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Delays in the work-up and definitive management of patients with prostate cancer are common, with logistics of additional work-up after initial prostate biopsy, specialist referrals, and psychological reasons being the most common causes of delays. During the COVID-19 pandemic and the subsequent surges, timing of definitive care delivery with surgery or radiotherapy has become a topic of significant concern for patients with prostate cancer and their providers alike. In response, recommendations for the timing of definitive management of prostate cancer with radiotherapy and radical prostatectomy were published but without a detailed rationale for these recommendations. While the COVID-19 pandemic is behind us, patients are always asking the question: "When should I start radiation or undergo surgery?" In the absence of level I evidence specifically addressing this question, we will hereby present a narrative review to summarize the available data on the effect of treatment delays on oncologic outcomes for patients with localized prostate cancer from prospective and retrospective studies.
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Explainable artificial intelligence (XAI) has experienced a vast increase in recognition over the last few years. While the technical developments are manifold, less focus has been placed on the clinical applicability and usability of systems. Moreover, not much attention has been given to XAI systems that can handle multimodal and longitudinal data, which we postulate are important features in many clinical workflows. In this study, we review, from a clinical perspective, the current state of XAI for multimodal and longitudinal datasets and highlight the challenges thereof. Additionally, we propose the XAI orchestrator, an instance that aims to help clinicians with the synopsis of multimodal and longitudinal data, the resulting AI predictions, and the corresponding explainability output. We propose several desirable properties of the XAI orchestrator, such as being adaptive, hierarchical, interactive, and uncertainty-aware.
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The treatment landscape for metastatic hormone-sensitive prostate cancer continues to evolve, with systemic treatment being the mainstay of current treatment. Prognostic and predictive factors such as tumour volume and disease presentation have been studied to assess responses to different treatments. Intensification and de-escalation strategies arouse great interest, so several trials are being developed to further personalize the therapy in these populations. Is there an optimal sequence and a possible option to de-intensify treatment in selected patients with a favourable profile? This and other goals will be the subject of this review.
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PURPOSE: Despite growing evidence for bilateral pelvic radiotherapy (whole pelvis RT, WPRT) there is almost no data on unilateral RT (hemi pelvis RT, HPRT) in patients with nodal recurrent prostate cancer after prostatectomy. Nevertheless, in clinical practice HPRT is sometimes used with the intention to reduce side effects compared to WPRT. Prostate-specific membrane antigen positron emission tomography / computed tomography (PSMA-PET/CT) is currently the best imaging modality in this clinical situation. This analysis compares PSMA-PET/CT based WPRT and HPRT. METHODS: A propensity score matching was performed in a multi-institutional retrospective dataset of 273 patients treated with pelvic RT due to nodal recurrence (214 WPRT, 59 HPRT). In total, 102 patients (51 in each group) were included in the final analysis. Biochemical recurrence-free survival (BRFS) defined as prostate specific antigen (PSA) < post-RT nadir + 0.2ng/ml, metastasis-free survival (MFS) and nodal recurrence-free survival (NRFS) were calculated using the Kaplan-Meier method and compared using the log rank test. RESULTS: Median follow-up was 29 months. After propensity matching, both groups were mostly well balanced. However, in the WPRT group there were still significantly more patients with additional local recurrences and biochemical persistence after prostatectomy. There were no significant differences between both groups in BRFS (p = .97), MFS (p = .43) and NRFS (p = .43). After two years, BRFS, MFS and NRFS were 61%, 86% and 88% in the WPRT group and 57%, 90% and 82% in the HPRT group, respectively. Application of a boost to lymph node metastases, a higher RT dose to the lymphatic pathways (> 50 Gy EQD2α/ß=1.5 Gy) and concomitant androgen deprivation therapy (ADT) were significantly associated with longer BRFS in uni- and multivariate analysis. CONCLUSIONS: Overall, this analysis presents the outcome of HPRT in nodal recurrent prostate cancer patients and shows that it can result in a similar oncologic outcome compared to WPRT. Nevertheless, patients in the WPRT may have been at a higher risk for progression due to some persistent imbalances between the groups. Therefore, further research should prospectively evaluate which subgroups of patients are suitable for HPRT and if HPRT leads to a clinically significant reduction in toxicity.
