Intermediate Risk Localized Prostate Cancer Research Articles

Active Surveillance for Intermediate-Risk Prostate Cancer: Systematic Review and Meta-analysis of Current Protocols and Outcomes.

Current guidelines allow active surveillance for intermediate-risk prostate cancer patients but do not provide comprehensive recommendations for selection. We performed a systematic review and meta-analysis of outcomes for active surveillance in intermediate- and low-risk groups. We performed a systematic literature search of intermediate-risk localized prostate cancer patients undergoing active surveillance using 3 literature search engines (Medline, Web of Science, and Scopus) over the past 10 years. The primary outcome was the percentage of patients who remain under surveillance. Secondary outcomes included cancer-specific survival, overall survival, and metastasis-free survival. For articles including both low- and intermediate-risk patients undergoing active surveillance, comparisons between the two groups were made. The proportion of patients who remained on active surveillance was comparable between the low- and intermediate-risk groups after 10 and 15 years' follow-up (odds ratio [OR], 0.97; 95% confidence interval [CI], 0.83-1.14; and OR, 0.86; 95% CI, 0.65-1.13). Cancer-specific survival was worse in the intermediate-risk group after 10 years (OR, 0.47; 95% CI, 0.31-0.69) and 15 years (OR, 0.34; 95% CI, 0.2-0.58). The overall survival rate showed no statistical difference at 5 years' follow-up (OR, 0.84; 95% CI, 0.45-1.57) but was worse in the intermediate-risk group after 10 years (OR, 0.43; 95% CI, 0.35-0.53). Metastases-free survival did not significantly differ after 5 years (OR, 0.55; 95% CI, 0.2-1.53) and was worse in the intermediate-risk group after 10 years (OR, 0.46; 95% CI, 0.28-0.77). Active surveillance could be offered to patients with intermediate-risk prostate cancer. However, they should be informed of the need for regular monitoring and the possibility of discontinuation as a result of a higher rate of progression. Available data indicate that 5-year survival rates between intermediate- and low-risk patients do not differ; 10-year survival rates are worse. To assess the long-term effectiveness and safety of active surveillance, it is necessary to develop unified algorithms for patient selection and management, and to prospectively conduct studies with long-term surveillance.

Sequential or concomitant radiotherapy treatment for patients with localized prostate cancer.

e17610 Background: External Beam radiotherapy is a standard treatment for patients with intermediate risk localised prostate cancer. Commonly the radiotherapy plan is delivered in two phases with adequate margins, the first phase to the prostate and seminal vesicles and the second phase to the prostate alone. The two phases can be delivered by intensity modulated radiotherapy as a sequential or concomitant treatment. We compared the toxicities and clinical outcomes of patients who received radiotherapy either as sequential or as concomitant treatment. Methods: Two hundred and twenty five consecutive patients with intermediate risk prostate cancer were included in the study. The patients who had sequential treatment received 60 Gy in 30 fractions to the prostate and seminal vesicles,, while patients who had concomitant treatment received 60 Gy in 37 fractions. All patients received 74 Gy in 37 fractions to the prostate. The Genitourinary (GU) and Gastrointestinal (GI) toxicity data and outcomes in terms of biochemical progression free survival were compared. Results: One hundred eighty patients received sequential radiotherapy, while forty five patients received concomitant radiotherapy. Acute GI toxicity was significantly less in the patients who received concomitant radiotherapy, during weeks four(p = 0.03), six(p = 0.03) and eight(p = 0.06) of treatment, compared to patients who receive sequential radiotherapy. Acute GU toxicities were similar in both groups of patients during treatment. Late GU and GI toxicity at 1 year and 2 years were similar. 3 year biochemical Progression free survival was 90 % for patients who received either sequential compared to 75 % for patients who received concomitant radiotherapy, though not statistically significant (log rank p value = 0.173). Conclusions: Concomitant radiotherapy to prostate and seminal vesicles resulted in lower acute gastrointestinal toxicity compared to sequential radiotherapy to the prostate and seminal vesicles as two phases. The genitourinary and late toxicities were similar. Biochemical progression free survival for patients who received concomitant radiotherapy treatment, could however be inferior to sequential treatment, probably due to the lower dose per fraction to the seminal vesicles and margins.

