Intermediate-risk Prostate Cancer Patients Research Articles

Validation of baseline health-related quality of life as prognostic indicator for survival outcome in men with intermediate risk prostate cancer undergoing radical prostatectomy.

340 Background: Accurate prediction of cancer outcomes remains a key component of prostate cancer (PC) treatment decision-making. Intermediate-risk PC patients represent a heterogeneous group with highly variable prognoses and it is challenging to provide uniform treatment recommendations for those patients. Previous studies have shown baseline health-related quality of life (HRQOL) to be a robust prognostic indicator for survival outcomes of different cancer entities in the metastatic setting, with scarce evidence on PC. We therefore sought to validate the predictive value of baseline HRQOL for survival outcomes in men with intermediate risk PC undergoing radical prostatectomy (RP). Methods: We identified 4780 patients with intermediate risk PC according to NCCN risk stratification and prospectively assessed baseline HRQOL prior RP. Patients were stratified by global health status (GHS) domain of the QLQ-C30 questionnaire. Oncologic endpoints were metastasis-free survival (MFS) and overall survival (OS). Multivariable Cox regression models were applied to assess the predictive value of baseline GHS on survival outcomes. Harrell's discrimination C-index was applied to calculate the predictive accuracy of the model. Decision curve analysis (DCA) was performed to validate the clinical net benefit associated with adding GHS to our multivariable model ( P < .05). Results: Median follow up was 51mo. In multivariable analysis, GHS was confirmed as an independent predictor for increased MFS (HR .98, 95% CI .97-.99; P = .028) and OS (HR .97, 95% CI .95-.99; P = .008), indicating a relative risk reduction of 1.7% for MFS and 2.8% for OS per 1-point increase of baseline GHS. Adding GHS to our model improved predictive accuracy of prognosis for MFS by 6% (c-index .75 vs .72) and for OS by 8% (c-index .78 vs .74). Validation with DCA revealed a net benefit over all thresholds in prediction of MFS and OS when adding GHS to our model. Conclusions: Our findings highlight that baseline HRQOL is a valuable and robust prognostic factor for patients with intermediate-risk PC prior RP. Baseline HRQOL data improve prognostic accuracy of MFS and OS and can therefore support treatment decision-making. [Table: see text]

Clinical implications of endogenous testosterone density on prostate cancer progression in patients with very favorable low and intermediate risk treated with radical prostatectomy.

We tested the association between endogenous testosterone density (ETD; the ratio between endogenous testosterone [ET] and prostate volume) and prostate cancer (PCa) aggressiveness in very favorable low- and intermediate-risk PCa patients who underwent radical prostatectomy (RP). Only patients with prostate-specific antigen (PSA) within 10 ng ml -1 , clinical stage T1c, and International Society of Urological Pathology (ISUP) grade group 1 or 2 were included. Preoperative ET levels up to 350 ng dl -1 were classified as abnormal. Tumor quantitation density factors were evaluated as the ratio between percentage of biopsy-positive cores and prostate volume (biopsy-positive cores density, BPCD) and the ratio between percentage of cancer invasion at final pathology and prostate weight (tumor load density, TLD). Disease upgrading was coded as ISUP grade group >2, and progression as recurrence (biochemical and/or local and/or distant). Risk associations were evaluated by multivariable Cox and logistic regression models. Of 320 patients, 151 (47.2%) had intermediate-risk PCa. ET (median: 402.3 ng dl -1 ) resulted abnormal in 111 (34.7%) cases (median ETD: 9.8 ng dl -1 ml -1 ). Upgrading and progression occurred in 109 (34.1%) and 32 (10.6%) cases, respectively. Progression was predicted by ISUP grade group 2 (hazard ratio [HR]: 2.290; P = 0.029) and upgrading (HR: 3.098; P = 0.003), which was associated with ISUP grade group 2 (odds ratio [OR]: 1.785; P = 0.017) and TLD above the median (OR: 2.261; P = 0.001). After adjustment for PSA density and body mass index (BMI), ETD above the median was positively associated with BPCD (OR: 3.404; P < 0.001) and TLD (OR: 5.238; P < 0.001). Notably, subjects with abnormal ET were more likely to have higher BPCD (OR: 5.566; P = 0.002), as well as TLD (OR: 14.998; P = 0.016). Independently by routinely evaluated factors, as ETD increased, BPCD and TLD increased, but increments were higher for abnormal ET levels. In very favorable cohorts, ETD may further stratify the risk of aggressive PCa.

Clinical value of normal saline injection for expansion of the anterior perirectal space during prostate cryoablation.

The objective of this study is to describe the technique and evaluate the clinical value of normal saline (NS) injection for expanding the anterior perirectal space during prostate cryoablation for prostate cancer (PCa) patients. PCa patients who received cryoablation between August 2014 and December 2019 were enrolled, and the technique of NS injection was adopted. The complications were evaluated. The prostate-specific antigen (PSA) nadir and biochemical progression-free survival (bPFS) were measured in localized PCa patients who received cryoablation as the primary treatment. A total of 159 PCa patients were included. Among 147 patients with the data of anterior perirectal space, the median (interquartile range [IQR]) distance of estimated iceball edge beyond the prostatic capsule was 8.3 (7.0-10.0) mm. No cases of urethrorectal fistula were reported; 29 patients developed urinary retention and 25 patients presented scrotal edema. All complications below Clavien-Dindo grade IIIb disappeared within 7 weeks after surgery. Urinary incontinence was reported in 6 patients. Among localized PCa patients, the median (IQR) follow-up time was 56.5 (36.0-73.5) months. The estimated 5-year bPFS was 82.3% overall, 82.8% for low-to intermediate-risk PCa patients, and 82.1% for high-risk PCa patients. For 52 patients received cryoablation alone, the median (IQR) PSA nadir was 0.147 (0.027-0.381) ng/mL. The technique of NS injection for expanding the anterior perirectal space during cryoablation surgery could avoid urethrorectal fistula and might benefit localized PCa patients with lower PSA nadir and longer bPFS.

