Seminal Vesicle Involvement Research Articles

Assessing the influence of prostate tissue traits on Gallium-68 prostate-specific membrane-antigen positron-emission tomography/computed tomography: Predictive factors for image positivity and locoregional recurrence in prostate cancer patients treated with radical prostatectomy and without prior or salvage treatment.

BACKGROUNDGallium-68 prostate-specific membrane-antigen positron-emission tomography/computed tomography (68Ga-PSMA-11 PET/CT) has recently emerged as a novel imaging modality, potentially improving oncologic outcomes for prostate cancer patients. This study aimed to assess the potential predictive factors associated with 68Ga-PSMA-11 PET/CT positivity following persistent prostate-specific antigen (PSA) levels and primary biochemical recurrence post-radical prostatectomy (RP), focusing on prostate specimen characteristics. Furthermore, we aim to identify predictive factors for locoregional recurrence. METHODSWe conducted a retrospective analysis of 230 prostate cancer patients treated with RP and without prior salvage or adjuvant radiotherapy or systemic treatments. All patients underwent 68Ga-PSMA-11 PET/CT scans to detect prostate cancer recurrence detection. Pathological findings were carefully examined and correlated with 68Ga-PSMA-11 PET/CT positivity and locoregional recurrence. RESULTSOur analysis showed that 68Ga-PSMA-11 PET/CT positivity was associated with ISUP grade group ≥ 3, presence of positive lymph node invasion at the time of RP, positive extraprostatic extension, involvement of seminal vesicles and post-RP PSA levels ≥ 0.1 ng/ml. Additionally, we identified ISUP grade group 2 and ISUP grade group ≥ 3, whether with or without positive lymph node invasion, along with extraprostatic extension, involvement of seminal vesicles and post-RP PSA ≥ 0.1 ng/ml, were identified as factors associated with pelvic node recurrence. CONCLUSIONSPathological findings emerge as robust predictors of 68Ga-PSMA-11 PET/CT positivity and locoregional recurrences in cases of initial biochemical recurrence or persistence without prior adjuvant or salvage treatment. This diagnostic approach facilitates potential adjustments in management strategies, such as PSMA-guided radiotherapy or PSMA-guided lymphadenectomy.

Simulation of Focal Boosting in Online Adaptive MRI-Guided SBRT for Patients With Locally Advanced Prostate Cancer With Seminal Vesicle Involvement

To evaluate the feasibility and accuracy of focal boosting in online adaptive MRI-guided stereotactic body radiation therapy (SBRT) for patients with prostate cancer (PCa) with seminal vesicle invasion (T3b) by analyzing the impact of intrafraction motion on the dose planned for the gross tumor volume (GTV) and clinical target volume (CTV). Data from 23 patients with T1-T3a PCa who received focal boosting SBRT on a 1.5T MR-Linac was used. A radiation oncologist replaced clinical GTVs with artificial GTVs representative for T3b tumor(s). For each MRI used for daily adaptation (MRIadapt), an automated treatment plan was generated (Df1-5) using the adapted contours. Patients were planned to receive 35 Gy to the CTV, with an isotoxic focal boost to the GTV up to 50 Gy. During each fraction, an additional MRI was acquired to assess intrafraction motion (MRIduring). Dose accumulation of all fractions was performed by deformable registration of MRIadapt, f2-5 to MRIadapt, f1 (DACC, planned). The Df1-5 were projected to their corresponding MRIduring, which were used to reconstruct DACC, delivered, likewise. Our results were compared to patients with tumor(s) without seminal vesicle invasion (T1-T3a). The median (10th-90th percentile) D98%ACC, planned to the GTV, which correlates most strongly with outcome, was 41.1 Gy (40.1-43.0 Gy) in the plans for patients with artificial T3b tumors, compared to 43.0 Gy (40.4-47.2 Gy) in the plans for patients with T1-T3a tumors. The D98%ACC, delivered to the GTV, taking into account intrafraction motion, was 41.0 Gy (39.3-42.6 Gy) and 42.5 Gy (40.0-46.6 Gy) in the plans for the artificial and clinical GTVs, respectively. MRI-guidance can ensure high accuracy of focal boosting in patients with T3b disease. Because of the unfavorable location of the GTV, a lower boost dose was feasible compared to patients with T1-T3a PCa.

MRI assessment of seminal vesicle involvement by prostate cancer using T2 signal intensity and volume.

Seminal vesicle involvement (SVI) in patients with newly diagnosed prostate cancer is associated with high rates of treatment failure and tumor recurrence; correct identification of SVI allows for effective management decisions and surgical planning. This single-center retrospective study analyzed MR images of the seminal vesicles from patients undergoing radical prostatectomy with confirmed T3b disease, comparing them to a control group without SVI matched for age and Gleason grade with a final stage of T2 or T3a. Seminal vesicles were segmented by an experienced uroradiologist, "raw" and bladder-normalized T2 signal intensity, as well as SV volume, were obtained. Among the 82 patients with SVI, 34 (41.6%) had unilateral invasion, and 48 (58.4%) had bilateral disease. There was no statistically significant difference in the degree of distension between normal and involved seminal vesicles (P = 0.08). Similarly, no statistically significant difference was identified in the raw SV T2 signal intensity (P = 0.09) between the groups. In the 159 patients analyzed, SVI was prospectively suspected in 10 of 82 patients (specificity, 100%; sensitivity, 12.2%). In all these cases, lesions macroscopically invaded the seminal vesicle, and the raw T2 signal intensity was significantly lower than that in the SVI and control groups (P = 0.02 and 0.01). While signal intensity measurements in T2-weighted images may provide insight into T3b disease, our findings suggest that this data alone is insufficient to reliably predict SVI, indicating the need for further investigation and complementary diagnostic approaches.

