intermediate-risk disease. Median follow-up was 6.2 years (IQR 4.9-7.9). The cumulative incidence of biochemical failure and metastasis, and overall survival at 6 years was 7%, 0.6% and 97%, respectively. The cumulative incidence of biochemical failure at 6 years if 4yPSARR < 0.4ng/mL was 1.7%, compared to 27% if 4yPSARR ≥ 0.4 ng/mL (P < 0.0001). On multivariable competing risk analysis, 4yPSARR was a statistically significant predictor of biochemical failure-free survival (sHR 15.3, 95% CI 7.5-31.3, P < 0.001) and metastasis-free survival (sHR 31.2, 95% CI 3.1-311.6, P = 0.003).4yPSARR is an encouraging early predictor of outcome in patients with intermediate-risk PCa treated with SBRT. Validation in prospective trials is warranted.

Early surrogate measures for ablative therapies for intermediate-risk prostate cancer patients.

241 Background: Stereotactic body radiotherapy (SBRT) is increasingly used to treat patients with intermediate-risk prostate cancer (IR-PCa), but there is a lack of early surrogate measures in this patient population treated with SBRT to guide clinicians and patients. We aim to explore the outcomes of IR-PCa patients treated with SBRT and to assess the role of PSA response at 4 years (4yPSARR) as an early surrogate measure given its encouraging results in patients treated with brachytherapy. Methods: Individual patient data from 6 institutions for 820 patients with IR-PCa treated with SBRT between 2006 and 2014 were analyzed. Cumulative incidence of biochemical recurrence (defined by Phoenix criteria) was calculated using Nelson-Aalen estimates, and metastases-free survival and overall survival were calculated using the Kaplan-Meier method. Biochemical recurrence-free survival was analyzed according to 4yPSARR with groups dichotomized based on PSA &lt; 0.4 ng/mL or &gt;0.4 ng/mL and compared using Log-rank test. Results: 820 patients were included, including 549 (67%) with favorable intermediate and 271 (33%) with unfavorable intermediate risk disease defined by NCCN risk group classification. Median age at time of treatment was 70 years. The most common dose, fractionation and treatment schedule was 36.25 Gy in 5 fractions prescribed to the planning target volume delivered every other day. Androgen deprivation therapy was used in combination with SBRT in 9.2% of patients for a median duration of 3 months. Median follow-up was 5.9 years. The cumulative incidence of biochemical recurrence was 7.9% at 5 years. Metastases-free survival and overall survival rates at 5 years were 99.4% and 94.6%, respectively. Median 4yPSARR (n = 504) was 0.2 ng/mL. Biochemical recurrence-free survival in patients with 4yPSARR &lt; 0.4 ng/mL (n = 387) was 99.2%, and in patients with 4yPSARR &gt;0.4 ng/mL (n = 117) was 81.5% at 5 years (p &lt; 0.0001). Conclusions: Prostate SBRT is an effective treatment modality in men with IR-PCa with at least comparable rates of biochemical failure and metastases compared to other standard treatment modalities in patients with IR-PCa. 4yPSARR may represent an early surrogate measure for use in this patient population treated with SBRT and should be included for further study in prospective SBRT trials.

Personalizing Localized Prostate Cancer: Validation of a Combined Clinical Cell-cycle Risk (CCR) Score Threshold for Prognosticating Benefit From Multimodality Therapy.

The combined clinical cell-cycle risk (CCR) score is a validated model that combines the cell-cycle progression (CCP) score with the University of California San Francisco Cancer of the Prostate Risk Assessment (CAPRA) score. This score determines the risk of progressive disease for men with prostate cancer. Here, we further validate the prognostic ability of the CCR score and evaluate its ability to help determine which patients may safely forgo multimodality therapy. We evaluated the CCR and a CCR-based multimodality threshold (2.112) in a retrospective, multi-institutional cohort of men with National Comprehensive Cancer Network intermediate- or high-risk localized disease (N= 718). These men received single or multimodality therapy (androgen deprivation with radiation [RT], or surgery with adjuvant RT or hormones). CCR score prognosticated metastasis for single-modality therapy, as a continuous variable (hazard ratio, 3.97; 95% confidence interval [CI], 2.61-6.06) and when dichotomized at the threshold (hazard ratio, 15.90; 95% CI, 5.43-46.52). The 10-year Kaplan-Meier risk for those receiving single-modality (RT or surgical) therapy with CCR scores below and above the threshold for single-modality treatment was 4.3% (95% CI, 1.0%-17.1%) and 20.4% (95% CI, 13.2%-30.7%), respectively. Using the threshold, 27% of men with newly diagnosed high-risk and 73% with unfavorable intermediate-risk disease could avoid multimodality therapy. Patients with CCR scores below the multimodality threshold (2.112) may safely forgo multimodality therapy. The CCR score can be used as a decision aid to counsel men whether or not single-modality therapy would be sufficient for their intermediate- or high-risk prostate cancer.

Decision support for men with prostate cancer: Concordance between treatment choice and tumor risk.

Decision support tools improve decisional conflict and elicit patient preferences related to prostate cancer treatment. It was hypothesized that men using the Personal Patient Profile-Prostate (P3P) would be more likely to pursue guideline-concordant treatment. Men from a trial assessing the P3P decision support intervention were identified. The primary exposure was allocation to P3P (vs usual care), and the outcome was appropriate treatment per guidelines (eg, low risk = active surveillance). It was assessed whether providers recommended against any treatment options (ie, restricted). A multivariable model was fit for men with low-risk cancer that estimated the odds of the outcome of interest. This study identified 295 men in the cohort: 113 (38%) had low-risk disease, 119 (40%) had favorable intermediate-risk disease, and 63 (21%) had unfavorable intermediate-risk disease. Among low-risk patients, more men pursued active surveillance after using P3P whether they were given unrestricted (62% vs 54% with usual care; P = .54) or restricted options (71% vs 59% with usual care; P = .34). After adjustments, only Black race (odds ratio [OR], 0.31; 95% CI, 0.11-0.89) and restricted options (OR, 0.23; 95% CI, 0.08-0.65) had an inverse association with the receipt of surveillance for patients with low-risk prostate cancer. An impact associated with P3P versus usual care (OR, 0.89; 95% CI, 0.36-2.20) was not observed. Among men in a trial assessing a decision support tool, Black race and restricted treatment options were associated with less use of active surveillance for low-risk prostate cancer. Although the P3P instrument ameliorates decisional conflict, its use was not associated with more appropriate alignment of treatment with disease risk.