Is trimodal therapy the current standard for muscle-invasive bladder cancer?

OBJECTIVE: The aim of this review is to summarize the current evidence and future perspectives of bladder-sparing treatment for MIBC. METHODS: A non-systematic literature search in Medline/Pubmed was performed in October 2023 with the following keywords "bladder cancer", "bladder-sparing", "trimodal therapy", "chemoradiation", "biomarkers", "immunotherapy", "neoadjuvant chemotherapy", "radiotherapy". RESULTS: Urology guidelines recommend radical cystectomy as the standard curative treatment for muscle-invasive urothelial bladder cancer, reserving radiotherapy for patients who are unfit or who want to preserve their bladder. Given the morbidity and mortality of cystectomy and its impact on quality of life and bladder function, modern oncologic therapies are increasingly oriented toward organ preservation and maximizing functional outcomes while maintaining treatment efficacy. Trimodal therapy, which incorporates maximal transurethral resection followed by radiotherapy with concurrent radiosensitizing chemotherapy, is an effective regimen for bladder function preservation in well-selected patients. Despite the absence of comparative data from randomized trials, the two approaches seem to provide comparable oncologic outcomes. Studies are evaluating the expansion of eligibility criteria for trimodal therapy, the optimization of radiotherapy and immunotherapy delivery to further improve outcomes, and the validation of biomarkers to guide bladder preservation. CONCLUSIONS: Trimodal therapy has shown acceptable outcomes for bladder preservation; therefore, it provides a valid treatment option in well-selected patients.

Enhancing Androgen Deprivation Therapy (ADT) integration in prostate cancer: Insights for Stereotactic Body Radiotherapy (SBRT) and brachytherapy modalities.

The utilization of Androgen Deprivation Therapy (ADT) in conjunction with Stereotactic Body Radiotherapy (SBRT) and Brachytherapy (BT) boost in prostate cancer treatment is a subject of ongoing debate and evolving clinical practice. While contemporary trends lean towards underutilizing ADT with these modalities, existing evidence suggests that its omission may lead to potentially inferior oncologic outcomes. Recommendations for ADT use should be patient-centric, considering individual risk profiles and comorbidities, with a focus on achieving optimal oncologic outcomes while minimizing potential side effects. Ongoing clinical trials, such as PACE-C, SPA, SHIP 0804, and SHIP 36B, are anticipated to provide valuable insights into the optimal use and duration of ADT in both SBRT and BT settings. Until new evidence emerges, it is recommended to initiate ADT for unfavorable intermediate-risk and high-risk prostate cancer patients undergoing radiotherapy, with a minimum duration of 6 months for unfavorable intermediate-risk patients and at least 12 months for those with high-risk characteristics. The decision to incorporate ADT into these radiation therapy modalities should be individualized, acknowledging the unique needs of each patient and emphasizing a tailored approach to achieve the best possible oncologic outcomes.

Clinical Usefulness of Prostate-specific Membrane Antigen-ligand Positron Emission Tomography/Computed Tomography for the Detection of Prostate Cancer Biochemical Recurrence after Primary Radiation Therapy in Patients with Prostate-specific Antigen Below the Phoenix Threshold: Systematic Review and Meta-analysis.