Comparison of Ga-68 PSMA PET/CT and Multiparametric MRI for Initial Detection and Staging of Prostate Cancer

Abstract Background Multiparametric magnetic resonance imaging (mpMRI) is widely used for the evaluation of prostate cancer and is known to have better accuracy. Gallium-68 prostate-specific membrane antigen (Ga-68 PSMA) is a radiotracer that shows high localization in prostate cancer cells. Purpose The purpose of this study was to assess the sensitivity and utility of Ga-68 PSMA positron emission tomography/computed tomography (PET/CT) in comparison with mpMRI as a noninvasive imaging technique for the initial diagnosis and locoregional staging of prostate cancer using transrectal ultrasound (TRUS)-guided biopsy as gold standard. Materials and Methods This prospective observational study conducted from August 2017 to April 2020 evaluated 60 men (n = 60) with biopsy-proven prostate carcinoma. They underwent mpMRI and Ga-68 PSMA PET/CT scans within 14 days with TRUS biopsy being gold standard. T staging of disease, N staging of lymph nodes within the pelvis, and M staging of lesions in pelvic bones (within the imaging field of mpMRI) were compared using PSPP version 1.0.1 statistical software. Results All 60 men with a mean age of 69.9 ± 9.35 years showed Ga-68 PSMA avid disease, whereas 55 were detected by mpMRI. The sensitivity in detection of prostate lesions (with 95% confidence interval) was 99.08% for Ga-68 PSMA PET/CT and 84.40% for mpMRI. Ga-68 PSMA PET/CT detected greater number of patients with regional lymph nodal involvement (19/60) as compared with mpMRI (12/60). Ga-68 PSMA PET/CT showed PSMA avid pelvic skeletal lesions in nine patients, whereas mpMRI detected pelvic lesions in six patients. In addition, four other patients showed extrapelvic skeletal lesions on Ga-68 PSMA PET/CT. Conclusion Ga-68 PSMA PET/CT has superior sensitivity in detection of primary prostate tumor, as compared with mpMRI. Both modalities correlate well in detection of seminal vesicle involvement. Ga-68 PSMA PET/CT outperformed mpMRI in detection of lymph nodal and skeletal metastases. Hence, Ga-68 PSMA PET/CT should be considered as first-line diagnostic modality for carcinoma prostate. Summary Statement: Ga-68 PSMA PET/CT shows superior diagnostic performance than mpMRI in the evaluation of prostate cancer.

Comparison of Multiparametric MRI, [68Ga]Ga-PSMA-11 PET-CT, and Clinical Nomograms for Primary T and N Staging of Intermediate-to-High-Risk Prostate Cancer.

Although multiparametric magnetic resonance imaging (mpMRI) is commonly used for the primary staging of prostate cancer, it may miss non-enlarged metastatic lymph nodes. Positron emission tomography-computed tomography targeting the prostate-specific membrane antigen (PSMA PET-CT) is a promising method to detect non-enlarged metastatic lymph nodes, but more data are needed. In this single-center, prospective study, we enrolled patients with intermediate-to-high-risk prostate cancer scheduled for radical prostatectomy with pelvic node dissection. Before surgery, prostate imaging with mpMRI and PSMA PET-CT was used to assess lymph node involvement (LNI), extra-prostatic extension (EPE), and seminal vesicle involvement (SVI). Additionally, we used clinical nomograms to estimate the risk of these three outcomes. Of the 74 patients included, 61 (82%) had high-risk prostate cancer, and the rest had intermediate-risk cancer. Histopathology revealed LNI in 20 (27%) patients, SVI in 26 (35%), and EPE in 52 (70%). PSMA PET-CT performed better than mpMRI at detecting LNI (area under the curve (AUC, 95% confidence interval): 0.779 (0.665-0.893) vs. 0.655 (0.529-0.780)), but mpMRI was better at detecting SVI (AUC: 0.775 (0.672-0.878) vs. 0.585 (0.473-0.698)). The MSKCC nomogram performed well at detecting both LNI (AUC: 0.799 (0.680-0.918)) and SVI (0.772 (0.659-0.885)). However, when the nomogram was used to derive binary diagnoses, decision curve analyses showed that the MSKCC nomogram provided less net benefit than mpMRI and PSMA PET-CT for detecting SVI and LNI, respectively. mpMRI and [68Ga]Ga-PSMA-11 PET-CT are complementary techniques to be used in conjunction for the primary T and N staging of prostate cancer.

