Localized Adenocarcinoma Of Prostate Research Articles

SEROLOGICAL OUTCOMES OF TREATMENT WITH 3D-CRT AND IMRT IN LOCALIZED PROSTATE CANCER.

Prostate cancer ranks the second most frequent cancer encountered worldwide in men. Radiotherapy has been effectively used to treat localized prostate cancer. Over the years more effective radiation techniques like 3D-Conformal Radiation Therapy (3D-CRT), Proton Therapy, Intensity Modulated Radiation Therapy (IMRT), and Brachytherapy has been evolved and effectively used to deliver radiation therapy. Herein, we compare serological outcomes of two radiation treatment techniques intensity modulated radiation therapy (IMRT) and 3- dimensional conformal radiation therapy (3DCRT) in localized prostate adenocarcinoma. It is a cohort study conducted at Department of Oncology, Dr Ziauddin Hospital, Karachi. Patients with localized prostate adenocarcinoma meeting the inclusion criteria were recruited from July 2016 to June 2022, underwent treatment with a total dose >74 Gy using two different advanced radiotherapy techniques, i.e., IMRT and 3D-CRT. Serum PSA levels were assessed prior to treatment, and 6 weeks and 12 months after treatment. Paired t-Test was applied to identify the difference in PSA levels before, and after the treatment. p-value less than 0.05 was taken as significant at 95% confidence interval. A total of 78 patients with 39 in each group. The mean age of patients in 3D-CRT group was 68±10 years while in IMRT group was 68±07 years. Six weeks after initiation of treatment, we observed that both the treatment methods, i.e., 3D-CRT and IMRT reduced the PSA levels significantly p-value = 0.001 respectively. There was no significant difference in the mean of PSA levels on 06th week and 12th months. Furthermore, the analysis of PSA levels at 12th months when compared with the baseline PSA levels came highly significant in both the groups as depicted in paired-t teat analysis of PSA levels with acceptable toxicity. Radiation therapy modalities 3D-CRT and IMRT both showed a significant serological response with minimal or acceptable gastrointestinal and genitourinary toxicities in the 3D-CRT group in comparison to the IMRT group. Although the sample size is relatively smaller, but the results of this study are encouraging to treat those patients on 3D-CRT, who cannot afford more expansive radiotherapy treatment technique like IMRT.

Escalade de dose en radiothérapie modérément hypofractionnée pour les cancers de la prostate localisés, ESHYPRO : résultats d’une série monocentrique rétrospective évaluant la toxicité et l’efficacité

PurposeProstate cancer is the most frequent cancer among men and radiotherapy hypofractionation regimens have become standard treatments for the localized stages, but the absence of increased risk of acute and late genitourinary or gastrointestinal toxicity of the dose escalation still must be demonstrated. Material and methodsThe study population included all patients with localized prostatic adenocarcinoma treated at the institut Curie from February 2016 to March 2018 by external radiation delivered by a linear accelerator using an image-guided conformal intensity modulation technique at a total dose of 75Gy in 30 fractions of 2.5Gy in the planning target volume that included the prostate and the proximal seminal vesicles, and could be paired with a prophylactic lymph node radiotherapy at 46Gy in 23 fractions with simultaneous integrated boost. ResultsA total of 166 patients were included. Among them, 68.6% were unfavourable intermediate or (very) high risk. The median age and follow-up were 71.4years and 3.96years. One hundred and forty-nine patients received prophylactic lymph node radiotherapy (89.8%). One hundred and thirty-one patients received hormonotherapy (78.9%). Genito-urinary toxicity events of grades 2 or above during radiotherapy, at 6months, 1year and 5years were respectively 36.7%, 8.8%, 3.1% and 4.7%. Two patients had late grade 4 toxicity at 5years (1.6%). Grade 2 gastrointestinal toxicity events during radiotherapy, 6months, 1year and 5years were respectively 15.1%, 1.9%, 14.6% and 9.3%. Of these, eight patients had grade 3 toxicity (6.2%). There was no grade 4 toxicity. Analyses did not reveal any predictive factor for toxicity. The 5-year overall, progression-free, and specific survival rates were respectively 82.4%, 85.7%, and 93.3%. Serum prostate specific antigen concentration and cardiovascular risk factors were found to be predictive factors of deterioration in overall survival (P=0.0028 for both). ConclusionExternal radiotherapy for localized prostatic cancer with our moderately hypofractionated dose escalation regimen is well tolerated. In the absence of increased late toxicity, the analysis of the modes of long-term relapses will be interesting to determine the benefit of this dose escalation on local and distant relapses.

Treatment Related Acute Toxicities Between Treatment with 3D-CRT and IMRT in Localised Prostate Cancer.