Long-term oncologic outcomes of low dose-rate brachytherapy compared to hypofractionated external beam radiotherapy for intermediate -risk prostate cancer

PURPOSETo compare the long-term oncologic outcomes of intermediate risk (IR) prostate cancer (PCa) patients treated with low dose-rate brachytherapy (LDR-BT) or moderate hypofractionated external beam radiotherapy (HF-EBRT). METHODS AND MATERIALSPatients diagnosed with IR PCa and treated with LDR-BT or HF-EBRT between January 2005 and December 2013 were included. Brachytherapy treatment involved a transperineal implant of iodine-125 to a dose of 145 Gy to the PTV, while HF-EBRT was delivered using intensity modulated radiotherapy with 60 Gy in 20 fractions. The Phoenix ‘‘nadir +2’’ threshold was used to define biochemical relapse (BR). The cumulative incidence function (CIF) of BR and metastases was reported for each group and compared using the Gray's test to account for the competing risk of death. The Kaplan-Meier (KM) method was used to estimate overall survival (OS) and prostate cancer specific survival (PCSS). Univariate (UVA) and multivariable (MVA) analysis of the CIF of BR and metastases were performed. A 2-tailed p-value ≤ 0.05 was considered statistically significant. RESULTSOverall, 122 and 124 patients were treated with LDR-BT and HF-EBRT respectively. Median follow-up was 95 months [interquartile range (IQR): 79–118] in the LDR-BT group and 96 months (IQR: 63–123) in the HF-EBRT group. BR was observed in 5 patients treated with LDR-BT and 34 treated with HF-EBRT. At 60 and 90 months, the CIF of BR was 0.9% and 3.5% in the LDR-BT group vs. 16.6% and 23.7% in the HF-EBRT (p < 0.001). The CIF of metastases at 90 and 108 months, was 0% and 1.6% vs. 3.4% and 9.1% in the LDR-BT and HF-EBRT groups (p = 0.003), respectively. At the last follow-up, 3 patients treated with HF-EBRT died from their cancer [PCSS of 97.5% at 8 years and none died in the LDR-BT group (p = 0.09). On UVA and MVA risk group and treatment modality were independently associated with CIF of BR. On UVA HF-EBRT and ISUP grade group 3 were associated with metastases. CONCLUSIONLDR-BT was associated with higher biochemical and metastases control in our cohort when compared to moderately HF-EBRT. In the absence of a randomized trial, LDR-BT when feasible should be offered to patients with a life expectancy of >8 years.

Pattern of Radiotherapy Treatment in Low-Risk, Intermediate-Risk, and High-Risk Prostate Cancer Patients: Analysis of National Cancer Database.

In this study, the utilization rates and survival outcomes of different radiotherapy techniques are compared in prostate cancer (PCa) patients stratified by risk group. We analyzed an extensive data set of N0, M0, non-surgical PCa patients diagnosed between 2004 and 2015 from the National Cancer Database (NCDB). Patients were grouped into six categories based on RT modality: an intensity-modulated radiation therapy (IMRT) group with brachytherapy (BT) boost, IMRT with/without IMRT boost, proton therapy, stereotactic body radiation therapy (SBRT), low-dose-rate brachytherapy (BT LDR), and high-dose-rate brachytherapy (BT HDR). Patients were also stratified by the National Comprehensive Cancer Network (NCCN) guidelines: low-risk (clinical stage T1-T2a, Gleason Score (GS) ≤ 6, and Prostate-Specific Antigen (PSA) &lt; 10), intermediate-risk (clinical stage T2b or T2c, GS of 7, or PSA of 10-20), and high-risk (clinical stage T3-T4, or GS of 8-10, or PSA &gt; 20). Overall survival (OS) probability was determined using a Kaplan-Meier estimator. Univariate and multivariate analyses were performed by risk group for the six treatment modalities. The most utilized treatment modality for all PCa patients was IMRT (53.1%). Over the years, a steady increase in SBRT utilization was observed, whereas BT HDR usage declined. IMRT-treated patient groups exhibited relatively lower survival probability in all risk categories. A slightly better survival probability was observed for the proton therapy group. Hormonal therapy was used for a large number of patients in all risk groups. This study revealed that IMRT was the most common treatment modality for PCa patients. Brachytherapy, SBRT, and IMRT+BT exhibited similar survival rates, whereas proton showed slightly better overall survival across the three risk groups. However, analysis of the demographics indicates that these differences are at least in part due to selection bias.

