PSA Values Research Articles

Effect of Variant Histopathology on Survival in Prostate Adenocarcinoma

Purpose: It was aimed to determine the possible effects of variant pathology associated with prostate adenocarcinoma on survival. Material and Methods: Data of patients who underwent radical prostatectomy for localized prostate cancer between January 2014 and 2020 were retrospectively analyzed. The survival rates according to the presence of variant histology associated with prostate adenocarcinoma were analyzed and compared in relation to the clinical and demographic data of the cases. Results: A total of 244 patients were operated for localized prostate cancer. Preoperative The ISUP grades and percentages of the patients were respectively as ISUP 1 (42%), ISUP 2 (38%), ISUP 3 (10%) and ISUP > 3 (10%). Variant histopathology was present in 26% of the patients [intraductal (81%), foamy cell (11%), ductal (6%) and neuroendocrine (2%)]. When prostate cancer and prostate cancer associated with variant histopathology groups were compared, the mean age and postoperative 1st month PSA values were 62.29± 6.36 vs 64.33± 5.77 years p=(0.025) and 0.32± 1.53 and 1.01± 2.98 ng/dl (p=0.022) respectively. Mean follow-up time for prostate cancer and prostate cancer associated with variant pathology was statistically similar (60.33±21.66 vs. 60.42±16.88 months). The mortality rates of the patients with and without variant histopathology were respectively as 11% and 14% (p=0.416). Conclusions: Associated variant pathology does not show a statistically significant decrease in survival rates of patients with localized prostate cancer receiving standard therapy. Rather, advanced age may have a role in the non-significant 3% difference in survival rate.

Patient adherence and early biochemical outcomes following relugolix with stereotactic body radiation therapy (SBRT) for unfavorable prostate cancer.

526 Background: Prostate SBRT offers an abbreviated treatment course with comparable efficacy to conventional radiotherapy. Injectable GnRH receptor agonists have been shown to improve cancer control when combined with radiotherapy. Relugolix is a new oral GnRH receptor antagonist which achieves rapid, sustained testosterone suppression. This prospective study sought to evaluate early testosterone suppression and PSA response following Relugolix and SBRT for unfavorable prostate cancer. Methods: This prospective study sought to evaluate early testosterone suppression and PSA response following Relugolix and SBRT for unfavorable prostate cancer. Relugolix was initiated at least 2 months prior to SBRT. PSA and total testosterone levels were obtained prior to and 1-4 months post SBRT. Profound castration was defined as serum testosterone < 20 ng/dL. Poor drug adherence was delineated as failure to reach profound castration. PSA nadir was defined as the lowest PSA value within 4 months of completion of SBRT. Per prior trials, we examined the percentage of patients who achieved PSA level of ≤ 0.5 ng/mL and < 0.2 ng/mL during the first 4 months post SBRT. Results: Between July 2021 and January 2023, 52 men were treated at Georgetown with Relugolix (4-6 months) and SBRT (36.25-40 Gy in 5 fractions) per an institutional protocol (IRB 12-1775). Median age was 71 years. 26.9% of patients were black and 28.8% were obese (BMI ≥30 kg/m2). The median pretreatment PSA was 9.1 ng/ml. 67% of patients were > Grade Group 3. 44 patients were intermediate- and 8 were high-risk. The disease volume was high (mean 43.6% of total cores involved). Patients initiated Relugolix at a median of 3.6 months prior to SBRT with a median of 6.2 total months. 92.3%of patients achieved profound castration during Relugolix treatment. Poor drug adherence was observed in 2 patients. A third patient chose to discontinue Relugolix due to side effects. By post-SBRT month 4, 87.2% and 74.4% of patients achieved PSA levels ≤ 0.5 ng/ml and ≤ 0.2 ng/ml, respectively. Conclusions: Relugolix combined with SBRT allows for high rates of profound castration with low early PSA nadirs. Given the potential benefits of Relugolix over injectable GnRH receptor agonists, its usage may be preferred, especially in specific patient populations (fear of needles, prior cardiovascular events). We observed a 96% compliance rate without the utilization of scheduled cues/reminders. This finding supports the notion that patients can consistently and successfully follow an oral ADT protocol in a real-world setting. Future studies should focus on barriers to medication access.

Identification of lymph node metastasis related genes in prostate cancer using weighted gene co-expression network analysis

Objective: To explore the molecular markers related to lymph node metastasis of prostate cancer (PCa) based on bioinformatics technology and carry out clinical verification. Methods: The differentially expressed genes of PCa with lymph node metastasis were screened from geo data, and the hub genes of the gene co expression network were constructed. The hub genes were incorporated into the support vector machine model to evaluate its prediction efficiency. The hub genes were verified in the TCGA data set and analyzed for immune infiltration. The clinical data of 80 patients with prostate cancer in the Fourth Hospital of Hebei Medical University from January 2019 to December 2022 were collected. The logistic risk model was used to evaluate the prediction efficiency of hub gene metastasis. Results: Five hub genes (GSK3B, TP53, PSMC6, SUMO1, PIK3CA) were identified, and the support vector machine model constructed by them had good diagnostic value (the accuracy rate was 83.87%). TCGA validation results showed that only PSMC6 was significantly differentially expressed in PCa tissues with lymph node metastasis (P<0.001). The results of immune infiltration analysis showed that the expression of PSMC6 was significantly correlated with 9 kinds of immune cells (B cells, DC, IDC, etc.). Clinical information analysis showed that the expression of PSMC6 was significantly correlated with lymph node metastasis, PSA value, T stage and Gleason score (P<0.01). Univariate logistic results showed that T stage (OR=3.230, 95%CI:1.192-8.757, P=0.021), Gleason score (OR=4.627, 95%CI:2.212-9.677, P<0.001), PSMC6 (OR=25.235, 95%CI:5.326-119.560, P<0.001) could be used as predictors of lymph node metastasis. Multivariate logistic analysis showed that PSMC6 (OR=16.537, 95%CI:2.928-93.393, P=0.001) could be used as an independent risk factor for predicting lymph node metastasis. Conclusion: PSMC6 may be used as a potential molecular marker for judging lymph node metastasis in patients with PCa.