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INTRODUCTION: Enzalutamide, a second-generation androgen receptor inhibitor, is indicated for the treatment of metastatic disease, as well as in the treatment of non-metastatic castration resistant prostate cancer (PCa). This systematic review aims to determine outcomes and toxicity in patients with non-metastatic castration sensitive prostate cancer (nmCSPC) treated with enzalutamide in the primary or salvage settings. METHOD: We performed a systematic review focusing on the role of Enzalutamide in the treatment of nmCSPC, using the PubMed/Medline database. Articles focusing on androgen receptor inhibitors in nmCSPC were included, while articles discussing exclusively metastatic or castration-resistant PCa were excluded. RESULTS: The initial search retrieved 401 articles, of which 15 underwent a thorough assessment for relevance. Ultimately, 12 studies with pertinent outcomes were meticulously examined. Among these, seven studies were dedicated to the investigation of enzalutamide in the primary setting, while the remaining five publications specifically addressed its use in salvage settings. Regardless of the treatment setting, our data revealed two distinct therapeutic strategies. The first advocates for the substitution of enzalutamide for androgen deprivation therapy (ADT), based on the premise of achieving equivalent, if not superior, oncological outcomes while minimizing treatment-related toxicity. The second, adopting a more conventional approach, entails augmenting the effectiveness of ADT by incorporating enzalutamide. CONCLUSION: Enzalutamide has considerable potential as a therapeutic strategy for nmCSPC, either used alone or in combination with ADT in the primary or in the salvage settings. The use of enzalutamide instead of ADT is an appealing strategy. However, more trials will be required to further understand the efficacy and side-effect profile of enzalutamide monotherapy.
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Benzamidas , Recurrencia Local de Neoplasia , Nitrilos , Feniltiohidantoína , Humanos , Feniltiohidantoína/uso terapéutico , Feniltiohidantoína/análogos & derivados , Masculino , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patología , Estudios Prospectivos , Ensayos Clínicos como Asunto , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/patología , Terapia Recuperativa , Antagonistas de Receptores Androgénicos/uso terapéuticoRESUMEN
PURPOSE: The European Association of Urology (EAU) proposed a risk stratification (high vs. low risk) for patients with biochemical recurrence (BR) following radical prostatectomy (RP). Here we investigated whether this stratification accurately predicts outcome, particularly in patients staged with PSMA-PET. METHODS: For this study, we used a retrospective database including 1222 PSMA-PET-staged prostate cancer patients who were treated with salvage radiotherapy (SRT) for BR, at 11 centers in 5 countries. Patients with lymph node metastases (pN1 or cN1) or unclear EAU risk group were excluded. The remaining cohort comprised 526 patients, including 132 low-risk and 394 high-risk patients. RESULTS: The median follow-up time after SRT was 31.0 months. The 3-year biochemical progression-free survival (BPFS) was 85.7 % in EAU low-risk versus 69.4 % in high-risk patients (p = 0.002). The 3-year metastasis-free survival (MFS) was 94.4 % in low-risk versus 87.6 % in high-risk patients (p = 0.005). The 3-year overall survival (OS) was 99.0 % in low-risk versus 99.6 % in high-risk patients (p = 0.925). In multivariate analysis, EAU risk group remained a statistically significant predictor of BPFS (p = 0.003, HR 2.022, 95 % CI 1.262-3.239) and MFS (p = 0.013, HR 2.986, 95 % CI 1.262-7.058). CONCLUSION: Our data support the EAU risk group definition. EAU risk grouping for BCR reliably predicted outcome in patients staged lymph node-negative after RP and with PSMA-PET before SRT. To our knowledge, this is the first study validating the EAU risk grouping in patients treated with PSMA-PET-planned SRT.