Prediction of biochemical recurrence after laparoscopic radical prostatectomy

BackgroundRadical prostatectomy (RP) has been considered primary treatment for localized prostate cancer. Biochemical recurrence (BCR) occur approximately 20–30% in five year after RP. We aim to develop a novel nomogram to predict BCR-free survival (BCRFS) and performed external validation using a validation cohort that may help clinicians to make better decision for tailoring adjuvant treatment to specific group of patients.Materials and methodsThis retrospective cohort study included 370 localized and regional prostate cancer patients who underwent laparoscopic radical prostatectomy (LRP) in Songklanagarind hospital between January 2010 and December 2019, the patients were divided into two groups (primary cohort and validation cohort). BCR-free survival was created using Kaplan-Meier curve. Predictive factors for BCR were identified with univariable and multivariable analysis using Cox proportional hazards model. Predictive nomogram was created using these identified factors and developed for the prediction of biochemical recurrence free survival (BCRFS) at 1 and 5 years after LRP.ResultsFor primary Songklanagarind cohort, BCR was found in 105 patients (44.7%). Overall 1-year BCR-free survival was 52.8%, and 5-year BCR-free survival was 45.7% with median time to BCR of 18.1 months. Multivariable analysis identified unfavorable factor to BCRRF which are high initial serum PSA (> 20) (p < 0.001; HR 3.2), ISUP Gleason grade group > = 3 (p 0.033; HR 2.2), positive surgical margins (p 0.046; HR 1.5), and seminal vesicle involvement (p < 0.001; HR 5.2) and using for develop a novel nomogram to predict BCR. Concordance index 0.78.ConclusionProstate cancer patients with unfavorable factors, including high initial PSA (> 20), ISUP Gleason grade group > = 3, positive margin and extra-prostatic tumor extension are considered high risks and independent predictors of biochemical recurrence. This predictive models could potentially improve the 1 and 5-year BCR prediction after RP, according to the study’s findings and will aid medical professionals in achieving the goal of clinical prediction and creating a proper management for the localized treatment of prostate cancer underwent laparoscopic radical prostatectomy.

Prostate-specific membrane antigen positron emission tomography in addition to multiparametric magnetic resonance imaging and biopsies to select prostate cancer patients for focal therapy.

To evaluate the additional value of prostate-specific membrane antigen positron emission tomography (PSMA-PET) to conventional diagnostic tools to select patients for hemi-ablative focal therapy (FT). We performed a retrospective analysis on a multicentre cohort (private and institutional) of 138 patients who underwent multiparametric magnetic resonance imaging (mpMRI), PSMA-PET, and systematic biopsies prior to radical prostatectomy between January 2011 and July 2021. Patients were eligible when they met the consensus criteria for FT: PSA <15 ng/mL, clinical/radiological T stage ≤T2b, and International Society of Urological Pathology (ISUP) grade 2-3. Clinically significant prostate cancer (csPCa) was defined as ISUP grade ≥2, extracapsular extension >0.5 mm or seminal vesicle involvement at final histopathology. The diagnostic accuracy of mpMRI, systematic biopsies and PSMA-PET for csPCa (separate and combined) was calculated within a four-quadrant prostate model by receiver-operating characteristic and 2 × 2 contingency analysis. Additionally, we assessed whether the diagnostic tools correctly identified patients suitable for hemi-ablative FT. In total 552 prostate quadrants were analysed and 272 (49%) contained csPCa on final histopathology. The area under the curve, sensitivity, specificity, positive predictive value and negative predictive value for csPCa were 0.79, 75%, 83%, 81% and 77%, respectively, for combined mpMRI and systematic biopsies, and improved after addition of PSMA-PET to 0.84, 87%, 80%, 81% and 86%, respectively (P < 0.001). On final histopathology 46/138 patients (33%) were not suitable for hemi-ablative FT. Addition of PSMA-PET correctly identified 26/46 (57%) non-suitable patients and resulted in 4/138 (3%) false-positive exclusions. Addition of PSMA-PET to the conventional work-upby mpMRI and systematic biopsies could improve selection for hemi-ablative FT and guide exclusion of patients for whom whole-gland treatments might be a more suitable treatment option.

Effects of Radiation Doses on Clinical Recurrence in Patients with Biochemically Recurrent Prostate Cancer after Prostatectomy.