The Association between Dose Escalation and Risk of Developing Metastases in Intermediate and High-Risk Prostate Cancer Patients Treated with Radiotherapy

<h3>Purpose/Objective(s)</h3> Radiotherapy dose escalation through brachytherapy or simultaneous integrated boost have been successfully introduced to clinical practice, facilitating improved local control of the tumor in intermediate and high-risk prostate cancer (PCa) patients, but not necessarily improved metastasis-free survival. Moreover, the improvement in clinical endpoints is often associated with increased risk of adverse effects. In this article, we analyzed effect of high dose-rate (HDR) brachytherapy boost (BT) dose escalation on freedom from metastases (FFM), based on real-world data. <h3>Materials/Methods</h3> The analysis was based on a multi-institutional retrospective database of 1641 consecutive intermediate (30%) or high risk (70%) prostate cancer patients treated with external beam radiotherapy (EBRT; 70.9%) or EBRT, combined with single or double fraction BT boost (29.1%). The majority of the patients (95%) received anti-androgen therapy (ADT). The biologically effective dose was calculated using α/β of 3 Gy. The follow-up data was acquired from institutional databases. The analysis included the Kaplan-Meier method and Cox regression models. A multivariable model was constructed utilizing backward stepwise feature selection based on Akaike information criterion. The model presented adjusted hazard ratios (HR) in multivariable analysis, and was further used to create a nomogram. C-index was used to assess the model. <h3>Results</h3> The median age was 63.8 years (IQR 62.9 – 73.5). Median FFM was not achieved, metastasis occurred in 234 patients (14.1%) over the course of follow up. The univariate analysis showed that BED was significantly associated with FFM (HR 0.99; CI 95% 0.98-0.99; p<0.001), along with Gleason grade group, PSA density, maximum PSA, pre-treatment PSA, T and N stage according to TNM, previous transurethral resection of the prostate, and NCCN risk group. Backward stepwise feature selection allowed to create multivariable model which included BED, prostate volume, Gleason grade group and NCCN risk groups. This model presented c-index of 0.665 and 5-fold cross-validation-corrected c-index of 0.652. The results are presented in Table 1. This model was used to create a clinical nomogram for FFM. <h3>Conclusion</h3> Biologically effective dose is an independent prognostic factor for developing metastases in patients treated with radiotherapy for intermediate or high-risk group prostate cancer. Dose escalation through brachytherapy boost can be used to decrease the risk of developing metastases in patients with adverse features.

Combined Brachytherapy and Ultra-Hypofractionated Radiotherapy for Intermediate-Risk Prostate Cancer: Comparison of Toxicity Outcomes Using a High-Dose Rate (HDR) vs. Low-Dose Rate (LDR) Brachytherapy Boost

<h3>Purpose/Objective(s)</h3> Combined brachytherapy and external beam radiotherapy is an accepted treatment for unfavorable intermediate-risk and high-risk prostate cancer. We compared genitourinary and gastrointestinal toxicity of low-dose-rate (LDR) and high-dose-rate (HDR) brachytherapy boost when combined with ultra-hypofractionated external beam radiation therapy (UH-EBRT) for prostate cancer. <h3>Materials/Methods</h3> 99 intermediate-risk prostate cancer patients underwent UH-EBRT (5 Gy x 5) combined with brachytherapy HDR (n=59) or LDR (n=40) boost. HDR brachytherapy consisted of 15 Gy using Iridium-192, and LDR brachytherapy consisted of Palladium-103 seed implantation (prescription dose=100 Gy). Median baseline IPSS was 5 for both cohorts. Median follow-up was 29.3 months. Toxicity assessment included Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, International Prostate Symptom Score (IPSS), and bowel symptom assessment. Cumulative incidences were calculated for toxicity outcomes. Fisher exact tests were used to evaluate associations. <h3>Results</h3> Overall incidence of grade 2 genitourinary toxicity at 12 and 24 months was 21% and 29%, respectively. The incidence of grade 2 genitourinary toxicity at 12 and 24 months was higher for LDR cohort compared with HDR cohort (45% versus 5.1%, and 55% versus 11%; p<0.001). No grade ≥3 or 4 toxicities were observed. On MVA, only treatment regimen (LDR versus HDR) was significantly associated with grade ≥2 genitourinary toxicity (p<0.001). Two patients had grade 2 rectal toxicity in each cohort. No grade ≥ 3 or 4 toxicities were observed. <h3>Conclusion</h3> Both LDR and HDR brachytherapy combined with UH-EBRT were associated with favorable toxicity profiles, but significantly less grade 2+ genitourinary toxicity was observed in patients receiving HDR compared with LDR brachytherapy.

Expanding Active Surveillance Criteria for Low- and Intermediate-risk Prostate Cancer: Can We Accurately Predict the Risk of Misclassification for Patients Diagnosed by Multiparametric Magnetic Resonance Imaging–targeted Biopsy?

Models predicting the risk of adverse pathology (ie, International Society of Urological Pathology [ISUP] grade group ≥3, pT3, and/or pN1) among patients operated by radical prostatectomy (RP) have been proposed to expand active surveillance (AS) inclusion criteria. We aimed to test these models in a set of 1062 low-risk and favorable intermediate-risk prostate cancer (PCa) patients diagnosed by multiparametric magnetic resonance imaging (MRI) and MRI-targeted biopsy. We hypothesized that the inclusion of radiological features into a novel model would improve patient selection. Performance was assessed using discrimination, calibration, and decision curve analysis (DCA). Available models were characterized by poor discrimination (areas under the receiver operating characteristic curve [AUCs] of 59% and 60%), underestimation of predicted risk on calibration plots, and a small amount of net benefit against a probability threshold of 40–50% at the DCA. The development of a novel model slightly improved discrimination (AUC of 63% vs 59%, p = 0.001, and 63% vs 60%, p = 0.07) and net benefit against threshold probabilities of ≥30%. This first multicenter study demonstrated the poor performance of models predicting adverse pathology and that implementation of MRI and MRI-targeted biopsy in this setting was not associated with a clear improvement in patient selection. Patients harboring low-risk or favorable intermediate-risk PCa and candidates for RP cannot be referred accurately to an AS program without a non-negligible risk of misclassification. Patient summaryWe tested prediction models that could expand the selection of prostate cancer patients for active surveillance. Models were inaccurate and associated with a high risk of misclassification despite the implementation of multiparametric magnetic resonance imaging and targeted biopsies.