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Recurrencia Local de Neoplasia , Prostatectomía , Neoplasias de la Próstata , Terapia Recuperativa , Humanos , Masculino , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugía , Terapia Recuperativa/métodos , Anciano , Estudios Retrospectivos , Persona de Mediana Edad , Medición de Riesgo , Tomografía de Emisión de Positrones , Antígeno Prostático Específico/sangre , Europa (Continente)RESUMEN
PURPOSE: In this systematic review and meta-analysis, we describe the oncologic and toxicity outcomes of definitive focal brachytherapy for prostate cancer. METHODS AND MATERIALS: A PROSPERO registered study (CRD42023410170) was conducted following the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) guidelines. PubMed, Embase, and The Cochrane Library were searched for studies between 2000 and 2022. Two authors independently performed the initial search. Biochemical recurrence-free survival (bRFS) was defined as the primary endpoint for the meta-analysis. Generalized linear mixed-effects models were conducted to calculate effect size and quantify heterogeneity. We also describe the side effects and local recurrence patterns of focal brachytherapy. RESULTS: Ten studies were identified and included 315 patients treated using focal brachytherapy as a definitive treatment. Mean (SD) age was 67.65 (7.9) years and mean (SD) PSA was 7.15 (2.7) ng/mL. Most patients (nâ¯=â¯236, 75%) underwent LDR Brachytherapy and 25% received HDR brachytherapy. Among the participants, 147 (46.5%) had a Gleason score ≤6, and 169 (53.5%) had a Gleason score ≥7. Only 11 (3.5%) patients received ADT. Overall, bRFS rate at median follow-up 4 years (Range: 1-6.42 years) was 91% (95% confidence interval [CI], 82-95%). Acute Grade ≤ 2 GU and GI toxicities were reported in 22 (7%) and 11 (3.5%) patients, respectively. Late Grade ≤ 2 GU and GI toxicity were reported in 6 (2%) and 14 (4.4%) patients, respectively. One case of prostate hemorrhage due to improper foley removal was noted but otherwise no acute or late Grade 3 or higher GI or GU toxicity related to radiotherapy was reported. CONCLUSION: Overall, definitive focal brachytherapy has a favorable toxicity profile. Oncologic outcomes are yet to mature. The evidence is limited by the small number of studies with low patients' number, across study heterogeneity, and possibility of publication bias.
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Braquiterapia , Neoplasias de la Próstata , Humanos , Braquiterapia/métodos , Masculino , Neoplasias de la Próstata/radioterapia , Recurrencia Local de Neoplasia/radioterapia , Clasificación del Tumor , Anciano , Resultado del Tratamiento , Antígeno Prostático Específico/sangre , Supervivencia sin EnfermedadRESUMEN
BACKGROUND: Prostate-related quality of life can be assessed with a variety of different questionnaires. The 50-item Expanded Prostate Cancer Index Composite (EPIC) and the International Prostate Symptom Score (IPSS) are two widely used options. The goal of this study was, therefore, to develop and validate a model that is able to convert between the EPIC and the IPSS to enable comparisons across different studies. METHODS: Three hundred forty-seven consecutive patients who had previously received radiotherapy and surgery for prostate cancer at two institutions in Switzerland and Germany were contacted via mail and instructed to complete both questionnaires. The Swiss cohort was used to train and internally validate different machine learning models using fourfold cross-validation. The German cohort was used for external validation. RESULTS: Converting between the EPIC Urinary Irritative/Obstructive subscale and the IPSS using linear regressions resulted in mean absolute errors (MAEs) of 3.88 and 6.12, which is below the respective previously published minimal important differences (MIDs) of 5.2 and 10 points. Converting between the EPIC Urinary Summary and the IPSS was less accurate with MAEs of 5.13 and 10.45, similar to the MIDs. More complex model architectures did not result in improved performance in this study. The study was limited to the German versions of the respective questionnaires. CONCLUSIONS: Linear regressions can be used to convert between the IPSS and the EPIC Urinary subscales. While the equations obtained in this study can be used to compare results across clinical trials, they should not be used to inform clinical decision-making in individual patients. TRIAL REGISTRATION: This study was retrospectively registered on clinicaltrials.gov on January 14th, 2022, under the registration number NCT05192876.
