The impact of baseline health factors on second primary cancer risk after radiotherapy for prostate cancer.

PURPOSE: In evaluating second primary cancers (SPCs) following External Beam Radiotherapy (EBRT), the role of lifestyle factors is frequently not considered due to data limitations. We investigated the association between smoking, comorbidities, and SPC risks within EBRT-treated patients for localized prostate cancer (PCa). PATIENTS & METHODS: The study included 1,883 PCa survivors aged 50-79, treated between 2006 and 2013, with intensity-modulated radiotherapy (IMRT) or three-dimensional conformal radiotherapy (3D-CRT). Clinical data were combined with SPC and survival data from the Netherlands Cancer Registry with a 12-month latency period. Standardized Incidence Ratios (SIRs) were calculated comparing the EBRT cohort with the general Dutch population. To explore the effect of patient and treatment characteristics on SPCs we conducted a Cox regression analysis. Lastly, we estimated cumulative incidences of developing solid SPC, pelvis SPC, and non-pelvis SPC using a competing risk analysis. RESULTS: Significantly increased SIRs were observed for all SPC (SIR = 1.21, 95% confidence interval [CI]: 1.08-1.34), pelvis SPC (SIR = 1.46, 95% CI: 1.18-1.78), and non-pelvis SPC (SIR = 1.18, 95% CI [1.04-1.34]). Smoking status was significantly associated with pelvic and non-pelvic SPCs. Charlson comorbidity index (CCI) ≥ 1 (Hazard Ratio [HR] = 1.45, 95% CI: 1.10-1.91), cardiovascular disease (HR = 1.41, 95% CI: 1.05-1.88), and chronic obstructive pulmonary disease (COPD) (HR = 1.91, 95% CI: 1.30-2.79) were significantly associated with non-pelvis SPC. The proportion of active smoking numbers in the cohort was similar to the general population. INTERPRETATION: We conclude that the presence of comorbidities in the EBRT population might be a relevant factor in observed excess non-pelvis SPC risk, but not for excess pelvis SPC risk.

Transcriptomic response of prostate cancer cells to carbon ion and photon irradiation with focus on androgen receptor and TP53 signaling.

BACKGROUND: Radiotherapy is essential in the treatment of prostate cancer. An alternative to conventional photon radiotherapy is the application of carbon ions, which provide a superior intratumoral dose distribution and less induced damage to adjacent healthy tissue. A common characteristic of prostate cancer cells is their dependence on androgens which is exploited therapeutically by androgen deprivation therapy in the advanced prostate cancer stage. Here, we aimed to analyze the transcriptomic response of prostate cancer cells to irradiation by photons in comparison to carbon ions, focusing on DNA damage, DNA repair and androgen receptor signaling. METHODS: Prostate cancer cell lines LNCaP (functional TP53 and androgen receptor signaling) and DU145 (dysfunctional TP53 and androgen receptor signaling) were irradiated by photons or carbon ions and the subsequent DNA damage was assessed by immuno-cytofluorescence. Furthermore, the cells were treated with an androgen-receptor agonist. The effects of irradiation and androgen treatment on the gene regulation and the transcriptome were investigated by RT-qPCR and RNA sequencing, followed by bioinformatic analysis. RESULTS: Following photon or carbon ion irradiation, both LNCaP and DU145 cells showed a dose-dependent amount of visible DNA damage that decreased over time, indicating occurring DNA repair. In terms of gene regulation, mRNAs involved in the TP53-dependent DNA damage response were significantly upregulated by photons and carbon ions in LNCaP but not in DU145 cells, which generally showed low levels of gene regulation after irradiation. Both LNCaP and DU145 cells responded to photons and carbon ions by downregulation of genes involved in DNA repair and cell cycle, partially resembling the transcriptome response to the applied androgen receptor agonist. Neither photons nor carbon ions significantly affected canonical androgen receptor-dependent gene regulation. Furthermore, certain genes that were specifically regulated by either photon or carbon ion irradiation were identified. CONCLUSION: Photon and carbon ion irradiation showed a significant congruence in terms of induced signaling pathways and transcriptomic responses. These responses were strongly impacted by the TP53 status. Nevertheless, irradiation mode-dependent distinct gene regulations with undefined implication for radiotherapy outcome were revealed. Androgen receptor signaling and irradiations shared regulation of certain genes with respect to DNA-repair and cell-cycle.

