Biochemical Failure-free Survival Research Articles

Prognostic impact of prostate-specific membrane antigen positron emission tomography (PSMA PET) staging for clinically node-positive prostate cancer.

In the current American Joint Committee on Cancer staging system, patients with pelvic nodal metastases are considered stage IV prostate cancer. This study aims to investigate whether men with prostate-specific membrane antigen positron emission tomography (PSMA PET)-detected pelvic node-positive prostate cancer at diagnosis have a better outcome compared to men with node-positive disease identified on conventional imaging. This is a retrospective cohort study comparing the outcomes of men with node-positive prostate cancer and disease confined to the pelvis, staged with conventional versus PSMA PET imaging. Men had to be treated definitively with a combination of androgen deprivation therapy and radiation treatment to the prostate and pelvic lymph nodes. Kaplan-Meier and Cox regression analysis was used to compare biochemical failure-free survival (BFFS) and overall survival (OS). Seventy-six men with nodal metastases confined to the pelvis were identified. Fifty-one were detected with PSMA PET while 25 were staged with conventional imaging. PSMA PET staged patients had a lower proportion of Gleason 8-10 disease (78% vs. 96%) as well as a lower median prostate-specific antigen (11 ng/mL vs. 26 ng/mL). BFFS at 4 years was 72% with PSMA PET-detected node-positive disease vs. 38% with conventionally detected node-positive disease. Four-year OS was 93% with PSMA PET staged patients vs. 76% with conventionally staged patients. On multivariate analysis, the PSMA PET staged group was associated with improved BFFS (Adjusted HR = 3.00, 95% CI 1.43, 6.29, P = 0.004) and OS (Adjusted HR = 5.81, 95% CI 1.43, 23.7, P = 0.007). Men with PSMA PET-detected node-positive prostate cancer confined to the pelvis have significantly better biochemical control and survival compared to those with node-positive pelvic disease identified through conventional staging.

The influence of Gleason score ≤ 6 histology on the outcome of high-risk localized prostate cancer after modern radiotherapy

We aimed to retrospectively review outcomes in patients with high-risk prostate cancer and a Gleason score ≤ 6 following modern radiotherapy. We analyzed the outcomes of 1374 patients who had undergone modern radiotherapy, comprising a high-risk low grade [HRLG] group (Gleason score ≤ 6; n = 94) and a high-risk high grade [HRHG] group (Gleason score ≥ 7, n = 1125). We included 955 patients who received brachytherapy with or without external beam radio-therapy (EBRT) and 264 who received modern EBRT (intensity-modulated radiotherapy [IMRT] or stereotactic body radiotherapy [SBRT]). At a median follow-up of 60 (2–177) months, actuarial 5-year biochemical failure-free survival rates were 97.8 and 91.8% (p = 0.017), respectively. The frequency of clinical failure in the HRLG group was less than that in the HRHG group (0% vs 5.4%, p = 0.012). The HRLG group had a better 5-year distant metastasis-free survival than the HRHG group (100% vs 96.0%, p = 0.035). As the HRLG group exhibited no clinical failure and better outcomes than the HRHG group, the HRLG group might potentially be classified as a lower-risk group.

Revolutionizing localized prostate cancer treatment: Stereotactic radiotherapy "Moroccan experience".

Prostate cancer is the most common urological cancer, and its incidence is increasing. Radical prostatectomy and radiotherapy are theprimary treatments for localized forms. Stereotactic Body RadioTherapy (SBRT), a new and innovative therapy, has been validated for some cancer localizations but not yet for localized prostate cancer. Our study aims to report the efficacy and tolerance results of SBRT for localized prostate cancer. This is a retrospective study of 27 patients with localized prostate cancer (CaP) who were treated with SBRT in our department from 2017 to 2021 using transponders for tumor tracking. The dose was 36.25 Gy delivered in five fractions of 7.25 Gy. The delineation and doses of organs at risk were determined based on the recommendations of the SFRO and the TG101 report of medical physics. All patients were treated using a latest-generation linear accelerator (True Beam STXÒ). Acute toxicities were observed in 33.3% of cases, with 22.2% grade 1 or 2 genitourinary (GU) and no grade 3 while 11.1% gastrointestinal (GI) toxicities were reported as grade 1-2 (7.4%) and one case grade 3 (3.7%). Late grade 1 or 2 GU toxicity was observed in 14.84% of cases, with no reports of late GI toxicity. After a 26-month follow-up period, the biochemical failure-free survival rate was 92.6%. The results of our study are consistent with the existing literature and support the safety and effectiveness of SBRT as a treatment option for localized prostate cancer (CaP). In the United States, both ASTRO and the NCCN recognize SBRT as a valid treatment option for localized CaP. Ongoing phase III trials are being conducted to further substantiate these long-term results and to establish SBRT as the future standard of care for localized CaP.

