Seminars In Radiation Oncology[JOURNAL]
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200 papers
Clinical Applications of Quantitative Imaging and Artificial Intelligence for Pancreatic Cance.
Kim Y, Martinus D, Tran TT … +4 more , Rooney MK, Pant A, Tino RB, Koay EJ
Semin Radiat Oncol · 2025 Oct · PMID 40935443 · Publisher ↗
Pancreatic cancer remains as a leading cause of cancer death in the United States due to the disease's deadly combination of evasiveness to detection, aggressive biology, and resistance to treatment. Quantitative imaging...
Pancreatic cancer remains as a leading cause of cancer death in the United States due to the disease's deadly combination of evasiveness to detection, aggressive biology, and resistance to treatment. Quantitative imaging and artificial intelligence (AI) methods are emerging as promising and innovative techniques to combat the extensive challenges facing the clinic in the diagnosis and treatment of pancreatic ductal adenocarcinoma. These methods extract data from the fabric of clinical images that allow for earlier diagnosis, improved prognostication, automation of treatment planning, and increased reliability for response assessment. This review examines quantitative imaging techniques from 2013 to 2025 and summarizes them into three parts: differential diagnosis for pancreatic disease, grading and staging of pancreatic tumors, and treatment response assessment and prognosis prediction. We outline key challenges specific to pancreatic cancer and potential mitigations for future direction. We also highlight developing areas such as MRI-guided adaptive radiotherapy, automated target delineation, and integrated radiomic-omics tools that may help incorporate quantitative imaging into routine care of pancreatic cancer. Altogether, the current investigation suggests that quantitative imaging will become an integral tool for this disease across the oncologic journey of a patient.
Beyond Opioids in Pancreatic Cancer: Palliative Radiotherapy and Celiac Plexus Radiosurgery.
Miszczyk M, Abrams RA, Lawrence YR
Semin Radiat Oncol · 2025 Oct · PMID 40935442 · Publisher ↗
This review examines established and evolving approaches for radiation therapy as a palliative treatment modality in patients with pancreatic cancer within the context of effective patient-provider communication and earl...
This review examines established and evolving approaches for radiation therapy as a palliative treatment modality in patients with pancreatic cancer within the context of effective patient-provider communication and early palliative care team based management. At presentation most patients with pancreatic cancer have advanced disease and a limited life expectancy. Typically, they suffer from multiple disease-related symptoms. Systemic therapies have limited palliative efficacy against symptoms associated with local disease. This is in contrast to radiation therapy, which appears efficient in achieving local symptom control. In addition to more conventional tumour-targeting stereotactic body radiation therapy (SBRT), and short-course conventional radiotherapy, a recent clinical trial demonstrated the effectiveness of a new approach - celiac plexus radiosurgery. In this article, we evaluate and compare the effectiveness of these treatment methods, demonstrating the important, yet underappreciated, role that hypofractionated radiation therapy has within the multidisciplinary management of patients with pancreatic cancer, including those with metastatic disease.
Quality and Quantity: Dual Benefits of Ablative Radiation in Oligometastatic Pancreatic Cancer.
Aguilera TA, Elamir AM, Ludmir EB
Semin Radiat Oncol · 2025 Oct · PMID 40935441 · Publisher ↗
Oligometastatic pancreatic cancer (OPanc) poses significant opportunities in management, as increasingly metastases can be safely and effectively targeted with local therapy. We review the existing literature on SABR for...
Oligometastatic pancreatic cancer (OPanc) poses significant opportunities in management, as increasingly metastases can be safely and effectively targeted with local therapy. We review the existing literature on SABR for OPanc, highlighting its potential benefits and limitations with an aim to define the trajectory of opportunity. SABR may offer a meaningful benefit to patients with OPanc, improving quality of life by enabling breaks from systemic therapy while potentially enhancing quantity of life or survival. Patient selection and clearly defined goals will be critical to demonstrate the value of this approach, and well powered prospective studies may be key. The most intriguing aspect of this discussion is the potential for SABR to enhance antitumor immunity that may play a role in prolonged minimal residual disease that can be achieved in some patients. This can translate to improved quality of life by reducing the need for systemic therapy. This approach may offer a novel solution to the treatment challenges associated with OPanc. Further research is needed to confirm the hypotheses and establish the definitive role of SABR in OPanc treatment.
Intraoperative Radiation for Pancreatic Cancer.
Elguindy A, Blakaj D, Grecula J … +1 more , Miller ED
Semin Radiat Oncol · 2025 Oct · PMID 40935440 · Full text
Pancreatic cancer (PDAC) remains a challenging disease to treat with a poor prognosis. Management of PDAC has evolved over the last several decades with the development of more effective systemic therapy making local con...