Percentage Gleason pattern 4 and PI-RADS score predict upgrading in biopsy Grade Group 2 prostate cancer patients without cribriform pattern

PurposeTo identify parameters to predict upgrading in biopsy Grade Group (GG) 2 prostate cancer patients without cribriform and intraductal carcinoma (CR/IDC) on biopsy.MethodsPreoperative biopsies from 657 men undergoing radical prostatectomy (RP) for prostate cancer were reviewed for GG, presence of CR/IDC, percentage Gleason pattern 4, and tumor length. In men with biopsy GG2 without CR/IDC (n = 196), clinicopathologic features were compared between those with GG1 or GG2 without CR/IDC on RP (GG ≤ 2−) and those with GG2 with CR/IDC or any GG > 2 (GG ≥ 2+). Logistic regression analysis was used to predict upgrading in the biopsy cohort.ResultsIn total 283 men had biopsy GG2 of whom 87 (30.7%) had CR/IDC and 196 (69.3%) did not. CR/IDC status in matched biopsy and RP specimens was concordant in 179 (63.3%) and discordant in 79 (27.9%) cases (sensitivity 45.1%; specificity 92.6%). Of 196 biopsy GG2 men without CR/IDC, 106 (54.1%) had GG ≥ 2+ on RP. Multivariable logistic regression analysis showed that age [odds ratio (OR): 1.85, 95% confidence interval (CI)1.09–3.20; p = 0.025], percentage Gleason pattern 4 (OR 1.54, 95% CI 1.17–2.07; p = 0.003), PI-RADS 5 lesion (OR 2.17, 95% CI 1.03–4.70; p = 0.045) and clinical stage T3 (OR 3.60; 95% CI 1.08–14.50; p = 0.049) were independent parameters to predict upgrading to GG ≥ 2+ on RP in these men.ConclusionsAge, clinical stage T3, percentage Gleason pattern 4 and presence of PI-RADS 5 lesions are independent predictors for upgrading in men with biopsy GG2 without CR/IDC. These findings allow for improved clinical decision-making on surveillance eligibility in intermediate-risk prostate cancer patients.

Author Reply

All authors of the article “Predictive value of Cribriform and Intraductal Carcinoma for the Nomogram-Based Selection of Prostate Cancer Patients for Pelvic Lymph Node Dissection” sincerely appreciate the editorial comment. Although multiple retrospective studies have shown that nodal metastases are significantly more common in patients with CR/IDC, 1 Ericson KJ Wu SS Lundy SD Thomas LJ Klein EA McKenney JK. Diagnostic accuracy of prostate biopsy for detecting cribriform Gleason pattern 4 carcinoma and intraductal carcinoma in paired radical prostatectomy specimens: implications for active surveillance. The Journal of urology. 2020; 203: 311-319 Crossref PubMed Scopus (0) Google Scholar , 2 Wang L Deng FM Huang H Lee P Melamed J.M Zhou M. Gleason score 7 and 8 prostate cancer with cribriform morphology diagnosed in prostate biopsy is more likely to have seminal vesicle invasion and pelvic lymph node metastasis in radical prostatectomy. Mod Pathol. 2017; 30: 266A Google Scholar , 3 Downes MR Xu B van der Kwast TH. Cribriform architecture prostatic adenocarcinoma in needle biopsies is a strong independent predictor for lymph node metastases in radical prostatectomy. Eur J Cancer [Internet]. 2020; (Available from)https://linkinghub.elsevier.com/retrieve/pii/S0959804920305244 PubMed Google Scholar CR/IDC status did not improve the prediction of nodal metastases in our study. However, the “Letter to the Editor” clearly points out that presence of cribriform and intraductal carcinoma (CR/IDC) could allow the selection of intermediate-risk prostate cancer patients for extended pelvic lymph node dissection. Unfortunately, the number of intermediate-risk patients in our study leave us underpowered to validate the clinical benefit of a CR/IDC-enriched nomogram in this cohort. Recently, Yu et al. retrospectively demonstrated that the addition of CR/IDC status to pretreatment prostate cancer classification tools (ie, the Cancer of Prostate Risk Assessment and National Comprehensive Cancer Network [NCCN] risk scores) particularly improves the outcome stratification of intermediate-risk prostate cancer patients. 4 Yu Y Lajkosz K Finelli A Fleshner N van der Kwast TH Downes MR Impact of cribriform pattern 4 and intraductal prostatic carcinoma on National Comprehensive Cancer Network (NCCN) and Cancer of Prostate Risk Assessment (CAPRA) patient stratification. Modern Pathol. 2022; : 1-7 PubMed Google Scholar Alterations in the risk stratification may eventually affect treatment recommendations for these patients. Given the increased interest in integrating CR/IDC into clinical decision making, not only for guiding nodal dissections, but eg also for the selection of patient for active surveillance, 5 Ericson KJ Wu SS Lundy SD Thomas LJ Klein EA McKenney JK. Diagnostic accuracy of prostate biopsy for detecting cribriform Gleason pattern 4 carcinoma and intraductal carcinoma in paired radical prostatectomy specimens: implications for active surveillance. J Urol. 2020; 203: 311-319 Crossref PubMed Scopus (21) Google Scholar prospective studies evaluating the value of biopsy-identified CR/IDC for oncological outcomes and clinical decision making in intermediate-risk prostate cancer patients are needed.