Long-Term Outcomes Following Fairly Brief Androgen Suppression and Stereotactic Radiation Therapy in High-Risk Prostate Cancer: Update From the FASTR/FASTR-2 Trials

There is limited data on the long-term outcomes of ultrahypofractionated radiation therapy in high-risk prostate cancer. The FASTR and FASTR-2 trials were designed to assess the tolerability of stereotactic ablative radiation therapy (SABR) in this context. Herein, the long-term results are reported. Eligible patients had localized high-risk prostate cancer and were either ≥70 years old, had a score of ≥3 on the Vulnerable Elderly Scale, or declined standard therapy. Nineteen patients from a single institution were enrolled on FASTR between 2011 and 2015. They received 40 Gy to the prostate and 25 Gy to the pelvic lymph nodes in 5 weekly fractions, with 12 months of androgen deprivation therapy (ADT). Thirty patients from the same institution were enrolled on FASTR-2 between 2015 and 2017. They received 35 Gy to the prostate alone in 5 weekly fractions, with 18 months of ADT. Updated toxicity and outcomes were assessed retrospectively. Kaplan-Meier estimates were calculated for biochemical failure-free survival, freedom from distant metastases, prostate cancer-specific survival, and overall survival. Forty-four patients were eligible for analysis, 16 from FASTR and 28 from FASTR-2. Thirty-four patients (77%) were >70 years old. High-risk features included Gleason score ≥8 (n=20, 46%), T3-T4 disease (n=12, 27%), and baseline prostate-specific antigen > 20 (n=22, 50%). Median follow-up was 6.4 years. The 5-year cumulative incidence of late grade ≥3 genitourinary/gastrointestinal toxicity was 32% in FASTR and 11% in FASTR-2. At 5 years, the combined rates of biochemical failure-free survival, freedom from distant metastases, prostate cancer-specific survival, and overall survival were 72%, 90%, 92%, and 83%, respectively. SABR can be safely delivered in high-risk prostate cancer by optimizing technical delivery, particularly with adherence to strict dose constraints for organs at risk. The clinical outcomes in FASTR and FASTR-2 were largely comparable to more standard fractionation schemes plus ADT, but further modifications may improve disease control. Larger randomized trials are necessary to better understand the efficacy and tolerability of this approach.

Long-Term Outcomes Following Fairly Brief Androgen Suppression and Stereotactic Radiation Therapy in High-Risk Prostate Cancer: Update from the FASTR/FASTR-2 Trials.

There has been emerging interest in the role of ultra-hypofractionated radiotherapy for high-risk prostate cancer, especially given its low α/β ratio. However, there is limited data on the long-term outcomes of this treatment strategy. The FASTR and FASTR-2 clinical trials were designed to assess the tolerability of stereotactic ablative body radiotherapy (SABR) in high-risk prostate cancer. FASTR was discontinued early due to unacceptable acute toxicity, whereas the acute toxicities in FASTR-2 were minimal. Herein, the long-term results from these trials are reported. Eligible patients had at least 1 high-risk feature as per the National Comprehensive Cancer Network criteria for high-risk prostate cancer, no evidence of metastatic disease, and either a score of 3+ on the Vulnerable Elderly Scale or declined standard therapy. A total of 19 patients from a single institution were enrolled on FASTR between 2011 and 2015. They received 40 Gy to the prostate and 25 Gy to the pelvic lymph nodes in 5 fractions delivered once weekly for 5 weeks, along with 1 year of androgen deprivation therapy (ADT). The excessive acute toxicity in FASTR prompted several modifications in FASTR-2, including the omission of nodal irradiation. A total of 30 patients from the same institution were enrolled on FASTR-2 between 2015 and 2017. They received 35 Gy to the prostate alone in 5 fractions delivered once weekly for 5 weeks, along with 18 months of ADT. A total of 44 patients were eligible for analysis, 16 from FASTR and 28 from FASTR-2. Most patients were >70 years old (77%). High-risk features included Gleason score ≥8 (46%), T3-T4 disease (27%) and baseline PSA >20 (50%). With a median follow-up of 6.4 years, the cumulative incidence of grade ≥3 genitourinary/gastrointestinal toxicity was 50% among FASTR patients and 7% among FASTR-2 patients. At 5 years, the combined rates of biochemical failure-free survival, freedom from distant metastases, prostate cancer-specific survival and overall survival were 72%, 90%, 92% and 83%, respectively. A total of 12 patients (27%) required further treatment. No significant differences in clinical outcomes were noted between the FASTR and FASTR-2 cohorts. SABR for high-risk prostate cancer is an attractive option for reducing treatment burden. Clinical outcomes and toxicity with the FASTR-2 protocol were comparable to conventionally-fractionated radiotherapy plus ADT. Larger prospective, randomized trials exploring the role of SABR with ADT in high-risk disease are necessary to better understand the efficacy and tolerability of this approach.