Pancreatic cancer (PDAC) remains a challenging disease to treat with a poor prognosis. Management of PDAC has evolved over the last several decades with the development of more effective systemic therapy making local control of the primary tumor paramount in patients with both resectable and unresectable disease. Local recurrence after resection or progression of an unresectable tumor are significant causes of morbidity and potential mortality for patients with PDAC. Emerging data in PDAC suggest that improved local control and favorable survival can be achieved with radiation dose escalation. However, adjacent radiosensitive organs limit the ability to deliver higher doses of radiation therapy to patients. Intraoperative radiation therapy provides an ideal way to deliver large doses of radiation directly to the tumor or tumor bed while minimizing the radiation dose to adjacent normal organs. The purpose of this review is to provide an overview of the current literature demonstrating the utility of intraoperative radiation therapy in patients with resectable and unresectable PDAC.
Optimal Target Volume Delineation for Pancreatic Cancer: Triangulating What Should be Targeted.
Narang A
Semin Radiat Oncol · 2025 Oct · PMID 40935439 · Publisher ↗
Optimal target volume delineation for pancreatic cancer remains an unanswered question across all stages of disease. To-date, target volume delineation has been highly variable across major clinical trials that have expl...
Optimal target volume delineation for pancreatic cancer remains an unanswered question across all stages of disease. To-date, target volume delineation has been highly variable across major clinical trials that have explored the role of radiation for this disease, which undoubtedly has contributed to the significant variation in outcomes that have been observed between such trials and the current controversy that has therefore been generated surrounding the role of radiation for pancreatic cancer. Importantly, emerging data has increasingly suggested that elective volume targeting is critical for this disease and that volume delineation should be driven by those patterns of locoregional spread that drive locoregional failure, namely extra-pancreatic perineural invasion. Herein, we review the historical approaches that have been used for target volume delineation across key studies to-date as well as recent data that provide critical insights into optimal target volume delineation in the setting of radiation for pancreatic cancer.
The Role of MR Guided Radiation Therapy in Pancreatic Cancer Treatment.
D'Souza A, Jiang S, Chuong MD … +1 more , Kim H
Semin Radiat Oncol · 2025 Oct · PMID 40935438 · Publisher ↗
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Definitive Radiotherapy for Locally Advanced Unresectable Pancreatic Cancer: Historical Review, Current State and Future Directions.
Kumar AR, Sanford NN
Semin Radiat Oncol · 2025 Oct · PMID 40935437 · Publisher ↗
Based on available Level 1 evidence, standard dose conventional chemoradiation does not improve survival in patients with locally advanced pancreas cancer (LAPC), thus chemotherapy remains the only widely accepted therap...
Based on available Level 1 evidence, standard dose conventional chemoradiation does not improve survival in patients with locally advanced pancreas cancer (LAPC), thus chemotherapy remains the only widely accepted therapy. Yet prognosis remains poor, and despite the negative trial outcomes, most would contend that the addition of radiotherapy does confer benefit in a subset of patients with LAPC. This work reviews the published data, then discusses several key considerations for designing radiotherapy trials in LAPC including choosing clinically meaningful patient-centered endpoints, optimizing patient selection and standardizing target volume delineation. Lastly, we review several promising single arm studies on dose-escalated radiotherapy in LAPC which have paved the way for upcoming Phase III randomized trials assessing this strategy.
Contemporary Advances, Evidence, and Considerations in Preoperative Therapy for Pancreatic Ductal Adenocarcinoma.
Sherry AD, Bennett AK, Carr RM … +2 more , Truty MJ, Jethwa KR
Semin Radiat Oncol · 2025 Oct · PMID 40935436 · Publisher ↗
Localized pancreatic ductal adenocarcinoma (PDAC) has been historically associated with poor disease control outcomes following surgical resection alone. Due to the high risk of occult locoregional and distant metastatic...
Localized pancreatic ductal adenocarcinoma (PDAC) has been historically associated with poor disease control outcomes following surgical resection alone. Due to the high risk of occult locoregional and distant metastatic disease and anatomic tumor complexity limiting margin-negative resectability, preoperative therapy has emerged as an appealing strategy for many patients across the spectrum of localized PDAC. Here, we critically review the context, evidence, and controversies regarding preoperative therapy for PDAC. We first discuss the natural history of PDAC, patterns of spread and postoperative therapy. We then consider current issues of resectability, patient selection, therapy sequencing, and specifically the role of radiation therapy, including chemoradiation and stereotactic body radiation therapy, in the preoperative paradigm respectively. We conclude by discussing ongoing trials attempting to provide further insights and illuminating the path towards the improvement of outcomes in this patient population.
