Freedom From Biochemical Failure Research Articles

Dosiomics for intensity-modulated radiotherapy in patients with prostate cancer: survival analysis stratified by baseline prostate-specific antigen and Gleason grade group in a 2-institutional retrospective study.

This study evaluated the prognostic impact of the quality of dose distribution using dosiomics in patients with prostate cancer, stratified by pretreatment prostate-specific antigen (PSA) levels and Gleason grade (GG) group. A total of 721 patients (Japanese Foundation for Cancer Research [JFCR] cohort: N = 489 and Tokyo Radiation Oncology Clinic [TROC] cohort: N = 232) with localized prostate cancer treated by intensity-modulated radiation therapy were enrolled. Two predictive dosiomic features for biochemical recurrence (BCR) were selected and patients were divided into certain groups stratified by pretreatment PSA levels and GG. Freedom from biochemical failure (FFBF) was estimated using the Kaplan-Meier method based on each dosiomic feature and univariate discrimination was evaluated using the log-rank test. As an exploratory analysis, a dosiomics hazard (DH) score was developed and its prognostic power for BCR was examined. The dosiomic feature extracted from planning target volume (PTV) significantly distinguished the high- and low-risk groups in patients with PSA levels >10 ng/mL (7-year FFBF: 86.7% vs 76.1%, P < .01), GG 4 (92.2% vs 76.9%, P < .01), and GG 5 (83.1% vs 77.8%, P = .04). The DH score showed significant association with BCR (hazard score: 2.04; 95% confidence interval: 1.38-3.01; P < .001). The quality of planned dose distribution on PTV may affect the prognosis of patients with poor prognostic factors, such as PSA levels >10 ng/mL and higher GGs. The effects of planned dose distribution on prognosis differ depending on the patient's clinical background.

Development and Validation of a Multi-institutional Nomogram of Outcomes for PSMA-PET–Based Salvage Radiotherapy for Recurrent Prostate Cancer

Prostate-specific antigen membrane positron-emission tomography (PSMA-PET) is increasingly used to guide salvage radiotherapy (sRT) after radical prostatectomy for patients with recurrent or persistent prostate cancer. To develop and validate a nomogram for prediction of freedom from biochemical failure (FFBF) after PSMA-PET-based sRT. This retrospective cohort study included 1029 patients with prostate cancer treated between July 1, 2013, and June 30, 2020, at 11 centers from 5 countries. The initial database consisted of 1221 patients. All patients had a PSMA-PET scan prior to sRT. Data were analyzed in November 2022. Patients with a detectable post-radical prostatectomy prostate-specific antigen (PSA) level treated with sRT to the prostatic fossa with or without additional sRT to pelvic lymphatics or concurrent androgen deprivation therapy (ADT) were eligible. The FFBF rate was estimated, and a predictive nomogram was generated and validated. Biochemical relapse was defined as a PSA nadir of 0.2 ng/mL after sRT. In the nomogram creation and validation process, 1029 patients (median age at sRT, 70 years [IQR, 64-74 years]) were included and further divided into a training set (n = 708), internal validation set (n = 271), and external outlier validation set (n = 50). The median follow-up was 32 months (IQR, 21-45 months). Based on the PSMA-PET scan prior to sRT, 437 patients (42.5%) had local recurrences and 313 patients (30.4%) had nodal recurrences. Pelvic lymphatics were electively irradiated for 395 patients (38.4%). All patients received sRT to the prostatic fossa: 103 (10.0%) received a dose of less than 66 Gy, 551 (53.5%) received a dose of 66 to 70 Gy, and 375 (36.5%) received a dose of more than 70 Gy. Androgen deprivation therapy was given to 325 (31.6%) patients. On multivariable Cox proportional hazards regression analysis, pre-sRT PSA level (hazard ratio [HR], 1.80 [95% CI, 1.41-2.31]), International Society of Urological Pathology grade in surgery specimen (grade 5 vs 1+2: HR, 2.39 [95% CI, 1.63-3.50], pT stage (pT3b+pT4 vs pT2: HR, 1.91 [95% CI, 1.39-2.67]), surgical margins (R0 vs R1+R2+Rx: HR, 0.60 [95% CI, 0.48-0.78]), ADT use (HR, 0.49 [95% CI, 0.37-0.65]), sRT dose (>70 vs ≤66 Gy: HR, 0.44 [95% CI, 0.29-0.67]), and nodal recurrence detected on PSMA-PET scans (HR, 1.42 [95% CI, 1.09-1.85]) were associated with FFBF. The mean (SD) nomogram concordance index for FFBF was 0.72 (0.06) for the internal validation cohort and 0.67 (0.11) in the external outlier validation cohort. This cohort study of patients with prostate cancer presents an internally and externally validated nomogram that estimated individual patient outcomes after PSMA-PET-guided sRT.

Treatment outcomes of postoperative ultra-hypofractionated stereotactic body radiotherapy in prostate cancer.