Characteristics of incidental prostate cancer in the United States.

Data regarding North-American incidental (cT1a/b) prostate cancer (PCa) patients is scarce. To address this, incidental PCa characteristics (age, PSA values at diagnosis, Gleason score [GS]), subsequent treatment and cancer-specific survival (CSS) rates were explored. Incidental PCa patients were identified within the Surveillance, Epidemiology, and End Results (SEER) database (2004-2015). Descriptive statistics, annual percentage changes (EAPC), Kaplan-Meier estimates, as well as Cox regression models were used. Bootstrapping technique was used to generate 95% confidence intervals for CSS at 6 years. Of all 344,031 newly diagnosed non metastatic PCa patients, 5155 harbored incidental PCa. Annual rates of incidental PCa increased from 1.9% (2004) to 2.5 % (2015; p = 0.02). PSA values at diagnosis were 0-4 ng/ml in 48% vs. 4-10 ng/ml in 31% vs. > 10 ng/ml in 21%. Of all incidental PCa patients, 64% harbored GS 6 vs. 25% GS 7 vs. 11% GS ≥ 8. Of all incidental PCa patients, 47% were aged < 70, 35% were between 70 and 79 and 18% were ≥ 80 years. Subsequently, 71% underwent no local treatment (NLT) vs. 16% radical prostatectomy (RP) vs. 14% radiotherapy (RT). Proportions of patients with NLT increased from 65 to 81% (p = 0.0001) over the study period (2004-2015). CSS at six years ranged from 58% in GS ≥ 8 patients with NLT to 100% in patients who harbored GS 6 and underwent either RP or RT. Incidental PCa in the United States is rare. Most incidental PCa patients are diagnosed in men aged less than 80 years of age. The majority of incidental PCa patients undergo NLT and enjoy excellent CSS.

Early biochemical outcomes following neoadjuvant/adjuvant relugolix with stereotactic body radiation therapy for intermediate to high risk prostate cancer.

Injectable GnRH receptor agonists have been shown to improve cancer control when combined with radiotherapy. Prostate SBRT offers an abbreviated treatment course with comparable efficacy to conventionally fractionated radiotherapy. Relugolix is a new oral GnRH receptor antagonist which achieves rapid, sustained testosterone suppression. This prospective study sought to evaluate early testosterone suppression and PSA response following relugolix and SBRT for intermediate to high prostate cancer. Relugolix was initiated at least 2 months prior to SBRT. Interventions to improve adherence were not utilized. PSA and total testosterone levels were obtained prior to and 1-4 months post SBRT. Profound castration was defined as serum testosterone ≤ 20 ng/dL. Early PSA nadir was defined as the lowest PSA value within 4 months of completion of SBRT. Per prior trials, we examined the percentage of patients who achieved PSA level of ≤ 0.5 ng/mL and ≤ 0.2 ng/mL during the first 4 months post SBRT. Between July 2021 and January 2023, 52 men were treated at Georgetown with relugolix (4-6 months) and SBRT (36.25-40 Gy in 5 fractions) per an institutional protocol (IRB 12-1775). Median age was 71 years. 26.9% of patients were African American and 28.8% were obese (BMI ≥30 kg/m2). The median pretreatment PSA was 9.1 ng/ml. 67% of patients were ≥ Grade Group 3. 44 patients were intermediate- and 8 were high-risk. Patients initiated relugolix at a median of 3.6 months prior to SBRT with a median duration of 6.2 total months. 92.3% of patients achieved profound castration during relugolix treatment. Poor drug adherence was observed in 2 patients. A third patient chose to discontinue relugolix due to side effects. By post-SBRT month 4, 87.2% and 74.4% of patients achieved PSA levels ≤ 0.5 ng/ml and ≤ 0.2 ng/ml, respectively. Relugolix combined with SBRT allows for high rates of profound castration with low early PSA nadirs. We observed a 96% testosterone suppresion rate without the utilization of scheduled cues/reminders. This finding supports the notion that patients with localized prostate cancer can consistently and successfully follow an oral ADT protocol without daily reminders. Given relugolix's potential benefits over injectable GnRH receptor agonists, its usage may be preferred in specific patient populations (fear of needles, prior cardiovascular events). Future studies should focus on boundaries to adherence in specific underserved populations.

EAU Biochemical Recurrence Risk Classification and PSA Kinetics Have No Value for Patient Selection in PSMA-Radioguided Surgery (PSMA-RGS) for Oligorecurrent Prostate Cancer.