Gene Abnormalities and Modulated Gene Expression Associated with Radionuclide Treatment: Towards Predictive Biomarkers of Response.

Molecular radiotherapy (MRT), also known as radioimmunotherapy or targeted radiotherapy, is the delivery of radionuclides to tumours by targeting receptors overexpressed on the cancer cell. Currently it is used in the treatment of a few cancer types including lymphoma, neuroendocrine, and prostate cancer. Recently reported outcomes demonstrating improvements in patient survival have led to an upsurge in interest in MRT particularly for the treatment of prostate cancer. Unfortunately, between 30% and 40% of patients do not respond. Further normal tissue exposure, especially kidney and salivary gland due to receptor expression, result in toxicity, including dry mouth. Predictive biomarkers to select patients who will benefit from MRT are crucial. Whilst pre-treatment imaging with imaging versions of the therapeutic agents is useful in demonstrating tumour binding and potentially organ toxicity, they do not necessarily predict patient benefit, which is dependent on tumour radiosensitivity. Transcript-based biomarkers have proven useful in tailoring external beam radiotherapy and adjuvant treatment. However, few studies have attempted to derive signatures for MRT response prediction. Here, transcriptomic studies that have identified genes associated with clinical radionuclide exposure have been reviewed. These studies will provide potential features for seeding multi-component biomarkers of MRT response.

Novel [68Ga/177Lu]Ga/Lu-AZ-093 as PSMA-Targeting Agent for Diagnosis and Radiotherapy.

Prostate-specific membrane antigen (PSMA) overexpressed in prostate cancer cells can serve as a target for imaging and radioligand therapy (RLT). Previously, [68Ga]Ga-P16-093, containing a Ga(III) chelator, N,N'-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N'-diacetic acid (HBED-CC), displayed excellent PSMA-targeting properties and showed a high tumor uptake and retention useful for diagnosis in prostate cancer patients. Recently, [177Lu]Lu-PSMA-617 has been approved by the U.S. food and drug administration (FDA) for the treatment of prostate cancer patients. Derivatives of PSMA-093 using AAZTA (6-amino-6-methylperhydro-1,4-diazepinetetraacetic acid), as the chelator, were designed as alternative agents forming complexes with both diagnostic and therapeutic radiometals, such as gallium-68 (log K = 22.18) or lutetium-177 (log K = 21.85). The aim of this study is to evaluate AAZTA-Gly-O-(methylcarboxy)-Tyr-Phe-Lys-NH-CO-NH-Glu (designated as AZ-093, 1) leading to a gallium-68/lutetium-177 theranostic pair as potential PSMA targeting agents. Synthesis of the desired precursor, AZ-093, 1, was effectively accomplished. Labeling with either [68Ga]GaCl3 or [177Lu]LuCl3 in a sodium acetate buffer solution (pH 4-5) at 50 °C in 5 to 15 min produced either [68Ga]Ga-1 or [177Lu]Lu-1 with high yields and excellent radiochemical purities. Results of in vitro binding studies, cell uptake, and retention (using PSMA-positive prostate carcinoma cells line, 22Rv1-FOLH1-oe) were comparable to that of [68Ga]Ga-P16-093 and [177Lu]Lu-PSMA-617, respectively. Specific cellular uptake was determined with or without the competitive blocking agent (2 µM of "cold" PSMA-11). Cellular binding and internalization showed a time-dependent increase over 2 h at 37 °C in the PSMA-positive cells. The cell uptakes were completely blocked by the "cold" PSMA-11 suggesting that they are competing for the same PSMA binding sites. In the mouse model with implanted PSMA-positive tumor cells, both [68Ga]Ga-1 and [177Lu]Lu-1 displayed excellent uptake and retention in the tumor. Results indicate that [68Ga]Ga/[177Lu]Lu-1 (68Ga]Ga/[177Lu]Lu-AZ-093) is potentially useful as PSMA-targeting agent for both diagnosis and radiotherapy of prostate cancer.