To compare the acute toxicities of two radiation treatment techniques, intensity modulated radiation therapy (IMRT), and 3-dimensional conformal radiation therapy (3D-CRT) in localised prostate adenocarcinoma. Descriptive study. Place and Duration of the Study:Department of Oncology, Dr. Ziauddin Hospital, Karachi, Pakistan, from July 2016 to June 2022. Patients with localised prostate adenocarcinoma who underwent treatment using two different advanced radiotherapy techniques i.e., IMRT and 3D-CRT were recruited during the study period. They were followed up for six months for acute gastrointestinal (GI) and genitourinary (GU) adverse events (acute toxicities) related to both treatment modalities according to Modified radiation therapy oncology group (RTOG) criteria. The acute toxicities were assessed at the 2nd, 4th, and 6th week during treatment and at the 3rd and 6th month after treatment. There were 78 patients, with 39 patients in each group. The mean age was 68 ± 10 years in the 3D-CRT and 68 ± 07 years in the IMRT group. Patients in the IMRT group exhibited markedly lower treatment-related acute GI and GU effects at the end of 4th and 6th weeks for anorectal pain (p = 0.04) and (p = 0.01) and burning micturition (p = 0.003) and (p = 0.01), respectively. Furthermore, at 3 months anorectal pain (p = 0.02), loose stools (p = 0.005), and burning micturition (p = 0.01) were present and at 6 months anorectal pain was (p = 0.01) still present. Radiation therapy modalities 3D-CRT and IMRT both showed acceptable toxicity profile in the management of localised prostate cancer, while IMRT group exhibited significantly lower treatment-related acute GI and GU effects. 3D-CRT (3-Dimensional Conformal Radiation Therapy), IMRT (Intensity-Modulated Radiation Therapy), Radiation toxicity.

Extreme hypofractionated stereotactic radiotherapy for localized prostate Cancer: Efficacy and late urinary toxicity according to transurethral resection of the prostate history

Background and purposeExtreme hypofractionated stereotactic body radiotherapy (SBRT) is a therapeutic alternative for localized low- or intermediate-risk prostate cancer. Despite the availability of several studies, the toxicity profile of SBRT has not been comprehensively described. This real-world evidence study assessed the efficacy and toxicities associated with this regimen, and potential prognosis factors for genitourinary toxicities. Materials and methodsThis retrospective study included 141 consecutive patients with localized prostatic adenocarcinoma treated with CyberKnife™ SBRT, as primary irradiation, at the Oscar Lambret Center between 2010 and 2020. The prescribed dose was 36.25 Gy in 5 fractions. Acute and late toxicities were graded according to the CTCAE (version 5.0). Biochemical recurrence-free survival (bRFS) and overall survival (OS) were estimated using the Kaplan–Meier method. The cumulative incidence of biochemical recurrence (cBR) was estimated using the Kalbfleisch–Prentice method. ResultsAmong the included patients, 13.5 % had a history of transurethral resection of the prostate (TURP). The median follow-up was 48 months. At 5 years, bRFS, cBR, and OS were 72 % (95 %CI: 61–81), 7 % (95 %CI: 3–14), and 82 % (95 %CI: 73–89), respectively. Twenty-nine patients experienced at least one late toxicity of grade ≥ 2; genitourinary (N = 29), including 3 cases of chronic hematuria, and/or gastrointestinal (N = 1). The cumulative incidence of late urinary toxicity of grade ≥ 2 was 20.6 % at 5 years (95 %CI: 13.9–28.1). Multivariate analysis revealed that a history of TURP was significantly associated with late urinary toxicity of grade ≥ 2, after adjusting for clinical target volume (Odds Ratio = 3.06; 95%CI: 1.05–8.86; P = 0.04). ConclusionExtreme hypofractionated SBRT is effective for localized prostate cancer with a low risk of late toxicity. A history of TURP is associated with a higher risk of late urinary toxicity. These findings may contribute to the optimal management of patients treated with this regimen, particularly those with a history of TURP.

Comprehensive 3DCRT Hypofractionated Radiotherapy Schedule for Localized Prostate Adenocarcinoma in the Era of IMRT: Dosimetric and Endoscopic Analysis.

Background: Moderate hypofractionated radiotherapy (MHRT) has emerged as the preferred treatment modality for localized prostate cancer based on randomized controlled studies regarding efficacy and toxicity using contemporary radiotherapy techniques. In the setting of MHRT, available data on dosimetric parameters and late rectal toxicity are limited. Aim: To present the effects of MHRT on late rectal toxicity while conducting an extensive dosimetric analysis in conjunction with rectoscopy results. Methods: This is a prospective study including patients with intermediate-risk prostate adenocarcinoma. All patients were treated with MHRT 44 Gy in 16 fractions to the seminal vesicles and to the prostate, followed by a sequential boost to the prostate alone of 16.5 Gy in 6 fractions delivered with three-dimensional conformal radiation therapy (3DCRT). Acute and late toxicity were assessed. Endoscopy was performed at baseline, every 3 months post-therapy for the first year, and every 6 months for the year after. The Vienna Rectoscopy Score (VRS) was used to assess rectal mucosal injury related to radiotherapy. Dosimetric analysis for the rectum, rectal wall, and its subsegments (upper, mid, and low 1/3) was performed. Results: Between September 2015 and December 2019, 20 patients enrolled. Grade 1 late gastrointestinal toxicity occurred in 10% of the patients, whereas 5% had a grade ≥2. Twelve months post radiotherapy: 4 (20%) patients had VRS 1; 2 (10%) patients had VRS 2; 1(5%) patient had VRS 3. 24 months post radiotherapy, VRS 1 was observed in 4 patients (20%) and VRS 2 in 3 (15%) patients. The dosimetric analysis demonstrated noticeable variations between the rectum, rectal wall, and rectal wall subsegments. The dosimetric analysis of the rectum, rectal wall, and its mid and low segments with respect to rectoscopy findings showed that the higher dose endpoints V52.17Gy and V56.52Gy are associated with rectal mucosal injury. Conclusions: A thorough delineation of the rectal wall and its subsegments, together with the dosimetric analysis of these structures, may reduce late rectal toxicity. Dosimetric parameters such as V52.17Gy and V56.52Gy were identified to have a significant impact on rectal mucosal injury; additional dose endpoint validation and its relation to late GI toxicity is needed.