To assess the influence of biochemical recurrence (BCR) risk groups and PSA kinetics on the outcomes of radioguided surgery against prostate-specific membrane antigen (PSMA-RGS). Currently, neither BCR risk group nor PSA doubling time (PSA-DT), or PSA velocity (PSA-V) are actively assigned or relevant for counseling prior to PSMA-RGS. We retrospectively analyzed PSMA-RGS cases for oligorecurrent prostate cancer between 2014 and 2023. BCR risk groups, PSA-DT, and PSA-V were analyzed as predictors for complete biochemical response (cBR, PSA < 0.2 ng/mL), BCR-free, and therapy-free survival (BCRFS, TFS). Of 374 included patients, only 21/374 (6%) and 201/374 (54%) were classified as low- and high-risk BCR (no group assignment possible in 152/374, 41%). A total of 13/21 (62%) patients with low- and 120/201 (60%) with high-risk BCR achieved cBR (p = 1.0). BCR classification was no predictor for BCRFS (HR:1.61, CI: 0.70-3.71, p = 0.3) or subsequent TFS (HR:1.07, CI: 0.46-2.47, p = 0.9). A total of 47/76 (62%) patients with PSA-DT ≤ 6 mo and 50/84 (60%) with PSA-DT > 6 mo achieved cBR (p = 0.4). PSA-DT was not associated with cBR (OR: 0.99, CI: 0.95-1.03, p = 0.5), BCRFS (HR: 1.00, CI: 0.97-1.03, p = 0.9), or TFS (HR: 1.02, CI: 0.99-1.04, p = 0.2). Consistent negative findings were recorded for PSA-V. The BCR risk groups and PSA kinetics do not predict the oncological success of PSMA-RGS performed at low absolute PSA values. Indolent low-risk BCR is rarely treated by PSMA-RGS.

Association of Prostate Specific Antigen Kinetics after Testosterone Recovery with Subsequent Recurrence: Secondary Analysis of a Phase III Randomized Controlled Trial.

The combination of short-term androgen deprivation therapy (ST-ADT) with prostate radiotherapy (RT) is a standard of care for patients with localized prostate cancer (LPCa). After cessation of ST-ADT, it takes about 8 to 10 months for the testosterone (T) to recover to supracastrate levels, which could drive changes in PSA kinetics. It largely remains unknown whether early changes in PSA kinetics after T recovery could predict for subsequent biochemical relapse. We performed a secondary analysis of a phase III randomized controlled trial in which patients with newly diagnosed LPCa with Gleason score £7, clinical stage T1b to T3a, and PSA <30 ng/mL were randomly allocated to neoadjuvant and concurrent ADT for 6 months starting 4 months before prostate RT (76 Gy in 38 fractions over 7.5 weeks) or concurrent and adjuvant ADT for 6 months starting simultaneously with prostate RT. Clinical assessment and laboratory investigations were repeated 1 month after completion of ADT, every 4 months for the first 2 years, every 6 months for the next 3 years, and annually thereafter. We calculated the PSA doubling time (PSADT) based on PSA values up to 18 months after recovery of T to a supracastrate level (>50 ng/dL). Patients with ³3 PSA measurements after T recovery to supracastrate level were included in this analysis. Fine and Gray cumulative incidence of biochemical recurrence (BCR) was calculated in patients with PSADT at or above median versus below median. Deaths were considered as competing events. All endpoints were calculated from the time of T recovery to supracastrate level. Subdistribution hazard ratios (sHR) with 95% confidence intervals (CI) were estimated for association of PSADT with relative incidence of recurrence using competing risk regression after adjusting for tumor stage, pre-treatment PSA, Gleason score, treatment regimen, and age at randomization. Overall, 311 patients were eligible for this analysis. Median PSADT was 8 months. Cumulative incidence of BCR at 10 years was 31.0% and 20.7% in patients with PSADT <8 months and ³8 months, respectively. Longer PSADT was associated with a significantly lower risk of cumulative incidence of BCR (sHR for PSADT as a continuous variable 0.43, 95% CI: 0.28-0.66; sHR for PSADT ³8 months 0.54, 95% CI: 0.30-0.99). After adjustment for time to recovery of T to supracastrate level in addition to the aforementioned variables, longer PSADT (³8 months) was associated with lower risk of cumulative incidence of BCR (sHR: 0.53, 95% CI: 0.27-1.01). These findings suggest that early PSA kinetics within 18 months of recovery of T to a supracastrate level predict for subsequent biochemical failure. Taking account of early changes in PSA after testosterone recovery may allow for recognition of potential failures earlier in the disease course and thereby permit greater personalization of management decisions.

Indications for Adjuvant Radiation after Radical Prostatectomy as Predicted by Artificial Intelligence-Derived Dominant Intraprostatic Lesion Volume.