This study aimed to evaluate the safety and efficacy of ultra-hypofractionated stereotactic body radiation therapy (SBRT) to prostate bed. Sixty-six prostate cancer patients treated with postoperative ultra-hypofractionated SBRT between 2018 and 2020 were retrospectively reviewed. All patients received a total dose of 35 Gy to prostate bed in 5 fractions. Biochemical complete response (BCR), biochemical failure (BF), acute and late toxicities were assessed. After a median follow-up of 24.2 months (range, 6.4-37.2), seven patients (10.6%) developed BF, and the 2-year freedom from BF (FFBF) rate was 88.4%. BCR was observed in 57 patients (86.4%). The 2-year FFBF in patients with pre-SBRT PSA value of <0.2 ng/mL was higher than those with pre-SBRT PSA of ≥0.2 ng/mL (100% vs. 81.4%; P = 0.04). The 2-year FFBF in patients with BCR was significantly higher than in those without BCR (94.5% vs. 58.3%; P < 0.001). In multivariate analysis, pre-SBRT PSA and post-SBRT PSA values were prognostic factors for FFBF (P = 0.009 and P = 0.01, respectively). Nine patients (13.6 %) developed acute and late grade 2 genitourinary (GU) toxicities. There was no acute or late grade ≥3 GU toxicity. Acute and late grade ≥2 gastrointestinal (GI) toxicity was observed in 9 (13.6%) and 2 (3%) patients, respectively. Postoperative ultra-fractionated SBRT showed no severe acute toxicity and late toxicity rates of about 15%, in addition to excellent biochemical control rates. Pre- and post-SBRT PSA levels may be a predictor of BCR in patients receiving post-operative ultra-fractionated SBRT.

The impact of the apparent diffusion coefficient for the early prediction of the treatment response after definitive radiotherapy in prostate cancer patients

PurposeWe assessed early changes in apparent diffusion coefficient (ADC) and serum prostate specific antigen (PSA) values after definitive radiotherapy (RT) without androgen deprivation treatment in low- and intermediate-risk prostate cancer (PC) patients. Materials and MethodsThe clinical data and ADC parameters of 229 PC patients were retrospectively evaluated. Pre-treatment and post-treatment serum PSA and primary tumor ADC values were calculated. Post-treatment DW-MRI was performed median 4.1 months after completion of definitive RT. The prognostic factors predicting freedom from biochemical failure (FFBF) and progression-free survival (PFS) were analyzed using univariable and multivariable analyses. ResultsWith a median follow-up time of 80.8 months, the 5-year FFBF and PFS rates were 95.9% and 89.3%, respectively. Eleven patients (4.8%) had PSA relapse, with a median of 34.4 months after the completion of RT. A statistically significant difference in post-treatment ADC values was noted between patients with and without recurrence (0.94 ± 0.07 vs. 1.10 ± 0.20 × 10-3 mm2/sec; p< 0.001). Patients with a Gleason score (GS) of 6 and low-risk disease had significantly higher post-treatment tumor ADC and PSA levels than patients with a GS of 7 and intermediate-risk disease. The 5-year FFBF rate in patients with tumor ADC ≤ 0.96 × 10-3 mm2/sec was significantly lower than patients with tumor ADC > 0.96 × 10-3 mm2/sec (85.5% vs. 100; p< 0.001). In the multivariable analysis, a lower ADC value, GS 4 + 3 and intermediate-risk disease were independent predictors of worse FFBF. In the multivariate analysis, a lower post-treatment ADC value and a GS of 4 + 3 were significant prognostic factors for a lower PFS. ConclusionThese findings suggest that the post-treatment tumor ADC value could be used for early treatment response evaluation after definitive RT in PC patients.

Outcomes after PD-103 versus I-125 for low dose rate prostate brachytherapy monotherapy: An international, multi-institutional study

Background and PurposePd-103 and I-125 are commonly used in low dose rate (LDR) brachytherapy for prostate cancer. Comparisons of outcomes by isotope type are limited, but Pd-103 has distinct radiobiologic advantages over I-125 despite its lesser availability outside the United States. We evaluated oncologic outcomes after Pd-103 vs I-125 LDR monotherapy for prostate cancer. Materials and MethodsWe retrospectively analyzed databases at 8 institutions for men who received definitive LDR monotherapy with Pd-103 (n = 1,597) or I-125 (n = 7,504) for prostate cancer. Freedom from clinical failure (FFCF) and freedom from biochemical failure (FFBF) stratified by isotope were analyzed by Kaplan-Meier univariate and Cox multivariate analyses. Biochemical cure rates (prostate-specific antigen level ≤ 0.2 ng/mL between 3.5 and 4.5 years of follow-up) by isotype were calculated for men with at least 3.5 years of follow-up and compared by univariate and multivariate logistic regression. ResultsCompared with I-125, Pd-103 led to higher 7-year rates of FFBF (96.2% vs 87.6%, P < 0.001) and FFCF (96.5% vs 94.3%, P < 0.001). This difference held after multivariate adjustment for baseline factors (FFBF hazard ratio [HR] = 0.31, FFCF HR = 0.49, both P < 0.001). Pd-103 was also associated with higher cure rates on univariate (odds ratio [OR] = 5.9, P < 0.001) and multivariate (OR = 6.0, P < 0.001) analyses. Results retained significance in sensitivity analyses of data from the 4 institutions that used both isotopes (n = 2,971). ConclusionsPd-103 monotherapy was associated with higher FFBF, FFCF, and biochemical cure rates, and suggests that Pd-103 LDR may lead to improved oncologic outcomes compared with I-125.

Development and validation of a multi-institutional nomogram of outcomes for PSMA-PET–based salvage radiotherapy in recurrent prostate cancer.