Radiation Oncologists' Perspectives on Oligometastatic Prostate Cancer: A Survey from Korean Oligometastasis Working Group.

BACKGROUND: Interest in the oligometastatic prostate cancer (OMPC) is increasing, and various clinical studies have reported the benefits of metastasis-directed radiation therapy (MDRT) in OMPC. However, the recognition regarding the adopted definitions, methodologies of assessment, and therapeutic approaches is diverse among radiation oncologists. This study aims to evaluate the level of agreement for issues in OMPC among radiation oncologists. METHODS: We generated 15 key questions (KQs) for OMPC relevant to definition, diagnosis, local therapies, and endpoints. Additionally, three clinical scenarios representing synchronous metastatic prostate cancer (mPC) (case 1), metachronous mPC with visceral metastasis (case 2), and metachronous mPC with castration-resistance and history of polymetastasis (case 3) were developed. The 15 KQs were adapted according to each scenario and transformed into 23 questions with 6-9 per scenario. The survey was distributed to 80 radiation oncologists throughout the Republic of Korea. Answer options with 0.0-29.9%, 30-49.9%, 50-69.9%, 70-79.9%, 80-89.9%, and 90-100% agreements were considered as no, minimal, weak, moderate, strong, and near perfect agreement, respectively. RESULTS: Forty-five candidates voluntarily participated in this study. Among 23 questions, near perfect (n = 4), strong (n = 3), or moderate (n = 2) agreements were shown in nine. For the case recognized as OMPC with agreements of 93% (case 1), near perfect agreements on the application of definitive radiation therapy (RT) for whole metastatic lesions were achieved. While ≥70% agreements regarding optimal dose-fractionation for metastasis-directed RT (MDRT) has not been achieved, stereotactic body RT (SBRT) is favored by clinicians with higher clinical volume. CONCLUSION: For the case recognized as OMPC, near perfect agreement for the application of definitive RT for whole metastatic lesions was reached. SBRT was more favored as a MDRT by clinicians with a higher clinical volume.

Exogenous APN protects normal tissues from radiation-induced oxidative damage and fibrosis in mice and prostate cancer patients with higher levels of APN have less radiation-induced toxicities.

Radiation causes damage to normal tissues that leads to increased oxidative stress, inflammation, and fibrosis, highlighting the need for the selective radioprotection of healthy tissues without hindering radiotherapy effectiveness in cancer. This study shows that adiponectin, an adipokine secreted by adipocytes, protects normal tissues from radiation damage invitro and invivo. Specifically, adiponectin (APN) reduces chronic oxidative stress and fibrosis in irradiated mice. Importantly, APN also conferred no protection from radiation to prostate cancer cells. Adipose tissue is the primary source of circulating endogenous adiponectin. However, this study shows that adipose tissue is sensitive to radiation exposure exhibiting morphological changes and persistent oxidative damage. In addition, radiation results in a significant and chronic reduction in blood APN levels from adipose tissue in mice and human prostate cancer patients exposed to pelvic irradiation. APN levels negatively correlated with bowel toxicity and overall toxicities associated with radiotherapy in prostate cancer patients. Thus, protecting, or modulating APN signaling may improve outcomes for prostate cancer patients undergoing radiotherapy.

[Does radiation therapy for prostate cancer increase the risk of second cancers?] / La radiothérapie du cancer de la prostate augmente-t-elle le risque de seconds cancers ?

PURPOSE: The increased risk of second cancer after prostate radiotherapy is a debated clinical concern. The objective of the study was to assess the risk of occurrence of second cancers after prostate radiation therapy based on the analysis the literature, and to identify potential factors explaining the discrepancies in results between studies. MATERIALS AND METHODS: A review of the literature was carried out, comparing the occurrence of second cancers in patients all presenting with prostate cancer, treated or not by radiation. RESULTS: This review included 30 studies reporting the occurrence of second cancers in 2,112,000 patients treated or monitored for localized prostate cancer, including 1,111,000 by external radiation therapy and 103,000 by brachytherapy. Regarding external radiation therapy, the average follow-up was 7.3years. The majority of studies (80%) involving external radiation therapy, compared to no external radiation therapy, showed an increased risk of second cancers with a hazard ratio ranging from 1.13 to 4.9, depending on the duration of the follow-up. The median time to the occurrence of these second cancers after external radiotherapy ranged from 4 to 6years. An increased risk of second rectal and bladder cancer was observed in 52% and 85% of the studies, respectively. Considering a censoring period of more than 10 years after irradiation, 57% and 100% of the studies found an increased risk of rectal and bladder cancer, without any impact in overall survival. Studies of brachytherapy did not show an increased risk of second cancer. However, these comparative studies, most often old and retrospective, had many methodological biases. CONCLUSION: Despite numerous methodological biases, prostate external radiation therapy appears associated with a moderate increase in the risk of second pelvic cancer, in particular bladder cancer, without impacting survival. Brachytherapy does not increase the risk of a second cancer.