AIMS: After primary radiotherapy, biochemical recurrence is defined according to the Phoenix criteria as a prostate-specific antigen (PSA) value >2 ng/ml relative to the nadir. Several studies have shown that prostate-specific membrane antigen (PSMA)-ligand positron emission tomography/computed tomography (PET/CT) can help in detecting recurrence in patients with low PSA values. This study aimed to assess the detection rate and patterns of PSMA-ligand PET/CT uptake in patients with suspected biochemical recurrence after primary radiotherapy and with PSA levels below the Phoenix threshold. MATERIALS AND METHODS: The meta-analysis was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Articles providing data on patients with suspected prostate cancer recurrence after primary radiotherapy with a PSA value below the Phoenix threshold and who underwent PSMA-ligand PET/CT were included. Quality assessment was carried out using the Quality Assessment of Diagnostic Accuracy Studies-2 tool (QUADAS-2). RESULTS: In total, five studies were included, recruiting 909 patients (202 with PSA ≤2 ng/ml). The PSMA-ligand detection rate in the patients with ≤2 ng/ml ranged from 66 to 83%. The most frequent source of PSMA-ligand PET/CT uptake was local recurrence, followed by lymph node metastasis and bone metastasis. PSMA-ligand PET/CT uptake due to local-only recurrence was more likely in patients with PSA ≤2 ng/ml compared with PSA > 2 ng/ml: risk ratio 0.72 (95% confidence interval 0.58-0.89), P = 0.003. No significant differences were observed in the detection of PSMA-ligand uptake in other areas. Limitations include a lack of biopsy confirmation, cohort reports with small sample sizes and a potentially high risk of bias. CONCLUSION: A significant detection of PSMA-ligand-avid disease was observed in patients with PSA levels below the Phoenix threshold. There was a higher likelihood of detecting local-only uptake when the PSA value was ≤2 ng/ml. The findings suggest that a critical review of the Phoenix criteria may be warranted in the era of PSMA-ligand PET/CT and highlight the need for further prospective trials.

Stereotactic Body Radiotherapy for Kidney Cancer: Ready for Prime Time?

The standard treatment for renal cell carcinoma (RCC) is surgery. However, a number of patients will not be candidates for surgical treatment or will reject this therapeutic approach. Therefore, alternative approaches are required. Historically, radiotherapy has been considered an ineffective treatment for RCC due to the radioresistance of renal tumour cells to conventional fractionation and the increased rate of toxicity. Stereotactic body radiotherapy (SBRT) is a radiotherapy technique that provides a non-invasive ablative treatment with remarkable rates of local control in both primary tumours and metastases in several locations, with a low associated morbidity due to the highly conformal dose and the use of image-guided techniques. Current evidence shows that a higher dose per fraction, achieving a higher biological effective dose, can overcome the radioresistance of RCC cells. Therefore, SBRT, as well as the combination of SBRT and new emerging immune therapies, has a potential role in the local treatment of primary RCC and oligometastatic RCC patients.

SEOR SBRT-SG stereotactic body radiation therapy consensus guidelines for non-spine bone metastasis.

The use of stereotactic body radiation therapy (SBRT) to treat non-spine bone metastases (NSBM) is becoming increasingly common in clinical practice. The clinical advantages of SBRT include good pain control and high local control rates, although only limited data are available. The Spanish Society of Radiation Oncology (SEOR) SBRT group recently convened a task force of experts in the field to address key questions related to SBRT for NSBM, including treatment indications, planning, techniques, and dose fractionation. The task force reviewed the available literature to develop evidence-based recommendations for the safe application of NSBM SBRT and to standardize and optimize SBRT processes. The present document provides a comprehensive analysis of the available data, including ongoing clinical trials and controversies, providing clinically applicable recommendations.