Salvage radiotherapy (SRT) to the prostate bed is the only curative treatment for patients with biochemical recurrence (BCR) after radical prostatectomy (RP). Although several systematic reviews indicated that a dose escalation in the range of 60-70 Gy improved biochemical control, the effects of radiation doses on clinical relapse after SRT remain unclear. Our aim was to investigate the relationship between radiation doses and clinical relapse-free survival (cRFS) after SRT. We identified 295 eligible patients receiving SRT for biochemically recurrent prostate cancer after RP between 2005 and 2018 at 15 institutions. Sixteen patients (5%) received short-term (< 6 months) androgen deprivation therapy (ADT) following RP and/or concurrently with SRT. SRT was delivered to the prostate and seminal vesicle bed using photon beams at a median (range) dose of 66 Gy (61-85) in 1.8-3.0 Gy fractions. The primary outcome was cRFS. Clinical relapse was identified on radiological imaging and/or biopsy and included local recurrence, lymph node metastasis, and distant metastasis. In all analyses, doses were recalculated as an equivalent dose in 2-Gy fractions (EQD2) with α/β = 1.5 Gy. Clinical RFS between the EQD2 ≥ 66 Gy (n = 229) and EQD2 < 66 Gy (n = 66) groups were compared using the Log-rank test, followed by univariate and multivariate Cox regression analyses and a subgroup analysis. The median follow-up duration was 73 months. Among patients with BCR (n = 119), 79 of 96 (82%) in the EQD2 ≥ 66 Gy group and 21 of 23 (91%) in the EQD2 < 66 Gy group received second salvage ADT (p = 0.36). Among all patients (n = 295), clinical relapse was identified in 22 (7%) patients after SRT. Six-year biochemical relapse-free survival (bRFS), cRFS, cancer-specific survival (CSS), and overall survival (OS) rates were 58%, 93%, 98%, and 94%, respectively. Six-year cRFS rates were 94% (95% confidence interval [CI], 90-97) in the EQD2 ≥ 66 Gy group and 87% (95% CI, 75-93) in the EQD2 < 66 Gy group (p = 0.020). The multivariate analysis revealed that EQD2 < 66 Gy, Gleason score ≥ 8, seminal vesicle involvement, and PSA at BCR ≥ 0.5 ng/ml correlated with clinical relapse (p = 0.0016, 0.014, 0.011, and 0.027, respectively). The subgroup analysis showed the consistent benefit of EQD2 ≥ 66 Gy in patients across most subgroups including PSA at BCR after RP, extracapsular extension, and age at SRT. This large multi-institutional observational study demonstrated that a higher SRT dose (EQD2 ≥ 66 Gy) resulted in superior cRFS. The present result supports the dose recommendations in the 2023 National Comprehensive Cancer Network guidelines (64-72 Gy) even in terms of clinical relapse. Prospective trial is warranted to investigate an upper threshold for optimal SRT dose.

A Phase I/II Dose-Escalation Study Evaluating the Safety of 21 Gy, 23 Gy, and 25 Gy for High Dose Rate (HDR) Prostate Brachytherapy: An Interim Toxicity Report.

Single-fraction high dose rate (HDR) prostate brachytherapy has shown improved actuarial biochemical control rates from 66% to 82% with dose escalation from 19 to 20.5 Gy, respectively, but is still inferior to the reported low dose rate brachytherapy control rates of over 90%. We aimed to identify whether dose escalation to 21, 23, and 25 Gy can be safely accomplished. Patients with previously untreated, pathologically confirmed, low-risk (cT1-T2a, Gleason ≤6, PSA <10 ng/mL) or favorable intermediate risk (Gleason 3+4, percentage of positive biopsy cores <50%, ≤1 NCCN intermediate risk factor) prostate adenocarcinoma were enrolled from a single institution. PSA and toxicity assessment were performed at baseline and at routine 6-month follow-ups. From May 9, 2018 to May 12, 2022, 18 patients were enrolled. None had received prior androgen deprivation therapy, 44% had low risk disease, and 61% were ECOG 0 at baseline. Median age was 68 years (total range: 43-79), and 83% were Caucasian. Eight patients received 21 Gy, nine patients received 23 Gy, and one patient received 25 Gy, with the 25 Gy cohort still accruing. The mean prostate size and range, determined by pre-operative prostate volume study on trans-rectal ultrasound, were as follows: 21Gy cohort (mean: 41.2cc; range: 21.9-63.1cc), 23Gy Cohort (mean: 41.2cc, range 28.3-71.7cc), 25Gy cohort (65.3cc). A median of 17 catheters (range: 16-20) were implanted. At a median follow-up of 35.7 months (range: IQR 4.4 - 50.2), only one grade 3 toxicity was reported, which was an ulcerative colitis (UC) flare noted in a patient whose UC was poorly controlled, requiring multiple courses of prednisone in the 6 months prior to his brachytherapy. Regarding toxicities attributable to therapy, fourteen and four patients experienced a grade 1 and 2 genitourinary toxicity respectively; four and four patients experienced a grade 1 and 2 reproductive system toxicity respectively; one patient experienced a grade 1 GI toxicity. Two patients needed foley catheters upon discharge, with neither requiring the foley long term. There were two treatment failures in the 21Gy cohort at 1.39 and 1.67 years from date of HDR brachytherapy; date of failure was defined by the first PSA 2.0ng/mL over nadir. Of these patients, one underwent focal salvage HDR, whilst the other underwent radical prostatectomy with only 1% of the volume involved by prostate cancer. Of note, there was seminal vesicle involvement on restaging prostate biopsy for the patient that underwent radical prostatectomy, however, this was not appreciated on the final prostatectomy specimen. Both patients have no evidence of disease currently. HDR brachytherapy appears well tolerated in patients with low to favorable intermediate risk prostate cancer at 21 and 23 Gy, with more accrual needed at 25Gy. Long-term follow-up needed to assess efficacy.