Bladder trigone sparing radiotherapy in prostate cancer treatment.

INTRODUCTION: Evidence suggests the bladder trigone to be a potential organ at risk (OAR) in predicting acute and late genitourinary (GU) side effects when treating prostate cancer with radiotherapy. METHODS: A search of MEDLINE, Cinahl, EMBASE, PubMed, the Cochrane Database of Systematic Reviews and OpenGrey was conducted and no current or underway systematic reviews or scoping reviews on the topic were identified. A systematic literature review was carried out assessing the quality of this evidence. All evidence that prospectively or retrospectively reviewed radiotherapy or modelled radiotherapy dose to the bladder trigone were included. The search was conducted on the 8th July 2021 with 32 studies included in this review. This was repeated 10th June 2023 and two additional studies were identified. Any evidence published since this date have not been included and are a limitation of this review. RESULTS: MRI imaging is recommended to assist in delineating the trigone which has been shown to have a high amount of inter-observer variability and the use of specific training may reduce this. Across all radiotherapy treatment modalities, trigone dose contributed to GU acute and late toxicity symptoms. Trigone motion is relative to prostate motion but further research is required to confirm if the prostate can be used as a reliable surrogate for trigone position. The dose tolerance given for specific trigone related toxicities is debated within the literature, and on analysis the authors of this review suggest bladder trigone dose limits: Dmean < 45.8 Gy, V61.0Gy < 40%, V59.8Gy < 25%, V42.5Gy-V41.0Gy < 91% and V47.4Gy-V43.2Gy < 91% with α/ß of 3 Gy to reduce acute and late GU toxicities. CONCLUSION: There is evidence to support further research into bladder trigone sparing radiotherapy to improve patient outcomes. IMPLICATION FOR PRACTICE: Using the bladder trigone as an organ at risk is possible and the authors are currently seeking funding for a feasibility trial to further investigate this.

Receptor-Targeted Peptide Conjugates Based on Diphosphines Enable Preparation of 99mTc and 188Re Theranostic Agents for Prostate Cancer.

Benchtop 99Mo/99mTc and 188W/188Re generators enable economical production of molecular theranostic 99mTc and 188Re radiopharmaceuticals, provided that simple, kit-based chemistry exists to radiolabel targeting vectors with these radionuclides. We have previously described a diphosphine platform that efficiently incorporates 99mTc into receptor-targeted peptides. Here, we report its application to label a prostate-specific membrane antigen (PSMA)-targeted peptide with 99mTc and 188Re for diagnostic imaging and systemic radiotherapy of prostate cancer. Methods: Two diphosphine-dipeptide bioconjugates, DP1-PSMAt and DP2-PSMAt, were formulated into kits for radiolabeling with 99mTc and 188Re. The resulting radiotracers were studied in vitro, in prostate cancer cells, and in vivo in mouse xenograft models, to assess similarity of uptake and biodistribution for each 99mTc/188Re pair of agents. Results: Both DP1-PSMAt and DP2-PSMAt could be efficiently radiolabeled with 99mTc and 188Re using kit-based methods to furnish the isostructural compounds M-DP1-PSMAt and M-DP2-PSMAt (M = [99mTc]Tc, [188Re]Re). All 99mTc/188Re radiotracers demonstrated specific uptake in PSMA-expressing prostate cancer cells, with negligible uptake in prostate cancer cells that did not express PSMA or in which PSMA uptake was blocked. M-DP1-PSMAt and M-DP2-PSMAt also exhibited high tumor uptake (18-30 percentage injected dose per gram at 2 h after injection), low retention in nontarget organs, fast blood clearance, and excretion predominantly via a renal pathway. Importantly, each pair of 99mTc/188Re radiotracers showed near-identical biologic behavior in these experiments. Conclusion: We have prepared and developed novel pairs of isostructural PSMA-targeting 99mTc/188Re theranostic agents. These generator-based theranostic agents have potential to provide access to the benefits of PSMA-targeted diagnostic imaging and systemic radiotherapy in health care settings that do not routinely have access to either reactor-produced 177Lu radiopharmaceuticals or PET/CT infrastructure.