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Próstata , Neoplasias de la Próstata , Masculino , Humanos , Calidad de Vida , Encuestas y Cuestionarios , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/radioterapia , AlemaniaRESUMEN
INTRODUCTION: Despite radical prostatectomy (RP) and radiotherapy (RT) being established treatments for localised prostate cancer, a significant number of patients experience recurrent disease. While conventionally fractionated RT is still being used as a standard treatment in the postoperative setting, ultra-hypofractionated RT has emerged as a viable option with encouraging results in patients with localised disease in the primary setting. In addition, recent technological advancements in RT delivery and precise definition of isolated macroscopic recurrence within the prostate bed using prostate-specific membrane antigen-positron emission tomography (PSMA-PET) and multiparametric MRI (mpMRI) allow the exploration of ultra-hypofractionated schedules in the salvage setting using five fractions. METHODS AND ANALYSIS: In this single-arm prospective phase II multicentre trial, 36 patients with node-negative prostate adenocarcinoma treated with RP at least 6 months before trial registration, tumour stage pT2a-3b, R0-1, pN0 or cN0 according to the UICC TNM 2009 and evidence of measurable local recurrence within the prostate bed detected by PSMA PET/CT and mpMRI within the last 3 months, will be included. The patients will undergo focal ultra-hypofractionated salvage RT with 34 Gy in five fractions every other day to the site of local recurrence in combination with 6 months of androgen deprivation therapy. The primary outcome of this study is biochemical relapse-free survival at 2 years. Secondary outcomes include acute side effects (until 90 days after the end of RT) of grade 3 or higher based on Common Terminology Criteria for Adverse Events V.5, progression-free survival, metastasis-free survival, late side effects and the quality of life (based on European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30, QLQ-PR25). ETHICS AND DISSEMINATION: The study has received ethical approval from the Ethics Commission of the Canton of Bern (KEK-BE 2022-01026). Academic dissemination will occur through publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT05746806.
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Próstata , Neoplasias de la Próstata , Masculino , Humanos , Próstata/diagnóstico por imagen , Próstata/cirugía , Próstata/patología , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/cirugía , Resultado del Tratamiento , Antagonistas de Andrógenos/uso terapéutico , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Estudios Prospectivos , Calidad de Vida , Recurrencia Local de Neoplasia/patología , Prostatectomía , Terapia Recuperativa/métodos , Antígeno Prostático Específico , Estudios Multicéntricos como Asunto , Ensayos Clínicos Fase II como AsuntoRESUMEN
PURPOSE: This systematic review and meta-analysis aimed to evaluate the evidence for ultrahypofractionated pelvic nodal irradiation in patients with prostate cancer, with a focus on reported acute and late toxicities. METHODS AND MATERIALS: A comprehensive search was conducted in 5 electronic databases (PubMed, Scopus, Web of Science, Cochrane Library, ClinicalTrials.gov) from inception until March 23, 2023. Eligible publications included patients with intermediate- and high-risk and node-positive prostate cancer who underwent elective or therapeutic ultrahypofractionated pelvic nodal irradiation. Primary outcomes included the presence of grade ≥2 rates of acute and late gastrointestinal and genitourinary toxicity based on the Common Terminology Criteria for Adverse Events or Radiation Therapy Oncology Group scales. Quality assessment was performed using National Institutes of Health tools for noncontrolled beforeand after (single arm) clinical trials, as well as single-arm observational studies. Because all outcomes were categorical variables, proportion was calculated to estimate the effect size and compare the outcomes after the intervention. RESULTS: We identified 16 publications that reported the use of ultrahypofractionated radiation therapy to treat the pelvis in prostate cancer. Seven publications met our criteria and were included in the meta-analysis, including 417 patients. The median total dose to the pelvic lymph nodes was 25 Gy (range, 25-28.5 Gy), with a median of 5 fractions. The prostate received a median dose of 40 Gy (range, 35-47.5 Gy). All studies used androgen deprivation therapy for a median duration of 18 months. The median follow-up period was 3 years (range, 0.5-5.6 years). The rates of acute grade ≥2 gastrointestinal and genitourinary toxicity were 8% (95% CI, 1%-15%) and 29% (95% CI, 18%-41%), respectively. For late grade ≥2 gastrointestinal and genitourinary toxicity, the rates were 13% (95% CI, 5%-21%) and 29% (95% CI, 17%-42%), respectively. CONCLUSIONS: Ultrahypofractionated pelvic nodal irradiation appears to be a safe approach in terms of acute and late genitourinary and gastrointestinal toxicity.