355 Background: We aimed to develop and to validate a multi-institutional nomogram of outcomes for PSMA-PET based salvage radiotherapy (sRT) following radical prostatectomy (RP) for patients with recurrent or persistent prostate cancer (PCa). Methods: Data from patients with a detectable post-RP prostate-specific antigen (PSA) treated with sRT with or without concurrent androgen-deprivation therapy (ADT) were obtained from 11 academic institutions from 5 countries. All patients had a PSMA-PET scan prior sRT and patients with distant metastases on PET were excluded from this analysis. The freedom from biochemical failure (FFBF) rate was estimated, and a predictive nomogram was generated and validated. Biochemical relapse (BR) was defined as PSA nadir +0.2 ng/ml after sRT. Results: Overall, 1029 patients (training set n=821, external validation set n=208) with a median follow-up of 33 months were included. On PSMA-PET, 427 (42%) and 313 (30%) patients had local and nodal recurrences, respectively. Elective pelvic lymphatics were irradiated in 368 (36%) patients. All patients received sRT to the prostatic fossa receiving a dose of &lt;66 Gy, 66-70 Gy and &gt;70 Gy in 103 (10%), 551 (54%) and 375 (36%) patients, respectively. Androgen deprivation therapy (ADT) was given in 325 (32%) patients. On multivariable Cox regression analysis, pre-SRT PSA, ISUP grade, pT stage, surgical margins, ADT use, sRT dose and nodal recurrence on PSMA PET were associated with FFBF. The nomogram concordance index was 0.7 for FFBF in external validation. Conclusions: We present an externally validated contemporary nomogram which can estimate individual patient outcomes after PSMA-PET guided sRT. Positive lymph nodes on PSMA-PET seem to be a new risk factor for BR after sRT.

Racial Analysis of Clinical and Biochemical Outcomes in Patients With Prostate Cancer Treated With Low-Dose-Rate Brachytherapy

Black men in the United States experience significantly higher incidence of and mortality from prostate cancer (PCa) than non-Black men. The cause of this disparity is multifactorial, though inequitable access to curative radiation modalities, including low-dose-rate (LDR) brachytherapy, may contribute. Despite this, there are few analyses evaluating the potential of different radiation therapies to mitigate outcome disparities. Therefore, we examined the clinical outcomes of Black and non-Black patients treated with definitive LDR brachytherapy for PCa. Data were collected for all patients treated with definitive LDR brachytherapy between 2005 and 2018 on a retrospective institutional review board approved protocol. Pearson χ2 analysis was used to assess demographic and cancer differences between Black and non-Black cohorts. Freedom from biochemical failure (FFBF) was calculated using Kaplan-Meier analysis. Univariate and multivariate analyses were used to identify factors predictive of biochemical failure. One hundred and sixty-seven patients were included in the analysis (Black: n=81; 48.5%) with a median follow-up of 88.4 months. Black patients were from lower income communities (P < .01), had greater social vulnerability (P < .01), and had a longer interval between diagnosis and treatment (P=.011). Overall cumulative FFBF was 92.3% (95% confidence interval [CI], 87.8%-96.8%) at 5 years and 87.7% (95% CI, 82.0%-93.4%) at 7 years. There was no significant difference in FFBF in Black and non-Black patients (P=.114) and Black race was not independently predictive of failure (hazard ratio, 1.51; 95% CI, 0.56-4.01; P=.42). Overall survival was comparable between racial groups (P=.972). Only nadir prostate-specific antigen was significantly associated with biochemical failure on multivariate (hazard ratio, 3.57; 95% CI, 02.44-5.22; P < .001). Black men treated with LDR brachytherapy achieved similar FFBF to their non-Black counterparts despite poorer socioeconomic status. This suggests that PCa treatment with brachytherapy may eliminate some disparities in clinical outcomes.

10-Year Outcomes Following Proton Therapy for Localized Prostate Cancer

To report 10-year outcomes for patients treated with proton therapy for localized prostate cancer.The 10-year outcomes from a prospective outcome tracking protocol were assessed and reported for 1272 men with localized prostate cancer. Risk groups were classified per NCCN guidelines. Median proton therapy dose was 78 GyRBE (72 to 82 GyRBE) delivered at 1.8 to 2 GyRBE per fraction. Androgen deprivation therapy (ADT) was received by 193 men for a median 6 months (range 1 to 36 months). Biochemical control was defined using the Phoenix definition. Common Terminology Criteria for Adverse Events, version 5.0, was used for toxicity scoring. The International Prostate Symptom Score (IPSS) and Expanded Prostate Index Composite (EPIC) was used for patient-reported outcomes. Freedom from biochemical failure (FFBF) and toxicity rates were calculated using the Kaplan Meier method. EPIC domain score changes considered clinically significant were 5 (bowel), 6 (urinary irritative /obstructive), 7 (urinary incontinence), and 11 (sexual).The median follow-up time was 10.2 years. The 10-year FFBF rates for patients with very low-risk, low-risk, favorable intermediate-risk, unfavorable intermediate-risk, high-risk, and very high-risk prostate cancer were 97%, 96%, 88%, 82%, 68%, 49%, respectively. Median PSA nadir was 0.2 ng/mL. On multivariate analysis, risk category, PSA, and the presence of perineural invasion predicted 10-year biochemical control. The 7- and 10-year grade 3+ gastrointestinal and urologic toxicity rates were 1.0% and 1.3% and 4.1% and 6.2%, respectively. On multivariate analysis (MVA), the use of prescription blood thinners significantly increased the 10-year risk for grade 3+ gastrointestinal toxicity. The use of prescription blood thinners, the presence of diabetes mellitus, a prostate volume 40+ grams, the use of pretreatment alpha blockers, an IPSS score of 15+, and the use of ADT were associated with late grade 3+ genitourinary (GU) toxicity on MVA. The dose-volume histogram parameter V70 (GyRBE) of bladder volume (< 33 cc vs. 33+ cc) also predicted for late grade 3+ GU toxicity on MVA. A clinically significant decline in EPIC sexual summary scores occurred at 10 years (67 to 41). No other clinically significant change was seen in EPIC summary scores.These long-term results show that proton therapy can provide favorable biochemical control outcomes for patients with localized prostate cancer. Additional strategies are needed to improve disease control for patients with very high-risk disease. Late grade 3+ GI toxicity rates are low and, as noted with other radiation modalities, the rate of late grade 3+ GU toxicity increases with time even after 5 years. There was an expected decline in overall sexual function as the patient cohort aged following proton therapy. These long-term results establish benchmarks for future comparative trials.