In prostate cancer, PI-RADs scores of dominant intraprostatic lesions (DILs) in multi-parametric magnetic resonance imaging (mpMRI) are prognostic; however, their inter-observer agreement is only moderate. Artificial intelligence (AI) may be a powerful tool for prognostication by analyzing a large number of scans consistently in a short amount of time. This study investigated whether the DIL volume (DILvol) provided by an AI deep-learning segmentation algorithm could predict adverse findings at radical prostatectomy (RP), some of which could warrant adjuvant radiation therapy (RT). We conducted a retrospective study of 185 consecutive patients with localized prostate cancer who underwent an endorectal coil, high B-value (> = 1000 s/mm2), 3-Tesla mpMRI followed by RP between 2015 and 2017. Using a previously trained deep learning nnUNet algorithm for providing DIL segmentations from patients treated with definitive RT, we segmented the DIL for the RP cohort. We evaluated the association of AI DILvol with the risks of adverse pathologic factors, including positive margins, pathologic T3 (pT3) disease, and pathologic Gleason (pGS8-10) disease, using separate univariate logistic regression models. We then included AI DILvol, pT3 (vs pT2), pGS8-10 (vs pGS6-7), margin status, and pre-RP PSA for predicting post-RP PSA values utilizing multivariate linear regression analysis. Finally, we included these same factors into a multivariate logistic regression analysis for predicting the risk of meeting adjuvant RT indications (PSA persistence post-RP > = 0.1 ng/mL or positive lymph nodes). The median time between RP and post-PSA value was 1.6 months. The Pearson's correlation coefficient between AI and reference DILvol (sum of manually contoured PI-RADS 3-5 lesions) was 0.86 (p < 0.001). The Pearson's correlation coefficient between AI DILvol and pathologic tumor size was 0.63 (p < 0.001). Utilizing separate univariate logistic regression models, we found that AI DILvol was significantly associated with the risks of positive margins (OR 1.31 [1.10, 1.58]; p = 0.003), pT3 (OR 1.59 [95% CI: 1.30, 1.99]; p < 0.001), and pGS8-10 (OR 1.28 [1.07, 1.56]; p = 0.01). On multivariate linear regression, AI DILvol (0.27/mL [0.25, 0.29]; p < 0.001) was significantly correlated with post-RP PSA values, after controlling for adverse factors and pre-RP PSA. On multivariate logistic regression, AI DILvol (adjusted OR 1.32 [1.05, 1.69]; p = 0.03) was the only factor significantly associated with the risk of meeting adjuvant RT indications after controlling for these same factors. For localized prostate cancer treated with RP, AI DILvol was the only factor significantly associated with the risk of meeting adjuvant RT indications, even after controlling for pathologic factors at RP. Further studies are needed to determine if AI DILvol is prognostic for long-term oncologic outcomes after RP.

Diagnostic Utility of PSMA 18F-DCFPyL PET/TC in Occult Biochemical Recurrence of Prostate Carcinoma with PSA Values

To analyze the diagnostic capability of PET-PSMA in clinical practice in patients with occult biochemical recurrence of prostate carcinoma with PSA values less than 2ng/ml. The first 116 patients who underwent PSMA 18F-DCFPyL PET/TC at the centers participating in the study for occult biochemical recurrence of prostatic neoplasia were selected. All patients had low PSA values (<2ng/ml). The studies were visually assessed by two experts in Nuclear Medicine, and classified dichotomously as positive or negative/inconclusive. The diagnostic capacity of the test was determined according to the PSA values, as well as the densities by groups. Descriptive statistical analysis was performed. The AUC was evaluated, determining the optimal cut-off point and its precision parameters. The retrospective analysis showed that 66/116 patients (56.9%) were positive, with statistically significant differences in the medians of the positive group (AUC 0.77) and 50/116 (43.1%) patients were negative (AUC 0.42). The study of densities by group showed a marked clustering of the negative/ inconclusive studies in PSA values less than 0.5 ng/ml. Correlation was observed between the PSA values and the detection capability of the test (AUC: 0,74). The optimal cut-off point calculated was 0,55 which showed a sensitivity of 0,75 and specificity of 0,68. PET-PSMA shows excellent diagnostic capability even in strictly selected patients with PSA values < 2ng/ml. Its indication with values < 0.5ng/mL should be assessed according to individual risk. In 56.9% of the patients in the study the positive result could influence changes in therapeutic strategy.

Change in Therapeutic Approach after PET/TC PSMA-18F DCFPyL in Occult Biochemical Recurrence of Prostate Carcinoma with Low PSA Values

To analyze changes in therapeutic attitude after PET-PSMA. in patients with occult biochemical recurrence after primary treatment with low PSA values. Retrospective study of patients diagnosed with prostate carcinoma who after primary treatment with curative intent present biochemical recurrence with low PSA values (<2ng/ml) and negative imaging tests (ultrasound, CT-Scan, MRI, GGO and/or PET-Choline). The assessment was performed by two expert nuclear physicians. All patients underwent a study with 300-350MBq PSMA-18F DCFPyL PET/TC, and after a follow-up of no less than six months we assessed whether there were changes in therapeutic attitude directly related to the results of the test. The clinical/therapeutic evaluation was performed by expert radiation oncologists. Descriptive statistical analysis was performed. RoC curves (sensitivity vs. 1-specificity) and the corresponding areas under the curve were calculated to assess the predictive power of the study. PET-PSMA with complete follow-up was performed on 85 patients aged 48-78 years (mean age 69 years) with occult biochemical recurrence. Most patients were staged T2 (50.58%) - T3 (48.23%), cases N1 (10.58%), Gleason score ≥ 7 (96%) with mean PSA level 11.24 ng/ml at diagnosis. The mean nadir PSA values of 0.13 mg/dl following primary treatment with radical intent. In 48.2% of patients (41/85) had a positive PET-PSMA during follow-up, pre-study the median PSA levels were 0,62 ng/dl. There is a correlation between the PSA value and the ability to detect disease in the PET-PSMA study (AUC: 0,74). In 75% of patients with positive PET-PSMA (31/41) there were changes in the therapeutic approach. This proportion was significantly lower (25%) in those without pathological PET findings (11/44). In PET-PSMA-positive patients the therapeutic changes found were classified as indicating or changing the planning of salvage radiotherapy treatment and/or initiating systemic treatment with hormone therapy (median PSA levels after treatment changes were 0.08 ng/dl). In cases with negative PET-PSMA a watchful waiting attitude was adopted. PET-PSMA is a powerful diagnostic tool that conditions significant changes in the therapeutic approach in those patients with occult biochemical recurrence with low PSA, changing the treatment in 75% of the cases when the study is positive.