Adjuvant Radiation for Resected Pancreatic Cancer: Historical Review and Current State.
Starner J, Wuu YR, Hornstein N … +4 more , Goodman KA, Herman JM, Abrams R, Tchelebi LT
Semin Radiat Oncol · 2025 Oct · PMID 40935435 · Publisher ↗
Pancreatic cancer is the third leading cause of cancer-related deaths, projected to become the second leading cause by 2040. Curative intent resection remains the only non-palliative treatment strategy; however, the 5-ye...
Pancreatic cancer is the third leading cause of cancer-related deaths, projected to become the second leading cause by 2040. Curative intent resection remains the only non-palliative treatment strategy; however, the 5-year overall survival rate remains 20% among resected patients. Postoperative treatments, including radiation therapy, have been studied to improve outcomes for patients, but the data remains inconclusive. Owing to improvements in radiation treatment quality and advancements in systemic therapy to control micrometastatic disease, further research is critical to determine the role of adjuvant radiation therapy in pancreatic cancer patients and to identify which patients derive the most benefit. Herein, we review the role of adjuvant radiation therapy in resected pancreatic ductal adenocarcinoma, evaluate the current state, and discuss future directions.
Optimizing Radiation Therapy for Localized Prostate Cancer: Exploring Synergies With Androgen Deprivation Therapy and Novel Systemic Agents.
Patel KR, Abel M, Basourakos SP … +2 more , Citrin DE, Madan RA
Semin Radiat Oncol · 2025 Jul · PMID 40516982 · Full text
Although radiation therapy has been used as a curative treatment option for patients with localized prostate cancer for decades, there remains a continued need to improve outcomes for patients with localized disease. Sys...
Although radiation therapy has been used as a curative treatment option for patients with localized prostate cancer for decades, there remains a continued need to improve outcomes for patients with localized disease. Systemic therapy in the form of androgen deprivation therapy (ADT) is an important adjunct to radiation therapy which may serve to improve the curative potential of treatment; however, not all forms of systemic therapy which have demonstrated activity in metastatic prostate cancer will improve outcomes for patients with localized disease. Research into the use of radiation therapy with ADT, androgen receptor signaling inhibitors (ARSIs), chemotherapy, poly(ADP-ribose) polymerase (PARP) inhibitors, immunotherapy, and other small molecule inhibitors is ongoing and will help to define not only which of these may be beneficial for patients localized prostate cancer but also which patients may be optimal candidates to receive these adjunctive therapies.
Radiopharmaceuticals in Prostate Cancer: General Considerations and Utility in Combination With EBRT.
Civan C, Guberina N, Krafft U … +3 more , Fendler WP, Stuschke M, Herrmann K
Semin Radiat Oncol · 2025 Jul · PMID 40516981 · Publisher ↗
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 t...
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.
The Evolving Management of Radiorecurrent Prostate Cancer.
Pozin J, Bhandari M, Valle L … +10 more , Nickols NG, Kishan AU, Kamran SC, Baumann B, Efstathiou JA, Crook J, Pasquier D, Liauw SL, Harkenrider MM, Solanki AA
Semin Radiat Oncol · 2025 Jul · PMID 40516980 · Publisher ↗
The detection of local radiorecurrence (LRR) of prostate cancer in the prostate or prostate bed after radiation therapy is increasingly common with the advent of advanced imaging modalities such as the PSMA PET/CT. Our a...
The detection of local radiorecurrence (LRR) of prostate cancer in the prostate or prostate bed after radiation therapy is increasingly common with the advent of advanced imaging modalities such as the PSMA PET/CT. Our aim is to review the literature and define the optimal workup for identifying LRR and discuss the key principals in management, with a focus on salvage re-irradiation. We performed a narrative review of the literature and ongoing studies centered on LRR workup and treatment. Workup for biochemical recurrence postradiation therapy includes PSMA PET/CT, multiparametric MRI, and systematic and targeted biopsy to confirm and define the extent of LRR. Historically, treatment options have included observation, palliative androgen deprivation therapy (ADT), or salvage local therapy to eradicate the LRR. Salvage local re-irradiation can be delivered using stereotactic body radiotherapy (SBRT), high dose rate (HDR) brachytherapy, or low dose rate (LDR) brachytherapy. Commonly used treatment regimens and practical considerations for the different salvage re-irradiation modalities based on the available literature are discussed. Salvage re-irradiation is a safe and effective treatment approach that offers a second chance to "cure" prostate cancer, while also delaying the need for palliative hormonal therapy. Salvage re-irradiation should be carefully considered in patients with LRR after weighing potential benefits against risks. Further data are needed to identify the optimal volume, dose and fractionation regimens.