Can Dosiomics Features Be Relevant Predictive Factors for Biochemical Recurrence After Radiotherapy in Prostate Cancer Patients?

<h3>Purpose/Objective(s)</h3> Radiotherapy is one of the main treatment strategies for localized prostate cancer. Although several patients receive external radiotherapy, the relationships between dosimetric factors related to the treatment planning and biochemical recurrence (BCR) remain unclear. The aims of the present study were to develop a prediction model for BCR by integrating dose-based radiomics (dosiomics) features and clinical variables in prostate cancer patients, and to clarify the relationships between the dosimetric factors and BCR. <h3>Materials/Methods</h3> A total of 489 patients with adenocarcinoma of the prostate who had been prescribed a dose of 78 Gy in 39 fractions with intensity modulated radiation therapy from 2007 to 2014 were retrospectively enrolled. A total of 2,475 dosiomic features were calculated from the 3D doses in prostate, clinical target volume (CTV), and planning target volume (PTV), and relevant 8 clinical variables for BCR were also considered. Feature selection was performed to eliminate redundant or not significant features. Multivariate cox proportional hazards regression model was trained on the training cohort of 342 patients using the selected features, and the predictive performance was validated on the validation cohort of 147 patients using the concordance index (C-index). Kaplan-Meir curves with log-rank analysis was used to assess the univariate discrimination of freedom from biochemical failure (FFBF) between high- and low-risk BCR groups. <h3>Results</h3> A total of 96 patients developed BCR with the median time of 55.2 months. Two dosiomic features (1 from CTV and 1 from PTV) and three clinical variables were selected as predictive factors. Of the five, CTV (HGLRE) (hazard ratio [HR]: 0.73; 95% confidence intervals [CI]: 0.57-0.93; <i>P</i> = 0.01), pretreatment prostate-specific antigen (HR: 1.27; 95% CI: 1.04–1.55; <i>P</i> = 0.02) and positive biopsy core rate (HR: 1.40; 95% CI: 1.07–1.82; <i>P</i> = 0.01), were significantly associated with BCR. The C-index of the model in the validation cohort was 0.67 (95% CI: 0.65–0.68). CTV_wavelet-HHH_glrlm_HGLRE could significantly distinguish the patients into high- and low-risk groups (8-year FFBF: 76.6% vs. 87.5%, <i>P</i> < 0.01). <h3>Conclusion</h3> The dosiomic feature extracted from CTV can be a relevant predictive factor for BCR after radiotherapy in prostate cancer patients and may be useful as new metric for evaluating the quality of a treatment plan, instead of conventional dose indices.

High Dose Rate Brachytherapy as Monotherapy vs. External Beam With HDR Boost in Unfavorable Intermediate Risk Localized Prostate Cancer: A Matched-Pair Analysis

Both high-dose-rate brachytherapy as monotherapy (HDR-M) as well as combined with external beam radiotherapy as a boost (HDR-B) are acceptable treatment approaches for intermediate risk prostate cancer, but data directly comparing relative outcomes of these two approaches for unfavorable intermediate risk (UIR) patients is lacking. This matched-pair analysis compares clinical outcomes for National Comprehensive Cancer Network (NCCN) defined unfavorable intermediate-risk (UIR) patients treated with HDR-M relative to those treated with HDR-B.Patients with NCCN UIR prostate cancer [Gleason grade group 3, ≥ 50% biopsy cores positive, or ≥ 2 of the following: PSA > 10 and ≤ 20 ng/mL, Gleason score 7, or clinical stage T2b-T2c] were identified in a prospectively maintained, single institution database. Criteria for the matched pair analysis included: 1) age ± 3 years, 2) Gleason Score (minor and major), and 3) clinical T stage. Brachytherapy doses were based on our current institutional standards: 10.5 Gy x 2 for HDR-B and 13.5 Gy x 2 for HDR-M. HDR-B patients received 45-46 Gy in 23-25 fractions EBRT to the prostate, seminal vesicles, and pelvic lymph nodes. Follow-up time was measured from the date of first HDR implant to the date of last recorded follow-up. Biochemical failure was defined as PSA nadir + 2. Kaplan-Meier method was used to estimate overall survival (OS), cause specific survival (CSS), disease-free survival (DFS), loco-regional recurrence (LRR) and freedom from biochemical failure (FFBF).51 matched pairs were identified and included in the analysis. HDR-M had a shorter median follow-up time of 39 months vs 100 months in HDR-B (P < 0.001). Race and pre-treatment PSA were well balanced. No significant differences in OS, CSS, or DFS at 1, 3, 5, or 8 years were identified. OS was 100%, 97.9%, 97.9%, 86.8% (HDR-B) vs 100%, 100%, 100%, 85.7% (HDR-M, P = 0.870). CSS was 100%, 100%, 100%, 94.6% (HDR-B) vs 100%, 100%, 100%, 100% (HDR-M, P = 0.426). Kaplan-Meier FFBF at 1/3/5/8 years was 100%, 91.7%, 91.7%, 91.7% (HDR-B) vs 95.7%, 92.1%, 92.1%, 92.1% (HDR-M, P = 0.821). Disease-free survival at 1/3/5/8 years was 82.4%, 76.2%, 76.2%, 76.2% (HDR-B) vs 92%, 88.4%, 88.4%, 88.4% (HDR-M, P = 0.092).HDR brachytherapy as monotherapy represents a highly effective upfront therapy without the added toxicity of pelvic radiation for appropriately selected UIR prostate cancer patients.