Prospective Characterization of Circulating Tumor Cells in Hormone Sensitive Oligometastatic Prostate Cancer Patients on a Metastasis-Directed Therapy Trial

Prospective data have shown that metastasis-directed therapy (MDT) can alter the natural history of oligometastatic disease. In hormone-sensitive prostate cancer (HSPC), the clinical effect of MDT has been validated by STOMP, ORIOLE and SABR-COMET phase II trials. Circulating tumor cells (CTCs) are likely the source for the formation of macroscopic metastases. CTCs may provide an approach for identifying subgroups of patients with oligometastatic HSPC (oligoHSPC) that would benefit most from MDT. Our main goal was to evaluate the feasibility of CTC detection and subtypes in oligoHSPC patients that may benefit from MDT. ORIOLE randomized men with recurrent HSPC with 1-3 metastases to observation (Obs) vs. stereotactic ablative radiotherapy (SABR) MDT. Blood samples were prospectively collected at baseline (D0) and 6-mos (D180) and shipped for analysis on Epic Sciences liquid biopsy platform (Epic Sciences, San Diego, CA). Machine learning algorithms identified CTCs and characterized androgen receptor (AR) and PSMA expression. Association with clinical factors and outcomes were examined. Biochemical failure-free survival (BFFS) event was a PSA rise of at least 2 ng/mL and 25% above nadir. Progression-free survival (PFS) was a composite endpoint including BFFS event, radiologic progression (RECIST v1.1); symptomatic progression; initiation of ADT; or death. Comparisons of patient and tumor characteristics performed by two-sample t-tests. Survival curves were generated by the Kaplan-Meier method and evaluated by the log-rank test. Effect of SABR on post-SABR on CTC levels were calculated by McNemar test. A total of 82 samples were collected in ORIOLE: 70 SABR (35 D0 and 35 D180) and 12 Obs (7 D0 and 5 D180). 30/42 men had CTCs detected on D0 (71%; AR+ = 7, PSMA+ = 13) and in 26/40 on D180 (65%; AR+ = 9, PSMA+ = 8). Median follow-up was 41.7-mos. There was no association between CTC presence or subtypes (AR+ or PSMA+) with Gleason score or PSA. PFS was significantly lower in the patients with AR+ vs. AR- CTCs on D0 in the SABR arm (p = 0.011, median PFS: AR+ = 9.3- vs. AR+ = 27.1-mos). The median BFFS trended towards a difference for AR+ = 12.9- vs. AR- = 29.2-mos (D180, p = 0.058). SABR had no effect on the presence or subtypes of CTC at D180. Baseline and dynamic CTC levels and their subtypes in oligoHSPC from the ORIOLE randomized trial of MDT was examined. AR+ CTCs at baseline and 6-mos were correlated with clinical outcomes following SABR. Longer follow-up, further analysis and a greater number of patients are needed for a more comprehensive conclusion.

Late Urinary Toxicity and QoL with Curative Radiotherapy for High-Risk Prostate Cancer: Dose-Effect Relations in the POP-RT Randomized Phase III Trial

Whole pelvic radiotherapy (WPRT) showed better biochemical failure-free survival and metastasis-free survival than prostate-only radiotherapy (PORT) in the phase III randomized POP-RT trial for high and very high-risk prostate cancer, albeit with higher RTOG grade 2 late urinary toxicity. We report updated long term, symptom-wise comparison and dose-effect relations from this trial. Late urinary toxicity, and cumulative severity of each symptom over the follow-up period was graded using CTCAE v5.0. Grade 2+ toxicities were compared between the trial arms by chi square test. Bladder dosimetry in 5-Gy increments (V5, V10, V15...V65 Gy, V68 Gy) from the trial database of approved radiotherapy plans, was compared for each urinary symptom and overall late gr2+ toxicity by student t-test. Observed differences in dosimetric parameters were tested using multivariable logistic regression analysis, including age at diagnosis, known diabetes, tumor stage, trial arm, and prior transurethral resection of prostate (TURP). Urinary QOL scores were compared between arms using generalised linear mixed model. Combined late symptom-wise toxicity and dose-volume data were available for analysis for 193/224 patients. At a median follow-up of 75 months, cumulative CTCAE gr2+ late urinary toxicity remained higher with WPRT than PORT, though not statistically significant (36.5% vs 26.8%, p = 0.15). Grade 3 toxicity was low and similar in both arms. Symptom-wise cumulative rates showed no significant difference between arms (Table 1). Dosimetric comparison showed significantly higher bladder V5-V15 in patients with gr2+ toxicity over those with <gr2 urinary toxicity. On symptom-wise analysis, V5-V40 range was significantly higher for presence of dysuria, hematuria, and urgency. No significant differences were observed over higher dose range for any urinary symptom. On multivariable analysis, no significant association was identifiable between bladder dosimetry and urinary symptoms. Urinary QOL scores was similar between both the arms for all the symptoms. Compared to prostate-only radiotherapy, whole pelvic radiotherapy resulted similar Grade 3 urinary toxicity of about 5% with about 10% higher cumulative grade 2+ urinary toxicity over long term follow up. This difference was not reflected in patient-reported QOL. WPRT particularly increased urgency and hematuria. Larger bladder volume being irradiated with 5Gy to 15Gy dose range could contribute to increase in urinary symptoms.