Active Surveillance in Intermediate-Risk Prostate Cancer: A Review of the Current Data.

Simple SummaryAS is an option for the initial management of selected patients with intermediate-risk PC. The proper way to predict which men will have an aggressive clinical course or indolent PC who would benefit from AS has not been unveiled. Genetics and MRI can help in the decision-making, but it remains unclear which men would benefit from which tests. In addition, there are several differences between AS protocols in inclusion criteria, monitoring follow-up, and triggers for active treatment. Large series and a few RCTs are under investigation, and more research is needed to establish an optimal therapeutic strategy for patients with intermediate-risk PC. This study summarizes the current data on patients with intermediate-risk PC under AS, recent findings, and discusses future directions.Active surveillance (AS) is a monitoring strategy to avoid or defer curative treatment, minimizing the side effects of radiotherapy and prostatectomy without compromising survival. AS in intermediate-risk prostate cancer (PC) has increasingly become used. There is heterogeneity in intermediate-risk PC patients. Some of them have an aggressive clinical course and require active treatment, while others have indolent disease and may benefit from AS. However, intermediate-risk patients have an increased risk of metastasis, and the proper way to select the best candidates for AS is unknown. In addition, there are several differences between AS protocols in inclusion criteria, monitoring follow-up, and triggers for active treatment. A few large series and randomized trials are under investigation. Therefore, more research is needed to establish an optimal therapeutic strategy for patients with intermediate-risk disease. This study summarizes the current data on patients with intermediate-risk PC under AS, recent findings, and discusses future directions.

Differences in rates of pelvic lymph node dissection in National Comprehensive Cancer Network favorable, unfavorable intermediate- and high-risk prostate cancer across United States SEER registries.

The National Comprehensive Cancer Network (NCCN) guidelines recommend pelvic lymph node dissection (PLND) in NCCN high- and intermediate-risk prostate cancer patients. We tested for PLND nonadherence (no-PLND) rates within the Surveillance Epidemiology and End Results (2010-2015). We identified all radical prostatectomy patients who fulfilled the NCCN PLND guideline criteria (n = 23,495). Nonadherence rates to PLND were tabulated and further stratified according to NCCN risk subgroups, race/ethnicity, geographic distribution, and year of diagnosis. Overall, the no-PLND rate was 26%; it was 41%, 25%, and 11% in the NCCN intermediate favorable, intermediate unfavorable, and high-risk prostate cancer patients, respectively (p < 0.001). Over time, the no-PLND rates declined in the overall cohort and within each NCCN risk subgroup. Georgia exhibited the highest no-PLND rate (49%), whereas New Jersey exhibited the lowest (15%). Finally, no-PLND race/ethnicity differences were recorded only in the NCCN intermediate unfavorable subgroup, where Asians exhibited the lowest no-PLND rate (20%) versus African Americans (27%) versus Whites (26%) versus Hispanic-Latinos (25%). The lowest no-PLND rates were recorded in the NCCN high-risk patients followed by NCCN intermediate unfavorable and favorable risk in that order. Our findings suggest that unexpectedly elevated differences in no-PLND rates warrant further examination. In all the NCCN risk subgroups, the no-PLND rates decreased over time.

Hypofractionated Radiotherapy in Intermediate-Risk Prostate Cancer Patients: Long-Term Results.

Background: To evaluate outcomes in terms of survival and toxicity in a series of intermediate-risk prostate cancer (PCa) patients treated with hypofractionated radiotherapy (HyRT) + hormonal therapy (HT) with or without image guidance (IGRT) and to investigate the impact of different variables. Methods: This is a multi-centric study. From January 2005 to December 2019, we treated 313 intermediate-risk PCa patients (T2b–T2c, Gleason score 7, or pre-treatment PSA 10 to 20 ng/mL) with HyRT. Patients received 54.75 Gy in 15 fractions in 5 weeks plus 9 months of neo-adjuvant, concomitant, and adjuvant HT with or without IGRT. Results: Median follow-up was 91.6 months (range 5.1–167.8 months). Median OS was not reached, and the 8- and 10-year OS was 81.9% and 72.4%, respectively. Median CSS was not reached, and the 8- and 10-year CSS was 97.9% and 94.5%, respectively. PSA at first follow-up <0.8 ng/mL was significantly related to better oncological outcomes (CSS, bRFS, LRFS, cPFS, and MFS) in both univariate and multivariate analysis. After Propensity Score matching, grade 2–3 acute and cumulative late GU (p = 0.153 and p = 0.581, respectively) and GI (p = 0.196 and p = 0.925, respectively) toxicity were not statistically different in patients treated with or without IGRT. Conclusions: HyRT is effective and safe regardless of the use of IGRT. PSA at first follow-up is an easily accessible prognostic factor that may help the clinicians to identify patients who require a treatment intensification.

