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.

Increasing the radiation-induced cytotoxicity by silver nanoparticles and docetaxel in prostate cancer cells.

BACKGROUND: Radiation therapy is utilized for treatment of localized prostate cancer. Nevertheless, cancerous cells frequently develop radiation resistance. While higher radiation doses have not always been effective, radiosensitizers have been extensively studied for their ability to enhance the cytotoxic effects of radiation. So, this study aims to evaluate the possible radiosensitization effects of docetaxel (DTX) and silver nanoparticles (SNP) in LNCaP cells. METHODS: The cytotoxic effects of DTX, SNP and 2 Gy of X-Ray radiation treatments were assessed in human LNCaP cell line using the MTT test after 24 h. Moreover, the effects of DTX, SNP and radiation on Epidermal growth factor (EGF), Caspase 3, inducible nitric oxide synthase and E-cadherin gene expression were analyzed using the Real-time PCR method. The level of Hydrogen peroxide (H2O2), an oxidative stress marker, was also detected 24 h after various single and combined treatments. RESULTS: The combinations of SNP (in low toxic concentration) and/or DTX (0.25× IC50 and 0.5 × IC50 concentrations for triple and double combinations respectively) with radiation induced significant cytotoxicity in LNCaP cells in comparison to monotherapies. These cytotoxic effects were associated with the downregulation of EGF mRNA. Additionally, H2O2 levels increased after Radiation + SNP + DTX triple combination and double combinations including Radiation + SNP and Radiation + DTX versus single treatments. The triple combination treatment also increased Caspase 3 and and E-cadherin mRNA levels in compared to single treatments in LNCaP cells. CONCLUSION: Our results indicate that the combination of SNP and DTX with radiation induces significant anti-cancer effects. Upregulation of Caspase 3 and E-cadherin gene expression, and decreased mRNA expression level of EGF may be exerted specifically by use of this combination versus single treatments.

Chronic radiation proctitis refractory to steroid enema was successfully treated by metformin and sodium butyrate: a case report.

BACKGROUND: Radiation proctitis (RP) is a significant complication of pelvic radiation. Effective treatments for chronic RP are currently lacking. We report a case where chronic RP was successfully managed by metformin and butyrate (M-B) enema and suppository therapy. CASE PRESENTATION: A 70-year-old Asian male was diagnosed with prostate cancer of bilateral lobes, underwent definitive radiotherapy to the prostate of 76 Gy in 38 fractions and six months of androgen deprivation therapy. Despite a stable PSA nadir of 0.2 ng/mL for 10 months post-radiotherapy, he developed intermittent rectal bleeding, and was diagnosed as chronic RP. Symptoms persisted despite two months of oral mesalamine, mesalamine enema and hydrocortisone enema treatment. Transition to daily 2% metformin and butyrate (M-B) enema for one week led to significant improvement, followed by maintenance therapy with daily 2.0% M-B suppository for three weeks, resulting in continued reduction of rectal bleeding. Endoscopic examination and biopsy demonstrated a good therapeutic effect. CONCLUSIONS: M-B enema and suppository may be an effective treatment for chronic RP.

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

OBJECTIVE:  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. STUDY DESIGN: Descriptive study. Place and Duration of the Study: Department of Oncology, Dr. Ziauddin Hospital, Karachi, Pakistan, from July 2016 to June 2022. METHODOLOGY: 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. RESULTS:  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. CONCLUSION: 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. KEY WORDS: 3D-CRT (3-Dimensional Conformal Radiation Therapy), IMRT (Intensity-Modulated Radiation Therapy), Radiation toxicity.

Functional imaging guided stereotactic ablative body radiotherapy (SABR) with focal dose escalation and bladder trigone sparing for intermediate and high-risk prostate cancer: study protocol for phase II safo trial.