Long-term outcomes of whole-pelvis radiation therapy using volumetric modulated arc therapy for high-risk prostate cancer†.

This study investigated the outcomes of whole-pelvis radiation therapy (WPRT) using volumetric modulated arc therapy (VMAT) for high-risk prostate cancer. We retrospectively analysed 112 patients with high-risk prostate cancer who started WPRT at our hospital between August 2011 and August 2015. The prescribed dose was 78Gy in 39 fractions to the prostate and 46.8Gy in 26 fractions to the pelvic lymph node (LN) area. All patients received long-term androgen deprivation therapy. We evaluated late gastrointestinal (GI) and genitourinary (GU) toxicities using the Common Terminology Criteria for Adverse Events version 4.0. The median follow-up period for censored cases was 97 (interquartile range [IQR] = 85-108) months. The median age was 72 (IQR = 67-75) years. The high-risk and very-high-risk groups included 41 (36.6%) and 71 patients (63.4%), respectively. The median risk of LN invasion calculated by the Roach formula was 36.9 (IQR = 26.6-56.3) %. The 8-year overall survival, biochemical failure-free survival, disease-free survival and distant metastasis-free survival rates were 88.4, 91.9, 83.8 and 98.0%, respectively. Only one patient experienced common iliac LN recurrence, which was outside the pelvic irradiation area. All patients with recurrent disease were categorized into the very-high-risk group. The 8-year cumulative rates of ≥Grade 2 late GI and GU toxicities were 12.8 and 11.8%, respectively. No patients experienced Grade 4 or higher toxicities. WPRT using VMAT for high-risk prostate cancer was well tolerated and effective.

Long-term outcomes of SBRT for PSMA PET detected oligometastatic prostate cancer

BackgroundOligometastatic disease in prostate cancer (PCa) is a challenging clinical scenario encountered more frequently with the widespread adoption of PSMA-PET. SBRT aims to defer androgen deprivation and may deliver sustained biochemical failure (BF) free survival in selected patients. Little long-term data is currently available regarding the effectiveness of this approach.MethodsA retrospective single institution study of PSMA-PET directed SBRT without initial ADT for oligo-metachronous PCa. Median dose/fractionation was 24 Gy in 2# to bones and 30 Gy in 3# to lymph nodes. The primary endpoint was time to BF (PSA + 0.2 ug/L above nadir). Secondary endpoints included time to ADT for relapse (i.e. palliative ADT), BF defined as PSA nadir + 2 ug/L, toxicity, patterns of failure and survival. Patients were excluded if they received ADT with their SBRT, had short disease-free interval, or > 3 metastases on PSMA-PET.Results103 patients treated from November-2014 to December-2019 were analysed from our prospective database. Median follow-up was 5 years. 64 patients were treated for nodal only disease, 35 bone only and 4 mixed. 15% were free of any BF at 5 years with median time to BF of 1.1 years. 32% (33/103) of patients had further curative-intent radiation treatment following their first BF after SBRT, including subsequent SBRT. Eight patients underwent potentially curative treatment for their second or third relapse. Allowing for salvage treatment, 29/103 (28%) were biochemically disease free at last follow up. At 5 years, 39% of patients had never received any ADT and 55% had not started ADT for relapse with a median time to ADT for relapse of 5.5 years. There were 2 grade 3 toxicities (rib fracture and lymphoedema), and no local failures.ConclusionPSMA-PET guided SBRT for oligo-metachronous PCa recurrence in appropriately triaged patients results in excellent local control, low toxicity and over 50% ADT free at 5 years.

Prognostic value of E‑26 transformation‑specific‑related gene in prostate cancer based on immunohistochemistry analysis.

E-26 transformation-specific-related gene (ERG) has been implicated in prostate cancer; however, its prognostic role remains unclear. Therefore, the present study aimed to investigate the association of ERG with the prognosis after radical prostatectomy in patients with prostate cancer. Patient data were collected at the Huadong Hospital, affiliated with Fudan University, between January 2016 and March 2020. ERG protein expression was detected using immunohistochemistry. Independent-sample t-tests and χ2 tests were used to evaluate prostate cancer prognosis depending on ERG levels. The Kaplan-Meier method was used to estimate biochemical failure-free survival (BFFS) and the log-rank test was used to test the distribution. Prognostic factors were determined using Cox regression analysis. The median patient age was 69 years (range, 47-82 years). The median prostate-specific antigen (PSA) and free-PSA levels before treatment were 9.58 ng/ml (range, 0.003-187.400 ng/ml) and 1.13 ng/ml (range, 0.0059-30.6100 ng/ml), respectively. ERG protein expression was positive in 43 (16.6%) and negative in 216 (83.4%) cases. The median follow-up period and BFFS were 30 and 28 months, respectively. There was a significant difference in biochemical recurrence (P=0.017) between patients with positive and negative ERG expression. Patients with positive ERG expression had significantly worse BFFS curves compared with those with negative ERG expression (P=0.0038). In the multivariate Cox regression analysis, positive ERG expression was found to be an independent prognostic factor in patients with prostate cancer who underwent radical prostatectomy (hazard ratio, 4.08; 95% confidence interval, 2.03-8.17; P=0.000074). In conclusion, positive ERG expression is an independent prognostic risk factor for prostate cancer. These findings may be valuable for improvements in the clinical application of ERG immunohistochemistry.