Salvage low dose rate brachytherapy for prostate cancer recurrence following definitive external beam radiation therapy

PurposeWe sought to describe the safety and efficacy of salvage low dose rate (LDR) brachytherapy for local prostate cancer recurrence following definitive RT. Materials and methodsWe included patients from two prospectively maintained institutional databases who underwent salvage LDR brachytherapy for biopsy confirmed intra-prostatic recurrence following primary RT. All patients were without evidence of metastatic disease. Freedom from biochemical failure (FFbF), prostate cancer specific survival (PCaSS), and overall survival (OS) were determined using the Kaplan–Meier estimates. Cox proportional hazard models were used to identify factors predictive of FFbF. Toxicity was graded by Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Results108 patients were included. Median follow-up was 6.3 years. The 5- and 10-year actuarial survival outcomes were as follows: FFbF, 63.1% and 52.0%; PCaSS, 90.5% and 77.8%; OS, 80.9% and 56.7%. On multivariate modeling, increasing grade group (HR 1.41, 95% CI 1.02–1.95, p = 0.036) and initial PSA at diagnosis (HR 1.02, 95% CI 1.004–1.05, p = 0.022) were associated with worse FFbF. Grade 3 toxicity occurred in 16.7% of patients; including genitourinary events in 15.7% and gastrointestinal events in 2.8% of patients. IPSS scores increased following implant, peaking at 2 months (median IPSS 20, p = 0.002) and thereafter remaining elevated throughout follow-up. ConclusionsSalvage LDR brachytherapy is safe and efficacious, with acceptable grade 3+ toxicity and good biochemical control on long-term follow-up. Patients with higher grade group and higher PSA at initial diagnosis may be at increased risk for biochemical failure.

Prostate Cancer Radiotherapy: Increased Biochemical Control and Late Toxicity in Men With Medication Allergies.

BackgroundGiven similarities in the mediators of medication allergy (MA) and tissue response to radiotherapy, we assessed whether outcomes following prostate radiotherapy differ in patients with MAs.MethodsA total 587 men with known MA history and nonmetastatic prostate cancer underwent radiotherapy from 1989 to 2006. Clinicopathologic and treatment variables were analyzed for association with freedom from biochemical failure (FFBF) and late treatment–related, physician-defined Radiation Therapy Oncology Group gastrointestinal (GI) and genitourinary (GU) toxicity. Covariates identified on univariate analysis for toxicity and disease control were examined on multivariable analysis. All statistical tests were 2-sided, and a P less than .05 was considered statistically significant.ResultsA total of 155 of 587 men (26.4%) had 1 or more MAs, most commonly to penicillin (n = 71), sulfa (n = 35), and aspirin or nonsteroidal antiinflammatory drugs (n = 28). On univariate analysis, men with MAs had superior 10-y FFBF (71.5% vs 63.5%, P = .02) and higher incidence of late GI grade 2 or higher (G2+; 20.6% vs 13.2%, P = .04) and grade 3 or higher (G3+; 7.5% vs 3.9%, P = .08) as well as late GU G2+ (42.5% vs 33.2%, P = .04) and G3+ (7.5% vs 3.0%, P = .02) toxicity than men without MAs. On multivariable analysis, MA history remained a statistically significant predictor of FFBF (hazard ratio [HR] = 0.64, 95% confidence interval [CI] = 0.43 to 0.93, P = .02), late G2+ GI (HR = 1.76, 95% CI = 1.06 to 2.90, P=.03), and G3+ GU (HR = 2.69, 95% CI = 1.16 to 6.27, P = .02) toxicity after controlling for corresponding covariates in each model.ConclusionsMen with MAs had improved FFBF and increased treatment-related toxicity following radiotherapy for prostate cancer. MA history could be a relevant consideration in the management of men with localized prostate cancer.