BACKGROUND: Stereotactic ablative body radiotherapy (SABR) is an emerging treatment alternative for patients with localized low and intermediate risk prostate cancer patients. As already explored by some authors in the context of conventional moderate hypofractionated radiotherapy, focal boost of the index lesion defined by magnetic resonance imaging (MRI) is associated with an improved biochemical outcome. The objective of this phase II trial is to determine the effectiveness (in terms of biochemical, morphological and functional control), the safety and impact on quality of life, of prostate SABR with MRI guided focal dose intensification in males with intermediate and high-risk localized prostate cancer. METHODS: Patients with intermediate and high-risk prostate cancer according to NCCN definition will be treated with SABR 36.25 Gy in 5 fractions to the whole prostate gland with MRI guided simultaneous integrated focal boost (SIB) to the index lesion (IL) up to 50 Gy in 5 fractions, using a protocol of bladder trigone and urethra sparing. Intra-fractional motion will be monitored with daily cone beam computed tomography (CBCT) and intra-fractional tracking with intraprostatic gold fiducials. Androgen deprivation therapy (ADT) will be allowed. The primary endpoint will be efficacy in terms of biochemical and local control assessed by Phoenix criteria and post-treatment MRI respectively. The secondary endpoints will encompass acute and late toxicity, quality of life (QoL) and progression-free survival. Finally, the subgroup of high-risk patients will be involved in a prospective study focused on immuno-phenotyping. DISCUSSION: To the best of our knowledge, this is the first trial to evaluate the impact of post-treatment MRI on local control among patients with intermediate and high-risk prostate cancer undergoing SABR and MRI guided focal intensification. The results of this trial will enhance our understanding of treatment focal intensification through the employment of the SABR technique within this specific patient subgroup, particularly among those with high-risk disease, and will help to clarify the significance of MRI in monitoring local responses. Hopefully will also help to design more personalized biomarker-based phase III trials in this specific context. Additionally, this trial is expected to be incorporated into a prospective radiomics study focused on localized prostate cancer treated with radiotherapy. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT05919524; Registered 17 July 2023. TRIAL SPONSOR: IRAD/SEOR (Instituto de Investigación de Oncología Radioterápica / Sociedad Española de Oncología Radioterápica). STUDY SETTING: Clinicaltrials.gov identifier: NCT05919524; Registered 17 July 2023. TRIAL STATUS: Protocol version number and date: v. 5/ 17 May-2023. Date of recruitment start: August 8, 2023. Date of recruitment completion: July 1, 2024.

Managing Inconsistent Bladder Volumes in the Prostate Cancer Patient Using Daily Online Adaptive RT: A Case Report.

PURPOSE: We report the use of online adaptive radiotherapy (OART) aiming to improve dosimetric parameters in the prostate cancer patient who had lower urinary tract symptoms that caused him not to adhere to the standard bladder filling protocol. METHODS AND MATERIALS: The reference treatment plan for adaptive radiotherapy plan was generated for the pelvis and the solitary bony lesion using the Ethos treatment planning system. For each treatment session, high-quality iterative reconstructed cone beam CT (CBCT) images were acquired, and the system automatically generated an optimal adaptive plan after verification of contours. Image-guided RT (IGRT) plans were also created using the reference plan recalculated on the CBCT scan and were compared with adaptive plans. RESULTS: The reference bladder volume in the planning CT scan was 173 cc, and the mean bladder volume difference over the course was 25.4% ± 16.6%. The ART offered superior target coverage for PTV 70 Gy over online IGRT (V95: 90.5 ± 3.2 % Vs 97.3 ± 0.4%; p=0.000) and the bladder was also better spared from the high dose (V65 Gy: 17.9 ± 9.1% vs 14.8 ± 3.6%; p=0.03). However, the mean rectum V65 doses were very similar in both plans. CONCLUSION: Managing the inconsistent bladder volume was feasible in the prostate cancer patient using the CBCT-guided OART and our analysis confirmed that adaptive plans offered better target coverage while sparing the bladder from high radiation doses in comparison to online IGRT plans. KEY WORDS: radiotherapy, CBCT, online adaptive radiotherapy, image-guided RT.

[The place of radiation therapy following radical prostatectomy in 2024]. / La place de la radiothérapie après une prostatectomie dans les cancers de la prostate en 2024.

Radiation therapy after prostatectomy for a prostate cancer is a recommended treatment in case of biochemical relapse (rising PSA) following surgery. Controversies regarding its optimal use, delivery, and toxicities are often discussed, not only within scientific congresses but also during multidisciplinary oncological boards. This article aims at making an assessment of up-to-date knowledge and recommendations to guide decision making regarding the treatments of patients with prostate cancer.

La radiothérapie après prostatectomie pour un cancer de prostate est un traitement recommandé en cas de «récidive biochimique¼ (ré-élévation du PSA) après l'opération. Des controverses quant à son utilisation optimale, sa réalisation, et ses toxicités font régulièrement l'objet de discussio, que ce soit au sein des sociétés scientifiques ou lors des concertations oncologiques multidisciplinaires. Cet article a pour but de faire l'état des lieux des connaissances actuelles et des recommandations existantes afin de guider nos réflexions et prises de décision concernant les traitements des patients présentant un cancer de la prostate.