Case-Matched Outcomes of Proton Beam and Intensity-Modulated Radiation Therapy for Localized Prostate Cancer.

Although both intensity-modulated radiation therapy (IMRT) and proton beam therapy (PBT) offer effective long-term disease control for localized prostate cancer (PCa), there are limited data directly comparing the 2 modalities. The data from 334 patients treated with conventionally fractionated (79.2 GyRBE in 44 fractions) PBT or IMRT were retrospectively analyzed. Propensity score matching was used to balance factors associated with biochemical failure-free survival (BFFS). Age, race, and comorbidities (not BFFS associates) remained imbalanced after matching. Univariable and covariate-adjusted multivariable (MVA) Cox regression models were used to determine if modality affected BFFS. Of 334 patients, 176 (52.7%) were included in the matched cohort with exact matching to National Comprehensive Cancer Network (NCCN) risk group. With a median follow-up time of 9.0 years (interquartile range [IQR]: 7.8-10.2 years), long-term BFFS was similar between the IMRT and PBT matched arms with 8-year estimates of 85% (95% CI: 76%-91%) and 91% (95% CI: 82%-96%, P = .39), respectively. On MVA, modality was not significantly associated with BFFS in both the unmatched (hazard ratio [HR] = 0.75, 95% CI: 0.35-1.63, P = .47) and matched (HR = 0.87, 95% CI: 0.33-2.33, P = .78) cohorts. Prostate cancer-specific survival (PCSS) and overall survival (OS) were also similar (P > .05). However, in an unmatched analysis, the PBT arm had significantly fewer incidences of secondary cancers within the irradiated field (0.6%, 95% CI: 0.0%-3.1% versus 4.5%, 95% CI: 1.8%-9.0%, P = .028). Both PBT and IMRT offer excellent long-term disease control for PCa, with no significant differences between the 2 modalities in BFFS, PCSS, and OS in matched patients. In the unmatched cohort, fewer incidences of secondary malignancy were noted in the PBT group; however, owing to overall low incidence of secondary cancer and imbalanced patient characteristics between the 2 groups, these data are strictly hypothesis generating and require further investigation.

Meta-Analysis of Candidate Surrogate End Points in Advanced Prostate Cancer

BackgroundThe Intermediate Clinical Endpoints in Cancer of the Prostate (ICECaP) working group identified metastasis-free survival as a valid surrogate end point for overall survival (OS) for patients with localized prostate cancer. No comparably validated surrogate end points exist in advanced prostate cancer.MethodsWe searched for trials in advanced prostate cancer, defined as node-positive, metastatic castration-sensitive, nonmetastatic, or metastatic castration-resistant prostate cancer. Eligible randomized trials reported OS and one or more intermediate clinical end points, including biochemical failure (BF), clinical failure, biochemical failure–free survival (BFS), progression-free survival (PFS), and radiographic PFS. Candidacy for surrogacy was assessed by using the second condition of the meta-analytic approach; R2 was weighted by the inverse variance of the log intermediate clinical end point hazard ratio and defined as R2>0.70.ResultsA total of 143 randomized trials (n=75,601 patients) were included. No candidate end points met the criteria for surrogacy (R2 BF [n=28,922], 0.42 [95% confidence interval (CI), 0.18 to 0.64]; BFS [n=25,741], 0.57 [95% CI, 0.37 to 0.73]; clinical failure [n=22,616], 0.31 [95% CI, 0.075 to 0.56]; PFS [n=52,639], 0.50 [95% CI, 0.35 to 0.63]; and radiographic PFS [n=52,548], 0.50 [95% CI, 0.35 to 0.63]). Within preplanned subgroups according to castration-sensitive or castration-resistant disease or according to treatment type, neither BFS nor PFS consistently met criteria for surrogacy. Sensitivity analyses showed that candidacy for surrogacy of all end points tested did not change over time.ConclusionsOur aggregate screening method for surrogate end points in advanced prostate cancer showed that commonly used clinical end points are not clear valid surrogate end points for OS. (Funded by the Prostate Cancer Foundation and the National Cancer Institute.)