Toxicity and Patient Reported Quality of Life after PSMA-PET and mpMRT-Based Focal Dose Escalated Definitive Radiotherapy in Prostate Cancer Patients: 2-Year Follow-Up of the HypoFocal Phase II Trial

The prospective, 2-armed non-randomized HypoFocal phase II trial investigates the safety and feasibility of focal dose escalated external beam radiotherapy (EBRT) and high-dose-rate brachytherapy (HDR-BT) for prostate cancer (PCa) patients based on PSMA-PET and multiparametric MRI. This approach improves tumor coverage and thus putatively treatment effectiveness but leads to larger boost volumes. Here we present toxicity and patient reported quality of life (QoL) results after 2 years follow-up (FU) MATERIALS/METHODS: Patients with intermediate- or high-risk PCa and cN0/cM0 stage were included. Patients in arm A received 60 Gy in 20 fractions to the prostate with an integrated boost of up to 75 Gy. Patients in arm B received one session HDR-BT with 15 Gy to the prostate and a boost of up to 19 Gy, followed by EBRT of 44 Gy in 20 fractions. Boost volumes were defined by PSMA-PET and mpMRI based on validated approaches. Genitourinary (GU) and gastrointestinal (GI) toxicity (CTCAE v5.0) and QoL with IPSS and EORTC questionnaires (QLQ30 and PR25) were assessed. Fifty patients were treated in both arms in two centers (Freiburg and Berlin). Table 1 shows patients characteristics. In arm, A grade 2 GU and GI toxicity rates after 2 years were 8% and 4%. There were no grade 3 GU toxicities. Two patients experienced grade 3 GI toxicities due to multifactorial causes. In Arm B grade 2 GU and GI toxicity rates after 2 years were 17% and 0%. No grade 3 toxicities were observed in arm B. Toxicities were not statistically significantly different between baseline and 2y FU (p>0.055). QoL analysis was performed with patients with available questionnaires at baseline and 2y FU (12-15 in Arm A and 13-15 in Arm B). Only bowel function (p = 0.0005, median 4 vs 25 points) in Arm A and sexual- (p = 0.016, median 25 vs 50 points) and bowel function (p = 0.004, median 0 vs 8 points) and dyspnea (p = 0.031, median 0 vs 0 points) in Arm B decreased significantly after 2 year FU. Other QoL items were not significantly different. Bowel symptoms were significantly worse in Arm A compared to Arm B (p = 0.003). Median PSA values after 2 years were 0.23 ng/ml in Arm A and 0.33 ng/ml in Arm B. Despite large boost volumes, the 2 years FU of the HypoFocal-Phase II trials shows no significantly increased GU and GU toxicities compared to baseline symptoms. Patients reported about a good QoL but increased bowel symptoms after 2 years, particularly if treated with EBRT only. Implementation of PSMA-PET into focal dose escalated radiotherapy approaches appears safe and feasible. However, radioproctitis demands careful management. The current PSA values suggest a highly effective therapy, but longer FU is needed to evaluate oncological outcomes. The HypoFocal-SBRT phase III trial will evaluate the PSMA-PET and mpMRI-based focal dose escalated SBRT.

Focal Boosted IMRT Treatment of Prostate Cancer to 84 Gy in 28 Fractions: Preliminary Clinical Outcomes and Dosimetry

The FLAME trial reported that focal boosting of prostate tumor to 95 Gy in 35 fractions improves biochemical control. However, this treatment is not commonly used in the United States. We investigated a focally boosted treatment of 84 Gy in 28 fractions (EQD2 108 Gy, BED 252 Gy). Between 2019-2022, men with unfavorable intermediate risk (uIR) and high risk (HR) prostate cancer were enrolled on a prospective registry and received a novel IMRT regimen. The dose levels were 84 Gy to the gross tumor volume (GTV) as defined on mpMRI (T2W and ADC) with no added margin, 70 Gy to the prostate and proximal seminal vesicles, and optional 50.4 Gy to elective pelvic lymph nodes (all 28 fractions). Patients received fiducial markers and hydrogel spacer. The treatment planning goal was to cover 95% of the GTV at 84 Gy, and also meet the target and normal tissue dosimetry criteria of the hypofractionated treatment arm of NRG-GU005. VMAT was used for treatment delivery. ADT was given at the discretion of the treating physician. A total of 20 men were included in the study, 2 (10%) uIR and 18 (90%) HR. 9 (45%) tumors were GS 7, 7 (35%) were GS 8, and 4 (20%) were GS 9. There were 13 (65%) stage cT1, 4 (20%) cT2 and 3 (15%) cT3. One (5%) patient received short term ADT, 18 (95%) long term ADT, and 1 (5%) refused ADT. 18 (90%) men received elective nodal radiation. The mean baseline PSA was 25.1 (range 4.2-73.4). The median baseline IPSS score was 11.1 (IQR 4.5-12), and 4 patients had severe baseline urinary symptoms (IPSS ≥20). The mean baseline prostate volume was 57.4 cc (range 26.8-198.3). The mean volume of the 84 Gy boost target was 7.1 cc (range 2.3-15.0) and the mean proportion of the prostate boosted was 14.8% (range 2% - 47%). There were 10 (50%) men with 1 boost target, 6 (30%) with two, 3 (15%) with three, and 1 (5%) had 4 boost targets. Targets were located in peripheral zone (85%), transition zone (30%), and central zone (5%). Patients met all per-protocol normal tissue criteria of NRG-GU005, except for bladder D0.03cc. The mean±SD (Gy) rectum D15%, D25%, and D30% were 51±5, 45±5, 42±4. The mean±SD (Gy) bladder D0.03cc, D30%, D50% were 79±4, 50±8, 38±10. At a median follow up time of 21.3 months (range 7.1-38.2), no patients have developed biochemical progression, local recurrence, distant progression, or death from prostate cancer. One patient died at 18 months from metastatic colorectal cancer, unrelated to prostate cancer treatment. Acute grade 1-2 GU toxicity occurred in 13 (65%) patients, and acute grade 1-2 GI toxicity occurred in 4 (20%) patients. No patients developed grade 3+ acute or late GU or GI toxicity. Two patients required temporary foley catheter for obstruction during RT, and both had IPSS >20 at baseline. The patient who refused ADT had a PSA bounce of magnitude 2.2 ng/mL at 14 months, PSA values declined without additional treatment. A novel 28-fraction focal boosted IMRT treatment is feasible and has an acceptable early toxicity profile. Oncologic results are promising but require longer follow up.