Postoperative Radiation Therapy and Controversies Regarding Hormonal Therapy in the Management of Prostate Cancer.
Achard V, Pra AD, Sargos P
Semin Radiat Oncol · 2025 Jul · PMID 40516979 · Publisher ↗
Biochemical recurrence (BCR) after radical prostatectomy (RP) remains a clinical challenge, with significant heterogeneity in outcomes and optimal management strategies. Salvage radiotherapy (sRT) is the standard approac...
Biochemical recurrence (BCR) after radical prostatectomy (RP) remains a clinical challenge, with significant heterogeneity in outcomes and optimal management strategies. Salvage radiotherapy (sRT) is the standard approach, yet the role and duration of concurrent hormonal therapy (ADT) are still debated. Four key randomized controlled trials-RTOG 9601, GETUG-AFU 16, RTOG 0534 SPPORT, and RADICALS-HD-have explored the addition of ADT to sRT. While ADT consistently improved progression-free survival metastasis-free survival (MFS) benefit was not consistently observed, and overall survival (OS) gains were limited and primarily confined to patients with higher pre-sRT PSA levels (>0.6-0.7 ng/mL). Toxicity associated with long-term ADT, including metabolic and cardiovascular effects, underscores the importance of patient selection. Emerging tools such as PSMA PET/CT and the Decipher genomic classifier show promise in refining risk stratification. PSMA PET/CT can identify occult metastases and guide treatment planning, while Decipher can help predict who may benefit from ADT. Retrospective and prospective data support their integration into clinical practice. Recent trials evaluating intensified systemic therapy with androgen receptor pathway inhibitors (ARPIs) in combination with sRT suggest potential benefit in high-risk BCR populations, although added toxicity remains a concern. The optimal role and timing of ARPIs in the early salvage setting require further investigation. In conclusion, the decision to add ADT to sRT in BCR patients should be individualized based on PSA kinetics, imaging, and genomic profiling. Shared decision-making and future biomarker-driven trials will be key to personalizing therapy and improving outcomes while minimizing harm.
Debate 3: Oligometastatic Hormone Sensitive Prostate Cancer Management: Systemic Therapy Approach.
von Amsberg G, Kaune M, Coym A … +5 more , Strewinsky N, Falkenbach F, Hohenhorst JL, Tilki D, Dyshlovoy S
Semin Radiat Oncol · 2025 Jul · PMID 40516978 · Publisher ↗
Oligometastatic prostate cancer (OMPC) represents an intermediate stage between localized and extensive metastatic disease, characterized by a limited number of metastatic lesions. While metastasis-directed therapy (MDT)...
Oligometastatic prostate cancer (OMPC) represents an intermediate stage between localized and extensive metastatic disease, characterized by a limited number of metastatic lesions. While metastasis-directed therapy (MDT) has gained traction for its potential to delay systemic therapy, systemic therapy itself is falling behind. In our view, this is not appropriate at the current stage. In the context of this controversy, we highlight the points that emphasize the role of systemic therapy in OMPC and point out weaknesses of data available on local treatment concepts. The lack of a standardized OMPC definition complicates the comparison of results across studies. Imaging inconsistencies, ranging from conventional techniques to advanced PSMA-PET/CT, further challenge accurate classification. Additionally, the biological basis of OMPC remains unclear, with no definitive biomarkers distinguishing it from polymetastatic disease. While MDT has demonstrated improved progression-free survival in small trials, its impact on overall survival remains inconclusive. Conversely, systemic therapy with androgen receptor pathway inhibitors (ARPIs) has shown a significant survival advantage in phase 3 trials. Subgroup analyses from large trials indicate a benefit of systemic therapy, particularly in low-volume disease. Combination strategies incorporating MDT and systemic therapy may optimize outcomes. Further research is needed to refine patient selection, integrate molecular biomarkers, and establish the optimal treatment paradigm. Until robust evidence emerges, systemic therapy remains the standard of care for OMPC.
Debate 3: Metastasis Directed Therapy in Oligometastatic Prostate Cancer.
Singh M, Murthy V, Ost P
Semin Radiat Oncol · 2025 Jul · PMID 40516977 · Publisher ↗
Oligometastatic prostate cancer (OMPC), characterized by limited metastatic burden (≤5 lesions), encompasses 3 major subtypes: de novo synchronous oligometastatic hormone-sensitive prostate cancer (om-HSPC), metachronous...