Mainstream Model of Genetic Testing for Prostate Cancer at a Large Tertiary Cancer Centre

BackgroundAn estimated 20% to 30% of men with advanced prostate cancer carry a mutation in DNA damage repair genes, of which half are estimated to be germline. Eligibility criteria for germline genetic testing expanded significantly for Ontario patients in May 2021 and many centers adopted a “mainstream” model, defined as oncologist-initiated genetic testing. MethodsWe conducted a retrospective chart review to report on the first-year mainstream experience of a large tertiary oncologic center, the Sunnybrook Odette Cancer Centre. All patients who underwent mainstream at the discretion of their treating physician were included. A subset underwent somatic profiling as part of clinical trial screening. Descriptive statistics were used to report baseline clinicopathologic characteristics and treatments received. ResultsBetween May 1, 2021, and May 30, 2022, 174 patients with prostate cancer underwent mainstream germline genetic testing with a 19-gene panel. Median age was 75 (IQR 68-80), and 82% of patients were diagnosed with either de novo metastatic or high-risk localized prostate adenocarcinoma. Fourteen patients (8%; 95% CI 4%-12%) were found to have a deleterious germline mutation, including pathogenic or likely pathogenic variants in BRCA1/2, ATM, CHEK2, PMS2, RAD51C, HOXB13, and BRIP1. Forty-nine patients (28%; 95% CI 21%-35%) were found to have a variant of uncertain significance. Thirty-four patients also had next-generation sequencing (NGS) of their somatic tissue. Among this subset, 8 of 34 (23%) had an alteration in homologous recombination repair (HRR) genes. Of the 14 patients with a germline mutation, none had a prior personal history of malignancy and 6 (43%) did not have any first- or second-degree relatives with history of prostate, pancreatic, breast, or ovarian cancer. ConclusionWe report on the real-world characteristics of prostate cancer patients who underwent mainstream germline genetic testing. Personal history and family history of cancer cannot reliably stratify patients for the presence of pathogenic germline variants.

Induction of double-strand breaks with the non-steroidal androgen receptor ligand flutamide in patients on androgen suppression: a study protocol for a randomized, double-blind prospective trial

BackgroundProstate cancer remains the most prevalent malignancy and the second-leading cause of cancer-related death in men in the USA. Radiation therapy, typically with androgen suppression, remains a mainstay in the treatment of intermediate- and high-risk, potentially lethal prostate cancers. However, local recurrence and treatment failure remain common. Basic and translational research has determined the potential for using androgen receptor (AR) ligands (e.g., dihydrotestosterone and flutamide) in the context of androgen-deprived prostate cancer to induce AR- and TOP2B-mediated DNA double-strand breaks (DSBs) and thereby synergistically enhance the effect of radiation therapy (RT). The primary aim of this study is to carry out pharmacodynamic translation of these findings to humans.MethodsPatients with newly diagnosed, biopsy-confirmed localized prostatic adenocarcinoma will be recruited. Flutamide, an oral non-steroidal androgen receptor ligand, will be administered orally 6–12 h prior to prostate biopsy (performed under anesthesia prior to brachytherapy seed implantation). Key study parameters will include the assessment of DNA double-strand breaks by γH2A.x foci and AR localization to the nucleus. The initial 6 patients will be treated in a single-arm run-in phase to assess futility by establishing whether at least 2 subjects from this group develop γH2A.x foci in prostate cancer cells. If this criterion is met, the study will advance to a two-arm, randomized controlled phase in which 24 participants will be randomized 2:1 to either flutamide intervention or placebo standard-of-care (with all patients receiving definitive brachytherapy). The key pharmacodynamic endpoint will be to assess whether the extent of γH2A.x foci (proportion of cancer cells positive and number of foci per cancer cell) is greater in patients receiving flutamide versus placebo. Secondary outcomes of this study include an optional, exploratory analysis that will (a) describe cancer-specific methylation patterns of cell-free DNA in plasma and urine and (b) assess the utility of serum and urine samples as a DNA-based biomarker for tracking therapeutic response.DiscussionThis study will confirm in humans the pharmacodynamic effect of AR ligands to induce transient double-strand breaks when administered in the context of androgen deprivation as a novel therapy for prostate cancer. The findings of this study will permit the development of a larger trial evaluating flutamide pulsed-dose sequencing in association with fractionated external beam RT (+/− brachytherapy). The study is ongoing, and preliminary data collection and recruitment are underway; analysis has yet to be performed.Trial registrationClinicalTrials.gov NCT03507608. Prospectively registered on 25 April 2018.