Do Dosiomic Features Extracted From Planned 3-Dimensional Dose Distribution Improve Biochemical Failure-Free Survival Prediction: an Analysis Based on a Large Multi-Institutional Data Set

The objective of this work was to investigate whether including additional dosiomic features can improve biochemical failure-free survival prediction compared with models with clinical features only or with clinical features as well as equivalent uniform dose and tumor control probability. This retrospective study included 1852 patients who received diagnoses of localized prostate cancer between 2010 and 2016 and were treated with curative external beam radiation therapy in Albert, Canada. A total of 1562 patients from 2 centers were used for developing 3 random survival forest models: Model A included only 5 clinical features; Model B included 5 clinical features, equivalent uniform dose, and tumor control probability; and Model C considered 5 clinical features and 2074 dosiomic features derived from the planned dose distribution of the clinical target volume and planning target volume with further feature selection to determine prognostic features. No feature selection was performed for models A and B. Two hundred ninety patients from another 2 centers were used for independent validation. Individual model-based risk stratification was examined, and the log-rank tests were performed to test statistically significant differences between the risk groups. The 3 models' performances were evaluated using Harrell's concordance index (C-index) and compared using one-way repeated-measures analysis of variance with post hoc paired t test. Model C selected 6 dosiomic features and 4 clinical features to be prognostic. There were statistically significant differences between the 4 risk groups for both training and validation data sets. The C-index for the out-of-bag samples of the training data set was 0.650, 0.648, and 0.669 for models A, B, and C, respectively. The C-index for the validation data set for models A, B, and C was 0.653, 0.648, and 0.662, respectively. Although gains were modest, Model C was statistically significantly better than models A and B. Dosiomics contain information beyond common dose-volume histogram metrics from planned dose distributions. Incorporation of prognostic dosiomic features in biochemical failure-free survival outcome models can lead to statistically significant although modest improvement in performance.

Simultaneous integrated boost (SIB) stereotactic body radiotherapy (SBRT) for prostate and pelvic nodes in high risk, node positive and oligometastatic prostate cancers: Safety, efficacy and quality of life outcome measures.

121 Background: SBRT in high risk (HR), node positive (N+) and oligometastatic (OM) prostate cancers is limited by pelvic nodal coverage, larger treatment volumes and use of hormone therapy. We report the safety, efficacy and patient reported quality of life measures (QOL) for SIB-SBRT for prostate and pelvic nodal treatment in HR, N+ and OM (non-regional node or skeletal deposits) cohorts. Methods: 22 patients of NCCN category HR, N+, OM adenocarcinoma prostate and all staged by MRI prostate and PSMA PETCT scan received SIB-SBRT from April 2019 to October 2021. All received long term androgen (ADT) deprivation therapy (80%) or surgical castration (20%). ADT was neo-adjuvant, concomitant and adjuvant for at least 2 years and for OM 2nd generation hormone treatment. SIB-SBRT to prostate and pelvic nodal regions (until common iliac level) was 35-36.25 Gy and 25 Gy in 5 fractions respectively. Post ADT gross PSMA avid nodes and skeletal deposits received 30 Gy in 5 fractions. SIB-SBRT was by volumetric modulated arc therapy (VMAT) with intrafraction imaging and hexapod robotic couch corrections on alternate days. Baseline IPSS and Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP) QOL recorded and then post SIB-SBRT at 6 weeks and then 3 monthly till 2 years. Dosimetry followed standard published literature. Results: 22 patients were treated over 3 years with median age of 70 years. The median PSA at baseline was 45ng/ml with 90% Gleason score 8+. The OM disease included nonregional nodes or 1-2 skeletal deposits. After median follow up of 20 months acute grade 2 genitourinary (GU) and gastrointestinal (GI) toxicities were 10% and 12%, respectively. Late grade 2 GU and GI toxicities were 4% and 9%, respectively. Late grade 3 GU and GI toxicity was seen in 2 patients each requiring medical management. 2- year overall survival and biochemical failure-free survival was 95% and 90% respectively. Baseline median IPSS score was 9 and median EPIC CP score was 12/60. Mean urinary incontinence domain scores worsened significantly from baseline to 6 months and obstructive scores improved from baseline to 6 months with more than 95% patients not using any pads at 6 months. Bowel frequency scores were maximum at 6 weeks post SBRT and it persisted till 6 months. Sexual function scores declined gradually and recovered only in a few at last follow up. Vitality/hormonal scores were unchanged from baseline till 6 months. Conclusions: SIB-SBRT for HR, N+ and OM prostate cancers is safe and effective, with good QOL. The encouraging PSA control and minimal grade 3 toxicity and favorable therapeutic ratio achieved reflect the feasibility of LINAC based SIB-SBRT. This warrants long term follow-up with effective bladder/rectal protocol measures and optimal use of ADT in a prospective setting.

Biochemical disease control outcomes of stereotactic body radiation therapy (SBRT) or moderate hypo-fractionation (HFRT) for low- and intermediate-risk prostate cancer (PrCa): Retrospective analysis of 12 years of experience at two Canadian cancer centers.