Oligometastatic prostate cancer (OMPC), characterized by limited metastatic burden (≤5 lesions), encompasses 3 major subtypes: de novo synchronous oligometastatic hormone-sensitive prostate cancer (om-HSPC), metachronous oligorecurrent HSPC (or-HSPC), and oligoprogressive castrate-resistant prostate cancer (op-CRPC). Metastasis-directed therapy (MDT), particularly stereotactic body radiotherapy (SBRT), has been widely adopted and offers a noninvasive approach for delaying disease progression and achieving durable local control while maintaining the quality of life (QoL). This review examines the evolving evidence supporting MDT across OMPC spectrum. In de novo om-HSPC, early prospective studies suggest benefit when combining MDT with systemic therapy and local prostate radiation therapy (RT). However, conclusive randomized evidence for benefit of MDT in de-novo om-HSPC is lacking. For or-HSPC, randomized trials (STOMP, ORIOLE) demonstrate that SBRT-MDT safely delays systemic therapy initiation and prolongs progression-free survival (PFS). In nodal or-HSPC, the PEACE V-STORM trial has shown superior biochemical and locoregional control with elective nodal radiotherapy (ENRT) compared to SBRT alone. For well selected patients with OMPC, systemically augmented MDT (SBRT with short-course ADT±ARPI) is an attractive strategy to improve outcomes with no added QoL detriment and has shown more durable responses than either modality alone (EXTEND, RADIOSA trials). The recent WOLVERINE meta-analysis has shown that MDT improves PFS and overall survival across OMPC subtypes. Patient selection remains crucial, with PSA kinetics, PSMA-PET findings, and genomic factors emerging as potential biomarkers for personalizing the OMPC therapeutic landscape. While several phase III trials are ongoing, current evidence supports MDT integration into clinical practice for appropriately selected OMPC patients.
Debate 2: The Case for Focal External Beam Radiation Therapy Boost Over Brachytherapy Boost for Prostate Cancer.
Dornisch AM, Seibert TM
Semin Radiat Oncol · 2025 Jul · PMID 40516976 · Publisher ↗
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 t...
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.
Debate 2: Primary Localized Prostate Cancer: The Case for Whole-Gland Brachytherapy Boost.
Chowdhury AA, Hoskin PJ
Semin Radiat Oncol · 2025 Jul · PMID 40516975 · Publisher ↗
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...
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.
Debate 1: High-Risk Localized Prostate Cancer: Why Combination Hormone Therapy and Radiotherapy is the Optimal Treatment Strategy for Most Men.
Rooney MK, El Kouzi Z, Kouzy R … +2 more , Mohamad O, Hoffman KE
Semin Radiat Oncol · 2025 Jul · PMID 40516974 · Publisher ↗
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 locore...
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.
Debate 1: Radical Prostatectomy For the Right Patient With High-Risk Prostate Cancer.
Sundaresan VM, Leapman MS
Semin Radiat Oncol · 2025 Jul · PMID 40516973 · Publisher ↗
Prostate cancer is a heterogeneous disease with varying degrees of metastatic potential and responsiveness to treatment. Whether surgical removal or radiation therapy combined with androgen deprivation therapy (ADT) is t...
Prostate cancer is a heterogeneous disease with varying degrees of metastatic potential and responsiveness to treatment. Whether surgical removal or radiation therapy combined with androgen deprivation therapy (ADT) is the best initial course of treatment for those with 'high risk' features poses an enduring clinical dilemma. In the absence of an adequate randomized clinical trial to resolve this question, contemporary decision-making seeks to balance expected treatment effectiveness and health-related quality of life over the long time horizon expected by most facing this choice. In this article, we distill the following 5 evidence-based arguments that commonly motivate patients to select radical prostatectomy as initial treatment of 'high-risk' prostate cancer. The first is that surgery alone provides excellent long-term cancer control and disease-related survival. Second, radical prostatectomy provides definitive local and regional disease staging, serving as the backbone for multimodality treatment if needed. Third, the sequencing of surgery before radiation is viewed as preferable beca by preserving options for effective local salvage. Fourth, initial surgery successfully defers or avoids the adverse effects of long-term androgen deprivation therapy in a substantial proportion of patients. Lastly, fifth, prostatectomy offers manageable impacts on urinary and sexual function, minimizing risk of gastrointestinal toxicity or secondary malignancy, and averts local symptomatic progression in most.
Elective Regional Nodal Irradiation in Prostate Cancer.
Chilukuri S, Sayan M, Pra AD … +1 more , Murthy V
Semin Radiat Oncol · 2025 Jul · PMID 40516972 · Publisher ↗
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...
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.
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