The prognostic significance of a negative PSMA-PET scan prior to salvage radiotherapy following radical prostatectomy

AimThe optimal management for early recurrent prostate cancer following radical prostatectomy (RP) in patients with negative prostate-specific membrane antigen positron-emission tomography (PSMA-PET) scan is an ongoing subject of debate. The aim of this study was to evaluate the outcome of salvage radiotherapy (SRT) in patients with biochemical recurrence with negative PSMA PET finding.MethodsThis retrospective, multicenter (11 centers, 5 countries) analysis included patients who underwent SRT following biochemical recurrence (BR) of PC after RP without evidence of disease on PSMA-PET staging. Biochemical recurrence-free survival (bRFS), metastatic-free survival (MFS) and overall survival (OS) were assessed using Kaplan-Meier method. Multivariable Cox proportional hazards regression assessed predefined predictors of survival outcomes.ResultsThree hundred patients were included, 253 (84.3%) received SRT to the prostate bed only, 46 (15.3%) additional elective pelvic nodal irradiation, respectively. Only 41 patients (13.7%) received concomitant androgen deprivation therapy (ADT). Median follow-up after SRT was 33 months (IQR: 20–46 months). Three-year bRFS, MFS, and OS following SRT were 73.9%, 87.8%, and 99.1%, respectively. Three-year bRFS was 77.5% and 48.3% for patients with PSA levels before PSMA-PET ≤ 0.5 ng/ml and > 0.5 ng/ml, respectively. Using univariate analysis, the International Society of Urological Pathology (ISUP) grade > 2 (p = 0.006), metastatic pelvic lymph nodes at surgery (p = 0.032), seminal vesicle involvement (p < 0.001), pre-SRT PSA level of > 0.5 ng/ml (p = 0.004), and lack of concomitant ADT (p = 0.023) were significantly associated with worse bRFS. On multivariate Cox proportional hazards, seminal vesicle infiltration (p = 0.007), ISUP score >2 (p = 0.048), and pre SRT PSA level > 0.5 ng/ml (p = 0.013) remained significantly associated with worse bRFS.ConclusionFavorable bRFS after SRT in patients with BR and negative PSMA-PET following RP was achieved. These data support the usage of early SRT for patients with negative PSMA-PET findings.

The diagnostic accuracy of radiolabeled PSMA-ligand PET for tumour staging in newly diagnosed prostate cancer patients compared to histopathology: a systematic review and meta-analysis.

The current clinical recommendations posit the deployment of specific approved radiolabeled prostate-specific membrane antigen-ligand positron emission tomography (PSMA PET) for detecting metastatic prostate cancer during primary staging. Nevertheless, the precise efficacy of such ligands in localizing intraprostatic tumours (index tumour) and T-staging is not well established. Consequently, the objective of this inquiry is to ascertain the diagnostic accuracy of PSMA-PET in the tumour staging of newly diagnosed prostate cancer by means of a meta-analysis that integrates studies utilizing histological confirmation as the reference standard. In this study, we conducted a systematic literature search of the PubMed, Embase, Web of Science, and Cochrane Library databases using a predefined collection of search terms. These terms included 'PSMA PET', 'primary staging', and 'prostate cancer'. Subsequently, two independent reviewers evaluated all the studies based on predetermined inclusion criteria, extracted pertinent data, and assessed the quality of evidence. Any disparities were resolved by a third reviewer. A random effects Sidik-Jonkman model was applied to conduct a meta-analysis and estimate the diagnostic accuracy on a per-patient basis, along with 95% confidence intervals. Moreover, an appraisal regarding the likelihood of publication bias and the impact of small-study effects was performed utilizing both Egger's test and a graphical examination of the funnel plot. The present analysis comprised a total of twenty-three scientific papers encompassing 969 patients and involved their analysis by both qualitative and quantitative approaches. The results of this study demonstrated that the estimated diagnostic accuracy of PSMA PET/CT and PSMA PET/MRI, for the detection of intraprostatic tumours, regardless of the type of PSMA-ligand, was 86% (95% CI: 76-96%) and 97% (95% CI: 94-100%), respectively. Furthermore, the diagnostic accuracy for the detection of extraprostatic extension (EPE) was 73% (95% CI: 64-82%) and 77% (95% CI: 69-85%), while the diagnostic accuracy for the detection of seminal vesicle involvement (SVI) was 87% (95% CI: 80-93) and 90% (95% CI: 82-99%), respectively. The present investigation has demonstrated that PSMA PET/MRI surpasses currently recommended multiparametric magnetic resonance imaging (mpMRI) in terms of diagnostic accuracy as inferred from a notable data trajectory, whereas PSMA-PET/CT exhibited comparable diagnostic accuracy for intraprostatic tumour detection and T-staging compared to mpMRI. Nevertheless, the analysis has identified certain potential limitations, such as small-study effects and a potential for publication bias, which may impact the overall conclusions drawn from this study.

Unravelling the Role of P300 and TMPRSS2 in Prostate Cancer: A Literature Review.

Prostate cancer is one of the most common malignant diseases in men, and it contributes significantly to the increased mortality rate in men worldwide. This study aimed to review the roles of p300 and TMPRSS2 (transmembrane protease, serine 2) in the AR (androgen receptor) pathway as they are closely related to the development and progression of prostate cancer. This paper represents a library-based study conducted by selecting the most suitable, up-to-date scientific published articles from online journals. We focused on articles that use similar techniques, particularly those that use prostate cancer cell lines and immunohistochemical staining to study the molecular impact of p300 and TMPRSS2 in prostate cancer specimens. The TMPRSS2:ERG fusion is considered relevant to prostate cancer, but its association with the development and progression as well as its clinical significance have not been fully elucidated. On the other hand, high p300 levels in prostate cancer biopsies predict larger tumor volumes, extraprostatic extension of disease, and seminal vesicle involvement at prostatectomy, and may be associated with prostate cancer progression after surgery. The inhibition of p300 has been shown to reduce the proliferation of prostate cancer cells with TMPRSS2:ETS (E26 transformation-specific) fusions, and combining p300 inhibitors with other targeted therapies may increase their efficacy. Overall, the interplay between the p300 and TMPRSS2 pathways is an active area of research.