I-125 or Pd-103 for brachytherapy boost in men with high-risk prostate cancer: A comparison of survival and morbidity outcomes

PurposeBrachytherapy boost improves biochemical recurrence rates in men with high-risk prostate cancer (HRPC). Few data are available on whether one isotope is superior to another. We compared the oncologic and morbidity outcomes of I-125 and Pd-103 in men with HRPC receiving brachytherapy. Methods and MaterialsOf 797 patients with HRPC, 190 (23.8%) received I-125 or 607 received Pd-103 with a median of 45 Gy of external beam irradiation. Freedom from biochemical failure (FFBF), freedom from metastases (FFMs), cause-specific survival (CSS), and morbidity were compared for the two isotopes by the ANOVA and the χ2 test with survival determined by the Kaplan–Meier method and Cox regression. ResultsMen treated with I-125 had a higher stage (p < 0.001), biological equivalent dose (BED) (p < 0.001), and longer hormone therapy (neoadjuvant hormone therapy, p < 0.001), where men treated with Pd-103 had a higher Gleason score (GS, p < 0.001) and longer followup (median 8.3 vs. 5.3 years, p < 0.001). Ten-year FFBF, FFM, and CSS for I-125 vs. Pd-103 were 77.5 vs. 80.2% (p = 0.897), 94.7 vs. 91.9% (p = 0.017), and 95.4 vs. 91.8% (p = 0.346), respectively. Men with T3 had superior CSS (94.1 vs. 79.5%, p = 0.001) with I-125. Significant covariates by Cox regression for FFBF were prostate specific antigen (PSA), the GS, and the BED (p < 0.001), for FFM PSA (p < 0.001) and GS (p = 0.029), and for CSS PSA, the GS (p < 0.001) and the BED (p = 0.022). Prostate cancer mortality was 7/62 (15.6%) for BED ≤ 150 Gy, 18/229 (7.9%) for BED >150–200 Gy, and 20/470 (5.9%) for BED >200 Gy (p = 0.029). Long-term morbidity was not different for the two isotopes. ConclusionsBrachytherapy boost with I-125 and Pd-103 appears equally effective yielding 10-year CSS of over 90%. I-125 may have an advantage in T3 disease. Higher doses yield the most favorable survival.

Analysis of outcomes after non-contour-based dose painting of dominant intra-epithelial lesion in intra-operative low-dose rate brachytherapy

PurposeTo compare the outcomes of patients with intermediate risk prostate cancer (IR-PCa) treated with low-dose rate I-125 seed brachytherapy (LDR-BT) and targeted dose painting of a histologic dominant intra-epithelial lesion (DIL) to those without a DIL. Methods455 patients with IR-PCa were treated at a single center with intra-operatively planned LDR-BT, each following the same in-house dose constraints. Patients with a DIL on pathology had hot spots localized to that region but no specific contouring during the procedure. Results396 (87%) patients had a DIL. Baseline tumor characteristics and overall prostate dosimetry were similar between patients with and without DIL except the median number of biopsy cores taken: 10 (10–12) vs 12 (10–12) (p = 0.002).19 (5%) and 18 (5%) of patients with and 1 (2%) and 0 (0%) of those without DIL experienced CTCAE grade 2 and 3 toxicity respectively. Overall, toxicity grade did not significantly correlate with presence of DIL (p = 0.10).Estimated 7-year freedom from biochemical failure (FFBF) was 84% (95% confidence interval: 79–89) and 70% (54–89) in patients with and without a DIL (log-rank p = 0.315). In DIL patients, cox regression revealed location of DIL (“Base” vs “Apex” HR: 1.03; 1.00–1.06; p = 0.03) and older age (70 vs 60 HR: 1.62; 1.06–2.49; p = 0.03) was associated with poor FFBF. ConclusionsTargeting DIL through dose painting during intraoperatively planned LDR-BT provided no statistically significant change in FFBF. Patients with DILs in the prostate base had slightly lower FFBF despite DIL boost.

Long-term biochemical control and cause-specific survival in men with Gleason grade Group 4 and 5 prostate cancer treated with brachytherapy and external beam irradiation

PurposeMen with Gleason grade Group (GG) 4 and 5 prostate cancer have high failure rates when treated by conventional therapy. We investigated the effect of higher radiation doses on freedom from biochemical failure (FBF) and prostate cancer mortality (cause-specific survival [CSS]) in men treated with a combination of permanent implant and external beam irradiation (EBRT). Methods and MaterialsThree hundred twenty men with GG4 (n = 186) and 5 (n = 134) prostate cancer were treated with I-125 or Pd-103 implant followed by 45 Gy of EBRT. Radiation doses were converted to the biological equivalent dose (BED). The median age, prostate-specific antigen (PSA), time on hormone therapy, BED, and followup were 69 years, 9.0 ng/mL, 9 months, 210 Gy, and 6.5 years, respectively. FBF and CSS were calculated by Kaplan–Meier method with associations determined by log rank and Cox regression. ResultsTen-year FBF for GG4 vs. 5 was 77.8 vs. 61.3% (p = 0.015), and CSS was 94 vs. 79.3% (p = 0.001). Men with lower PSA had improved FBF and CSS (p < 0.001). Thirty-one of 320 died of prostate cancer of which 10/186 (5.4%) had GG4 and 21/134 (15.7%) GG5 (OR 3.3, p = 0.002). BED <200 Gy was associated with a 2.2× greater BF (p = 0.004) and 2.4× prostate cancer mortality (p = 0.020). Significant covariates on regression analysis for FBF and CSS were PSA (p = 0.014), GG (p = 0.007), BED (p = 0.009), and GG (p = 0.001). ConclusionsSurvival rates for high-grade prostate cancer are favorable when diagnosed in men with lower PSA and treated with doses of BED > 200 Gy. Higher BED is achieved with a combination of I-125 (110 Gy) or Pd-103 (100 Gy) and 45 Gy EBRT.