PD17-01 OUTPATIENT TRANS-RECTAL MR-GUIDED LASER FOCAL THERAPY PHASE II CLINICAL TRIAL: TEN-YEAR INTERIM RESULTS

You have accessJournal of UrologyProstate Cancer: Localized: Ablative Therapy I (PD17)1 Apr 2020PD17-01 OUTPATIENT TRANS-RECTAL MR-GUIDED LASER FOCAL THERAPY PHASE II CLINICAL TRIAL: TEN-YEAR INTERIM RESULTS John Feller*, Bernadette Greenwood, Wes Jones, Rob Toth, Steve Gunberg, Jeffrey Herz, and Indian Wells, CA John Feller* John Feller* More articles by this author , Bernadette GreenwoodBernadette Greenwood More articles by this author , Wes JonesWes Jones More articles by this author , Rob TothRob Toth More articles by this author , Steve GunbergSteve Gunberg More articles by this author , Jeffrey HerzJeffrey Herz More articles by this author , and Indian Wells, CAIndian Wells, CA More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000860.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: In the United States alone, new prostate cancer cases for 2019 were estimated at 174,650 and deaths at 31,620. Focal therapies for low risk and intermediate risk localized prostate cancer are increasingly being explored. Our objective is to investigate the efficacy of using MR-guided laser focal therapy for MR visible prostate cancer utilizing a trans-rectal approach for laser applicator placement and therapy delivery in an outpatient setting for treatment naive and salvage patients. METHODS: All MR-guided therapy was delivered using a 1.5 Tesla Philips Achieva XR system (Philips Healthcare, Best, The Netherlands) for both image acquisition and real-time thermometry. DynaCAD and DynaLOC (Invivo, Orlando, FL, USA) software were used for image analysis and laser fiber placement planning. Laser focal therapy was delivered using a Visualase (Medtronic, Minneapolis, MN, USA) 15W, 980 nm diode laser applicator introduced trans-rectally using the DynaTRIM (Invivo, Orlando, FL, USA). RESULTS: Under an IRB-approved, HIPAA-compliant protocol, 158 men and 248 cancer foci were treated. No serious adverse events or morbidity were reported. Of the 122 men that underwent 6 mo. biopsy of the treatment site, 32/122 (26%) of men were positive and clinically significant*, while 71/122 (59%) of men were negative. The remaining 18 men (15%) were positive but clinically insignificant. In addition, while most of the positive results were of marginal recurrence, 6 men (5%) had clinically significant incidence cancers. We observed a 37% decrease in mean PSA at 12 months post therapy and no statistically significant change in IPSS and SHIM scores. At ten years, the metastasis free survival rate is 99%, the prostate cancer specific survival rate is 100%, and the overall survival rate is 98%. * Excludes Gleason score 3+3 (Grade Group 1) CONCLUSIONS: Ten year outcomes data indicate that outpatient, trans-rectally delivered MRI-guided laser focal therapy for prostate cancer has similar oncologic control as whole-gland therapy without the associated morbidity. In 94% of the treatment naive patients, whole gland therapy was safely avoided. Focal treatment of prostate cancer may be an attractive option in a subset of men appropriately risk stratified. The precision and safety achieved using laser focal therapy under MRI-guidance may have a favorable impact on cost effectiveness and quality of life without eliminating the possibility of whole-gland treatment. We will continue to follow these men for twenty years as part of an IRB-approved clinical trial (NCT# 02243033)3. Source of Funding: Patient funded research. © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e369-e369 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information John Feller* More articles by this author Bernadette Greenwood More articles by this author Wes Jones More articles by this author Rob Toth More articles by this author Steve Gunberg More articles by this author Jeffrey Herz More articles by this author Indian Wells, CA More articles by this author Expand All Advertisement PDF downloadLoading ...

MP23-13 DEFINING INTERMEDIATE-RISK PROSTATE CANCER SUITABLE FOR ACTIVE SURVEILLANCE WITH PSA 10-20NG/ML: PATHOLOGICAL OUTCOME ANALYSIS OF A POPULATION-LEVEL DATASET