Comparison of quality of life after radical treatment in prostate cancer: radical prostatectomy versus external radiotherapy.

OBJECTIVE: To assess and compare the functional and quality of life results in patients treated with curative intent for localized prostate cancer during 2015 in our hospital. METHOD: 77 patients treated by radical prostatectomy or external radiotherapy with androgen deprivation were prospective enrolled. Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP) questionnaire at 3-year follow-up and Spanish Questionnaire on Quality of Life in Patients with Prostate Cancer (CAVIPRES-30) at diagnosis and at 3-year follow-up were registered. RESULTS: 68 patients were included, 39 patients treated by radical prostatectomy and 29 received external radiotherapy with androgen deprivation. Among the operated patients, 61.5% were dry and 17.9% use three or more daily pads, compared to 72.4% and 6.8%, respectively, in the radiotherapy group. 48.7% of prostatectomized patients reported very poor or no capacity to have a sufficiently rigid erection, compared to 69% of the radiated group. After surgery, 43.6% considered bad or very bad quality-of-life, compared to 68.9% in the radiotherapy group. In the comparison of the data of the pre- and post-treatment questionnaire can be seen that the patients had a superior perception before the procedure. CONCLUSIONS: Patients treated by surgery have a better perception of quality-of-life compared to those treated by radiotherapy.

OBJETIVO: Determinar y comparar los resultados funcionales y de calidad de vida de pacientes con cáncer de próstata tratados con intención curativa durante el año 2015 en nuestro centro. MÉTODO: Se incluyeron 77 pacientes sometidos a prostatectomía radical (PR) o radioterapia externa con terapia de deprivación androgénica (TDA). Se realizaron el Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP) tras 3 años de seguimiento y el Cuestionario Español de Calidad de Vida en Pacientes con Cáncer de Próstata (CAVIPRES-30) al diagnóstico y a los 3 años. RESULTADOS: Se incluyeron 68 pacientes, 39 con PR y 29 con radioterapia más TDA. De los pacientes intervenidos, el 61.5% están secos y el 17.9% usan tres o más compresas, diarias frente al 72.4% y el 6.8%, respectivamente, en el grupo de radioterapia. El 48.7% de los prostatectomizados refieren erecciones muy malas o ninguna, frente al 69% de los radiados. Tras la cirugía, el 43.6% refieren mala o muy mala calidad de vida, frente al 68.9% de los radiados. En la comparación de los datos del cuestionario pre- y postratamiento, los pacientes tenían una percepción superior antes del procedimiento. CONCLUSIONES: Los pacientes tratados mediante cirugía tienen una mejor percepción de su calidad de vida relacionada con la salud que los radiados.

Dosimetric benefits and preclinical performance of steerable needles in HDR prostate brachytherapy.

Prostate cancer patients with an enlarged prostate and/or excessive pubic arch interference (PAI) are generally considered non-eligible for high-dose-rate (HDR) brachytherapy (BT). Steerable needles have been developed to make these patients eligible again. This study aims to validate the dosimetric impact and performance of steerable needles within the conventional clinical setting. HDR BT treatment plans were generated, needle implantations were performed in a prostate phantom, with prostate volume > 55 cm3 and excessive PAI of 10 mm, and pre- and post-implant dosimetry were compared considering the dosimetric constraints: prostate V100 > 95 % (13.50 Gy), urethra D0.1cm3 < 115 % (15.53 Gy) and rectum D1cm3 < 75 % (10.13 Gy). The inclusion of steerable needles resulted in a notable enhancement of the dose distribution and prostate V100 compared to treatment plans exclusively employing rigid needles to address PAI. Furthermore, the steerable needle plan demonstrated better agreement between pre- and post-implant dosimetry (prostate V100: 96.24 % vs. 93.74 %) compared to the rigid needle plans (79.13 % vs. 72.86 % and 87.70 % vs. 81.76 %), with no major changes in the clinical workflow and no changes in the clinical set-up. The steerable needle approach allows for more flexibility in needle positioning, ensuring a highly conformal dose distribution, and hence, HDR BT is a feasible treatment option again for prostate cancer patients with an enlarged prostate and/or excessive PAI.