SEOR SBRT-SG survey on SRS/SBRT dose prescription criteria in Spain

Aim Stereotactic body radiotherapy (SBRT) and stereotactic radiosurgery (SRS) are essential tools in radiation oncology. In Spain, the use of these techniques continues to grow as older linear accelerators (linacs) are replaced with modern equipment. However, little is known about inter-centre variability in prescription and dose heterogeneity limits. Consequently, the SBRT-Spanish Task Group (SBRT-SG) of the Spanish Society of Radiation Oncology (SEOR) has undertaken an initiative to assess prescription and homogeneity in SRS/SBRT treatment. In the present study, we surveyed radiation oncology (RO) departments to obtain a realistic overview of prescription methods used for SBRT and SRS treatment in Spain. Methods A brief survey was developed and sent to 34 RO departments in Spain, mostly those who are members of the SEOR SBRT-SG. The survey contained seven questions about the specific prescription mode, dose distribution heterogeneity limits, prescription strategies according to SRS/SBRT type, and the use of IMRT–VMAT (Intensity Modulated Radiation Therapy–Volumetric Modulated Arc Therapy). Results Responses were received from 29 centres. Most centres (59%) used the prescription criteria D95% ≥ 100%. Accepted dose heterogeneity was wide, ranging from 107 to 200%. Most centres used IMRT–VMAT (93%). Conclusions This survey about SRS/SBRT prescription and dose heterogeneity has evidenced substantial inter-centre variability in prescription criteria, particularly for intended and accepted dose heterogeneity. These differences could potentially influence the mean planning target volume dose and its correlation with treatment outcomes. The findings presented here will be used by the SEOR SBRT-SG to develop recommendations for SRS/SBRT dose prescription and heterogeneity (AU)

Recommended procedures and responsibilities for radiosurgery (SRS) and extracranial stereotactic body radiotherapy (SBRT): report of the SEOR in collaboration with the SEFM

Today, patient management generally requires a multidisciplinary approach. However, due to the growing knowledge base and increasing complexity of Medicine, clinical practice has become even more specialised. Radiation oncology is not immune to this trend towards subspecialisation, which is particularly evident in ablative radiotherapy techniques that require high dose fractions, such as stereotactic radiosurgery (SRS), and stereotactic body radiotherapy (SBRT). The aim of the present report is to establish the position of the Spanish Society of Radiation Oncology (SEOR), in collaboration with the Spanish Society of Medical Physics (SEFM), with regard to the roles and responsibilities of healthcare professionals involved in performing SRS and SBRT. The need for this white paper is motivated due to the recent changes in Spanish Legislation (Royal Decree [RD] 601/2019, October 18, 2019) governing the use and optimization of radiotherapy and radiological protection for medical exposure to ionizing radiation (article 11, points 4 and 5) [1 ], which states: “In radiotherapy treatment units, the specialist in Radiation Oncology will be responsible for determining the correct treatment indication, selecting target volumes, determining the clinical radiation parameters for each volume, directing and supervising treatment, preparing the final clinical report, reporting treatment outcomes, and monitoring the patient’s clinical course.” Consequently, the SEOR and SEFM have jointly prepared the present document to establish the roles and responsibilities for the specialists—radiation oncologists (RO), medical physicists (MP), and related staff —involved in treatments with ionizing radiation. We believe that it is important to clearly establish the responsibilities of each professional group and to clearly establish the professional competencies at each stage of the radiotherapy process (AU)

SEOR SBRT-SG survey on SRS/SBRT dose prescription criteria in Spain.

AIM: Stereotactic body radiotherapy (SBRT) and stereotactic radiosurgery (SRS) are essential tools in radiation oncology. In Spain, the use of these techniques continues to grow as older linear accelerators (linacs) are replaced with modern equipment. However, little is known about inter-centre variability in prescription and dose heterogeneity limits. Consequently, the SBRT-Spanish Task Group (SBRT-SG) of the Spanish Society of Radiation Oncology (SEOR) has undertaken an initiative to assess prescription and homogeneity in SRS/SBRT treatment. In the present study, we surveyed radiation oncology (RO) departments to obtain a realistic overview of prescription methods used for SBRT and SRS treatment in Spain. METHODS: A brief survey was developed and sent to 34 RO departments in Spain, mostly those who are members of the SEOR SBRT-SG. The survey contained seven questions about the specific prescription mode, dose distribution heterogeneity limits, prescription strategies according to SRS/SBRT type, and the use of IMRT-VMAT (Intensity Modulated Radiation Therapy-Volumetric Modulated Arc Therapy). RESULTS: Responses were received from 29 centres. Most centres (59%) used the prescription criteria D95% ≥ 100%. Accepted dose heterogeneity was wide, ranging from 107 to 200%. Most centres used IMRT-VMAT (93%). CONCLUSIONS: This survey about SRS/SBRT prescription and dose heterogeneity has evidenced substantial inter-centre variability in prescription criteria, particularly for intended and accepted dose heterogeneity. These differences could potentially influence the mean planning target volume dose and its correlation with treatment outcomes. The findings presented here will be used by the SEOR SBRT-SG to develop recommendations for SRS/SBRT dose prescription and heterogeneity.