You have accessJournal of UrologyProstate Cancer: Localized: Active Surveillance I (MP23)1 Apr 2020MP23-13 DEFINING INTERMEDIATE-RISK PROSTATE CANCER SUITABLE FOR ACTIVE SURVEILLANCE WITH PSA 10-20NG/ML: PATHOLOGICAL OUTCOME ANALYSIS OF A POPULATION-LEVEL DATASET Peter E Lonergan*, Chang Wook Jeong, Samuel L Washington, Annika Herlemann, Peter R Carroll, and Matthew R Cooperberg Peter E Lonergan*Peter E Lonergan* More articles by this author , Chang Wook JeongChang Wook Jeong More articles by this author , Samuel L WashingtonSamuel L Washington More articles by this author , Annika HerlemannAnnika Herlemann More articles by this author , Peter R CarrollPeter R Carroll More articles by this author , and Matthew R CooperbergMatthew R Cooperberg More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000856.013AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The most recent National Comprehensive Cancer Network prostate cancer guidelines use grade group (GG) 2 or PSA 10-20 ng/mL as features that define favorable intermediate-risk disease and suggest that active surveillance (AS) may be an option for some men within this risk category. As a result, there is a need to more clearly define AS eligibility within this group. To address this, we utilized the Surveillance, Epidemiology, and End Results (SEER) Prostate with Watchful Waiting (SEER-WW) database to determine the risk of pathologic upgrading or upstaging according to PSA level (<10 vs 10-20 ng/mL) and GG (1 vs 2) in men with favorable intermediate-risk localized prostate cancer who underwent radical prostatectomy (RP). METHODS: The study population was obtained from the SEER-WW database, which captures men diagnosed with prostate cancer from 18 regional registries between 2010 and 2016. After multiple imputation, the cohort was restricted to men aged ≤80 years with clinically localized prostate cancer (cT1-2cN0M0), PSA ≤20ng/ml, biopsy GG ≤2 with percent positive cores (PPC) ≤33% who underwent RP (n=29,120). Patients with no surgical pathology information were excluded (n=2,572), giving a final patient cohort of 26,548 for the analyses. The primary outcome was adverse pathology, defined as any pathologic upgrading (≥GG 3) or any upstaging to non-organ confined disease (≥pT3a). Multivariable logistic regression was performed to determine predictors of adverse pathology at RP. RESULTS: Of 1,731 men with GG 1 disease and PSA 10-20 ng/mL, 382 (22.1%) harbored adverse pathology compared to 2,340 (28%) of 8,367 men with GG 2 and a PSA <10 ng/mL who had adverse pathology. The odds ratio of harboring adverse pathology with a PSA 10-20 ng/mL (vs <10 ng/mL, 1.87, 95% confidence interval [CI] 1.71-2.05, p<.001) was smaller than that of GG 2 (vs. GG 1, 2.56, 95% CI 2.40-2.73, p<0.001) after adjustment. CONCLUSIONS: Using data from the SEER-WW database, our findings show that men with GG 1 disease and a PSA of 10-20 mg/mL have a lower risk of adverse pathology after RP compared to men with GG 2 and a PSA <10 ng/mL. Our results support the expanding role of AS to men with PSA 10-20 ng/mL for GG 1 prostate cancer, which should be accompanied by informed decision-making. Source of Funding: None © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e343-e343 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Peter E Lonergan* More articles by this author Chang Wook Jeong More articles by this author Samuel L Washington More articles by this author Annika Herlemann More articles by this author Peter R Carroll More articles by this author Matthew R Cooperberg More articles by this author Expand All Advertisement PDF downloadLoading ...

Outcomes for Young Men With Localized Intermediate-Risk Prostate Cancer: An Analysis of the NCDB.

Primary management of localized, intermediate-risk prostate cancer consists of radical prostatectomy (RP), radiotherapy (RT) with short-course androgen deprivation therapy (ADT), or RT alone. The purpose of this study was to determine if these treatment strategies have equivalent overall survival (OS) in patients< 55 years old with intermediate-risk prostate cancer. We identified 35,134 patients in the National Cancer Data Base with localized intermediate-risk prostate cancer treated with RP, RT+ ADT, or RT from 2004 to 2013. Ten-year OS rates were estimated by the Kaplan-Meier method. Adjusted hazard ratios (HR) with 95% confidence intervals (CI) were computed by multivariate Cox regression. A total of 29,920 patients (85.2%) underwent RP, 1393 (4.0%) RT+ ADT, and 3821 (10.9%) RT. Median patient age was 51 years old, and median follow-up was 59.9 months. Ten-year OS was estimated to be 94.2% for RP, 80.7% for RT+ ADT, and 85.2% for RT (P< .0001). On multivariate analysis, treatment with RT+ ADT or RT was associated with significantly worse OS compared to treatment with RP (RT+ ADT HR= 2.06, 95% CI 1.67-2.54, P< .0001; RT HR= 2.0, 95% CI 1.71-2.33, P< .0001). Patients who metall 3 of the intermediate-risk criteria showed worse OS compared to patients who met only one criterion (HR= 1.80; 95% CI, 1.32-2.44; P= .0002). RP is significantly more likely than RT+ ADT or RT to be used as a primary treatment for young men with localized intermediate prostate cancer. RP was also associated with improved OS compared to RT+ ADT and RT.

A phase Ib/II trial of perioperative intratumoral MVA-BN-brachyury (MVA) plus systemic PROSTVAC and atezolizumab (Atezo) for intermediate-risk and high-risk localized prostate cancer (AtezoVax).