Overview of Radiation Therapy in the Management of Localized and Metastatic Prostate Cancer.

PURPOSE OF REVIEW: The goal is to describe the evolution of radiation therapy (RT) utilization in the management of localized and metastatic prostate cancer. RECENT FINDINGS: Long term data for a variety of hypofractionated definitive RT dose-fractionation schemes has matured, allowing patients and providers many standard-of-care options to choose from. Post-prostatectomy, adjuvant RT has largely been replaced by an early salvage approach. Multiparametric MRI and PSMA PET have enabled increasingly targeted RT delivery to the prostate and oligometastatic tumors. Areas of active investigation include determining the value of proton beam therapy and perirectal spacers, and optimally incorporate genomic tumor profiling and next generation hormonal therapies with RT in the curative setting. The use of radiation therapy to treat prostate cancer is rapidly evolving. In the coming years, there will be continued improvements in a variety of areas to enhance the value of RT in multidisciplinary prostate cancer management.

Identification of Factors Contributing to Testosterone Recovery After Hormone Therapy Combined With External Radiation Therapy.

BACKGROUND/AIM: When hormone therapy (HT) is combined with radiotherapy, understanding the recovery of testosterone levels after the end of HT becomes crucial for considering subsequent therapy. The aim of this study was to determine the factors influencing the time to recovery of testosterone levels after discontinuation of HT and the likelihood of recovery. PATIENTS AND METHODS: The study included a total of 108 patients with prostate cancer who were treated with GnRH agonist in combination with radiotherapy and followed up for at least 12 months after discontinuation of the GnRH agonist. The presence of recovery of testosterone levels and the time to recovery were investigated. Univariate and multivariate analyses were performed on several factors contributing to testosterone recovery, including age at initiation of HT, and the duration of HT. RESULTS: Testosterone levels recovered in 61 cases (56.5%). The median time to recovery was 14.8 months. There was a significant difference in the recovery of testosterone levels between patients aged ≥71 years and those aged <71 years at the start of HT (p=0.002), and between those who had been on HT for ≥34 months and those for <34 months (p=0.031). In both univariate and multivariate analyses, age at initiation of HT and duration of HT contributed to the recovery of testosterone levels. CONCLUSION: The rate of recovery of testosterone levels after long-term (median 34.3 months) HT was lower in patients who were older than 71 years at the start of HT.

Evaluation of Treatment Outcomes of Prostate Cancer Patients With Lymph Node Metastasis Treated With Definitive Radiotherapy: Comparative Analysis of PSMA PET/CT and Conventional Imaging.