Jorge clinical study: 10-year outcomes of risk-adapted radiotherapy defined by multiparametric MRI for prostate cancer.

To analyze the 10-year biochemical relapse-free survival (BRFS), locoregional relapse-free survival (LRFS), metastasis-free survival (MFS), and overall survival (OS) in patients diagnosed with localized prostate adenocarcinoma treated with radiotherapy (RT) ± androgen deprivation therapy (ADT), according to the risk groups based on multiparametric magnetic resonance imaging (mpMRI) instead of digital rectal exam (DRE). We retrospectively evaluated 140 consecutive patients diagnosed with localized prostate adenocarcinoma, stratified into different risk groups-low (LR), intermediate (IR), and high (HR) by mpMRI results. After a median follow-up of 104months, in LR group (n = 15), 10-year BRFS was 86.7%, 10-year LRFS was 86.7%, 10-year MFS was 93.3%, and 10-year OS was 100%. In IR group (n = 80), 10-year BRFS was 80.5%, 10-year LRFS was 86.1%, 10-year MFS was 92.6%, and 10-year OS was 76%. In HR group (n = 45), 10-year BRFS was 72.8%, 10-year LRFS was 78.7%, 10-year MFS was 82.1%, and 10-year OS was 77% (2 deaths from prostate cancer). According to mpMRI results, 36 (25.7%) patients change the risk group and 125 (89.28%) patients change the TNM stage. There was a trend for higher metastatic relapse in patients who switched from IR to HR (due to mpMRI) versus the patients who remained in the IR (20%, vs. 1.81% p = 0.059). Multivariate analysis showed that locoregional relapse was strongly associated with distant relapse (OR = 9.28; 95%CI: 2.60-33.31). There were no cases of acute grade 3 toxicity. Late grade 3 genitourinary, gastrointestinal, and sexual toxicity were 2.8%, 0.7%, and 1.2%, respectively. This is the first study with a 10-year median follow-up of patients diagnosed with localized prostate cancer treated with radiotherapy according to the risk groups established by mpMRI. Our findings show that mpMRI is a key tool to diagnose and establish risk groups in these patients, to optimize their treatment.

PE046 - Retrospective study and surgical implication of under-staging in localized prostatic adenocarcinoma

PE046 - Retrospective study and surgical implication of under-staging in localized prostatic adenocarcinoma

The Role of Salvage Radical Prostatectomy in Patients with Radiation-Resistant Prostate Cancer.

There are multiple treatment strategies for patients with localized prostate adenocarcinoma. In intermediate- and high-risk patients, external beam radiation therapy demonstrates effective long-term cancer control rates comparable to radical prostatectomy. In patients who opt for initial radiotherapy but have a local recurrence of their cancer, there is no unanimity on the optimal salvage approach. The lack of randomized trials comparing surgery to other local salvage therapy or observation makes it difficult to ascertain the ideal management. A narrative review of existing prospective and retrospective data related to salvage radical prostatectomy after radiation therapy was undertaken. Based on retrospective and prospective data, post-radiation salvage radical prostatectomy confers oncologic benefits, with overall survival ranging from 84 to 95% at 5 years and from 52 to 77% at 10 years. Functional morbidity after salvage prostatectomy remains high, with rates of post-surgical incontinence and erectile dysfunction ranging from 21 to 93% and 28 to 100%, respectively. Factors associated with poor outcomes after post-radiation salvage prostatectomy include preoperative PSA, the Gleason score, post-prostatectomy staging, and nodal involvement. Salvage radical prostatectomy represents an effective treatment option for patients with biochemical recurrence after radiotherapy, although careful patient selection is important to optimize oncologic and functional outcomes.

Same-day versus delayed simulation imaging after placement of a perirectal hydrogel spacer for prostate radiotherapy.

Placement of a perirectal hydrogel spacer has been demonstrated to reduce the risk of rectal toxicity from prostate radiation. Practices vary regarding the timing of CT simulation after hydrogel placement, and the ideal schedule remains unknown. Thirty patients with localized prostate adenocarcinoma underwent transrectal ultrasound-guided placement of an iodinated SpaceOAR™ hydrogel prior to radiotherapy. Per evolving practice, 15 completed same-day simulation and 15 returned for simulation 1-2 weeks later. Hydrogel volume, perirectal distance, air-void volume, and rectal dosimetry per NRG GU005 were compared between CT simulation, 1st fraction Cone-Beam-CT (CBCT), and final CBCT. CT simulation occurred 8.8 ± 2.4 days after placement in the delayed group, with no significant difference in the interval between simulation and 1st fraction between groups (p = 0.165). Greater observed de-creases in hydrogel volume (0.57 cc vs. 0.04 cc, p = 0.0002), and perirectal distance at both mid-gland (1.32mm vs. 0.17mm) and tallest point (2.40mm vs. 0.04mm) were seen on 1st-fraction CBCT in the same-day group (p = 0.0039; p = 0.0002). Per dosimetry recalculated on 1st fraction CBCT, five (D3 cc and D50%) versus one (D50%) rectal dose parameters were exceeded in the same-day and delayed groups, respectively, and 10 versus one parameters had a relative increase of ≥ 20%. Due to the evolving anatomic changes in the days following hydrogel placement, same-day simulation scanning may introduce unintended variability in rectal dosimetry at the time of prostate radiotherapy.

