Caner Civan , Nika Guberina , Ulrich Krafft , Wolfgang P. Fendler , Martin Stuschke , Ken Herrmann
{"title":"Radiopharmaceuticals in Prostate Cancer: General Considerations and Utility in Combination With EBRT","authors":"Caner Civan , Nika Guberina , Ulrich Krafft , Wolfgang P. Fendler , Martin Stuschke , Ken Herrmann","doi":"10.1016/j.semradonc.2025.04.003","DOIUrl":"10.1016/j.semradonc.2025.04.003","url":null,"abstract":"<div><div>The management of prostate cancer has posed challenges for clinicians in determining optimal treatment strategies. Over the years, various radiopharmaceuticals have been utilized for both the diagnosis and treatment of the prostate cancer. Recent advancements in prostate specific membrane antigen (PSMA) based imaging have enabled the early and precise detection of local recurrence, lymph nodes or distant metastases, resulting a paradigm shift, which significantly influenced clinical decision making. Moreover, PSMA targeted treatments, as a part of theranostic approach, have introduced novel treatment options for patients with castration resistant metastatic prostate cancer, who were previously limited to palliative treatment alternatives. The clinical integration of PSMA based imaging and treatment has led to the commencement of collaborative studies across multiple disciplines including radiation oncology. Radiopharmaceuticals led by PSMA have the potential to facilitate accurate treatment decision making through earlier and more precise lesion detection, as well as improve patient outcomes when combined with radiotherapy. We aimed to review the role of radiopharmaceuticals in diagnosis and treatment of prostate cancer, focusing on their utility in guiding radiotherapy and the potential benefits of combining these radiopharmaceuticals with radiotherapy.</div></div>","PeriodicalId":49542,"journal":{"name":"Seminars in Radiation Oncology","volume":"35 3","pages":"Pages 463-473"},"PeriodicalIF":2.6,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144271449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Valentino Dragonetti , Marzia Colandrea , Laura Travaini , Lighea Simona Airò Farulla , Francesco Ceci , Francesco Mattana
{"title":"PSMA-PET Guided Radiotherapy in Prostate Cancer: A Critical Review of Current Applications and Future Directions","authors":"Valentino Dragonetti , Marzia Colandrea , Laura Travaini , Lighea Simona Airò Farulla , Francesco Ceci , Francesco Mattana","doi":"10.1016/j.semradonc.2025.05.004","DOIUrl":"10.1016/j.semradonc.2025.05.004","url":null,"abstract":"<div><div>Prostate-specific membrane antigen/positron emission tomography (PSMA-PET) changed the diagnostic approach in prostate cancer (PCa), providing superior diagnostic accuracy compared to conventional imaging (CI) modalities like computed tomography (CT), bone scintigraphy (BS) or other PET radiopharmaceuticals like choline or fluciclovine. This improved diagnostic accuracy plays a crucial role in its synergy with radiotherapy, particularly in the context of metastasis-directed therapy. Even in advanced stages of prostate cancer, the synergy with radiotherapy is evident in the promising results emerging from the combination of RT and RLT. To evaluate the value of PSMA as biomarker, the technological advancements in PSMA-PET, and its integration into clinical practice, focusing on its impact on RT and RLT. A comprehensive nonsystematic literature review was performed using PubMed/MEDLINE and EMBASE biomedical databases. Literature search was updated until March 2025. The most relevant studies have been summarized, giving priority to registered clinical trials and multicenter collaborations. The higher accuracy of PSMA-PET is advancing RT planning in PCa, from initial staging to salvage and metastasis-directed therapy. Ongoing trials combining RLT with external beam radiotherapy (EBRT) may expand its role into earlier stages. Key challenges include the need for long-term outcome data, standardization, cost-effectiveness, and avoiding overtreatment. Future efforts should optimize PSMA-guided RT, evaluate novel RLT combinations, and identify predictive biomarkers for personalized care. The synergy between PSMA-PET and radiotherapy enables a more effective therapeutic approach across both early and advanced stages of PCa, particularly through the promising integration with RLT.</div></div>","PeriodicalId":49542,"journal":{"name":"Seminars in Radiation Oncology","volume":"35 3","pages":"Pages 317-324"},"PeriodicalIF":2.6,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144271434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Srinivas Chilukuri , Mutlay Sayan , Alan Dal Pra , Vedang Murthy