Moderately hypofractionated proton beam therapy for localized prostate cancer: 5-year outcomes of a phase II trial.

The usefulness of moderately hypofractionated radiotherapy for localized prostate cancer has been extensively reported, but there are limited studies on proton beam therapy (PBT) using similar hypofractionation schedules. The aim of this prospective phase II study is to confirm the safety of a shortened PBT course using 70 Gy relative biological effectiveness (RBE) in 28 fractions. From May 2013 to June 2015, 102 men with localized prostate cancer were enrolled. Androgen deprivation therapy was administered according to risk classification. Toxicity was assessed using Common Terminology Criteria for Adverse Events version 4.0. Of the 100 patients ultimately evaluated, 15 were classified as low risk, 43 as intermediate risk, and 42 as high risk. The median follow-up time of the surviving patients was 96 months (range: 60-119 months). The 5-year cumulative incidences of grade 2 gastrointestinal/genitourinary adverse events were 1% (95% CI: 0.1-6.9) and 4% (95% CI: 1.5-10.3), respectively; no grade ≥ 3 gastrointestinal/genitourinary adverse events were observed. The current study revealed a low incidence of late adverse events in prostate cancer patients treated with moderately hypofractionated PBT of 70 Gy (RBE) in 28 fractions, indicating the safety of this schedule.

Online Adaptive MR-Guided Ultrahypofractionated Radiotherapy of Prostate Cancer on a 1.5 T MR-Linac: Clinical Experience and Prospective Evaluation.

The use of hypofractionated radiotherapy in prostate cancer has been increasingly evaluated, whereas accumulated evidence demonstrates comparable oncologic outcomes and toxicity rates compared to normofractionated radiotherapy. In this prospective study, we evaluate all patients with intermediate-risk prostate cancer treated with ultrahypofractionated (UHF) MRI-guided radiotherapy on a 1.5 T MR-Linac within our department and report on workflow and feasibility, as well as physician-recorded and patient-reported longitudinal toxicity. A total of 23 patients with intermediate-risk prostate cancer treated on the 1.5 T MR-Linac with a dose of 42.7 Gy in seven fractions (seven MV step-and-shoot IMRT) were evaluated within the MRL-01 study (NCT04172753). The duration of each treatment step, choice of workflow (adapt to shape-ATS or adapt to position-ATP) and technical and/or patient-sided treatment failure were recorded for each fraction and patient. Acute and late toxicity were scored according to RTOG and CTC V4.0, as well as the use of patient-reported questionnaires. The median follow-up was 12.4 months. All patients completed the planned treatment. The mean duration of a treatment session was 38.2 min. In total, 165 radiotherapy fractions were delivered. ATS was performed in 150 fractions, 5 fractions were delivered using ATP, and 10 fractions were delivered using both ATS and ATP workflows. Severe acute bother (G3+) regarding IPS-score was reported in five patients (23%) at the end of radiotherapy. However, this tended to normalize and no G3+ IPS-score was observed later at any point during follow-up. Furthermore, no other severe genitourinary (GU) or gastrointestinal (GI) acute or late toxicity was observed. One-year biochemical-free recurrence survival was 100%. We report the excellent feasibility of UHF MR-guided radiotherapy for intermediate-risk prostate cancer patients and acceptable toxicity rates in our preliminary study. Randomized controlled studies with long-term follow-up are warranted to detect possible advantages over current state-of-the-art RT techniques.

Comparative analysis of treatment decision-making in patients with localized prostate and cervical cancer: what influences receiving surgery or radiotherapy?

PURPOSE: This study focused on identifying the factors influencing the decision-making process in patients with localized prostate and cervical cancer in Japan and specifically examining the choice between surgery and radiotherapy. METHODS: Patients with specific cancer stages registered with a healthcare research company for whom radical surgery or radiotherapy was equally effective and recommended participated in this cross-sectional online survey. RESULTS: The responses of 206 and 231 patients with prostate and cervical cancer, respectively, revealed that both groups relied heavily on the physicians' recommendations (prostate: odds ratio (OR) = 40.3, p < 0.001; cervical: OR = 5.59, p < 0.001) and their impression of radiotherapy (prostate: OR = 9.22, p < 0.001; cervical: OR = 2.31, p < 0.001). Factors such as hypertension (OR = 6.48, p < 0.05), diabetes mellitus (OR = 9.68, p < 0.05), employment status (OR = 0.08, p < 0.01), and impressions of surgery (OR = 0.14, p < 0.01) also played a significant role in patients with prostate cancer. In contrast, the specialty of the physician (OR = 4.55, p < 0.05) proposing the treatment influenced the decision-making process of patients with cervical cancer. Information sources varied between the two groups: patients with prostate cancer were more inclined towards printed materials, whereas patients with cervical cancer were more inclined towards interpersonal relationships. CONCLUSION: Although several limitations, such as the sample and recall bias, were noted, this study emphasizes the role of psychosocial factors in the decision-making process and the requirement for tailored information sources.