The diagnostic accuracy of 68 Ga-PSMA-PET/CT in primary staging of patients with high-risk nonmetastatic prostate cancer treated with radical prostatectomy: A single-center cohort analysis.

68 Ga-prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography(CT) is a recommended imaging modality for patients with recurrent prostate cancer (PCa). Its routine implementation before radical prostatectomy (RP) may allow avoiding undertreatment. We aimed to analyze the diagnostic accuracy of 68 Ga-PSMA-PET/CT for pelvic lymph node metastases in a large cohort of patients treated with RP and extended pelvic lymph node dissection (ePLND) for high-risk PCa. This is a retrospective analysis of an institutional database of patients who underwent 68 Ga-PSMA-PET/CT before RP and ePLND for high-risk PCa. The diagnostic estimates of 68 Ga-PSMA-PET/CT with 95% confidence intervals (CIs) for lymph node involvement were calculated. We included 165 high-risk PCa patients. The median PSA value was 24.5 ng/mL (range: 6.7-185) and all the patients had biopsy Grade Group 4-5. In total, 46 (28%) of patients had clinical lymph node involvement at 68 Ga-PSMA-PET/CT. A mean number of resected lymph nodes per patient was 22 (range: 15-45) and 149 (4.2%) of all resected nodes were positive for lymph node metastasis at final pathology. The diagnostic estimates for the detection of pN+ disease at RP were as follows: sensitivity 63% (95% CI: 51-75), specificity 97% (95% CI: 91-99), positive predictive value 94% (95% CI: 82-99), and negative predictive value 79% (95% CI: 70-86). The total accuracy of PSMA-PET was 83% (95% CI: 76-88). Our analyses support high specificity and positive predictive value of pretreatment 68 Ga-PSMA PET/CT for the detection of pelvic lymph node metastasis in patients treated with RP for high-risk PCa. While a positive finding should be considered as robust indicator for clinical decision-making, a negative result cannot reliably rule out the presence of lymph node involvement in high-risk PCa; there is a need for advanced risk stratification in those patients.

5-Years Analysis of Effectivity and Toxicity of Ultra-Hypofractionated Proton Radiotherapy in the Treatment of Low- and Intermediate-Risk Prostate Cancer-A Retrospective Analysis.

We retrospectively analyzed the 5-year biochemical disease-free survival (bDFS) and occurrence of late toxicity in prostate cancer patients treated with pencil beam scanning (PBS) proton radiotherapy. In the period from January 2013 to June 2018, 853 patients with prostate cancer were treated with an ultra-hypofractionated schedule (36.25 GyE/five fractions). The mean PSA value was 6.7 (0.7-19.7) µg/L. There were 318 (37.3%), 314 (36.8%), and 221 (25.9%) patients at low (LR), favorable intermediate (F-IR), and unfavorable intermediate risk (U-IR), respectively. Neoadjuvant hormonal therapy was administered to 197 (23.1%) patients, and 7 (0.8%) patients had adjuvant hormonal therapy. The whole group of patients reached median follow-up time at 62.7 months, and their mean age was 64.8 (40.0-85.7) years. The bDFS rates and late toxicity profile were evaluated. Median treatment time was 10 (7-38) days. Estimated 5-year bDFS rates were 96.5%, 93.7%, and 91.2% for low-, favorable intermediate-, and unfavorable intermediate-risk groups, respectively. Cumulative late toxicity (CTCAE v4.0) of G2+ was as follows: gastrointestinal (GI)-G2: 9.1%; G3: 0.5%; genitourinary (GU)-G2: 4.3%, and no G3 toxicity was observed. PSA relapse was observed in 58 (6.8%) patients: 16 local, 22 lymph node, 4 bone recurrences, and 10 combined sites of relapse were detected. Throughout the follow-up period, 40 patients (4.7%) died, though none due to prostate cancer. Ultra-hypofractionated proton beam radiotherapy is an effective treatment for low- and favorable intermediate-risk prostate cancer, with long-term bDFS rates comparable to other techniques. It is promising for unfavorable intermediate-risk prostate cancer and has acceptable long-term GI and favorable GU toxicity.