363 Background: SBRT uses highly conformal radiotherapy to deliver high dose per fraction treatment. Advantages of SBRT include short treatment times, decreased costs and limited toxicity. Randomized trial outcomes of 7-fraction SBRT for low or intermediate PrCa were reported but results of studies that compared 5-fraction SBRT with conventional and HFRT are pending. Here, we reviewed the 12-year experience with SBRT and HFRT at the Juravinski and Walker Family Cancer Centers in Ontario. Methods: We reviewed patients with low or intermittent-risk PrCa treated with SBRT alone or HFRT alone in the period of July 2010 and February 2022. Database search criteria included treatments with SBRT 35-40Gy in 5 fractions and HFRT 60-62Gy in 20 fractions. Overall survival (OS), time to biochemical failure (per Phoenix criteria: i.e., 2ng/mL above PSA nadir) and biochemical failure-free survival (bFFS) were reviewed. Kaplan-Meier curves were used to assess OS and bFFS. Results: We identified 314 patients with low or intermediate-risk PrCa who were treated with SBRT and 258 patients who were treated with HFRT. Intermediate-risk category composed 86.0% and 95.7% of the SBRT and HFRT cohorts. ISUP Grade Group (GG) distributions for the SBRT and HFRT patients were: GG1: 19.4% and 9.3%, GG2: 72.9% and 74.0%, and GG3: 7.6% and 16.7%, respectively. OS rates at 5 years were 96.6% for SBRT vs. 95.8% for HFRT-treated patients. The 5-year bFFS rates for SBRT and HFRT were 92.3% and 90.1%, respectively. The 7-year bFFS rate for the SBRT cohort was 90.2%. Mean time to biochemical failure was 40.4 months after SBRT vs. 35.8 months after HFRT. Conclusions: SBRT is an effective treatment option for low to intermediate-risk PrCa with encouraging OS and bFFS rates comparable with HFRT. Pending randomized trial results will determine whether SBRT is the new standard of care for this population.

Prognostic impact of circulating tumor cells in oligometastatic hormone-sensitive prostate cancer following metastasis-directed therapy.

199 Background: Contained within the spectrum of metastatic cancer is an oligometastatic state where metastases are limited in number. Recent prospective data have shown that metastasis directed therapy (MDT) can alter the natural history of oligometastatic disease. In hormone-sensitive prostate cancer (HSPC), the positive clinical effect of MDT has been observed by the phase II STOMP and ORIOLE trials. Circulating tumor cells (CTCs) are a likely origin of the formation of macroscopic metastases. CTCs thus may provide an approach for identifying subgroups of patients with oligometastatic HSPC (oligoHSPC) that would benefit most from MDT. Our main goal was to evaluate the association between presence of CTCs at baseline or day 180 with clinical outcomes in the ORIOLE trial. Methods: ORIOLE was a phase II trial randomizing men with recurrent oligoHSPC with 1-3 metastases to observation (Obs) versus stereotactic ablative radiotherapy (SABR) MDT. Blood samples were prospectively collected at baseline and day 180. Progression-free survival (PFS) was a composite endpoint including any of the following: a PSA rise of at least 2 ng/dL and 25% above nadir; radiologic progression by CT, MRI or bone scan (RECIST v1.1); symptomatic progression of disease; initiation of ADT; or death. Patient blood samples were shipped for analysis on Epic Sciences liquid biopsy platform (Epic Sciences, San Diego, CA). Machine learning algorithms identified CTCs and characterized androgen receptor (AR) expression. Comparisons of patient and tumor characteristics between the groups were performed by two-sample t-tests. Survival curves were generated using the Kaplan-Meier method and p-values were calculated using log-rank test. Analysis was performed using SPSS version 28. Results: A total of 82 samples were collected: 70 from the SABR arm (35 baseline and 35 on day 180) and 12 Obs (7 baseline and 5 on day 180). CTCs were detected in 30/42 samples at baseline (71%, AR+= 7) and in 26/40 samples on day 180 (65%, AR+= 9). In the SABR group there was no difference between CTC+ versus CTC- and AR + versus AR- groups for PSA evaluated at baseline, day 90 or day 180 or Gleason score. With a median follow-up of 41.7 months, PFS was significantly lower in the patients with AR+ versus AR- CTCs at baseline in the SABR arm (p = 0.011, mean PFS: AR+ = 9.3 months, AR- = 27.1 months). The mean biochemical failure-free survival was AR+= 12.9 versus AR-= 29.2 months (p = 0.058). Conclusions: Our preliminary results demonstrate an association between AR+ CTCs at baseline and Day 180 with clinical outcomes following SABR MDT in oligoHSPC. This is the first report examining baseline and dynamic presence of CTCs in oligoHSPC treated from a prospective randomized trial of SABR. Longer follow-up, further analysis and a greater number of patients are needed for a more comprehensive conclusion.

Salvage high-dose-rate interventional radiotherapy (brachytherapy) for locally relapsed prostate cancer after radical prostatectomy and subsequent external irradiation.