TPS382 Background: Many patients with intermediate or high-risk localized prostate cancer relapse after prostatectomy, identifying an unmet need. Cancer vaccines increase the infiltrating lymphocyte concentration in localized and metastatic prostate cancer (PMID 25255802, 29858218). We hypothesize that treatment with a combination of two vaccines plus PD-L1 inhibition will be safe and significantly stimulate immune infiltration within the tumor microenvironment. MVA is a modified vaccinia virus that is replication-deficient, inducing the generation of tumor antigen-specific killer T-cells. PROSTVAC is a poxviral based cancer vaccine using a vaccinia virus prime and fowlpox based boost along with co-stimulatory molecules B7.1, leukocyte function-associated antigen-3, and intercellular adhesion molecule-1. Methods: This study is a single-arm,, phase I/II investigator initiated trial (NCT04020094). Primary objectives: 1) Safety, 2) Quantitative change in infiltrating CD8+ lymphocytes between the biopsy and prostatectomy as measured by immunofluorescence. Secondary endpoints: 1) 6- and 12-month undetectable PSA rate; 2) PSA-PFS compared to institutional historic control. Inclusion criteria: unfavorable intermediate to very high-risk prostate adenocarcinoma (per NCCN). Exclusion criteria: non-adenocarcinoma histology and metastatic disease (including regional nodal metastasis). A total of 22 patients will be enrolled starting with a 6 patient safety lead in. Prostate MRI will be obtained prior to treatment. Treatment schema: 2 neoadjuvant cycles (Atezo + MVA + PROSTVAC), followed by prostatectomy then 6 additional adjuvant cycles (Atezo + PROSTVAC). Neoadjuvant cycle 1: atezolizumab (1200mg IV Q3wks), PROSTVAC-V (Prime, 2x108 Inf.U subcutaneous), MVA (2 x 108 Inf.U/0.5 ml, intra-tumoral injection, volume determined by MRI). Neoadjuvant cycle 2: atezolizumab, PROSTVAC-F (Boost, 1x109 Inf.U, subcutaneous), MVA. Adjuvant: atezolizumab and PROSTVAC-F. Clinical trial information: NCT04020094.

Evaluation of Efficacy of TOOKAD® (VTP) Versus Active Surveillance for Intermediate Risk Localized Prostate Cancer

Evaluation of Efficacy of TOOKAD® (VTP) Versus Active Surveillance for Intermediate Risk Localized Prostate Cancer

Cryotherapy shows no inferiority compared with radical Prostatectomy for low-risk and intermediate-risk localized Prostate Cancer: a real-world study from the SEER database

Background: For localized prostate cancer (PCa) with a low disease burden, whole-gland resection seems like overtreatment, while focal therapy, including cryosurgery, can achieve similar outcomes. We aimed at comparing the long-term survival outcomes of cryotherapy and radical prostatectomy (RP) and further exploring whether RP can be replaced by cryosurgery for those with low-risk PCa.Methods: We conducted analyses from the Surveillance, Epidemiology, and End Results (SEER) database (2004-2015) and performed propensity score matching and used an instrumental variate to reduce the influence of bias and unmeasured confounders to the greatest extent.Results: In the multivariate regression, patients who received cryotherapy had higher risk of overall mortality (OM) (hazard ratio [HR] = 2.52, 95% confidence interval [CI] 1.99-3.20, p < 0.001), but no significant difference was observed in decreasing cancer-specific mortality (CSM) (HR = 1.38, 95% CI 0.63-3.03, p = 0.41) after adjusting the confounders. After propensity score matching, patients who underwent cryotherapy had higher OM and CSM rates (HR = 2.70 [95% CI 1.99-3.66, p < 0.001] and HR = 2.99 [95% CI 1.19-7.48, p = 0.02], respectively). In the IV-adjusted analyses, RP was superior to cryotherapy in decreasing OM (HR = 2.52, 95% CI 1.99-3.20), while no obvious decrease of CSM was observed in the comparison of RP and cryotherapy (HR = 1.38, 95% CI 0.63-3.03). The subgroup analyses showed that RP displayed an obvious benefit in decreasing CSM (HR = 5.02, 95% CI 1.30-19.39, p = 0.02) for those with a prostate-specific antigen (PSA) level higher than 10 ng/ml.Conclusion: RP ranked as the best treatment in regard to tumor control, but the advantages of cryotherapy became evident when taking functional and oncological outcomes into account, especially for low- and intermediate-risk PCa with low PSA levels.

A polymeric paste-drug formulation for intratumoral treatment of prostate cancer.