Value of 68Ga-labeled bombesin antagonist (RM2) in the detection of primary prostate cancer comparing with [18F]fluoromethylcholine PET-CT and multiparametric MRI—a phase I/II study

ObjectivesThe bombesin derivative RM2 is a GRPr antagonist with strong binding affinity to prostate cancer (PCa). In this study, the impact of [68Ga]Ga-RM2 positron emission tomography-computed tomography (PET-CT) for the detection of primary PCa was compared with that of [18F]FCH PET-CT and multiparametric magnetic resonance imaging (mpMRI).MethodsThis phase I/II study was conducted in 30 biopsy-positive PCa subjects. The patients were stratified into high (10 patients), intermediate (10 patients), and low risk (10 patients) for extraglandular metastases as defined by National Comprehensive Cancer Network (NCCN) criteria (NCCN Clinical Practice Guidelines in Oncology, 2016). The prostate gland was classified in 12 anatomic segments for data analysis of the imaging modalities as well as histopathologic findings. The segment with the highest radiotracer uptake was defined as the “index lesion.” All cases were scheduled to undergo prostatectomy with pelvic lymph node (LN) dissection in intermediate- and high-risk patients. Intraprostatic and pelvic nodal [68Ga]Ga-RM2 and [18F]FCH PET-CT findings were correlated with mpMRI and histopathologic results.ResultsOf the 312 analyzed regions, 120 regions (4 to 8 lesions per patient) showed abnormal findings in the prostate gland. In a region-based analysis, overall sensitivity and specificity of [68Ga]Ga-RM2 PET-CT in the detection of primary tumor were 74% and 90%, respectively, while it was 60% and 80% for [18F]FCH PET-CT and 72% and 89% for mpMRI. Although the overall sensitivity of [68Ga]Ga-RM2 PET-CT was higher compared to that of [18F]FCH PET-CT and mpMRI, the statistical analysis showed only significant difference between [68Ga]Ga-RM2 PET-CT and [18F]FCH PET-CT in the intermediate-risk group (p = 0.01) and [68Ga]Ga-RM2 PET-CT and mpMRT in the high-risk group (p = 0.03). In the lesion-based analysis, there was no significant difference between SUVmax of [68Ga]Ga-RM2 and [18F]FCH PET-CT in the intraprostatic malignant lesions ([68Ga]Ga-RM2: mean SUVmax: 5.98 ± 4.13, median: 4.75; [18F]FCH: mean SUVmax: 6.08 ± 2.74, median: 5.5; p = 0.13).Conclusions[68Ga]Ga-RM2 showed promising PET tracer for the detection of intraprostatic PCa in a cohort of patients with different risk stratifications. However, significant differences were only found between [68Ga]Ga-RM2 PET-CT and [18F]FCH PET-CT in the intermediate-risk group and [68Ga]Ga-RM2 PET-CT and mpMRT in the high-risk group. In addition, GRP-R-based imaging seems to play a complementary role to choline-based imaging for full characterization of PCa extent and biopsy guidance in low- and intermediate-metastatic-risk PCa patients and has the potential to discriminate them from those at higher risks.Key Points• [68Ga]Ga-RM2 is a promising PET tracer with a high detection rate for intraprostatic PCa especially in intermediate-risk prostate cancer patients.• GRPr-based imaging seems to play a complementary role to choline-based or PSMA-based PET/CT imaging in selected low- and intermediate-risk PCa patients for better characterization and eventually biopsy guidance of prostate cancer disease.

Four-year quality-of-life outcomes in low- to intermediate-risk prostate cancer patients following definitive stereotactic body radiotherapy versus management with active surveillance.

To review quality-of-life (QoL) metrics between patients who underwent definitive stereotactic body radiotherapy (SBRT) versus active surveillance (AS) for management of low- to intermediate-risk prostate cancer (PCa). A prospectively maintained PCa database was reviewed containing results of patient-reported QoL surveys. Patients with localized disease who chose AS or SBRT and completed at least one survey within four years of treatment were included. Patients who received salvage therapy were excluded. Survey results were compared across time using mixed-effects repeated measures analysis of covariance models that adjusted for factors significant in univariate analysis. A group x time interaction effect was examined to compare rate of change over time between AS and SBRT. P < 0.05 was significant. 148 AS and 161 SBRT patients were included. Significantly more SBRT patients had intermediate-risk disease (p < 0.0001). AS had significantly worse sexual function compared to SBRT across time. While not significant, bowel function scores were lower for SBRT patients across time points. SBRT patients had significantly lower anxiety than AS patients at 24months (p < 0.011) and 36months (p < 0.010). Urinary function though worse in SBRT patients at 12months in EPIC, was not significantly different in both groups across time points. SBRT patients have excellent QoL compared to AS with regard to anxiety post treatment. Though SBRT patients initially have worse urinary and bowel function than AS, scores were eventually similar in both cohorts by 48 months. SBRT patients have significantly worse sexual function post treatment. This study may help facilitate counseling in patients choosing PCa treatment.

After ASCENDE-RT: Biochemical and survival outcomes following combined external beam radiotherapy and low-dose-rate brachytherapy for high-risk and unfavourable intermediate-risk prostate cancer, a population-based analysis