The pathway of isolated seminal vesicle invasion has a different impact on biochemical recurrence after radical prostatectomy and pelvic lymphadenectomy.

Prostate cancer with seminal vesicle invasion (SVI) has been considered an aggressive cancer. To evaluate the prognostic significance of different patterns of isolated SVI in patients undergoing radical prostatectomy (RP) and pelvic lymphadenectomy. We retrospectively analyzed all patients who underwent RP between 2007 and 2019. Inclusion criteria were localized prostate adenocarcinoma, SVI at RP, at least 24-months follow-up, and no adjuvant treatment. Patterns of SVI were following Ohori's classification: type 1: direct spread along the ejaculatory duct from inside; type 2: seminal vesicle invasion outside the prostate, through the capsule; type 3: the presence of cancer island(s) in the seminal vesicle with no continuity from the primary tumor (discontinuous metastases). Patients with type 3 SVI (isolated or in association) were included in the same group. Biochemical recurrence (BCR) was defined as any postoperative PSA ≥0.2 ng/ml. A logistic regression analysis was performed to assess predictors of BCR. Time to BCR was investigated using the Kaplan-Meier analysis with the log-rank test. Sixty-one out of 1,356 patients were included. Median age was 67(7.2) years. Median PSA was 9.4(8.92) ng/ml. Mean follow-up was 85.28 ± 45.27 months. BCR occurred in 28(45.9%) patients. Logistic regression showed that a positive surgical margin (OR 19.964, 95%CI:1.172-29.322, P = 0.038) was predictor of BCR. Kaplan-Meier analysis demonstrated that patients with pattern 3 had a significantly shorter time to BCR compared to other groups (log-rank, P = 0.016). The estimated time to BCR was 48.7 months in type 3, 60.9 months in pattern 1 + 2, 74.8, and 100.8 months in isolated patterns 1 and 2, respectively. In patients with negative surgical margins, pattern 3 confirmed a shorter time to BCR compared to other types of invasions, with an estimated time to BCR of 30.8 months. Patients with type 3 SVI demonstrated a shorter time to BCR compared to other patterns.

Characterisation of cell lines derived from prostate cancer patients with localised disease.

Prostate cancer is a broad-spectrum disease, spanning from indolent to a highly aggressive lethal malignancy. Prostate cancer cell lines are essential tools to understanding the basic features of this malignancy, as well as in identifying novel therapeutic strategies. However, most cell lines routinely used in prostate cancer research are derived from metastatic disease and may not fully elucidate the molecular events underlying the early stages of cancer development and progression. Thus, there is a need for new cell lines derived from localised disease to better span the disease spectrum. Prostatic tissue from the primary site, and adjacent non-cancerous tissue was obtained from four patients with localised disease undergoing radical prostatectomy. Epithelial cell outgrowths were immortalised with human papillomavirus type 16 (HPV16) E6 and E7 to establish monoclonal cell lines. Chromosomal ploidy was imaged and STR profiles were determined. Cell morphology, colony formation and cell proliferation characteristics were assessed. Androgen receptor (AR) expression and AR-responsiveness to androgen treatment were analysed by immunofluorescence and RT-qPCR, respectively. RNA-seq analysis was performed to identify prostate lineage markers and expression of prostate cancer tumorigenesis-related genes. Two benign cell lines derived from non-cancer cells (AQ0420 and AQ0396) and two tumour tissue derived cancer cell lines (AQ0411 and AQ0415) were immortalised from four patients with localised prostatic adenocarcinoma. The cell lines presented an epithelial morphology and a slow to moderate proliferative rate. None of the cell lines formed anchorage independent colonies or displayed AR-responsiveness. Comparative RNA-seq expression analysis confirmed the prostatic lineage of the four cell lines, with a distinct gene expression profile from that of the metastatic prostate cancer cell lines, PC-3 and LNCaP. Comprehensive characterization of these cell lines may provide new in vitro tools that could bridge the current knowledge gap between benign, early-stage and metastatic disease.

Abstract 4631: Multiplex IHC assay to explore regional heterogeneity of FAP and inflammatory cell density in localized prostatic adenocarcinoma