First in vitro measurement of VHEE relative biological effectiveness (RBE) in lung and prostate cancer cells using the ARES linac at DESY.

Very high energy electrons (VHEE) are a potential candidate for radiotherapy applications. This includes tumours in inhomogeneous regions such as lung and prostate cancers, due to the insensitivity of VHEE to inhomogeneities. This study explores how electrons in the VHEE range can be used to perform successful in vitro radiobiological studies. The ARES (accelerator research experiment at SINBAD) facility at DESY, Hamburg, Germany was used to deliver 154 MeV electrons to both prostate (PC3) and lung (A549) cancer cells in suspension. Dose was delivered to samples with repeatability and uniformity, quantified with Gafchromic film. Cell survival in response to VHEE was measured using the clonogenic assay to determine the biological effectiveness of VHEE in cancer cells for the first time using this method. Equivalent experiments were performed using 300 kVp X-rays, to enable VHEE irradiated cells to be compared with conventional photons. VHEE irradiated cancer cell survival was fitted to the linear quadratic (LQ) model (R2 = 0.96-0.97). The damage from VHEE and X-ray irradiated cells at doses between 1.41 and 6.33 Gy are comparable, suggesting similar relative biological effectiveness (RBE) between the two modalities. This suggests VHEE is as damaging as photon radiotherapy and therefore could be used to successfully damage cancer cells during radiotherapy. The RBE of VHEE was quantified as the relative doses required for 50% (D0.5) and 10% (D0.1) cell survival. Using these values, VHEE RBE was measured as 0.93 (D0.5) and 0.99 (D0.1) for A549 and 0.74 (D0.5) and 0.93 (D0.1) for PC3 cell lines respectively. For the first time, this study has shown that 154 MeV electrons can be used to effectively kill lung and prostate cancer cells, suggesting that VHEE would be a viable radiotherapy modality. Several studies have shown that VHEE has characteristics that would offer significant improvements over conventional photon radiotherapy for example, electrons are relatively easy to steer and can be used to deliver dose rapidly and with high efficiency. Studies have shown improved dose distribution with VHEE in treatment plans, in comparison to VMAT, indicating that VHEE can offer improved and safer treatment plans with reduced side effects. The biological response of cancer cells to VHEE has not been sufficiently studied as of yet, however this initial study provides some initial insights into cell damage. VHEE offers significant benefits over photon radiotherapy and therefore more studies are required to fully understand the biological effectiveness of VHEE.

Prostate intra-fraction motion recorded by transperineal ultrasound.

Infra-fraction motion of the prostate was recorded during 3.423 fractions of image guided radiotherapy (IGRT) in 191 patients, 14 of which were treated by intensity modulated radiation therapy (IMRT), and 177 of which were treated by volumetric arc therapy (VMAT). The prostate was imaged by three-dimensional and time-resolved transperineal ultrasound (4D-US) of type Clarity by Elekta AB, Stockholm, Sweden. The prostate volume was registered and the prostate position (center of volume) was recorded at a frequency of 2.0 samples per second. This raw data set contains a total of 1.985.392 prostate and patient couch positions over a time span of 272 hours, 52 minutes and 34 seconds of life radiotherapy as exported by the instrument software. This data set has been used for the validation of models of prostate intra-fraction motion and for the estimation of the dosimetric impact of actual intra-fraction motion on treatment quality and side effects. We hope that this data set may be reused by other groups for similar purposes.

Actinium-225 targeted alpha particle therapy for prostate cancer.