PURPOSETo evaluate the outcomes of unfavorable intermediate-risk (UIR) and high-risk (HR) prostate cancer patients treated with combined external beam radiation therapy (EBRT) and low-dose-rate prostate brachytherapy (LDR-PB). METHODS AND MATERIALSA population-based cohort of 568 prostate cancer patients treated with combined EBRT and LDR-PB from 2010 to 2016 was analyzed. All patients received EBRT followed by LDR-PB boost. Outcomes were compared with the results for the brachytherapy arm of the ASCENDE-RT trial. RESULTSThe median followup was 4.5 years. Sixty-nine percent (N = 391) had HR disease. Ninety-four percent of the HR and 57% of UIR were treated with androgen deprivation therapy (ADT) with a median duration of 12 months. The 5-year K-M biochemical progression-free survival (b-PFS), metastasis-free survival (MFS), and overall survival (OS) were 84 ± 2%, 90 ± 2%, and 88 ± 2%, similar to 89 ± 5%, 94 ± 4%, and 92 ± 4% for the ASCENDE-RT LDR-PB arm. The likelihood of achieving a PSA ≤0.2 ng/mL at 4 years was 88%, similar to 86% in the ASCENDE-RT LDR-PB arm. Thirty-three men (5.8%) would have been ineligible for ASCENDE-RT due to high-risk features. The 5-year K-M b-PFS, MFS and OS estimates were 86 ± 2%, 92 ± 1% and 89 ± 2% for the ASCENDE-RT eligible versus 56 ± 10% (p < 0.001), 73 ± 8% (p < 0.001), and 77 ± 9% (p = 0.098) for the ineligible patients. CONCLUSIONSIn this population-based cohort, combining LDR-PB with pelvic EBRT (+/- ADT) achieves very favorable b-PFS that compares to the LDR-PB arm of the ASCENDE-RT, supporting the generalizability of those results. Men ineligible for ASCENDE-RT, based on prognostic features, have a much higher risk of biochemical recurrence and metastatic relapse.

Feasibility of aspirin and/or vitamin D3 for men with prostate cancer on active surveillance with Prolaris® testing.

ObjectivesTo test the feasibility of a randomised controlled trial (RCT) of aspirin and/or vitamin D3 in active surveillance (AS) low/favourable intermediate risk prostate cancer (PCa) patients with Prolaris® testing.Patients and MethodsNewly‐diagnosed low/favourable intermediate risk PCa patients (PSA ≤ 15 ng/ml, International Society of Urological Pathology (ISUP) Grade Group ≤2, maximum biopsy core length <10 mm, clinical stage ≤cT2c) were recruited into a multi‐centre randomised, double‐blind, placebo‐controlled study (ISRCTN91422391, NCT03103152). Participants were randomised to oral low dose (100 mg), standard dose (300 mg) aspirin or placebo and/or vitamin D3 (4000 IU) versus placebo in a 3 × 2 factorial RCT design with biopsy tissue Prolaris® testing. The primary endpoint was trial acceptance/entry rates. Secondary endpoints included feasibility of Prolaris® testing, 12‐month disease re‐assessment (imaging/biochemical/histological), and 12‐month treatment adherence/safety. Disease progression was defined as any of the following (i) 50% increase in baseline PSA, (ii) new Prostate Imaging‐Reporting and Data System (PI‐RADS) 4/5 lesion(s) on multi‐parametric MRI where no previous lesion, (iii) 33% volume increase in lesion size, or radiological upstaging to ≥T3, (iv) ISUP Grade Group upgrade or (v) 50% increase in maximum cancer core length.ResultsOf 130 eligible patients, 104 (80%) accepted recruitment from seven sites over 12 months, of which 94 patients represented the per protocol population receiving treatment. Prolaris® testing was performed on 76/94 (81%) diagnostic biopsies. Twelve‐month disease progression rate was 43.3%. Assessable 12‐month treatment adherence in non‐progressing patients to aspirin and vitamin D across all treatment arms was 91%. Two drug‐attributable serious adverse events in 1 patient allocated to aspirin were identified. The study was not designed to determine differences between treatment arms.ConclusionRecruitment of AS PCa patients into a multi‐centre multi‐arm placebo‐controlled RCT of minimally‐toxic adjunctive oral drug treatments with molecular biomarker profiling is acceptable and safe. A larger phase III study is needed to determine optimal agents, intervention efficacy, and outcome‐associated biomarkers.

Rates of metastatic prostate cancer in newly diagnosed patients: Numbers needed to image according to risk level.

The numbers needed to image to identify pelvic lymph node and/or distant metastases in newly diagnosed prostate cancer (PCa) patients according to risk level are unknown. Relying on Surveillance, Epidemiology, and End Results (2010-2016), we tabulated rates and proportions of patients with (a) lymph node or (b) distant metastases according to National Comprehensive Cancer Network (NCCN) risk level and calculated the number needed to image (NNI) for both endpoints. Multivariable logistic regression analyses were performed. Of 145,939 newly diagnosed PCa patients assessable for analyses of pelvic lymph node metastases (cN1), 4559 (3.1%) harbored cN1 stage: 13 (0.02%), 18 (0.08%), 63 (0.3%), 512 (2.8%), and 3954 (14.9%) in low, intermediate favorable, intermediate unfavorable, high, and very high-risk levels. These resulted in NNI of 4619, 1182, 319, 35, and 7, respectively. Of 181,109 newly diagnosed PCa patients assessable for analyses of distant metastases (M1a-c ), 8920 (4.9%) harbored M1a-c stage: 50 (0.07%), 45 (0.1%), 161 (0.5%), 1290 (5.1%), and 7374 (22.0%) in low, intermediate favorable, intermediate unfavorable, high, and very high-risk. These resulted in NNI of 1347, 602, 174, 20, and 5, respectively. Our observations perfectly validated the NCCN recommendations for imaging in newly diagnosed high and very high-risk PCa patients. However, in unfavorable intermediate-risk PCa patients, in whom bone and soft tissue imaging is recommended, the NNI might be somewhat elevated to support routine imaging in clinical practice.