PURPOSE: We investigated the impact of prostate-specific membrane antigen (PSMA) PET/CT compared with conventional imaging on treatment outcomes for node-positive prostate cancer (PCa) patients who underwent androgen deprivation therapy (ADT) and external radiotherapy (RT). PATIENTS AND METHODS: A multicentric, retrospective study recruited patients with node-positive PCa patients who underwent conventional radiological evaluation or PSMA PET/CT and received ADT and RT at 3 hospitals from 2009 to 2021 were enrolled. Patients underwent prostate and pelvis RT, accompanied by a minimum of 6 months of ADT. The primary endpoints were progression-free survival (PFS) and PCa-specific survival (PCSS). Cox regression analyzed the association of survival with potential prognostic factors, whereas logistic regression identified the predictors of bone and lymph node metastasis. RESULTS: The median follow-up time was 64.0 months. The majority of patients (64.1%) underwent PSMA PET/CT for staging. The 5-year rates of PFS and PCSS were 63.7% and 83.7%, respectively. Disease progression was observed in 90 patients (36.3%). In multivariable analysis, ADT duration of less than 24 months and post-RT prostate-specific antigen (PSA) nadir were prognostic for PFS. Early clinical T stage and PSMA PET/CT predicted better PCSS. Patients staged with PSMA PET/CT had exhibited significantly higher 5-year PCSS rates than compared with those staged with conventional imaging (95.1% vs 76.9%; P = 0.01). Shorter ADT duration and higher PSA levels after RT independently predicted bone metastasis in multivariable logistic regression. Advanced T stage, shorter ADT duration, and higher PSA levels after neoadjuvant ADT predicted nonregional lymph node recurrence. CONCLUSIONS: ADT with pelvis RT is an effective treatment option for node-positive PCa patients. The PSMA PET/CT outperformed conventional imaging in PCSS, emphasizing the importance of precise clinical staging for patients undergoing definitive RT.

Androgen Deprivation Therapy and Outcomes After Radiation Therapy in Black Patients With Prostate Cancer.

Importance: Prostate cancer in Black men compared with White men may be more sensitive to radiation therapy resulting in better outcomes in equal-access settings. The outcomes of androgen-deprivation therapy (ADT) vs radiation therapy itself remains uncharacterized. Objectives: To quantify any outcome modification by receipt of ADT on the association between Black race and prostate cancer outcomes following radiation therapy. Design, Setting, and Participants: This was a retrospective, nationwide cohort study of Black and White patients treated in the US Veterans Healthcare system between 2000 and 2020 receiving definitive radiation for localized prostate cancer. Data were analyzed from January 2000 to December 2020. Exposure: Patient self-identified race and use of ADT defined as any gonadotrophin-releasing hormone agonist or antagonist prescription within 6 months of radiation. Main Outcomes and Measures: Biochemical recurrence (BCR) from time of completion of radiation therapy (prostate-specific antigen nadir plus 2 ng/mL) and development of metastatic disease or prostate cancer mortality (PCSM) from time of recurrence. Results: A total of 26 542 patients (8716 Black men with median [IQR] age of 64 [59-69] years and 17 826 White men with median [IQR] age of 67 [62-72] years) received definitive radiation therapy for nonmetastatic prostate cancer and had complete staging and follow-up data. A total of 5144 patients experienced BCR (3384 White and 1760 Black patients). The cumulative incidence of BCR at 10 years was not significantly different between Black and White men (1602 [22.14%] vs 3099 [20.13%], respectively) with multivariable hazard ratio (HR) of 1.03 (95% CI, 0.97-1.09; P = .33). In men receiving ADT, Black men had an HR for BCR of 0.90 (95% CI, 0.82-0.99; P = .03) compared with White men, and in men not receiving ADT, Black men had an HR of 1.13 (95% CI, 1.05-1.22; P = .002). Black race was associated with a decreased risk of developing metastatic disease (HR, 0.90; 95% CI, 0.82-0.98; P = .02) or PCSM (subdistribution HR, 0.72; 95% CI, 0.63-0.82; P < .001) from time of biochemical recurrence. Conclusions and Relevance: Black patients treated with radiation appear to specifically benefit from the addition of ADT with regard to biochemical control. Additionally, BCR in Black men results in a lower rate of metastatic disease and death from prostate cancer. Future analyses of radiosensitivity in Black men should evaluate for the possibility of outcome modification by ADT.

Managing prostate cancer after proctocolectomy and ileal pouch-anal anastomosis: feasibility and outcomes of single-port transvesical robot-assisted radical prostatectomy.