Focal therapy has emerged as a treatment option for low- to intermediate-risk localized prostate cancer (PCa) patients, to balance the risks for urinary and sexual morbidity of radical treatment with the psychological burden of active surveillance. In this context, we developed ST-4PC, an injectable, polymeric paste formulation containing docetaxel (dtx) and bicalutamide (bic) for image-guided focal therapy of PCa. The objective of this work was to evaluate the in vitro characteristics and in vivo toxicity and efficacy of ST-4PC. In vitro drug release was evaluated using high-performance liquid chromatography. In vivo toxicity of blank- and drug-loaded ST-4PC was assessed in mice and rats. Tumor growth inhibition was evaluated in LNCaP subcutaneous (s.c.) and LNCaP-luc orthotopic xenograft models. Using the s.c. model, mice were monitored weekly for weight loss, tumor volume (TV) and serum PSA. For the orthotopic model, mice were additionally monitored for bioluminescence as measure of tumor growth. ST-4PC demonstrated a sustained and steady release of incorporated drugs with 50% dtx and 20% bic being released after 14 days. While no systemic toxicity was observed, dose-dependent local side effects from dtx developed in the s.c. but not in the orthotopic model, illustrating the limitations of s.c. models for evaluating local cytotoxic therapy. In the s.c. model, 0.1%/4% and 0.25%/4% dtx/bic ST-4PC paste significantly reduced PSA progression, but did not have a significant inhibitory effect on TV. ST-4PC loaded with 1%/4% dtx/bic significantly reduced TV, serum PSA, and bioluminescence in the orthotopic xenograft model. Compared with drugs dissolved in DMSO, ST-4PC significantly delayed tumor growth. Image-guided focal therapy using ST-4PC demonstrated promising inhibition of PSA progression and orthotopic tumor growth in vivo without significant toxicity, and warrants further clinical evaluation.

Ablation of Prostate Tissue in Patients With Intermediate Risk Localized Prostate Cancer

Ablation of Prostate Tissue in Patients With Intermediate Risk Localized Prostate Cancer

Single Fraction Urethra-Sparing Prostate Cancer SBRT: Phase I Results of a Multicenter, Single Arm, Phase I/II Trial

To present the phase I results of a single fraction urethra-sparing stereotactic body radiotherapy (SBRT) schedule for localized prostate cancer (PCa) from the single arm, multicenter phase I/II ONE SHOT trial. From 08/2017 through 12/2018, 6 patients from two among the 5 participating institutions with low- and intermediate-risk localized PCa (cT1c-2cN0M0, Gleason ≤3+4, PSA ≤15 ng/ml, with ≤70 cc prostate volume and without significant tumor in the transitional zone) were recruited and treated with a 19 Gy single fraction to the prostate ± seminal vesicles (PTV= CTV + 5 mm isotropic expansion, except 3 mm posteriorly) using a VMAT technique and intrafractional motion control using intraprostatic electromagnetic transponders. The prostatic urethra, with a surrounding margin of 2 mm, received a lesser dose of 17 Gy. Genitourinary (GU) and gastrointestinal (GI) toxicity (CTCAE v4.03 grading scale), IPSS, IIEF-25 and QOL scores (EPIC) were assessed at baseline, at 5 days (D5), 6th (W6) and 12th weeks (W12) (acute toxicity) since SBRT. Primary endpoint of the phase I was safety as assessed by occurrence of Grade ≥3 acute side effects during the first 3 months in a "3 + 3” cohort-based. Median age and PSA at SBRT were 75 years old and 8.1 ng/ml. All patients underwent SBRT without interruption and doses constraints were respected for all plans. The toxicity stopping rule was never triggered, with no Grade ≥3 acute side effects observed during the first 3 months. Patients experienced mostly grade 1 or 2 GU toxicities (frequency/urgency) resolving from W6 (50% of grade 2 GU) with no grade 2 GI side effects and no rectal toxicity at W12 (33% of grade 1 GI). IPSS increased from baseline to D5 and W6 (mean, from 3.5 to 13.2 and 16.2, respectively) decreasing progressively at W12 (mean, 7.2). The EPIC urinary domain mean score was 92 pretreatment, 73 at D5, 79 at W6 and 87 at W12, while the EPIC bowel domain mean score remained overall stable over weeks (95, 91, 85, 90 at the four endpoints). No impact of SBRT was observed on IIEF-25 scores and the EPIC sexual domain between baseline and W12 (mean, from 10 to 9 and from 46 to 44, respectively). The PSA values showed a bounce at D5 (mean, from 7.9 to 18.3 ng/ml) decreasing successively up to a value of 3.3 ng/ml at W12. 19 Gy single-fraction SBRT irradiation of the whole prostate with urethra sparing to 17 Gy was feasible and well tolerated. This trial represents the first multicenter phase I/II trial assessing the efficacy and safety of a single-fraction SBRT monotherapy in the exclusive treatment of localized disease.

PT039 - Active surveillance in men with low to intermediate risk localized prostate cancer: A prospective multiple cohort study

PT039 - Active surveillance in men with low to intermediate risk localized prostate cancer: A prospective multiple cohort study

Stereotactic body radiotherapy (SBRT) versus conventional fractionated intensity-modulated radiotherapy (CF-IMRT) for patients with early-stage localized prostate cancer: One-year late toxicity results from a prospective randomized phase II study.