Recommended procedures and responsibilities for radiosurgery (SRS) and extracranial stereotactic body radiotherapy (SBRT): report of the SEOR in collaboration with the SEFM.

Today, patient management generally requires a multidisciplinary approach. However, due to the growing knowledge base and increasing complexity of Medicine, clinical practice has become even more specialised. Radiation oncology is not immune to this trend towards subspecialisation, which is particularly evident in ablative radiotherapy techniques that require high dose fractions, such as stereotactic radiosurgery (SRS), and stereotactic body radiotherapy (SBRT). The aim of the present report is to establish the position of the Spanish Society of Radiation Oncology (SEOR), in collaboration with the Spanish Society of Medical Physics (SEFM), with regard to the roles and responsibilities of healthcare professionals involved in performing SRS and SBRT. The need for this white paper is motivated due to the recent changes in Spanish Legislation (Royal Decree [RD] 601/2019, October 18, 2019) governing the use and optimization of radiotherapy and radiological protection for medical exposure to ionizing radiation (article 11, points 4 and 5) [1 ], which states: "In radiotherapy treatment units, the specialist in Radiation Oncology will be responsible for determining the correct treatment indication, selecting target volumes, determining the clinical radiation parameters for each volume, directing and supervising treatment, preparing the final clinical report, reporting treatment outcomes, and monitoring the patient's clinical course." Consequently, the SEOR and SEFM have jointly prepared the present document to establish the roles and responsibilities for the specialists-radiation oncologists (RO), medical physicists (MP), and related staff -involved in treatments with ionizing radiation. We believe that it is important to clearly establish the responsibilities of each professional group and to clearly establish the professional competencies at each stage of the radiotherapy process.

Time for radioimmunotherapy: an overview to bring improvements in clinical practice.

Harnessing the patient's own immune system against an established cancer has proven to be a successful strategy. Within the last years, several antibodies blocking critical "checkpoints" that control the activation of T cells, the immune cells able to kill cancer cells, have been approved for the use in patients with different tumours. Unfortunately, these cases remain a minority. Over the last years, radiotherapy has been reported as a means to turn a patient's own tumour into an in situ vaccine and generate anti-tumour T cells in patients who lack sufficient anti-tumour immunity. Indeed, review data show that the strategy of blocking multiple selected immune inhibitory targets in combination with radiotherapy has the potential to unleash powerful anti-tumour responses and improve the outcome of metastatic solid tumours. Here, we review the principal tumours where research in this field has led to new knowledge and where radioimmunotherapy becomes a reality.

PET/TC con 68Ga-PSMA, importancia en la práctica hospitalaria. Visión del oncólogo radioterápico / Importance of 68Ga-PSMA PET/CT in hospital practice. View of the radiation oncologist