INTRODUCTION: Patients with proctocolectomy and ileal pouch-anal anastomosis (PC-IPAA) face unique challenges in managing prostate cancer due to their hostile abdomens and heightened small bowel mucosa radiosensitivity. In such cases, external beam radiation therapy (EBRT) is contraindicated, and while brachytherapy provides a safer option, its oncologic effectiveness is limited. The Single-Port Transvesical Robot-Assisted Radical Prostatectomy (SP TV-RARP) offers promise by avoiding the peritoneal cavity. Our study aims to evaluate its feasibility and outcomes in patients with PC-IPAA. METHODS: A retrospective evaluation was done on patients with PC-IPAA who had undergone SP TV-RARP from June 2020 to June 2023 at a high-volume center. Outcomes and clinicopathologic variables were analyzed. RESULTS: Eighteen patients underwent SP TV-RARP without experiencing any complications. The median hospital stay was 5.7 h, with 89% of cases discharged without opioids. Foley catheters were removed in an average of 5.5 days. Immediate urinary continence was seen in 39% of the patients, rising to 76 and 86% at 6- and 12-month follow-ups. Half of the cohort had non-organ confined disease on final pathology. Two patients with ISUP GG3 and GG4 exhibited detectable PSA post-surgery and required systemic therapy; both had SVI, multifocal ECE, and large cribriform pattern. Positive surgical margins were found in 44% of cases, mostly Gleason pattern 3, unifocal, and limited. After 11.1 months of follow-up, no pouch failure or additional BCR cases were found. CONCLUSION: Patients with PC-IPAA often exhibit aggressive prostate cancer features and may derive the greatest benefit from surgical interventions, particularly given that radiation therapy is contraindicated. SP TV-RARP is a safe option for this group, reducing the risk of bowel complications and promoting faster recovery.

Time-resolved clinical dose volume metrics, calculations and predictions based on source tracking measurements and uncertainties to aid treatment verification and error detection for HDR brachytherapy-a proof-of-principle study.

Objective.High-dose-rate (HDR) brachytherapy lacks routinely available treatment verification methods. Real-time tracking of the radiation source during HDR brachytherapy can enhance treatment verification capabilities. Recent developments in source tracking allow for measurement of dwell times and source positions with high accuracy. However, more clinically relevant information, such as dose discrepancies, is still needed. To address this, a real-time dose calculation implementation was developed to provide more relevant information from source tracking data. A proof-of-principle of the developed tool was shown using source tracking data obtained from a 3D-printed anthropomorphic phantom.Approach.Software was developed to calculate dose-volume-histograms (DVH) and clinical dose metrics from experimental HDR prostate treatment source tracking data, measured in a realistic pelvic phantom. Uncertainty estimation was performed using repeat measurements to assess the inherent dose measuring uncertainty of thein vivodosimetry (IVD) system. Using a novel approach, the measurement uncertainty can be incorporated in the dose calculation, and used for evaluation of cumulative dose and clinical dose-volume metrics after every dwell position, enabling real-time treatment verification.Main results.The dose calculated from source tracking measurements aligned with the generated uncertainty bands, validating the approach. Simulated shifts of 3 mm in 5/17 needles in a single plan caused DVH deviations beyond the uncertainty bands, indicating errors occurred during treatment. Clinical dose-volume metrics could be monitored in a time-resolved approach, enabling early detection of treatment plan deviations and prediction of their impact on the final dose that will be delivered in real-time.Significance.Integrating dose calculation with source tracking enhances the clinical relevance of IVD methods. Phantom measurements show that the developed tool aids in tracking treatment progress, detecting errors in real-time and post-treatment evaluation. In addition, it could be used to define patient-specific action limits and error thresholds, while taking the uncertainty of the measurement system into consideration.

Cone beam CT doses in radiotherapy patient positioning in Finland-prostate treatments.

Imaging parameters, frequencies and resulting patient organ doses in treatments of prostate cancer were assessed in Finnish radiotherapy centres. Based on a questionnaire to the clinics, Monte Carlo method was used to estimate organ doses in International Commission on Radiological Protection standard phantom for prostate, bladder, rectum and femoral head. The results show that doses from cone beam computed tomography imaging have reduced compared to earlier studies and are between 3.6 and 34.5 mGy per image for the above-mentioned organs and for normal sized patients. There still is room for further optimization of the patient exposure, as many centres use the default imaging parameters, and the length of the imaged region may not be optimal for the purpose.

Prostate Cancer Recurrence: Examining the Role of Salvage Radiotherapy Field and Risk Factors for Regional Disease Recurrence Captured on 18F-DCFPyL PET/CT.