Abstract Cancer-associated fibroblasts (CAFs) expressing FAP promote tumor growth, invasion and immune suppression. FAP is a molecular imaging target in cancer and its protease activity is a potential anti-cancer drug target. While FAP expression was associated with biochemical recurrence after prostatectomy using tissue microarrays (TMAs)(DOI:10.1158/2767-9764.CRC-21-0183), its expression has not been comprehensively correlated with morphological features of disease aggressiveness beyond grade. 48 cases of localized prostatic adenocarcinoma were used for a multiplex immunohistochemical assay that included FAP, CD45, CD163, p63 and Keratin 8. Each of these markers were individually optimized by single-plex staining and were then performed as an iterative IHC assay (PMID:35188986) and quantification was performed using the HALO image analysis platform (Indica Labs). We developed a second multiplex assay including FAP, vimentin, smooth muscle actin, desmin, CD31, S100, keratin 8 and p63. FAP IHC staining was analytically validated using a series of positive and negative cell lines. In normal appearing (non-inflamed) prostate regions, FAP expression was negative. By contrast, upregulation of FAP was observed in the stromal compartment in regions of chronic inflammation and some proliferative inflammatory atrophy (PIA) lesions. In tumor regions, only 1 case was totally negative for FAP. Except for 2 cases, in which there was focal weak tumor cell staining, all FAP expression was present in the tumor stromal compartment (TSC). The vast majority of FAP expression was associated with Vim+/Des- fibroblasts, which at times were also positive for SMA (Vim+/Des-/SMA+), indicating they are myofibroblasts. There was very infrequent FAP expression associated with M2 macrophages, endothelial cells, nerves and vimentin-negative smooth muscle cells, indicating that the majority of FAP expression occurs in fibroblasts. Preliminary quantitative data using visual estimations of the fraction of TSC expressing FAP (range, 0-80%, mean=35.8%, median=30%, SD=23.7) was not associated with the overall GS/grade group, but was associated with non-organ confined disease. Furthermore, there was a trend towards increased FAP expression in cases showing intraductal carcinoma and large cribriform formation. Ongoing studies are in process to obtain quantitative data by image analysis and to correlate FAP expression with the presence of overall inflammatory cell density and the density of M2 macrophages. Additionally, we will characterize the cases in terms of molecular features including TMPRSS2-ERG status and PTEN genomic status. Future use of these panels will facilitate studies of associations of FAP with clinical outcome, MRI and PET imaging, response to specific treatments and to help characterize FAP as a predictor of response to emerging FAP inhibitors and FAP-targeted prodrugs. Citation Format: Fernanda Caramella Pereira, Alan K. Meeker, Kenneth Pienta, Qizhi Zheng, Tracy Jones, Srinivasan Yegnasubramanian, Jessica L. Hicks, Sujayita Roy, Angelo M. De Marzo, W. Nathaniel Brennen. Multiplex IHC assay to explore regional heterogeneity of FAP and inflammatory cell density in localized prostatic adenocarcinoma. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4631.

Pentafecta outcomes of robotic laparoscopically assisted radical prostatectomy during the initial experience in a university hospital

BackgroundRobotic laparoscopically assisted radical prostatectomy (RARP) is an option for the treatment of localized prostate cancer. The objective of the present study was to evaluate the pentafecta outcomes (biochemical recurrence, continence, potency, surgical complications and surgical margins) in patients undergoing RARP during the initial experience in a university hospital.MethodsThis is a retrospective study of patients who had RARP for localized prostate adenocarcinoma at a university hospital from August 2013 to October 2019 to evaluate pentafecta outcomes (biochemical recurrence, continence, potency, surgical complications and surgical margins). Data were collected and stored via Microsoft Office Excel program and analyzed using SPSS Software, version 20.0.ResultsOne hundred and sixty-three RARP were performed, the mean age is 64.16 ± 6.54 years, PSA 6.20 (IQR = 4.91–8.95) ng/dl, BMI 27.14 (IQR = 24.22–29.26) kg/m2, D’Amico risk classification was 35 (22.3%) low risk, 81 (51.6%) intermediate risk and 41 (26.1%) high risk. One hundred and fifty-four patients entered the analysis of pentafecta with a rate of 38.3% reaching this outcome. Complications: Twenty-three (14.1%) patients had minor complications (Clavien I and II) and eight patients had major complications (Clavien IIIa, IIIb and IVa). Surgical margins were negative in 69.9% of patients. The biochemical recurrence-free rate was 89.5%. The overall continence rate was 93.5%, and the potency rate was 63.5%. Multivariate analysis showed that T2 patients are 2.7 times more likely to achieve pentafecta outcome than patients ≥ T3 (p < 0.05), while younger age and lower BMI data were found as a protective factor with RR of 0.95 and 0.94, respectively.ConclusionsPreliminary pentafecta outcome of RARP in this university hospital is promising.

Magnetic Resonance Imaging–Guided vs Computed Tomography–Guided Stereotactic Body Radiotherapy for Prostate Cancer