{"title":"Elective Regional Nodal Irradiation in Prostate Cancer","authors":"Srinivas Chilukuri , Mutlay Sayan , Alan Dal Pra , Vedang Murthy","doi":"10.1016/j.semradonc.2025.04.010","DOIUrl":"10.1016/j.semradonc.2025.04.010","url":null,"abstract":"<div><div>Elective nodal radiotherapy (ENRT) targets microscopic pelvic lymph node metastases to improve locoregional control in prostate cancer. Recent randomized trials report improved outcomes, particularly in high-risk cohorts, albeit with modest increases in Grade 2 gastrointestinal (GI) and genitourinary (GU) toxicities. Molecular imaging has markedly refined patient selection, enabling precise identification of occult nodal disease and enhancing application of ENRT beyond traditional clinical parameters. Modern radiation therapy approaches, including image-guided intensity-modulated radiotherapy (IMRT) and stereotactic body radiotherapy (SBRT), have enhanced ENRT efficacy and safety by employing stringent organ-at-risk constraints. Recent evidence supports SBRT-based ENRT (25 Gy in 5 fractions), demonstrating both efficacy and acceptable toxicity profiles. In the postoperative adjuvant context, ENRT shows promise for patients with pathological nodal involvement (pN+), particularly those with ≥3 positive nodes, high-grade disease, or positive surgical margins. In the salvage setting, combining ENRT with short-term androgen deprivation therapy (ADT) may benefit patients with biochemical recurrence and adverse pathological features, even in node-negative cases. Until definitive data emerges from ongoing randomized trials, multidisciplinary evaluation and integration of modern imaging and radiotherapy techniques remain essential for optimal ENRT in prostate cancer.</div></div>","PeriodicalId":49542,"journal":{"name":"Seminars in Radiation Oncology","volume":"35 3","pages":"Pages 374-384"},"PeriodicalIF":2.6,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144271440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ulysses Gardner , Allison B. Randolph , Nancy Anabaraonye , Cyrus Washington , Curtiland Deville Jr
{"title":"Health Disparities and Inequities in Prostate Cancer Along the Continuum of Care","authors":"Ulysses Gardner , Allison B. Randolph , Nancy Anabaraonye , Cyrus Washington , Curtiland Deville Jr","doi":"10.1016/j.semradonc.2025.04.008","DOIUrl":"10.1016/j.semradonc.2025.04.008","url":null,"abstract":"<div><div>Prostate cancer remains one of the most commonly diagnosed malignancies worldwide, yet significant disparities and inequities persist across the continuum of care. Black men face a disproportionate burden, exhibiting the highest incidence and mortality rates. Older patients often receive less aggressive treatment despite higher risk profiles. Insurance status critically influences timely diagnosis and treatment; uninsured and underinsured individuals are more likely to experience delays in care, leading to worse prognoses. Rural residents and those with lower-income have limited access to specialized care while those of lower education status have reduced screening and later-stage diagnoses. Disparities extend to biopsy techniques and treatment decisions. Black and other underserved populations are less likely to undergo targeted biopsies, which have been shown to improve tumor characterization and risk stratification. Additionally, they are more likely to receive non-definitive management, even when presenting with high-risk, potentially lethal disease. Socioeconomic barriers, healthcare access, provider biases, and underrepresentation and exclusion from clinical trials further exacerbate these disparities, limiting opportunities for precision medicine approaches tailored to diverse populations. Addressing these inequities requires a multifaceted approach, including increasing access to advanced diagnostics and therapeutics, improving representation in research, and integrating social determinants of health into prostate cancer management strategies. Emerging evidence on radiogenomics and molecular biomarkers offers promising avenues for personalized care, but equitable implementation is crucial to avoid widening existing gaps. A concerted effort to eliminate disparities is essential to achieving equitable prostate cancer outcomes across all populations.</div></div>","PeriodicalId":49542,"journal":{"name":"Seminars in Radiation Oncology","volume":"35 3","pages":"Pages 304-316"},"PeriodicalIF":2.6,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144271452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Michael K. Rooney, Zakaria El Kouzi, Ramez Kouzy, Osama Mohamad, Karen E. Hoffman