Seminal Vesicle Treatment for Localized Prostate Cancer Treated with External Beam Radiotherapy.

This study retrospectively reviewed data from men with localized prostate cancer treated with external beam radiotherapy (EBRT). We identified 359 men with localized prostate cancer treated with curative EBRT at the Cross Cancer Institute between 2010-2011. The volume of seminal vesicles (SVs) treated as well as dose values were extracted. These volumes were compared to gold standard contours drawn by a trained expert based on consensus European Society for Radiotherapy and Oncology (ESTRO) contouring guidelines. Patient and tumor characteristics were extracted for these patients. Memorial Sloan Kettering prostate cancer nomogram was used to assign a predicted risk of SV involvement for each patient based on baseline tumor characteristics. In patients with a predicted risk of SV involvement greater than 15% (n = 184), 86.5% (SD = 18.6) of the base of the SVs were treated with EBRT, compared to 66.7% (SD = 32.6) for patients with a predicted risk of SV involvement less than 15% (n = 175, p < 0.0001). Similarly, the mean percentage of proximal and total SV volumes treated with EBRT was 75.6% (SD = 24.4) and 68.7% (SD = 26.0) for patients with a predicted risk of SV involvement of greater than 15%, compared to 50.3% (SD = 31.0, p < 0.0001) and 41.0% (SD = 27.8, p < 0.0001) for patients with a risk of less than 15%. The results indicate that all parts of the SVs are more likely to be contoured in men with >15% risk of SV involvement than those with <15% risk. However, radiation oncologists still contour a high percentage of SVs in men with <15% risk of SV involvement, suggesting that there may be over-treatment of SVs that increases the risk of rectal or bladder toxicity.

Salvage Cryoablation and Robotic Seminal Vesiculectomy: A Novel Salvage Treatment for Locally Recurrent Prostate Cancer.

Purpose: The purpose of this article was to describe a novel salvage surgical technique combining cryoablation of the prostate and robotic excision of the seminal vesicle (SV) for locally recurrent prostate cancer (LRPC) of the SV with or without prostate involvement following radiation therapy (RT) or focal therapy (FT). Materials and Methods: Seven men with biopsy-proven LRPC involving the SV with or without adjacent prostate following primary RT or FT underwent combined salvage focal cryoablation (FCA) and robotic excision of the SV. Descriptive statistics characterized the cohort and outcomes. Results: Median follow-up was 1.4 years. There were no surgical complications, and the length of stay was 1 day in all cases. No patients experienced any new urinary incontinence following removal of the catheter. Erectile function was preserved in both men exhibiting preoperative erections adequate for intercourse. Of the four patients developing recurrent disease, three involved only the contralateral SV; they all underwent a second salvage FCA and robotic seminal vesiculectomy (RSV). One patient presenting with high-risk disease developed systematic metastasis. He is alive and managed with androgen deprivation therapy (ADT). One patient developed persistent local disease recurrence and is on ADT. The other five patients are disease-free based on the most recent multi-parametric magnetic resonance imaging (mpMRI) and prostate specific antigen (PSA). Conclusions: This study highlights the feasibility and effectiveness of salvage FCA and RSV as a salvage treatment for LRPC of the SV with or without involvement of the prostate following primary RT or FT. Based on our outcomes, we recommend considering a bilateral salvage FCA and RSV in men with unilateral SV recurrence following primary RT. We recommend unilateral salvage FCA and seminal vesiculectomy in men with unilateral SV and prostate involvement following primary partial cryoablation provided no contralateral disease is identified.

Toxicity and Outcomes of Moderately Hypofractionated Radiation for Prostate Cancer With Seminal Vesicle Involvement

The aim of this study was to assess the toxicity and outcomes following treatment of prostate cancer with seminal vesicle involvement (SVI) evident on magnetic resonance imaging or clinical examination with moderately hypofractionated radiation therapy (MHRT). Forty-one patients treated with MHRT to the prostate and 1 or both seminal vesicles from 2013 to 2021 at a single institution were identified and propensity score matched to 82 patients treated during the same period with prescription dose given to the prostate alone. Dosimetry of the planning target volume, bladder, and rectum were compared. Urinary and bowel toxicity were scored by National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. Clinical outcomes including freedom from biochemical recurrence, prostate cancer-specific survival, and overall survival were assessed. Of the 41 patients identified with SVI, 26.8% had SVI by clinical examination and 95.1% had high-risk prostate cancer. Compared with the cohort without SVI, treatment plans to include SVI had a larger planning target volume (152.2 vs 109.9 cc; P < .001), maximum point dose (107.9% vs 105.8%; P < .001), and volume receiving 100% of the prescription dose (143.1 vs 95.9 cc; P < .001). No difference in bladder dosimetric variables between cohorts was observed, but there was an increase in the rectal maximum point dose (103.9% vs 102.8%; P=.030) and rectal volume receiving 100% of the prescription dose (1.8 vs 1.2 cc; P=.016). Despite these differences, there was no difference in the cumulative incidence of grade 2+ urinary (hazard ratio [HR], 0.73; 95% CI, 0.39-1.35; P=.31) or bowel (HR, 0.35; 95% CI, 0.04-3.03; P=.34) toxicity. Freedom from biochemical recurrence (HR, 0.47; 95% CI, 0.16-1.38; P=.17), prostate cancer-specific survival (HR, 0.31; 95% CI, 0.04-2.49; P=.31), and overall survival (HR, 0.35; 95% CI, 0.10-1.16; P=.09) also did not differ with or without SVI, respectively. Treatment of SVI to prescription dose with MHRT for localized prostate cancer does not increase bowel or urinary toxicity. Similar clinical outcomes were also observed with or without SVI.