27 Background: It remains uncertain whether stereotactic body radiotherapy (SBRT) is superior to conventional fractionated intensity-modulated radiotherapy (CF-IMRT) in the treatment of early-stage prostate cancer. Here we report the 1-year late toxicity results from this randomized phase II study comparing SBRT and CF-IMRT. Methods: The primary endpoint of this single centre randomized phase II study is the health-related quality of life (HRQOL), as measured by the bowel and urinary domains of the Expanded Prostate Cancer Index Composite (EPIC) instrument. The secondary endpoints include toxicities, biochemical control and overall survival. We enrolled low and intermediate risk localized prostate cancer patients (T1-T2, Gleason score ≤7 and PSA &lt;20). Patients were randomly assigned in a 1:1 ratio to receive either CF-IMRT with 38 fractions of 2 Gy in 7.5 weeks (five fractions per week) or SBRT with 5 fractions of 7.25 Gy in 2 weeks (three fractions per week). Neoadjuvant androgen-deprivation treatment is optional for the intermediate risk patients. A 1-year late adverse event is defined as the first occurrence of worst severity of the adverse event within 1 year after the completion of RT, and it was evaluated with the Common Terminology Criteria for Adverse Events (version 4.0). Patient recruitment was completed in May 2017. Results: Between Jan 2015 and May 2017, 68 patients were recruited and 4 patients were not eligible. 64 patients were randomized to treatments with SBRT (n=31) or CF-IMRT (n=33). At 1- year follow-up, two grade 3 genitourinary (GU) late toxicities, one in each arm (3%), were reported. SBRT patients experienced significantly less ≥ grade 1 late gastrointestinal (GI) toxicities (SBRT vs IMRT: 64% vs 84%, p=0.041) and similar ≥grade 1 late GU toxicities (SBRT vs IMRT: 93% vs 100%, p=0.2307) to IMRT patients. Conclusions: SBRT results in significantly less 1-year late GI toxicities than CF-IMRT in with low and intermediate risk prostate cancer. The study is registered at ClinicalTrials.gov (NCT02339701). Clinical trial information: NCT02339701.

Optimizing the use of androgen deprivation therapy in men with localized intermediate-risk prostate cancer in the era of modern dose-escalated radiation therapy.

109 Background: While level one evidence has shown an overall survival (OS) advantage with the addition of androgen deprivation therapy (ADT) to radiotherapy (RT) for intermediate risk prostate cancer (PCa), the benefit in the era of modern dose escalation is controversial, especially given the heterogeneity within this risk group. We assessed the impact of adding ADT to high dose RT on OS for intermediate risk PCa stratified by number of intermediate risk factors (IRF). Methods: We identified 114,339 men with intermediate risk PCa (Gleason 7, clinical stage T1-2, PSA &lt; 20 ng/mL) using the National Cancer Database. Men were stratified into the following subgroups based on the number of IRFs (Gleason 7, cT2b-c, PSA &gt; 10-20 ng/mL): A) Gleason 3+4 and no other IRF, B) Gleason 4+3 and no other IRF, C) two IRFs, and D) three IRFs. The addition of ADT to dose-escalated external beam RT (DE-EBRT, ≥ 75.6 Gy), brachytherapy (BT), or combination EBRT+BT on OS was assessed within each subgroup using Kaplan-Meier and log-rank tests in propensity score-matched cohorts in all men and subsequently only in those with Charlson-Deyo comorbidity index (CDI) of zero. Results: There was no OS benefit with the addition of ADT to DE-EBRT, BT, or EBRT+BT in groups A, B, and C, even after limiting the cohort to men with CDI = 0. However, in group D, the addition of ADT to DE-EBRT was associated with a trend for OS improvement in patients with CDI = 0 only (8-year OS with and without ADT 68.3% and 62.4%, respectively, log-rank P= .07). Conversely, there was a trend for OS decrement with the addition of ADT to DE-EBRT in men with CDI ≥ 1 (8-year OS with and without ADT 61.8% and 67.5%, respectively, log-rank P= .06). There was no OS benefit of ADT in group D treated with BT or EBRT+BT, regardless of comorbidity status. Conclusions: The OS benefit of ADT in men with intermediate risk PCa may be limited to those with 3 IRFs and minimal comorbidities treated with DE-EBRT. If prospectively validated, extreme dose escalation achieved with BT (alone or in combination with EBRT) may obviate the addition of ADT in all men with intermediate risk disease, especially in an era of advanced molecular imaging.

Four-year outcomes of hypofractionated proton therapy for localized prostate cancer.