To report the use of high-dose-rate (HDR) interventional radiotherapy (brachytherapy, IRT) as a salvage treatment for macroscopic histologically confirmed local relapse of prostatic cancer after prostatectomy and subsequent external irradiation. A retrospective study of patients with prostate adenocarcinoma, treated with HDR-IRT for an isolated local relapse after prostatectomy and external irradiation at our institution (2010-2020). Treatment results and treatment related-toxicity were recorded. Clinical outcomes were analyzed. Ten patients were identified. The median age was 63 years (range, 59-74 years), and the median follow-up time was 34 months (range, 10-68 months). Four patients had a biochemical relapse, and the mean time to prostate specific antigen (PSA) increase was 13 months. One-year biochemical failure-free survival (bFFS), 3-year bFFS, and 4-year bFFS were 80%, 60%, and 60%, respectively. Most of the treatment-related toxicities were grade 1-2. Two patients experienced grade 3 late genitourinary toxicity. HDR-IRT seems to be an effective treatment option showing acceptable toxicity for prostate cancer patients with isolated macroscopic histologically confirmed local relapse after prostatectomy and subsequent external irradiation.

Salvage external beam radiotherapy after HIFU failure in localized prostate cancer: A single institution experience

High-intensity focused ultrasound (HIFU) remains investigational as primary treatment for localized prostate cancer but is sometimes offered to select patients. At HIFU failure, data guiding salvage treatment is limited to small retrospective series with short follow-up. We evaluated our institutional experience using salvage radiation therapy (SRT) after HIFU failure. We conducted a retrospective analysis of patients with local failure post-HIFU who received salvage image-guided external beam radiation therapy (EBRT) delivered via intensity-modulated radiotherapy (IMRT). Our primary endpoint was biochemical failure-free survival (bFFS) defined as prostate-specific antigen (PSA) nadir + 2 ng/mL. Secondary endpoints included metastasis-free survival (MFS) and overall survival (OS). Endpoints were evaluated using Kaplan-Meier analysis. From 2013 to 2018, 12 out of 96 patients treated with primary HIFU received SRT via conventional or moderate hypofractionation. Median time from HIFU to SRT was 13.5 months. Seven patients had stage migration to high-risk disease at the time of SRT. Mean PSA prior to SRT was 8.2ug/L and mean nadir post-SRT was 1.2ug/L. Acute International Prostate Symptom Score (IPSS) as well as International Index of Erectile Dysfunction (IIEF) scores were similar to baseline (p = 0.5 and 0.1, respectively). Late toxicities were comparable to those reported after primary EBRT for localized prostate cancer. At a median follow-up of 46 months, the OS was 100%. The 5-year bFFS and MFS were both 83.3%. To our knowledge, we report one of the largest series on contemporary SRT post HIFU failure. We show that SRT is feasible, effective and carries no additional acute or delayed toxicity.

PO51 Presentation Time: 10:00 AM: Permanent I-125 Seeds Prostate Cancer Mono-Brachytherapy: Outcomes in 273 Patients

<h3>Purpose</h3> Report outcomes of patients undergoing I-125 seeds permanent low-dose-rate (LDR) mono-brachytherapy (mBT) in terms of OS, biochemical failure-free survival (BFFS), recurrence-free survival (RFS) and GU-GI toxicities in localized prostate cancer (LPC). <h3>Materials and Methods</h3> Between 2001 and 2015, 273 patients, undergoing I-125 LDR mBT with no prior curable treatment, with a prostate volume (pV) ≤50cc, cT1 à cT2c (NCCN classification) et iPSA ≤ 20 ng/ml were included and examined. <h3>Results</h3> With a median followup of 68 months, a biochemical failure occurred in 8 patients (4%) patients. The 5 and 8y-BFFS, defined by the Phoenix criterion, were 98.2% and 88.9%, worse for intermediate risk (IR) as compared with low risk (LR), with a 8y-BFFS of 85.7% and 91.5% respectively (p-value=0.01). The 8y-RFS were 96% and 90% for LR and IR respectively. The only factor statistically significant on OS was the age ≤ 65y with a 5 and 8y-OS of 93%/83% vs 89%/73% for ≤ 65y or >65y patients (p-value: 0.031). Surprisingly, we found in a sub-group analysis that 8y-OS for Gleason score 7 disease (GS 4+3 or 3+4) was higher than ≤ Gleason score 6 (83% vs 62%). No difference in outcomes between IR vs LR and ≤ 65y vs >65y patients was observed in terms of 8y-distant metastasis-free survival (DMFS) and prostate cancer specific survival (pCSS). The toxicity profiles suggested, from a follow-up of at least 2 years, that ≥ G3 urinary, GI and sexual toxicities were 5.5%,0.7%, 0% respectively. <h3>Conclusion</h3> I-125 permanent seeds LDR mBT provided excellent outcomes in this study. 8y-local recurrence was 6.5%. Therefore, LDR brachytherapy can be considered and still proposed as an effective treatment option for IR and LR LPC patients.

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.