Magnetic resonance imaging (MRI) guidance offers multiple theoretical advantages in the context of stereotactic body radiotherapy (SBRT) for prostate cancer. However, to our knowledge, these advantages have yet to be demonstrated in a randomized clinical trial. To determine whether aggressive margin reduction with MRI guidance significantly reduces acute grade 2 or greater genitourinary (GU) toxic effects after prostate SBRT compared with computed tomography (CT) guidance. This phase 3 randomized clinical trial (MRI-Guided Stereotactic Body Radiotherapy for Prostate Cancer [MIRAGE]) enrolled men aged 18 years or older who were receiving SBRT for clinically localized prostate adenocarcinoma at a single center between May 5, 2020, and October 1, 2021. Data were analyzed from January 15, 2021, through May 15, 2022. All patients had 3 months or more of follow-up. Patients were randomized 1:1 to SBRT with CT guidance (control arm) or MRI guidance. Planning margins of 4 mm (CT arm) and 2 mm (MRI arm) were used to deliver 40 Gy in 5 fractions. The primary end point was the incidence of acute (≤90 days after SBRT) grade 2 or greater GU toxic effects (using Common Terminology Criteria for Adverse Events, version 4.03 [CTCAE v4.03]). Secondary outcomes included CTCAE v4.03-based gastrointestinal toxic effects and International Prostate Symptom Score (IPSS)-based and Expanded Prostate Cancer Index Composite-26 (EPIC-26)-based outcomes. Between May 2020 and October 2021, 156 patients were randomized: 77 to CT (median age, 71 years [IQR, 67-77 years]) and 79 to MRI (median age, 71 years [IQR, 68-75 years]). A prespecified interim futility analysis conducted after 100 patients reached 90 or more days after SBRT was performed October 1, 2021, with the sample size reestimated to 154 patients. Thus, the trial was closed to accrual early. The incidence of acute grade 2 or greater GU toxic effects was significantly lower with MRI vs CT guidance (24.4% [95% CI, 15.4%-35.4%] vs 43.4% [95% CI, 32.1%-55.3%]; P = .01), as was the incidence of acute grade 2 or greater gastrointestinal toxic effects (0.0% [95% CI, 0.0%-4.6%] vs 10.5% [95% CI, 4.7%-19.7%]; P = .003). Magnetic resonance imaging guidance was associated with a significantly smaller percentage of patients with a 15-point or greater increase in IPSS at 1 month (6.8% [5 of 72] vs 19.4% [14 of 74]; P = .01) and a significantly reduced percentage of patients with a clinically significant (≥12-point) decrease in EPIC-26 bowel scores (25.0% [17 of 68] vs 50.0% [34 of 68]; P = .001) at 1 month. In this randomized clinical trial, compared with CT-guidance, MRI-guided SBRT significantly reduced both moderate acute physician-scored toxic effects and decrements in patient-reported quality of life. Longer-term follow-up will confirm whether these notable benefits persist. ClinicalTrials.gov Identifier: NCT04384770.

Palliative TURP Combined with Intermittent ADT Is A Curative Therapy to Some Elderly Men with Localized Prostate Adenocarcinoma.

Background: Radical prostatectomy is the preferred therapeutic option for patients with localized prostate adenocarcinoma whose life expectancy is greater than 10 years. But for elderly patients, this may not be the best option. In clinical work, we have observed that palliative transurethral resection of prostate (pTURP) combined with intermittent androgen deprivation therapy (ADT) has achieved significant good results in the treatment of elderly patients with localized prostate adenocarcinoma. Methods: Retrospective analysis was conducted on 30 elderly patients aged 71 to 88 years who were hospitalized for urinary retention from March 2009 to March 2015. These patients were diagnosed as localized prostate adenocarcinoma with stage T1 to T2 and benign prostatic hyperplasia (BPH) through MRI and prostate biopsy. Fifteen cases (group A) were given pTURP and intermittent ADT after surgery. Fifteen cases (group B) were given sustained ADT. Serum total prostate specific antigen (TPSA), testosterone, alkaline phosphatase (ALP), prostate acid phosphatase (PAP), International Prostate Symptom Score (IPSS), Quality of Life (QOL) score, maximum urinary flow rate (Qmax), average urinary flow rate (Qave), prostate volume and post-void residual urine (PVR) data were followed up for 5 years, and the differences between the two groups were compared. Results: The 5-year cumulative survival rate of group A was 100%. Prostate specific antigen (PSA) progression-free survival was 60.00%. The average duration of intermittent ADT was 23.93 months. Prostate volume reduction was significantly. The dysuria in all patients was significantly improved. Nine patients had TPSA lower than 4 ng/ml and had no local progression and metastasis. At the same time the 5-year cumulative survival rate of group B was 80%. PSA progression-free survival was 26.67%. Six cases of dysuria improved. There was no significant difference in serum TPSA, ALP and PAP between the two groups in five years (P>0.05). Serum testosterone, IPSS score, QOL score, prostate volume, Qmax, Qave, and PVR were significantly different between the two groups in five years (P<0.05). Conclusion: pTURP for elderly patients with localized prostate adenocarcinoma and BPH combined with intermittent ADT is an effective treatment. It is able to solve dysuria. The overall ADT time is short. The risk of progression to castrated resistant prostate cancer is low. Some of them have achieved tumor-free survival.