80 Background: Hypofractionated radiation therapy (HFRT) is an effective treatment for localized prostate cancer (LPC). This study was performed to determine the toxicity profile and biochemical-clinical failure (BCF) rates for patients with LPC treated with hypofractionated proton therapy (HFPT). Methods: Between 2010 and 2017, 184 men were enrolled on a trial of 70Gy in 28 fractions of HFPT for low to intermediate-risk LPC. Androgen suppression (AS) was allowed. Acute and late toxicity was evaluated using the Common Terminology Criteria for Adverse Events, version 4.0. Urinary and erectile quality of life changes were captured using the International Prostate Symptom Score (IPSS) and the International Index of Erectile Function (IIEF-5) Questionnaire, respectively. Results: Median follow-up was 49.2 months. Enrolled patients had low-risk [LR] (n = 18), favorable intermediate-risk [FIR] (n = 78), and unfavorable intermediate-risk [UIR] (n = 88) disease. Twenty-six percent of patients received neoadjuvant and concurrent AS, with a median duration of 6 months. Four-year rates of BCF free survival were 95.7%, 94.4%, 98.7%, and 93.2% in the overall group and the LR, FIR, and UIR cohorts, respectively (p = .21). Overall survival at 4 years was 97.3%. No deaths were attributable to prostate cancer. Median IPSS before and 1 year post-HFPT were 6 and 7 for LR patients, 6 and 6 for FIR patients, and 8 and 7 for UIR patients. Median IIEF-5 before and 1 year post-HFPT were 21 and 18 for LR patients, 18 and 16.5 for FIR patients, and 15 and 10.5 for UIR patients. The incidence of acute grade 2 or higher gastrointestinal (GI) and urologic (GU) toxicities were 3.8% and 12.5%, respectively. One acute grade 3 GI toxicity was reported. The 4-year incidence of late grade 2 or higher GU and GI toxicity was 7.6% and 13.6%, respectively. One late grade 3 GI toxicity was reported. The predominant late grade 2 GI and GU toxicities were rectal bleeding and urinary frequency, respectively, accounting for 79% and 57% events. All late toxicities were transient. Conclusions: HFPT is associated with low rates of toxicity in the treatment of prostate cancer. Further analyses are warranted to assess long term toxicity and understand differences between proton and photon HFRT. Clinical trial information: NCT01352429.

Dominant intraprostatic lesion boosting in sexual-sparing radiotherapy of prostate cancer: A planning feasibility study

AimRadical radiotherapy of prostate cancer requires a relatively high dose to achieve an optimal tumor control probability and a reduced dose to the critical structures related to the sexual function (S_OARs) in order to avoid erectile dysfunction. The aim of this study was to perform a planning feasibility analysis of a 3-level dose prescription with Simultaneous Integrated Boost (SIB) on the dominant intraprostatic lesion (DIL) and with S_OARs sparing. Material and methodsTwelve patients with clinically localized intermediate risk prostate cancer were included. The prostate, seminal vescicles, and DIL Clinical Target Volumes were delineated on rigid fused MRI-CT simulation images using mp-MRI as a separate guide. A 5 mm margin was added to define the PTVs. Penile bulb (PB), corpora cavernosa (CC), internal pudendal arteries (IPAs) and neurovascular bundles were contoured as S_OARs. The following doses were prescribed in 25 fractions: 56.25 Gy to PTVsv, 67.50 Gy to PTVp, and 75 Gy to PTVdil. Standard plans (SD-VMAT) were created to fulfil targets coverage and Quantec constraints for conventional OARs (SD_OARs: rectum, bladder, and femoral heads). For each patient, a new “sexual-sparing” plan (SS-VMAT) was created adding new objectives for S_OARs with priority to minimize mean doses to IPAs, CC, and PB. Dose-volume histogram end points were compared between the 2 plans using Wilcoxon test. ResultsD98% were >95% of prescribed doses for all targets and techniques. No significant differences were found in sparing SD_OARs for considered metrics. Regarding S_OARs, SS_VMAT plans provided a significant reduction of the dose. Mean dose reduction for IPAs, CC, PB, and neurovascular bundles was 32.4% (11.2 Gy, p = 0.002), 22.5% (4.1 Gy, p = 0.006), 10.0% (4.6 Gy, p = 0.010), and 2.6% (1.8 Gy, p = 0.020), respectively. ConclusionsWe showed that a significant dose sparing for S_OARs using VMAT-SIB strategy is feasible allowing “sexual-sparing” and highly conformal plans with dose escalation to the DIL.