Direct Patlak Reconstruction of [68Ga]Ga-PSMA PET for the Evaluation of Primary Prostate Cancer Prior Total Prostatectomy: Results of a Pilot Study.

To investigate the use of kinetic parameters derived from direct Patlak reconstructions of [68Ga]Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT) to predict the histological grade of malignancy of the primary tumor of patients with prostate cancer (PCa). Thirteen patients (mean age 66 ± 10 years) with a primary, therapy-naïve PCa (median PSA 9.3 [range: 6.3-130 µg/L]) prior radical prostatectomy, were recruited in this exploratory prospective study. A dynamic whole-body [68Ga]Ga-PSMA-11 PET/CT scan was performed for all patients. Measured quantification parameters included Patlak slope (Ki: absolute rate of tracer consumption) and Patlak intercept (Vb: degree of tracer perfusion in the tumor). Additionally, the mean and maximum standardized uptake values (SUVmean and SUVmax) of the tumor were determined from a static PET 60 min post tracer injection. In every patient, initial PSA (iPSA) values that were also the PSA level at the time of the examination and final histology results with Gleason score (GS) grading were correlated with the quantitative readouts. Collectively, 20 individual malignant prostate lesions were ascertained and histologically graded for GS with ISUP classification. Six lesions were classified as ISUP 5, two as ISUP 4, eight as ISUP 3, and four as ISUP 2. In both static and dynamic PET/CT imaging, the prostate lesions could be visually distinguished from the background. The average values of the SUVmean, slope, and intercept of the background were 2.4 (±0.4), 0.015 1/min (±0.006), and 52% (±12), respectively. These were significantly lower than the corresponding parameters extracted from the prostate lesions (all p < 0.01). No significant differences were found between these values and the various GS and ISUP (all p > 0.05). Spearman correlation coefficient analysis demonstrated a strong correlation between static and dynamic PET/CT parameters (all r ≥ 0.70, p < 0.01). Both GS and ISUP grading revealed only weak correlations with the mean and maximum SUV and tumor-to-background ratio derived from static images and dynamic Patlak slope. The iPSA demonstrated no significant correlation with GS and ISUP grading or with dynamic and static PET parameter values. In this cohort of mainly high-risk PCa, no significant correlation between [68Ga]Ga-PSMA-11 perfusion and consumption and the aggressiveness of the primary tumor was observed. This suggests that the association between SUV values and GS may be more distinctive when distinguishing clinically relevant from clinically non-relevant PCa.

External Validation of the IMPROD-MRI Volumetric Model to Predict the Utility of Systematic Biopsies at the Time of Targeted Biopsy.

Background: The aim of this study was to validate externally a nomogram that relies on MRI volumetric parameters and clinical data to determine the need for a standard biopsy in addition to a target biopsy for men with suspicious prostate MRI findings. Methods: We conducted a retrospective analysis of a prospectively maintained database of 469 biopsy-naïve men who underwent prostate biopsies. These biopsies were guided by pre-biopsy multiparametric Magnetic Resonance Imaging (mpMRI) and were performed at two different institutions. We included men with a PIRADSsv 2.1 score from 3 to 5. Each patient underwent both an MRI-ultrasound fusion biopsy of identified MRI-suspicious lesions and a systematic biopsy according to our protocol. The lesion volume percentage was determined as the proportion of cancer volume on MRI relative to the entire prostate volume. The study's outcomes were iPCa (Gleason Grade Group 1) and csPCa (Gleason Grade Group > 1). We evaluated the model's performance using AUC decision curve analyses and a systematic analysis of model-derived probability cut-offs in terms of the potential to avoid diagnosing iPCa and to accurately diagnose csPCa. Results: The nomogram includes age, PSA value, prostate volume, PIRADSsv 2.1 score, percentage of MRI-suspicious lesion volume, and lesion location. AUC was determined to be 0.73. By using various nomogram cut-off thresholds (ranging from 5% to 30%), it was observed that 19% to 58% of men could potentially avoid undergoing standard biopsies. In this scenario, the model might miss 0% to 10% of diagnosis of csPCa and could prevent identifying 6% to 31% of iPCa cases. These results are in line with findings from the multi-institutional external validation study based on the IMPROD trial (n = 122) and the MULTI-IMPROD trial (n = 262). According to DCA, the use of this nomogram led to an increased overall net clinical benefit when the threshold probability exceeded 10%. Conclusions: This study supports the potential value of a model relying on MRI volumetric measurements for selecting individuals with clinical suspicion of prostate cancer who would benefit from undergoing a standard biopsy in addition to a targeted biopsy.