{"title":"Debate 1: High-Risk Localized Prostate Cancer: Why Combination Hormone Therapy and Radiotherapy is the Optimal Treatment Strategy for Most Men","authors":"Michael K. Rooney, Zakaria El Kouzi, Ramez Kouzy, Osama Mohamad, Karen E. Hoffman","doi":"10.1016/j.semradonc.2025.05.003","DOIUrl":"10.1016/j.semradonc.2025.05.003","url":null,"abstract":"<div><div>Prostate cancer is the most commonly diagnosed malignancy among men in the United States, with high-risk localized disease accounting for approximately 15% of new cases. High-risk cancer portends increased risk of locoregional recurrence and distant metastases. Despite the longstanding use of radical prostatectomy (RP) and definitive radiotherapy (RT) with androgen deprivation therapy (ADT) as primary treatment options, there remains a lack of randomized data directly comparing these modalities. The ongoing SPCG-15 trial may eventually provide such evidence but its results are not expected until 2030. In the interim, clinicians must rely on existing observational studies to guide treatment selection. This review synthesizes current evidence comparing RP and RT+ADT for high-risk localized prostate cancer, highlighting oncologic outcomes, treatment-related toxicities, and patient-reported quality of life in survivorship. RT+ADT may offer biological advantages in addressing occult micrometastases with radiobiological foundations for synergy between modalities. Further, although observational data comparing RP and RT+ADT are heterogeneous and often methodologically limited, recent analyses using modern causal inference frameworks suggest improved distant metastatic control with RT+ADT. Toxicity profiles also differ significantly between modalities, with RT+ADT associated with fewer early and long-term urinary side effects, and less treatment regret but transient hormone-related and bowel symptoms during treatment. Here, we propose that under the shared-decision-making model RT+ADT will be the preferred first-line treatment for most men with high-risk localized prostate cancer, offering favorable oncologic control while preserving quality of life, particularly with modern advances in radiotherapy techniques.</div></div>","PeriodicalId":49542,"journal":{"name":"Seminars in Radiation Oncology","volume":"35 3","pages":"Pages 393-401"},"PeriodicalIF":2.6,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144271453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hypofractionation/Ultra-hypofractionation for Prostate Cancer Radiotherapy","authors":"Deep Chakrabarti , Harshani Green , Alison Tree","doi":"10.1016/j.semradonc.2025.04.004","DOIUrl":"10.1016/j.semradonc.2025.04.004","url":null,"abstract":"<div><div>Prostate cancer is the most commonly diagnosed cancer in men worldwide. Radiotherapy is an integral component for the treatment of localized prostate cancer. Radiobiologically, prostate cancer is sensitive to an increased dose of radiotherapy delivered per fraction, called “hypofractionation”, due to intrinsic differences in the rate of cancer cell growth and repair of DNA damage. Hypofractionation delivers planned treatment over fewer radiotherapy sessions compared to conventional fractionation and has been shown to be noninferior to conventional fractionation with an acceptable toxicity profile. Ultra-hypofractionation, often delivered via stereotactic body radiotherapy (SBRT), further reduces the number of treatments by using even larger doses per fraction and has shown promising results with high biochemical control rates and low rates of late toxicity. The adoption of hypofractionated and ultra-hypofractionated schedules improves resource utilization in radiation oncology without compromising patient safety or efficacy. Ongoing research continues to refine patient selection, fractionation schemes, and incorporates advanced imaging, precise treatment planning, and motion management techniques to help mitigate toxicity and optimize outcomes in localized intermediate and high-risk disease.</div></div>","PeriodicalId":49542,"journal":{"name":"Seminars in Radiation Oncology","volume":"35 3","pages":"Pages 333-341"},"PeriodicalIF":2.6,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144271436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Michael Melton , Antonio Angrisani , Andrew Simpson , Andrew McDonald , Thomas Zilli
{"title":"Radiation Therapy in Node-Positive Prostate Cancer: Current Evidence and Future Directions","authors":"Michael Melton , Antonio Angrisani , Andrew Simpson , Andrew McDonald , Thomas Zilli","doi":"10.1016/j.semradonc.2025.04.013","DOIUrl":"10.1016/j.semradonc.2025.04.013","url":null,"abstract":"<div><div>The management of node-positive prostate cancer (N1 PCa) remains a subject of ongoing debate, with growing evidence supporting the role of radiation therapy (RT) alongside systemic therapy. Traditionally, N1 disease was considered metastatic; however, advancements in imaging and treatment have redefined its clinical relevance. This narrative review evaluates current evidence, focusing on recent literature and ongoing clinical trials in N1 PCa, both in the definitive and postoperative setting. Prostate-specific membrane antigen (PSMA) positron emission tomography-computed tomography (PET/CT) has significantly improved staging accuracy, leading to stage migration and increased consideration of RT for patients with cN1 disease. Both retrospective and prospective studies suggest that RT combined with androgen deprivation therapy (ADT) improves survival compared to ADT alone. Robust data from large clinical trials and ongoing studies support the use of whole-pelvic RT (WPRT) with dose escalation to involved nodes. The optimal management of postoperative pN1 disease remains controversial, with strategies ranging from observation to early salvage or adjuvant RT, often combined with systemic therapy. The ideal RT volume, dose, and systemic therapy combinations continue to be investigated. However, several ongoing trials are paving the way for more refined and effective treatment approaches. This review highlights key trials that may significantly improve the management of N1 PCa in the near future.