Clinicopathologic Significance of Anterior Prostate Cancer: Comparison With Posterior Prostate Cancer in the Era of Multiparametric Magnetic Resonance Imaging.

Anterior prostate cancer (APC) has been considered an indolent tumor, most commonly arising in the transition zone (TZ). More recently, detection of APC has been facilitated through multiparametric magnetic resonance imaging and improved biopsy techniques, enabling earlier detection. The pathologic features and clinical significance of pure APC in a large contemporary series of well-characterized tumors have, to date, not been elucidated. Cases with APC defined as cancer present anterior to the urethra only were identified from 1761 consecutive radical prostatectomy specimens accessioned between January 2015 and August 2016. The clinicopathologic features of these cases were compared with those of pure posterior prostate cancer (PPC) and the features of anterior peripheral zone (APZ) cancers were compared with those of TZ cancers. In addition, the tumor series from 2015 to 2016 was compared with a cohort of 1054 patients accessioned before the utilization of multiparametric magnetic resonance imaging in the routine workup of patients with prostate cancer. In the 2015-2016 series, there were 188 (10.7%) patients with APC compared with 5.4% in the series from the pre-multiparametric magnetic resonance imaging era. No difference was observed between APC and PPC with regards to patient age or mean serum prostate-specific antigen at presentation. Mean tumor volume and positive surgical margin (PSM) rates were significantly higher in APC. In contrast, PPC was more commonly high grade with more frequent extraprostatic extension (EPE). None of the cases of APC had infiltration of the seminal vesicle or lymph node involvement, in contrast to PPC, with almost 14% of cases in each category. The 3- and 5-year biochemical recurrence-free survival was significantly higher in APC when compared with PPC, although this was not retained on multivariable analysis which included tumor location. On division of APCs according to anatomic zone of origin, 45% were APZ cancer and 37% TZ cancer. On comparison of APZ and TZ cancers, there were no significant differences in mean age and serum prostate-specific antigen at presentation as well as tumor volume, Gleason score, and PSM rate. High-grade malignancy (Gleason score >3 + 4=7) was seen in 26% of TZ cancers which compared with 44% of APZ cancers and 56% of PPC cancers. The rate of EPE was significantly higher in APZ when compared with TZ cancer ( P< 0.0005); however, the biochemical recurrence rate was not significantly different between the groups. The prevalence of APC in radical prostatectomy specimens has increased in recent times, in association with earlier detection at a stage amenable to curative surgical treatment. APC, when compared with PPC, is less commonly high grade with less frequent EPE, despite the APC group having larger tumors and a higher PSM rate at presentation. However, not all anterior cancers are indolent. Anterior cancers are more commonly seen in the APZ than the TZ and APZ cancers appear more locally aggressive than TZ cancers.

PD10-06 A NOMOGRAM TO PREDICT LYMPH NODE INVOLVEMENT IN CANDIDATES TO ROBOT-ASSISTED RADICAL PROSTATECTOMY WITH IT3 PROSTATE CANCER ON PREOPERATIVE MULTIPARAMETRIC MRI AS UNIQUE HIGH-RISK FEATURE

PD10-06 A NOMOGRAM TO PREDICT LYMPH NODE INVOLVEMENT IN CANDIDATES TO ROBOT-ASSISTED RADICAL PROSTATECTOMY WITH IT3 PROSTATE CANCER ON PREOPERATIVE MULTIPARAMETRIC MRI AS UNIQUE HIGH-RISK FEATURE

18F-JK-PSMA-7 PET/CT for staging intermediate- or high-risk prostate cancer patients before radical prostatectomy: a pilot study

BackgroundPositron emission tomography/computed tomography (PET/CT) using radiotracers that bind to the prostate-specific membrane antigen (PSMA) is mainly used in biochemical recurring prostate cancer. The aim of our study was to assess the usefulness of 18F-JK-PSMA-7 PET/CT for local and nodal staging in patients with intermediate- and high-risk prostate cancer (PCa) prior to radical prostatectomy, as compared to conventional imaging techniques.MethodsWe enrolled a total of 10 patients with intermediate- and high-risk PCa diagnosed by multiparametric-MRI followed by systematic and targeted biopsies, eligible for radical prostatectomy with extended lymph node dissection. Clinical team was blind to the results of the pre-surgery 18F-JK-PSMA-7 PET/CT at times of clinical decision and surgery. One month post-surgery, 18F-JK-PSMA-7 PET/CT was repeated and the results of both scans were unblinded. A third 18F-JK-PSMA-7 PET/CT could be acquired at a later time point depending on PSA progression.ResultsAll pre-surgery 18F-JK-PSMA-7 PET/CT was positive in the prostatic region, while MRI was negative in the prostate in one patient. We also detected positive pelvic lymph nodes in two patients (one high-risk, one intermediate-risk PCa) on pre-surgery and post-surgery 18F-JK-PSMA-7 PET/CT. No positive pelvic lymph nodes were reported on pre-surgical CT and MRI. 18F-JK-PSMA-7 PET/CT detected bladder involvement in one patient and seminal vesicles involvement in two patients; this malignant extension was undetected by the conventional imaging techniques. SUVmax in prostate lesions had an average value of 11.51 (range 6.90–21.49). SUVmean in prostate lesions had an average value of 7.59 (range 5.26–14.02).ConclusionThis pilot study indicates that pre-surgery 18F-JK-PSMA-7 PET/CT provides valuable information in intermediate- and high-risk PCa, for surgery planning with curative intent.