422 Local Anaesthetic Trans-Perineal Prostate Biopsy: Outcomes from Our First 250 Cases

Abstract Aim Trans-perineal ultrasound prostate biopsy (TPBx) with prior multiparametric MRI (mpMRI) represents the standard of care in prostate cancer diagnostic. We present our first experience with TPBx in our unit. We also looked at discrepancies between the mpMRI and the TPBx results. Method We performed a retrospective analysis of collected data from all the patients who underwent TPBx following mpMRI from March 2021 to June 2022. All patients had combined systematic and targeted prostate biopsies. Results The total 250 patients underwent TPBx. 10 patients were already known to have prostate cancer. The mean age was 69 years. The average PSA value was PSA: 8.41 ng/ml with an average PSA density of 0.23. 43 patients underwent previous transrectal ultrasound-guided prostate (TRUS) biopsy while 207 patients were biopsy naïve. The overall cancer detection rate was 76 %. In 25 % of patients, there were some discrepancies between the mpMRI lesion site and histology results. Majority of the histology results were ISUP grade group 2, 30 % of the case, grade group 3 in 22 % of the cases, grade group 4 in 14 % of the cases, grade group 1 in 6% of the cases grade group 5 in 2 % of the cases. Conclusions A higher PIRADs score is likely to be associated with a higher -grade group histology. Our cancer detection rate is acceptable in comparison to TRUS prostate biopsy (76 % vs 40 %), however there are some discrepancies between the mpMRI and biopsy results which suggests additional criteria are needed to aid in decision management (like PSA density).

First experiences using transurethral ultrasound ablation (TULSA) as a promising focal approach to treat localized prostate cancer: a monocentric study

PurposeTo share our experience using transurethral ultrasound ablation (TULSA) treatment for focal therapy of localized prostate cancer (PCa).Materials and methodsBetween 10/2019 and 06/2021 TULSA treatment for localized PCa was performed in 22 men (mean age: 67 ± 7 years, mean initial PSA: 6.8 ± 2.1 ng/ml, ISUP 1 in n = 6, ISUP 2 in n = 14 and 2 patients with recurrence after previous radiotherapy). Patients were selected by an interdisciplinary team, taking clinical parameters, histopathology from targeted or systematic biopsies, mpMRI and patients preferences into consideration. Patients were thoroughly informed about alternative treatment options and that TULSA is an individual treatment approach. High-intensity ultrasound was applied using an ablation device placed in the prostatic urethra. Heat-development within the prostatic tissue was monitored using MR-thermometry. Challenges during the ablation procedure and follow-up of oncologic and functional outcome of at least 12 months after TULSA treatment were documented.ResultsNo major adverse events were documented. In the 12 month follow-up period, no significant changes of urinary continence, irritative/obstructive voiding symptoms, bowel irritation or hormonal symptoms were reported according to the Expanded Prostate Cancer Index Composite (EPIC) score. Erectile function was significantly impaired 3–6 months (p < 0.01) and 9–12 months (p < 0.05) after TULSA. PSA values significantly decreased after therapy (2.1 ± 1.8 vs. 6.8 ± 2.1 ng/ml, p < 0.001). PCa recurrence rate was 23% (5/22 patients).ConclusionEstablishment of TULSA in clinical routine was unproblematic, short-term outcome seems to be encouraging. The risk of erectile function impairment requires elaborate information of the patient.

Role of DWI/ADC in the Assessment of Prostate Cancer Aggressiveness and Its Correlation to Gleason Score

Background Cancer prostate represents a major health problem. it is one of the most common solid malignancies among male population. Prostate cancer (PCa) is considered one of the most common cancers among male population. Its incidence increases with age, ranging from 34% in the fifth decade, to 70% over the 80 years. Aim of the Work The objective of the study is to correlate and compare the DWI and ADC values of prostate cancer with the histopathological grading via Gleason score. Patients and Methods During a period of 6 months duration thirty patients were enrolled in the study. All patients with elevated PSA values greater than 4 ng/ml underwent sextant TRUS guided biopsies. MRI examination was done either prior to the TRUS biopsy or at least 3 weeks after the TRUS biopsy. Results In our study, we found that the ADC values correlated significantly with Gleason score of prostate cancer based on TRUS biopsy with significant p value &amp;lt; 0.001 and were significantly predictive of high-grade prostate cancer. This outcome agrees with recent reports that found an inverse correlation between ADC and Gleason score. They confrmed the correlation between ADC derived DWI and tumor alteration. ADC analysis seems to show a high capability in defining the tumor aggressiveness, as in monitoring radiation therapy effect or surgical recurrence. Conclusion ADC values showed a negative correlation with GS. This study suggests that ADC values may allow the noninvasive assessment of biological aggressiveness of prostate cancer, which may contribute in targeting biopsy to MRI-positive foci using a fusion of MRI and transrectal ultrasound. Incorporating the GS on targeted biopsy with the ADC value will further improve the detection of highgrade cancer foci also plays a role in planning initial treatment strategies.

Application of 18F-PSMA-1007 PET/MR Imaging in Early Biochemical Recurrence of Prostate Cancer: Results of a Prospective Study of 60 Patients with Very Low PSA Levels ≤ 0.5 ng/mL.

Sixty patients with BCR after radical prostatectomy (RP) with PSA ranged 0.1-0.5 ng/mL were enrolled in a prospective study. All patients underwent simultaneous whole-body and pelvic 18F-PSMA-1007 PET/MR. The obtained results were verified by 12-month follow-up. Fifty-three lesions were detected in 45 patients with 75% detection rate. The mean PSA value was 0.31 ng/mL. Of all PSMA-positive foci, 91% were localized in the pelvis, and only 9% of lesions were located in the extrapelvic region. Local recurrences were detected in 29%, PSMA-positive lymph nodes were detected in 64% of patients and bone metastases lesions were detected in 7% of patients. 18F-PSMA-1007 PET/MR seems to be an excellent diagnostic tool in patients with early BCR with very low PSA levels, especially with dt PSA < 6 months. The synergistic effect of combining 18F-PSMA-1007 and whole-body PET/MR with precise multiparametric assessment of pelvic lesions is of particular benefit in early BCR.