</div></div>","PeriodicalId":49542,"journal":{"name":"Seminars in Radiation Oncology","volume":"35 3","pages":"Pages 362-373"},"PeriodicalIF":2.6,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144271439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Debate 2: The Case for Focal External Beam Radiation Therapy Boost Over Brachytherapy Boost for Prostate Cancer","authors":"Anna M Dornisch , Tyler M Seibert","doi":"10.1016/j.semradonc.2025.04.005","DOIUrl":"10.1016/j.semradonc.2025.04.005","url":null,"abstract":"<div><div>Modern trials demonstrate excellent outcomes for men with localized prostate cancer treated with radiation therapy. However, some patients experience recurrences, and more than one-third of recurrences are localized to the prostate. Treatment intensification through dose intensification could substantially benefit some patients with localized, unfavorable-risk prostate cancer. Currently, modern phase 3 randomized controlled trials support 2 treatment strategies. ASCENDE-RT evaluated whole-gland LDR brachytherapy boost, and FLAME evaluated a focal external beam radiation therapy (EBRT) boost to MRI-visible lesions. This review compares a FLAME-style EBRT boost vs a LDR brachytherapy boost in terms of oncologic outcomes, toxicity, and feasibility. The FLAME trial demonstrates that an EBRT boost to MRI visible lesions improves local control as well as regional and distant metastasis free survival without a significant increase in toxicity. In contrast, ASCENDE-RT reports an improvement in only biochemical recurrence free survival, and this comes at the expense of increased gastrointestinal and genitourinary toxicity. Beyond efficacy and toxicity, we discuss the challenges to widespread implementation of each technique, as treatment advances are only beneficial if they are available. While both techniques have unique barriers to implementation, we believe addressing the barriers for focal EBRT boost implementation are more addressable. In conclusion, we maintain that available high-level evidence supports a focal EBRT boost over brachytherapy because focal EBRT boost was shown to give a meaningful improvement in oncologic outcomes with minimal impact on quality of life.</div></div>","PeriodicalId":49542,"journal":{"name":"Seminars in Radiation Oncology","volume":"35 3","pages":"Pages 415-422"},"PeriodicalIF":2.6,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144271455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Debate 2: Primary Localized Prostate Cancer: The Case for Whole-Gland Brachytherapy Boost","authors":"Amani A. Chowdhury , Peter J. Hoskin","doi":"10.1016/j.semradonc.2025.04.006","DOIUrl":"10.1016/j.semradonc.2025.04.006","url":null,"abstract":"<div><div>Whole gland brachytherapy (BT) boost in combination with external beam radiotherapy (EBRT) improves biochemical relapse free survival (bRFS) for intermediate- and high-risk prostate cancer (PCa). Three randomized control studies (RCT) have demonstrated superiority over EBRT alone, and a meta-analysis alongside updated long-term data demonstrates an ongoing benefit with whole gland BT boost. There are concerns that improved tumor control comes at the expense of late genitourinary (GU) and gastrointestinal (GI) toxicities. Although studies investigating the role of a focal boost to the dominant intraprostatic lesion (DIL) have been conducted with promising outcomes and low toxicity rates, the multifocal and multiclonal nature of PCa as well as lack of head-to-head RCTs makes it difficult to justify the use of focal boost in place of whole gland boost. Similarly, many studies have used various EBRT techniques to deliver boost treatment despite the radiobiological advantages and stronger evidence base advocating for BT. On this basis, as well as the challenges of precise delineation of the DIL, whole gland BT boost in combination with EBRT remains the optimal radical radiotherapy regime for locally advanced PCa.</div></div>","PeriodicalId":49542,"journal":{"name":"Seminars in Radiation Oncology","volume":"35 3","pages":"Pages 402-414"},"PeriodicalIF":2.6,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144271454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}