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Neoplasias de la Próstata , Radioterapia de Intensidad Modulada , Masculino , Humanos , Neoplasias de la Próstata/patología , Antagonistas de Andrógenos/uso terapéutico , Fraccionamiento de la Dosis de Radiación , Pelvis , Sistema Urogenital , Radioterapia de Intensidad Modulada/métodosRESUMEN
AIM: The optimal management for early recurrent prostate cancer following radical prostatectomy (RP) in patients with negative prostate-specific membrane antigen positron-emission tomography (PSMA-PET) scan is an ongoing subject of debate. The aim of this study was to evaluate the outcome of salvage radiotherapy (SRT) in patients with biochemical recurrence with negative PSMA PET finding. METHODS: This retrospective, multicenter (11 centers, 5 countries) analysis included patients who underwent SRT following biochemical recurrence (BR) of PC after RP without evidence of disease on PSMA-PET staging. Biochemical recurrence-free survival (bRFS), metastatic-free survival (MFS) and overall survival (OS) were assessed using Kaplan-Meier method. Multivariable Cox proportional hazards regression assessed predefined predictors of survival outcomes. RESULTS: Three hundred patients were included, 253 (84.3%) received SRT to the prostate bed only, 46 (15.3%) additional elective pelvic nodal irradiation, respectively. Only 41 patients (13.7%) received concomitant androgen deprivation therapy (ADT). Median follow-up after SRT was 33 months (IQR: 20-46 months). Three-year bRFS, MFS, and OS following SRT were 73.9%, 87.8%, and 99.1%, respectively. Three-year bRFS was 77.5% and 48.3% for patients with PSA levels before PSMA-PET ≤ 0.5 ng/ml and > 0.5 ng/ml, respectively. Using univariate analysis, the International Society of Urological Pathology (ISUP) grade > 2 (p = 0.006), metastatic pelvic lymph nodes at surgery (p = 0.032), seminal vesicle involvement (p < 0.001), pre-SRT PSA level of > 0.5 ng/ml (p = 0.004), and lack of concomitant ADT (p = 0.023) were significantly associated with worse bRFS. On multivariate Cox proportional hazards, seminal vesicle infiltration (p = 0.007), ISUP score >2 (p = 0.048), and pre SRT PSA level > 0.5 ng/ml (p = 0.013) remained significantly associated with worse bRFS. CONCLUSION: Favorable bRFS after SRT in patients with BR and negative PSMA-PET following RP was achieved. These data support the usage of early SRT for patients with negative PSMA-PET findings.