La radioterapia es un tratamiento curativo indicado en pacientes con cáncer de próstata (CaP) primario y en aquellos con recurrencia bioquímica tras prostatectomía radical (PR). Además, recientemente, ha habido un aumento en el uso de técnicas de alta precisión como la radioterapia estereotáctica fraccionada corporal para tratar un número limitado de metástasis en pacientes con CaP oligometastásico. Las pruebas de imagen convencional (ecografía transrectal, tomografía computarizada [TC], resonancia magnética morfológica y gammagrafía ósea) tienen un papel menor en estos escenarios, debido a su bajo rendimiento diagnóstico. Recientemente, se ha desarrollado el radiotrazador 68Ga-PSMA, para la tomografía por emisión de positrones (PET), que es un ligando del antígeno de membrana específico de próstata (PSMA), una proteína transmembrana sobrexpresada en las células del CaP. Sus resultados son prometedores, con tasas de detección de lesiones tumorales mayores que la TC y mayor que la mejor técnica disponible actualmente, la PET con colina. Su superioridad es más evidente en pacientes con valores bajos de PSA (< 1 ng/ml). Esta mejora en el rendimiento diagnóstico representa un potencial impacto en el manejo terapéutico, especialmente en radioterapia. A pesar de que la prueba ya está disponible en la práctica clínica diaria de otros países europeos, en España su uso es muy limitado. En esta revisión, analizamos los principales estudios que investigan la utilidad de la PET/TC con 68Ga-PSMA en pacientes con CaP y su potencial impacto en los tratamientos de radioterapia. Además, comparamos la PET/TC con PSMA, con la resonancia magnética multiparamétrica y la PET/TC con colina, en los distintos escenarios clínicos

Radiotherapy is a treatment with curative intent, both in patients with primary diagnosis of prostate cancer (PCa) and in patients presenting with biochemical recurrence after radical prostatectomy (RP). Moreover, the use of stereotactic body radiotherapy as a metastasis directed therapy in patients with oligometastatic PCa has significantly increased in the recent years. Conventional imaging techniques, including transrectal ultrasound, computed tomography (CT), morphologic magnetic resonance and bone scintigraphy have traditionally played a minor role in all those clinical scenarios due to its low diagnostic accuracy. The recent development of the positron emission tomography (PET) radiotracer 68Ga-PSMA binding to the prostate specific membrane antigen (PSMA), a transmembrane glycoprotein overexpressed in PCa cells, has shown promising results. Detection rates for PCa lesions are higher than CT and higher than the best technique available, the PET/CT with choline. Its superiority has been demonstrated even at very low PSA levels (<1 ng/ml). This increase in diagnostic accuracy represents a potential impact on patient management, especially in radiotherapy. Even if this imaging technique is already available for routine clinical practice in some European countries, in Spain, unfortunately, there is very limited access. In this review, we analyze the main studies that investigate the usefulness of 68Ga-PSMA PET/CT in patients with PCa and its potential impact on radiotherapy treatments. In addition, we compared the 68Ga-PSMA PET/CT, with the multiparametric magnetic resonance imaging and the PET/CT with choline, in the different clinical scenarios

Importance of 68Ga-PSMA PET/CT in hospital practice. View of the radiation oncologist. / PET/TC con 68Ga-PSMA, importancia en la práctica hospitalaria. Visión del oncólogo radioterápico.

Radiotherapy is a treatment with curative intent, both in patients with primary diagnosis of prostate cancer (PCa) and in patients presenting with biochemical recurrence after radical prostatectomy (RP). Moreover, the use of stereotactic body radiotherapy as a metastasis directed therapy in patients with oligometastatic PCa has significantly increased in the recent years. Conventional imaging techniques, including transrectal ultrasound, computed tomography (CT), morphologic magnetic resonance and bone scintigraphy have traditionally played a minor role in all those clinical scenarios due to its low diagnostic accuracy. The recent development of the positron emission tomography (PET) radiotracer 68Ga-PSMA binding to the prostate specific membrane antigen (PSMA), a transmembrane glycoprotein overexpressed in PCa cells, has shown promising results. Detection rates for PCa lesions are higher than CT and higher than the best technique available, the PET/CT with choline. Its superiority has been demonstrated even at very low PSA levels (<1 ng/ml). This increase in diagnostic accuracy represents a potential impact on patient management, especially in radiotherapy. Even if this imaging technique is already available for routine clinical practice in some European countries, in Spain, unfortunately, there is very limited access. In this review, we analyze the main studies that investigate the usefulness of 68Ga-PSMA PET/CT in patients with PCa and its potential impact on radiotherapy treatments. In addition, we compared the 68Ga-PSMA PET/CT, with the multiparametric magnetic resonance imaging and the PET/CT with choline, in the different clinical scenarios.