Redefining the role of adjuvant versus salvage radiation therapy for prostate cancer after radical prostatectomy for T3 disease and/or positive margins.

367 Background: SWOG 8794 recommends adjuvant radiation therapy (ART) after radical prostatectomy (RP) for T3 and/or positive margins. Our purpose was to assess 12-year outcomes on 862 RP patients who had either T3 and/or positive margins who underwent surveillance, salvage radiation therapy (SRT), or hormonal therapy (HT), while categorizing these patients into very low risk (VLR), low risk (LR), high risk (HR), and ultra high risk (UHR) groups. Methods: From 2004 - 2007, 862 RP patients had adverse factors of extracapsular penetration (T3a), seminal vesicle invasion (T3b), positive margins, and/or detectable post-operative PSA. Management included surveillance (54.8%), SRT (36.8%), and HT (8.5%) as first salvage therapy, and 21.5% eventually received hormonal therapy. Twenty patients underwent ART, and were excluded from this analysis. We assessed prognostic factors using multivariable analysis, and 12-year estimates of freedom from biochemical failure (FFBF), freedom from salvage therapy (FFST), distant metastases-free survival (DMFS), prostate cancer-specific survival (PCSS), and overall survival (OS). VLR were those with Gleason Score (GS) of 6. LR were GS 3+4 with only T3a or positive margins, but an undetectable postoperative PSA &lt;0.1. HR were T3b with GS 7-10, any GS 7-10 with T3a/b and positive margins, but an undetectable PSA. UHR were those with a detectable PSA with a GS 7-10. Results: Median follow-up was 12.1 years. Median age was 61.6 years. Median time to first salvage treatment for VLR, LR, HR, and UHR were 10.8, 11.1, 5.3, and 0.6 years, p&lt;0.001. 12-year estimates of FFBF for VLR, LR, HR, and UHR were 60.2%, 52.9%, 28.4%, and 0%, p&lt;0.0001. For FFST, 70.9%, 68.6%, 40.5%, and 0%, p&lt;0.0001. For DMFS, 99.1%, 97.8%, 88.6%, and 63.6%, p&lt;0.0001. For PCSS, 99.4%, 99.5%, 93.5%, and 78.9%, p&lt;0.0001. For OS, 91.8%, 91.8%, 81.0%, and 69.9%, p&lt;0.0001. Conclusions: Outcomes of T3 and/or positive margins using surveillance or SRT as initial management yields excellent outcomes for VLR and LR groups, in which ART should be avoided. For HR, ART can be considered reasonable, since FFBF is only 28.4%. For VHR, these patients may benefit from combined hormonal therapy and ART.

A prospective study evaluating oral-only hormonal therapy with radiation for intermediate or high-risk prostate cancer in men age ≥ 70 years or with moderate comorbidity.

303 Background: Androgen deprivation therapy (ADT) improves disease control in intermediate (IR) and high risk (HR) prostate cancer (PCa) treated with radiation therapy (RT), but also causes toxicity which may be worse in men of older age or with comorbidity. We hypothesized that dual agent ADT, replacing GnRH agonist for an oral 5-alpha-reductase inhibitor (5AR), would improve hormonal health-related quality of life (HRQOL) without compromising PCa outcomes. Methods: Patients with localized IR or HR PCa, age &gt; 70 years and/or with Charlson comorbidity index (CCI) score &gt; 2 were treated with bicalutamide and finasteride or dutasteride (oADT). A synchronous standard of care (SOC) cohort received bicalutamide and GnRH agonist. Median RT dose was 78 Gy. Dual agent ADT was given for 4 months (mo), while 5AR or GnRH agonist continued for an additional 2 years. The primary endpoint was the Expanded Prostate Cancer Index Composite (EPIC-26) hormonal HRQOL global score at 6 mo, with success defined as &lt; 30% decline, requiring 40 men in the oADT group. Secondary endpoints included a log-rank comparison of freedom from biochemical failure (FFBF), and overall survival (OS). Results: Between 1/2011 and 8/2018, 40 and 30 men were prospectively enrolled in the oADT and SOC cohorts, respectively, with similar CCI scores &gt; 2 (73% vs 66%, p=0.58), and age (mean 71, p=0.99). Median follow-up was 36 mo. Global scores for hormonal HRQOL at baseline, 6 mo, and 2 yr were 89, 88, 84 for the oADT group, and 92, 81, 83 for the SOC group; the declines from baseline to 6 mo (p=0.04) and 2 yr (p=0.05) were smaller in the oADT group. Sexual HRQOL was better preserved at 6 mo (p&lt;0.01) in the oADT group, which maintained higher testosterone at 2 years (452 vs 44, p&lt;0.01). There were no differences in urinary or bowel HRQOL. The 3-year FFBF was 90% vs 96% (p=0.83) and OS was 83 vs 86% (p=0.77) between the oADT and SOC groups, respectively. Conclusions: oADT improves hormonal and sexual HRQOL compared to SOC ADT in men age ≥ 70 or moderate comorbidity treated with RT. These groups could be further evaluated in a randomized comparison; post-ADT RNA expression to evaluate the relative biologic effects will be performed. Clinical trial information: NCT01342367.