Traitement focal par HIFU versus prostatectomie radicale robot-assistée pour cancer de la prostate localisé : résultats carcinologiques et fonctionnels à 1 an

To analyse the functional and oncologic outcomes at one year of focal therapy with HIFU compared with total prostatectomy in patients with localised prostate cancer (PCa). Retrospective and monocentric study from 2008 to 2014 comparing 2 cohorts of patients with localised PCa (T1/T2 clinical stage, Gleason score≤3+4=7 and PSA<15ng/mL), one treated by focal therapy (HIFU-F group), one by robot-assisted total prostatectomy (RATP group). Primary outcome was a trifecta defined as: absence of urinary incontinence, erectile function with sexual relations without treatment, negative PSA with negative surgical margins (RATP group) or negative biopsy cores (HIFU-F group). The 53 patients included in the "HIFU-F" group and the 66 patients in the "RATP" group were similar in terms of preoperative PSA, D'Amico risk group, erectile function but were different in terms of age, prostatic volume, length of cancer, Gleason score. Complication rate was not different. In multivariate analyse with propensity score, "HIFU-F" group achieved a better trifecta score than "RATP" group (OR=8,3, p=0,005). In case of low or intermediate risk localised PCa, "HIFU-F" group had better functional outcomes than initial learning curse "RATP" group, at one year. A long-term evaluation by a common endpoint is necessary to judge the oncological equivalence of both techniques. 3.

ONE SHOT - single shot radiotherapy for localized prostate cancer: study protocol of a single arm, multicenter phase I/II trial

BackgroundStereotactic body radiotherapy (SBRT) is an emerging treatment alternative for patients with localized prostate cancer. Promising results in terms of disease control and toxicity have been reported with 4 to 5 SBRT fractions. However, question of how far can the number of fractions with SBRT be reduced is a challenging research matter. As already explored by some authors in the context of brachytherapy, monotherapy appears to be feasible with an acceptable toxicity profile and a promising outcome. The aim of this multicenter phase I/II prospective trialis to demonstrate early evidence of safety and efficacy of a single-fraction SBRT approach for the treatment of localized disease.MethodsPatients with low- and intermediate-risk localized prostate cancer without significant tumor in the transitional zone will be treated with a single SBRT fraction of 19 Gy to the whole prostate gland with urethra-sparing (17 Gy). Intrafractional motion will be monitored with intraprostatic electromagnetic transponders. The primary endpoint of the phase I part of the study will be safety as assessed by CTCAE 4.03 grading scale, while biochemical relapse-free survival will be the endpoint for the phase II. The secondary endpoints include acute and late toxicity, quality of life, progression-free survival, and prostate-cancer specific survival.DiscussionThis is the first multicenter phase I/II trial assessing the efficacy and safety of a single-dose SBRT treatment for patients with localized prostate cancer. If positive, results of ONE SHOT may help to design subsequent phase III trials exploring the role of SBRT monotherapy in the exclusive radiotherapy treatment of localized disease.Trial registrationClinicaltrials.gov identifier: NCT03294889; Registered 27 September 2017.

Clinical efficacy of intensity-modulated radiotherapy in treatment of 66 patients with intermediate risk localized prostate cancer

Objective To evaluate the clinical efficacy and adverse events of intensity-modulated radiotherapy (IMRT) in the treatment of intermediate risk localized prostate cancer, and analyze the significance of prostate-specific antigen (PSA) level changes. Methods Clinical data of 66 patients with intermediate risk localized prostate cancer admitted to our hospital between 2007 and 2018 were retrospectively analyzed. Sixty patients were treated with endocrine therapy before radiotherapy. The radiation field covered the pelvic lymph node drainage area in 6 cases. Forty-seven patients received image-guided radiotherapy (IGRT). The median dose in the prostate and seminal vesicle was 78 Gy and 48 Gy in the pelvic lymph node drainage area. The survival rate was calculated using the Kaplan-Meier method. Results The median age was 77 years. The median follow-up time was 71.3 months. The 5-year sample size was 47. The 3-and 5-year overall survival (OS) was 98% and 90%.The 3-and 5-year cancer-specific survival (CSS) was 100% and 93%.The 3-and 5-year biochemical relapse-free survival was 97% and 86%.The mean time of PSA declining to the nadir was 5.83 months. The median level of PSA nadir was 0.06 ng/ml after IMRT. The incidence of grade I and Ⅱ early adverse events in the urinary system was 38% and 6%. The incidence of grade I and Ⅱ early adverse events in the gastrointestinal system was 21% and 3%. The incidence of grade I and Ⅱ advanced-stage adverse events in the urinary system was 9% and 2%. The incidence of grade I advanced-stage adverse events in the gastrointestinal system was 5%. Conclusions IMRT yields high clinical efficacy in the treatment of intermediate risk localized prostate cancer with a low risk of adverse events in the early and advanced stage. The monitoring of PSA after IMRT contributes to the assessment of clinical prognosis. Key words: Prostate neoplasm/radiotherapy; Treatment outcome; Prostate-specific antigen

Survival outcomes for young men with localized intermediate-risk prostate cancer: An analysis of the NCDB.

e17085Background: There is no consensus on the optimal treatment of localized, intermediate-risk prostate cancer, especially in patients diagnosed at a young age with extended life expectancies. Pr...