Dolor irruptivo oncológico inducido por radioterapia: ¿es posible optimizar su tratamiento? / Radiotherapy-induced breakthrough cancer pain: is it possible to optimize its treatment?

Introducción: en el contexto de la radioterapia, el control del dolor irruptivo oncológico (DIO) supone un reto especial. El DIO ha sido definido por la Sociedad Española del Dolor (SED), la Sociedad Española de Oncología Médica (SEOM) y la Sociedad Española de Cuidados Paliativos (SECPAL) como una exacerbación del dolor súbita y transitoria, de gran intensidad (EVA > 7) y de corta duración (inferior a 20-30 minutos), que aparece sobre la base de un dolor persistente estable cuando este se encuentra reducido a un nivel tolerable (EVA < 5) mediante el uso de opioides mayores. Objetivos: el objetivo principal de este estudio fue evaluar la intensidad del DIO inducido por tratamientos oncológicos que incluyeran radioterapia (RT), tanto exclusiva como asociada a quimioterapia (RT/QT). Secundariamente, se evaluó la eficacia del tratamiento con fentanilo sublingual pautado para el control del DIO. Material y métodos: estudio observacional retrospectivo realizado en 110 pacientes reclutados en 19 Servicios de Radioterapia españoles. Los pacientes debían presentar DIO inducido por RT o RT/QT, con o sin medicación pautada y cuya intensidad fuera de una EVA > 6 en las últimas 24-48 h. Se establecieron controles en el momento basal, y a los 3, 7, 15 y 30 días. Resultados: se apreció un descenso en la media de los valores en la escala EVA según avanzó el estudio (EVA = 6 en el control 0 a EVA = 3 en el control 3), y las diferencias fueron significativas (p < 0,0001). La satisfacción con el tratamiento fue calificada como buena o excelente por el 85,3% de los pacientes y por el 92,7% de los investigadores. Conclusiones: los resultados de este estudio demuestran la eficacia del tratamiento del DIO con fentanilo sublingual en el contexto del tratamiento oncológico radioterápico, con un descenso significativo en los valores EVA frente al valor basal. La elevada satisfacción de los médicos y pacientes con este tratamiento refleja la eficacia y la comodidad del fentanilo sublingual en el control del DIO (AU)

Introduction: In the context of radiotherapy, control of breakthrough cancer pain (BTPc) is particularly challenging. BTPc has been defined by the Spanish Society of Pain (SED), the Spanish Society of Medical Oncology (SEOM) and the Spanish Society for Palliative Care (SECPAL) as a sudden and transient exacerbation of pain of great intensity (VAS > 7) and short (less than 20-30 minutes), which appears on the basis of a stable persistent pain when it is reduced to a tolerable level (VAS < 5) by using major opioids. Objectives: The main objective of this study was to assess the intensity of BTPc induced by cancer treatments that included radiotherapy (RT), both exclusive and associated with chemotherapy (RT/CT). Secondly, the efficacy of treatment was evaluated with fentanyl sublingual scheduled for BTPc control. Material and methods: Retrospective, observational study in 110 patients recruited in 19 Spanish Radiotherapy Services. Patients must have BTPc induced by RT or RT/CT, with or without medication prescribed and with an intensity outside a VAS > 6 in the last 24-48 h. Controls were established at baseline and at 3, 7, 15 and 30 days. Results: There was a decrease in mean values on the VAS scale as the study progressed (VAS = 6 in the control 0 to VAS = 3 in the control 3) and the differences were significant (p < 0.0001). Treatment satisfaction was rated as good or excellent by 85.3% of patients and 92.7% of researches. Conclusions: The results of this study demonstrate the efficacy of BTPc treatment with sublingual fentanyl in the context of the radiotherapy cancer treatment, with a significant decrease in VAS from baseline values . The high satisfaction among physicians and patients with this treatment reflects the efficacy and convenience of sublingual fentanyl in controlling BTPc (AU)