Targeted alpha particle therapy (TAT) has emerged as a promising strategy for the treatment of prostate cancer (PCa). Actinium-225 (225Ac), a potent alpha-emitting radionuclide, may be incorporated into targeting vectors, causing robust and in some cases sustained antitumor responses. The development of radiolabeling techniques involving EDTA, DOTA, DOTPA, and Macropa chelators has laid the groundwork for advancements in this field. At the forefront of clinical trials with 225Ac in PCa are PSMA-targeted TAT agents, notably [225Ac]Ac-PSMA-617, [225Ac]Ac-PSMA-I&T and [225Ac]Ac-J591. Ongoing investigations spotlight [225Ac]Ac-hu11B6, [225Ac]Ac-YS5, and [225Ac]Ac-SibuDAB, targeting hK2, CD46, and PSMA, respectively. Despite these efforts, hurdles in 225Ac production, daughter redistribution, and a lack of suitable imaging techniques hinder the development of TAT. To address these challenges and additional advantages, researchers are exploring alpha-emitting isotopes including 227Th, 223Ra, 211At, 213Bi, 212Pb or 149Tb, providing viable alternatives for TAT.

Photoimmunotherapy of Prostate Cancer With Antibody and Fab Fragments Targeting the Prostate Specific Membrane Antigen.

BACKGROUND/AIM: The standard treatment for localized prostate cancer involves surgical removal of the prostate with curative intent. However, when tumor cells persist in the operation site, there is high risk of local recurrence and tumor spread, leading to stressful follow-up treatments, impaired quality of life, and reduced overall survival. This study examined photoimmunotherapy (PIT) as a new treatment option for prostate cancer cells. MATERIALS AND METHODS: We generated conjugates consisting of either a humanized antibody or Fab fragments thereof targeting the prostate specific membrane antigen (PSMA), along with our silicon phthalocyanine photosensitizer dye WB692-CB1. PSMA-expressing prostate cancer cells were incubated with the antibody dye or Fab dye conjugates and cell binding was measured using flow cytometry. Cells were irradiated with varying doses of red light for dye activation, and cytotoxicity was determined by erythrosin B staining and subsequent analysis using a Neubauer counting chamber. RESULTS: Specific cytotoxicity was induced with the antibody dye conjugate in the prostate cancer cells in a light dose-dependent manner. Treatment of the cells with the Fab dye conjugate resulted in lower cytotoxicity, which could be attributed to a reduced binding affinity and a reduced dye uptake of the Fab fragment. CONCLUSION: Our new antibody dye and Fab dye conjugates offer potential for future intraoperative PIT in patients with localized prostate cancer, with the aim to ensure complete removal of tumor cells from the surgical area, to avoid local recurrence, and to improve clinical outcome.

Overall survival benefit of androgen suppression in addition to dose-escalated external beam radiotherapy for high-risk prostate cancer: Nationwide real-world data indicates a shift in men that benefit.

OBJECTIVE: To evaluate the real-world added value of androgen deprivation therapy (ADT) in addition to external beam radiotherapy (EBRT) in men with high-risk non-metastatic prostate cancer, in view of advances in radiotherapy and diagnostics. METHODS: All Dutch men diagnosed with high-risk non-metastatic prostate cancer (defined as: ≥cT2c-T3b N0M0, PSA ≥20-50 ng/ml, and/or Gleason score ≥8 (International Society of Urological Pathology [ISUP] grade ≥4)) from 2009 through 2019 and treated with EBRT with or without ADT were identified in the population-based Netherlands Cancer Registry. Propensity scores were used to match (1:1) men that received ADT to men that did not receive ADT. Subsequently, OS was compared. Analyses were also stratified by number of high-risk features, 1 (either ≥cT2c, PSA >20 ng/ml or Gleason score ≥8) versus ≥2 (out of ≥cT2c, PSA >20 ng/ml and Gleason score ≥8). RESULTS: A total of 14,773 men with high-risk non-metastatic prostate cancer were identified, 3,958 (27%) of which received EBRT alone. After matching, 3,427 men remained in both groups and baseline characteristics were well-balanced. After a median follow-up of 92 months, OS was better in men treated with EBRT and ADT compared to men treated with EBRT alone (10-year OS: 66.4% versus 61.8%; HR 0.88 [95%CI: 0.80-0.96]). There was no statistically significant difference in OS in the subgroup of men with only 1 high-risk feature (10-year OS 67.7% versus 64.9%; HR 0.95 [95%CI: 0.85-1.07]). CONCLUSIONS: In a contemporary cohort of men treated for high-risk non-metastatic prostate cancer with EBRT, an OS benefit of adding ADT was only observed in men with at least 2 high-risk features. These results suggest that improvements in diagnostics and treatment in recent decades have resulted in a stage shift of men benefiting from the addition of ADT to EBRT.