Topography of Prostate Cancer Recurrence: A Single-centre Analysis of Salvage Radical Prostatectomy Specimens and Implications for Focal Salvage Treatments

BackgroundMost prostate cancer (PCa) recurrences after nonsurgical first-line treatment are managed with androgen deprivation therapy (ADT). When local treatment is indicated, salvage focal treatment (FT) may achieve outcomes similar to those after salvage radical prostatectomy (sRP), with lower morbidity. However, descriptions of the topography of PCa recurrence are scarce. ObjectiveTo describe the characteristics and topography of recurrent PCa at sRP. Design, setting, and participantsWe performed a review of the final pathology for consecutive men undergoing sRP at a single centre between 2007 and 2021. Outcome measurements and statistical analysisClinical and pathological outcomes and recurrence localisation (standardised map) were recorded. Suitability for salvage FT was evaluated using criteria defined a priori. Results and limitationsWe included 41 men who underwent sRP after whole-gland treatment (82.9% primary radiotherapy). Of these, 68.3% had grade group ≥3 and 46.3% had pT3 disease, including nine men (22%) with seminal vesicle involvement >1 cm. The pN+ rate was 29.3%. Surgical margins were positive in 39% (mostly at the apex, 21.9%). PCa was located at <3 mm from the apex in 68% of cases. The segment most frequently involved was the mid-gland (93%). The median prostate and index lesion (IL) volume was 31.4 cm3 (interquartile range [IQR] 23–37) and 2 cm3 (IQR 0.5–6), respectively. A solitary IL was present in 63.4% of cases, while 7.3% had whole-gland PCa involvement. Overall, 56% of the men (n = 23) were deemed suitable for salvage FT (although seven had pN+ disease). The sample size, single-centre retrospective design, and unavailability of magnetic resonance imaging data are the main limitations. ConclusionsAccording to sRP pathology, radiorecurrent PCa is an aggressive disease, frequently showing extraprostatic extension, positive margins, and apical involvement. The majority of cases still harbour a solitary index lesion and a consistent proportion may be suitable for a gland-preserving strategy. Patient summaryIn this report we looked at the location of prostate cancer recurrence within the prostate gland after radiotherapy or ablation, in which energy (such as heat, cold, or laser energy) is used to kill cells. We found that although these recurrences are often high-grade locally advanced disease, around half of cases might be suitable for a gland-preserving salvage treatment.

Mucinous adenocarcinoma of the prostatic urethra after brachytherapy for prostatic adenocarcinoma: a case series

Mucinous adenocarcinoma of the urethra is extremely rare, even more so in a setting of postradiation therapy, with only 3 cases reported up to date including the first case published by our group in 2011. In the present study, we included the long-term follow-up on our previously reported case and report 3 additional cases. This is the first case series to date of this rare disease entity. The aim of this study is to review the clinicopathologic features of mucinous adenocarcinoma of the prostatic urethra in patients after receiving brachytherapy for prostatic adenocarcinoma. We identified 4 patients with a mean age of 72 years, and a mean interval of 14.8 years from brachytherapy for prostate carcinoma (grade group 1). Patients presented with hematuria or urinary retention. A colonoscopy was performed in three-fourth of patients and was within normal limits. Three patients underwent cystoprostatectomy and 1 had a transurethral resection of the prostate. On gross examination, only tumor formed a 3.5cm tan-gray, ulcerated, friable, and necrotic mass and 2 displayed either irregular red granular or thickened areas within the prostatic urethra. Abundant extracellular mucin pools dissecting the prostatic stroma were present in all tumors, with clusters of tumor cells floating in the mucin. The mucin pools were lined by pleomorphic pseudostratified columnar mucinous epithelium. Tumors were diffusely positive for CK20, CDX2 (4/4), and AMACR (2/2); they focally expressed CK7 (2/4), and lacked nuclear β-catenin expression (3/3). PSA, PSAP, NKX3.1, p63, and GATA3 were negative in the tumors tested. Among the 3 patients who underwent radical surgery, 2 had stage 2 tumors (confined to the prostatic urethra and prostate), and 1 had a stage 3 tumor, with seminal vesicle involvement. All 4 patients were alive without disease with a mean follow-up of 4.9 years. In conclusion, brachytherapy-associated mucinous adenocarcinoma of the prostatic urethra displays intestinal-type features as its non-radiation-related counterpart. It appears to lack a villous adenoma component, displays a different immunohistochemical profile with diffuse CK20 and CDX2 positivity, and is associated with lower stage and less aggressive behavior.