Assessing the impact of brachytherapy boost and androgen deprivation therapy on survival outcomes for patients with unfavorable intermediate-risk prostate cancer patients treated with external beam radiotherapy

BACKGROUNDCurrent recommendations regarding radiotherapy treatment for unfavorable intermediate-risk prostate cancer (UIR-PCa) include external beam radiotherapy (EBRT) ± brachytherapy boost (BT) ± androgen deprivation therapy (ADT). The ideal radiotherapy treatment approach for UIR-PCa has not been well-defined. We hypothesized that EBRT+BT±ADT is associated with improved overall survival (OS) relative to EBRT±ADT in men with UIR-PCa. MATERIALS AND METHODSThe National Cancer Database (NCDB) was used to retrospectively identify 32,246 men diagnosed between 2004 and 2015 with UIR-PCa who received EBRT (n = 13,265), EBRT+ADT (n = 13,123), EBRT+BT (n = 3440), or EBRT+BT+ADT (n = 2418). OS was the primary outcome. Inverse probability of treatment weighting was used to adjust for covariable imbalances and weight-adjusted multivariable analysis using Cox regression modeling was used to compare OS hazard ratios. RESULTSMedian follow-up was 60 months (range: 3–168 months). EBRT+ADT correlated with improved OS relative to EBRT alone on multivariable analysis (Hazard Ratio (HR): 0.92, [95% Confidence Interval: 0.87–0.98], p = 0.005). Compared to EBRT+ADT, EBRT+BT (HR: 0.77 [0.69–0.85], p = 3 × 10−7) and EBRT+BT+ADT (HR: 0.75 [0.67–0.83], p = 6 × 10−8) were associated with improved OS. Eight-years OS for the EBRT+ADT versus EBRT+BT+ADT was 70% and 78% (p < 0.0001), which is similar to historical clinical trials (ASCENDE-RT 9-year OS: 74% vs. 78%, p = 0.29). Relative to EBRT+BT, EBRT+BT+ADT was not associated with improved OS (HR: 0.99 [0.87–1.11], p = 0.82). CONCLUSIONSIn a large retrospective cohort, the addition of brachytherapy to EBRT correlated with improved survival in men with UIR-PCa. Men receiving EBRT+ADT+BT had improved OS relative to EBRT+ADT. The addition of ADT to EBRT, but not to EBRT+BT, correlated with improved OS.

MP57-16 IMPACT OF EXTENT OF LYMPHADENECTOMY ON ALL CAUSE MORTALITY IN PATIENTS WITH INTERMEDIATE AND HIGH-RISK PROSTATE CANCER MANAGED WITH RADICAL PROSTATECTOMY

You have accessJournal of UrologyCME1 May 2022MP57-16 IMPACT OF EXTENT OF LYMPHADENECTOMY ON ALL CAUSE MORTALITY IN PATIENTS WITH INTERMEDIATE AND HIGH-RISK PROSTATE CANCER MANAGED WITH RADICAL PROSTATECTOMY Furkan Dursun, Ahmed Elshabrawy, Hanzhang Wang, Michael A. Liss, Ronald Rodriguez, Dharam Kaushik, and Ahmed M. Mansour Furkan DursunFurkan Dursun More articles by this author , Ahmed ElshabrawyAhmed Elshabrawy More articles by this author , Hanzhang WangHanzhang Wang More articles by this author , Michael A. LissMichael A. Liss More articles by this author , Ronald RodriguezRonald Rodriguez More articles by this author , Dharam KaushikDharam Kaushik More articles by this author , and Ahmed M. MansourAhmed M. Mansour More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002640.16AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The role of limited versus extended pelvic lymph node dissection (PLND) in the surgical management of prostate cancer (PCa) remains controversial. We sought to evaluate the impact of the extent of PNLD on survival outcomes for patients with intermediate and high-risk PCa. METHODS: The NCDB was queried for patients with intermediate and high-risk PCa (according to AUA guidelines risk stratification), who were treated by radical prostatectomy (RP) and PLND from 2004 to 2013. We limited our cohort to men <70 years of age with a CCI=0. Patients were divided into 3 groups according to the number of excised LN as a surrogate for the extent of PLND (Group 1:1–9, Group 2:10–19, and Group 3:≥20 nodes). Primary outcome was overall survival (OS). All-cause mortality was evaluated using propensity score weighted Kaplan-Meir (KM) Curves and Cox regression models. RESULTS: 103,250 men had a new diagnosis of PCa, and 25.8% of those had high-risk PCa. The number of LN excised was <10 for 80.5%, 10-19 for 15.9%, and ≥20 for 3.6% of the patients. Figure 1 illustrates the KM curves in the propensity score-weighted cohorts. In intermediate-risk PCa patients, propensity score adjusted cox regression analysis showed OS benefit for group 2 compared to group 1 (HR0.86, CI0.79-0.93, p <0.001). Similarly, in high-risk patients, group 3 had better OS compared to group 1 (HR0.61, CI 0.47-0.78, p <0.001) (Table 1). pN+ disease rates were significantly higher in group 3 compared to group 1 and 2 in both intermediate and high-risk diseases. (Intermediate risk 9.3% vs. 1.5% and 4.5%, p <0.001; high risk 25.3% vs. 5.7% and 15.5%, p <0.001, respectively). CONCLUSIONS: Removal of ≥20 LNs during RP was associated with better OS for men with high-risk PCa. Similar survival benefit was noted in the intermediate-risk group with removal of 10-19 lymph nodes. Increased number of removed nodes was associated with increased likelihood of lymph node positivity and more accurate pathologic staging. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e988 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Furkan Dursun More articles by this author Ahmed Elshabrawy More articles by this author Hanzhang Wang More articles by this author Michael A. Liss More articles by this author Ronald Rodriguez More articles by this author Dharam Kaushik More articles by this author Ahmed M. Mansour More articles by this author Expand All Advertisement PDF DownloadLoading ...