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Próstata , Neoplasias de la Próstata , Masculino , Humanos , Próstata/patología , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/cirugía , Pronóstico , Antígeno Prostático Específico , Vesículas Seminales/patología , Estudios Retrospectivos , Antagonistas de Andrógenos , Recurrencia Local de Neoplasia/patología , Prostatectomía , Tomografía de Emisión de Positrones , Terapia Recuperativa , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodosRESUMEN
BACKGROUND: Up to 40% of patients with prostate cancer may develop biochemical recurrence after surgery, with salvage radiation therapy (SRT) being the only curative option. In 2016, Tendulkar et al. (Contemporary update of a multi-institutional predictive nomogram for salvage radiotherapy after radical prostatectomy. J Clin Oncol 2016;34:3648-54) published a nomogram to predict distant metastasis in a cohort of patients treated with SRT with pre-SRT prostate-specific antigen (PSA) of 0.5 ng/ml after radical prostatectomy. In modern practice, SRT is delivered at lower PSA values. OBJECTIVE: To train and externally validate a machine learning model to predict the risk of distant metastasis at 5 yr in a contemporary cohort of patients receiving SRT. DESIGN, SETTING, AND PARTICIPANTS: We trained a machine learning model on data from 2418 patients treated with SRT at one institution, with a median PSA value of 0.27 ng/ml. External validation was done in 475 patients treated at two different institutions. Patients with cM1, pN1, or pT4 disease were excluded, as were patients with PSA >2 ng/ml or PSA 0, and patients with radiation dose <60 or ≥80 Gy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Model performance was assessed using calibration and time-dependent area under the receiver operating curve (tAUC). RESULTS AND LIMITATIONS: Our model had better calibration and showed improved discrimination (tAUC = 0.72) compared with the Tendulkar model (tAUC = 0.60, p < 0.001). The main limitations of this study are its retrospective design and lack of validation on patients who received hormone therapy. CONCLUSIONS: The updated model can be used to provide more individualized risk assessments to patients treated with SRT at low PSA values, improving decision-making. PATIENT SUMMARY: Up to 40% of patients with prostate cancer may develop biochemical recurrence after surgery, with salvage radiation therapy as the only potentially curative option. We trained and validated a machine learning model using clinical and surgical data to predict a patient's risk of distant metastasis at 5 yr after treatment. Our model outperformed the reference tool and can improve clinical decision-making by providing more personalized risk assessment.
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Antígeno Prostático Específico , Neoplasias de la Próstata , Masculino , Humanos , Estudios Retrospectivos , Próstata/patología , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/cirugía , Neoplasias de la Próstata/patología , Prostatectomía/métodos , Terapia Recuperativa/métodosRESUMEN
PURPOSE: To compare two stereotactic body radiotherapy (SBRT) regimens in patients with intermediate- or high-risk prostate cancer with regards toxicity and efficacy. METHODS/MATERIAL: We retrospectively collected data from 198 patients treated with SBRT for prostate cancer at two different institutions. Patients received either 35-36.25 Gy in five fractions (group A) using Cyberknife robotic platform or 42.7 Gy in seven fractions (group B) using a C-arm LINAC (image-guided). Propensity score matching was done (2:1 nearest neighbor matching without replacement), resulting in 120 patients (80 patients for group A, 40 patients for group B). Toxicity, PSA nadir, biochemical failure and disease-free survival (DFS) were analyzed. RESULTS: Median follow up of all patients was 13 months (range 1-91 months). Overall, 23.3% of patients had ≥G2 acute GU toxicity (21.1% group A versus 30% group B (p = 0.222)) and 6.6% of patients ≥G2 GI toxicity (2.5% versus 15% (p = 0.010)). There was one acute G3 GU toxicity in arm A and one acute G4 rectal bleeding in group B (anticoagulated patient). Regarding late toxicity, 14.1% of patients had ≥G2 late GU toxicity (17.4% versus 6.6% (p = 0.159)) and 5.0% of patients had ≥G2 late GI toxicity (1.4% versus 13.3% (p = 0.013)). There was one G3 late GU toxicity in arm B and two G3 late GI toxicities, one in each arm. Relative median PSA reduction was 92.4% (-53.9-99.9%) from baseline PSA (93.7% (-53.9-99.9%) in group A versus 87.7% (39.8-99.9%) in group B (p = 0.043). In total, 4.2% of patients had biochemical relapse, 5.0% in group A and 2.5% in group B (p = 0.518). One-year DFS in the overall cohort was 97.3%, 98.8% in group A and 94.3% in group B (p = 0.318). CONCLUSION: Both SBRT regimens have acceptable acute and late toxicity and good efficacy. There are significantly more GI toxicities in the seven-fraction regimen. Longer follow-up is warranted for better comparison of long-term efficacy.