PURPOSE: The role of elective pelvic nodal irradiation in salvage radiotherapy (sRT) remains controversial. Utilizing 18F-DCFPyL PET/CT, this study aimed to investigate differences in disease distribution after whole pelvic (WPRT) or prostate bed (PBRT) radiotherapy and to identify risk factors for pelvic lymph node (LN) relapse. METHODS: This retrospective study included patients with PSA > 0.1 ng/mL post-radical prostatectomy (RP) or post-RP and sRT who underwent 18F-DCFPyL PET/CT. Disease distribution on 18F-DCFPyL PET/CT after sRT was compared using Chi-square tests. Risk factors were tested for association with pelvic LN relapse after RP and salvage PBRT using logistic regression. RESULTS: 979 18F-DCFPyL PET/CTs performed at our institution between 1/1/2022 - 3/24/2023 were analyzed. There were 246 patients meeting criteria, of which 84 received salvage RT after RP (post-salvage RT group) and 162 received only RP (post-RP group). Salvage PBRT patients (n = 58) had frequent pelvic nodal (53.6%) and nodal-only (42.6%) relapse. Salvage WPRT patients (n = 26) had comparatively lower rates of pelvic nodal (16.7%, p = 0.002) and nodal-only (19.2%, p = 0.04) relapse. The proportion of distant metastases did not differ between the two groups. Multiple patient characteristics, including ISUP grade and seminal vesicle invasion, were associated with pelvic LN disease in the post-RP group. CONCLUSION: At PSA persistence or progression, salvage WPRT resulted in lower rates of nodal involvement than salvage PBRT, but did not reduce distant metastases. Certain risk factors increase the likelihood of pelvic LN relapse after RP and can help inform salvage RT field selection.

Intrafractional motion and dosimetric analysis in prostate stereotactic body radiation therapy with auto beam hold technique.

Objective: To summarize our institutional prostate stereotactic body radiation therapy (SBRT) experience using auto beam hold (ABH) technique for intrafractional prostate motion and assess ABH tolerance of 10-millimeter (mm) diameter.Approach: Thirty-two patients (160 fractions) treated using ABH technique between 01/2018 and 03/2021 were analyzed. During treatment, kV images were acquired every 20-degree gantry rotation to visualize 3-4 gold fiducials within prostate to track target motion. If the fiducial center fell outside the tolerance circle (diameter = 10 mm), beam was automatically turned off for reimaging and repositioning. Number of beam holds and couch translational movement magnitudes were recorded. Dosimetric differences from intrafractional motion were calculated by shifting planned isocenter.Main Results: Couch movement magnitude (mean ± SD) in vertical, longitudinal and lateral directions were -0.7 ± 2.5, 1.4 ± 2.9 and -0.1 ± 0.9 mm, respectively. For most fractions (77.5%), no correction was necessary. Number of fractions requiring one, two, or three corrections were 15.6%, 5.6% and 1.3%, respectively. Of the 49 corrections, couch shifts greater than 3 mm were seen primarily in the vertical (31%) and longitudinal (39%) directions; corresponding couch shifts greater than 5 mm occurred in 2% and 6% of cases. Dosimetrically, 100% coverage decreased less than 2% for clinical target volume (CTV) (-1 ± 2%) and less than 10% for PTV (-10 ± 6%). Dose to bladder, bowel and urethra tended to increase (Bladder: ΔD10%:184 ± 466 cGy, ΔD40%:139 ± 241 cGy, Bowel: ΔD1 cm3:54 ± 129 cGy; ΔD5 cm3:44 ± 116 cGy, Urethra: ΔD0.03 cm3:1 ± 1%). Doses to the rectum tended to decrease (Rectum: ΔD1 cm3:-206 ± 564 cGy, ΔD10%:-97 ± 426 cGy; ΔD20%:-50 ± 251 cGy).Significance: With the transition from conventionally fractionated intensity modulated radiation therapy to SBRT for localized prostate cancer treatment, it is imperative to ensure that dose delivery is spatially accurate for appropriate coverage to target volumes and limiting dose to surrounding organs. Intrafractional motion monitoring can be achieved using triggered imaging to image fiducial markers and ABH to allow for reimaging and repositioning for excessive motion.