Dosimetric evaluation study of IMRT and VMAT techniques for prostate cancer based on different multileaf collimator designs

The hypofractionated radiotherapy modality was established to reduce treatment durations and enhance therapeutic efficiency, as compared to conventional fractionation treatment. However, this modality is challenging because of rigid dosimetric constraints. This study aimed to assess the impact of multi-leaf collimator (MLC) widths (10 mm and 5 mm) on plan quality during the treatment of prostate cancer. Additionally, this study aimed to investigate the impact of the MLC mode of energy on the Agility flattening filter (FF), MLC Agility-free flattening filter (FFF), and MLCi2 for patients receiving hypofractionated radiotherapy. Two radiotherapy techniques; Intensity Modulated Radiotherapy (IMRT) and Volumetric Modulated Arc Radiotherapy (VMAT), were used in this research. In the present study, computed tomography simulations of ten patients (six plans per patient) with localized prostate adenocarcinoma were analyzed. Various dosimetric parameters were assessed, including monitor units, treatment delivery times, conformity, and homogeneity indices. To evaluate the plan quality, dose-volume histograms (DVHs) were estimated for each technique. The results demonstrated that the determined dosimetric parameters of planning target volume (PTV)p (such as D mean, conformity, and homogeneity index) showed greater improvement with MLC Agility FF and MLC Agility FFF than with MLCi2. Additionally, the treatment delivery time was reduced in the MLC Agility FF (by 31%) and MLC Agility FFF (by 10.8%) groups compared to the MLCi2 group. It is concluded that for both the VMAT and IMRT techniques, the smaller width (5 mm) MLCs revealed better planning target volume coverage, improved the dosimetric parameters for PTV, reduced the treatment time, and met the constraints for OARs. It is therefore recommended to use 5 mm MLCs for hypofractionated prostate cancer treatment due to better target coverage and better protection of OARs.

Patient-reported Outcomes After External Beam Radiotherapy With Low Dose Rate Brachytherapy Boost vs Radical Prostatectomy for Localized Prostate Cancer: Five-year Results From a Prospective Comparative Effectiveness Study.

Data comparing radical prostatectomy and external beam radiation therapy with low dose rate brachytherapy boost are lacking. To better guide shared decision making regarding treatment, we compared patient reported outcomes through 5 years following radical prostatectomy or external beam radiation therapy with low dose rate brachytherapy boost for localized prostate cancer. From 2011-2012, men aged <80 years with localized prostate adenocarcinoma were enrolled and followed longitudinally. Patient reported outcomes included the Expanded Prostate Index Composite. Regression models adjusted for baseline scores and covariates were constructed. The study population included 112 men treated with external beam radiation therapy with low dose rate brachytherapy boost and 1,553 treated with radical prostatectomy. Compared to radical prostatectomy, external beam radiation therapy with low dose rate brachytherapy boost was associated with clinically meaningful worse urinary irritative/obstructive (adjusted mean score difference [95% confidence interval]: 5.0 [-8.7, -1.3]; P = .008 at 5 years) and better urinary incontinence function (13.3 [7.7, 18.9]; P < .001 at 5 years) through 5 years. Urinary function bother was similar between groups (P > .4 at all timepoints). Treatment with external beam radiation therapy with low dose rate brachytherapy boost was associated with worse bowel function (-4.0 [-6.9, -1.1]; P = .006 at 5 years) through 5 years compared to radical prostatectomy. Treatment with external beam radiation therapy with low dose rate brachytherapy boost was associated with better sexual function at 1 year (12.0 [6.5, 17.5]; P < .001 at 1 year) compared to radical prostatectomy, but there was insufficient evidence to reject the supposition that no difference was seen at 3 or 5 years. Compared to radical prostatectomy, external beam radiation therapy with low dose rate brachytherapy boost was associated with clinically meaningful worse urinary irritative/obstructive and bowel functions but better urinary incontinence function through 5 years after treatment. These patient-reported functional outcomes may clarify treatment expectations and help inform treatment choices for localized prostate cancer.

Impact of Left-Digit Age Bias in the Treatment of Localized Prostate Cancer.

Left-digit bias is a phenomenon in which the leftmost digit of a number disproportionately influences decision making. We measured the effect of left-digit age bias on treatment recommendations for localized prostate cancer. We included men with clinically localized prostate adenocarcinoma in Surveillance, Epidemiology, and End Results from 2004 to 2018 and the National Cancer Database from 2004 to 2016. Primary outcomes were recommendations for radiation therapy and radical prostatectomy. Regression discontinuity was used to assess whether age increase from 69 to 70 years was associated with disproportionate changes in treatment recommendations. In Surveillance, Epidemiology, and End Results, discontinuities were found in the proportion of patients recommended for radiation among the entire cohort (effect size 2.2%, P < .01) and among patients with Gleason 6 (1.6%, P < .01), Gleason 7 (2.5%, P < .01), and Gleason ≥8 (2.1%, P < .01) cancer, while the proportion recommended for prostatectomy decreased in the entire cohort (-1.4%, P < .01) and in patients with Gleason 7 cancer (-2.4%, P < .01). In the National Cancer Database, discontinuity from age 69 to 70 was found in recommendations for radiation in the entire cohort (effect size: 3.1%, P < .01) and in patients with Gleason 6 (2.2%, P < .01), Gleason 7 (4.0%, P < .01), and Gleason ≥8 (2.3%, P < .02) cancer, while the proportion recommended for prostatectomy decreased at this cutoff in the entire cohort (effect size: -2.7%, P < .01) and patients with Gleason 6 (-2.2%, P < .01) and Gleason 7 (-3.7%, P < .01) cancer. In patients with localized prostate cancer, left-digit age change from 69 to 70 was associated with disproportionately increased recommendations for radiation and decreased recommendations for prostatectomy.