Ten-Year Outcomes of Moderately Hypofractionated Salvage Postprostatectomy Radiation Therapy and External Validation of a Contemporary Multivariable Nomogram for Biochemical Failure

Although high-level evidence supports moderately hypofractionated radiation therapy for definitive prostate treatment, there is less evidence for its use in the postprostatectomy setting. We externally validated a contemporary nomogram predicting biochemical failure (BF) after salvage radiation therapy (SRT) and report long-term disease control outcomes for hypofractionated SRT to the prostate bed. A retrospective review was performed for 112 patients treated with hypofractionated SRT (52.5 Gy in 20 fractions using 3-dimensional conformal radiation therapy) for pT2-4R0-1N0/XM0 prostate adenocarcinoma, with postoperative prostate-specific antigen (PSA) greater than 0.1 ng/mL or rising. Freedom from BF (FFBF), distant metastasis, cancer-specific mortality, and overall survival were analyzed from commencement of radiation therapy. Cox regression was performed on FFBF to account for covariates. BF was defined as a PSA ≥0.4 ng/mL and rising after SRT. Early SRT was defined as SRT commencing at a pre-SRT PSA of ≤0.2 ng/mL. Median follow-up was 10.0 years (interquartile range, 9.3-10.7 years), median pre-SRT PSA was 0.4 ng/mL, and androgen deprivation therapy was used in 14% of patients. The 5/10-year FFBF, distant metastasis, cancer-specific mortality, and overall survival were 68%/51%, 7%/16%, 5%/11%, and 90%/75%, respectively. FFBF for early SRT compared with late SRT was 81% versus 66% at 5 years and 68% versus 49% at 10 years. On multivariable analysis, pre-SRT PSA, International Society of Urologic Pathology grade group, seminal vesicle invasion, and androgen deprivation therapy use were associated with FFBF. The nomogram c-index was 0.67, and it overestimated FFBF by 10% and 15% at 5 and 10 years, respectively, with confidence intervals overlapping the line of unity. Hypofractionated SRT provides long-term disease control outcomes comparable to conventionally fractionated radiation therapy. Early SRT provides improved disease control, with two-thirds of patients with pre-SRT PSA of ≤0.2 ng/mL free of BF at 10 years. We performed the first external validation of the Tendulkar salvage nomogram, which showed a robust model performance.

PI-RADS score is associated with biochemical control and distant metastasis in men with intermediate-risk and high-risk prostate cancer treated with radiation therapy

BackgroundNovel methods of risk stratification are needed for men with prostate cancer. The Prostate Imaging Reporting and Data System (PI-RADS) uses multiparametric MRI (mpMRI) to assign a score indicating the likelihood of clinically significant prostate cancer. We evaluated pretreatment mpMRI findings, including PI-RADS score, as a marker for outcome in patients treated with primary radiation therapy (RT). MethodsOne hundred and twenty-three men, 64% and 36% of whom had National Comprehensive Cancer Network (NCCN) intermediate-risk and high-risk disease, respectively, underwent mpMRI prior to RT. PI-RADS score and size of the largest nodule were analyzed with respect to freedom from biochemical failure (FFBF) and freedom from distant metastasis. ResultsA PI-RADS score of ≤3, 4, or 5 was defined in 7%, 49%, and 44%; with a median nodule size of 0, 8, and 18 mm, respectively (P < 0.001). Median follow-up was 67 months. Men with PI-RADS ≤ 3, 4, or 5 disease had 7-year FFBF of 100%, 92%, and 65% (P = 0.002), and a 7-year freedom from distant metastasis of 100%, 100%, and 82%, respectively (P = 0.014). PI-RADS (Hazard Ratio 5.4 for PI-RADS 5 vs. 4, P = 0.006) remained associated with FFBF when controlling for NCCN risk category (P = 0.063) and receipt of androgen deprivation therapy (P = 0.535). Nodule size was also associated with FFBF (Hazard Ratio 1.08 per mm, P < 0.001) after controlling for NCCN risk category (P = 0.156) and receipt of androgen deprivation therapy (P = 0.776). ConclusionmpMRI findings, including PI-RADS score and nodule size, may improve risk stratification in men treated with primary RT

Clinical Outcomes of Dose-escalated Radiotherapy for Localised Prostate Cancer: A Single-institution Experience.

To report the outcomes of patients with prostate cancer treated with dose-escalated radiotherapy over a 15-year period at our Institution. Patients with biopsy-proven cT1-4N0M0 disease who received radical external beam radiotherapy (EBRT) were reviewed. The endpoints were 5-year overall survival (OS), freedom from biochemical failure (FFBF) and late treatment toxicities. A total of 236 patients were eligible. Median follow-up was 70 months. Low-, intermediate- and high-risk disease was found in 9%; 29% and 62% of patients, respectively. The median radiation dose was 73.8 Gy. Overall 42% of patients had dose escalation to >74 Gy. Five-year OS and FFBF were 95.2%/81.6%/75.4% and 95.0%/98.0%/82.0% for low-/intermediate-/high-risk patients, respectively. Dose escalation to >74 Gy did not improve FFBF (hazard ratio=0.97, 95% confidence intervaI=0.43-2.19, p=0.93) and was associated with a 4.3-fold increase in the odds of grade 3 or more rectal bleeding (p<0.01). Dose escalation to >74 Gy did not improve OS or FFBF but was associated with a higher rate of grade 3 or more rectal haemorrhage.