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BACKGROUND: Treatment recommendations for patients with limited nodal recurrences are lacking, and different locoregional treatment approaches are currently being used. OBJECTIVE: The aim of this trial is to compare metastasis-directed therapy (MDT) with or without elective nodal pelvic radiotherapy (ENRT). DESIGN, SETTING, AND PARTICIPANTS: PEACE V-Salvage Treatment of OligoRecurrent nodal prostate cancer Metastases (STORM) is an international, phase 2, open-label, randomized, superiority trial (ClinicalTrials.gov identifier: NCT03569241). Patients diagnosed with positron emission tomography-detected pelvic nodal oligorecurrence (five or fewer nodes) following radical local treatment for prostate cancer were randomized in a 1:1 ratio between arm A (MDT and 6 mo of androgen deprivation therapy [ADT]) and arm B (ENRT [25 × 1.8 Gy] with MDT and 6 mo of ADT). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We report the secondary endpoint acute toxicity, defined as worst grade ≥2 Common Terminology Criteria for Adverse Events v4.0 gastrointestinal (GI) or genitourinary (GU) toxicity within 3 mo of treatment. The chi-square test was used to compare toxicity between treatment arms. We also compare the quality of life (QoL) using the European Organisation for Research and Treatment of Cancer QLQ C30 and PR25 questionnaires. RESULTS AND LIMITATIONS: Between June 2018 and April 2021, 196 patients were assigned randomly to MDT or ENRT. Ninety-seven of 99 patients allocated to MDT and 93 of 97 allocated to ENRT received per-protocol treatment. Worst acute GI toxicity proportions were as follows: grade ≥2 events in three (3%) in the MDT group versus four (4%) in the ENRT group (p = 0.11). Worst acute GU toxicity proportions were as follows: grade ≥2 events in eight (8%) in the MDT group versus 12 (13%) in the ENRT group (p = 0.95). We observed no significant difference between the study groups in the proportion of patients with a clinically significant QoL reduction from baseline for any subdomain score area. CONCLUSIONS: No clinically meaningful differences were observed in worst grade ≥2 acute GI or GU toxicity or in QoL subdomains between MDT and ENRT. PATIENT SUMMARY: We found no evidence of differential acute bowel or urinary side effects using metastasis-directed therapy and elective nodal radiotherapy for the treatment of patients with a pelvic lymph node recurrence.
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Objective: The optimal strategy to treat loco-regionally advanced squamous cell carcinoma of the larynx (LSCC) remains to be defined. The goal of this single institution retrospective study was to report on oncologic outcome of advanced LSCC treated with curative intent. Methods: Patients diagnosed and treated for stage T3-T4a LSCC between 2001 and 2014 were retrospectively analyzed. Time-to-event endpoints were calculated beginning from the date of histologic diagnosis, which were analyzed with log-rank test and Cox proportional hazard models. Results: The cohort was divided into two subgroups: primary radiotherapy with concomitant cisplatin (CRT) (n=30, 38%) and primary surgery (n=48, 62%). Median follow-up was 56 months. Locoregional control (LRC) for the primary surgery and CRT were 95% and 50% in 5 years, respectively (p<0.01). Progression free survival (PFS) for the primary surgery and CRT were 61% and 38% in 5 years, respectively (p=0.23). The overall survival (OS) after primary surgery and CRT in 5 years were 63% vs. 65%, respectively (p=0.93). The 5-years LRC was significantly superior after surgery compared to RT for cT3 primaries (100% vs 50%, p= 0.0022). No significant differences were observed in the remaining subgroups regarding cT stage and PFS or OS. Conclusion: Our series demonstrated superior LRC after primary surgery followed by risk-adapted adjuvant (C)RT compared to primary CRT in cT3 LSCC, but no significant difference in PFS or OS in locally-advanced LSCC. The optimal patient selection criteria for the ideal treatment for loco-regionally advanced LSCC still needs to be defined.
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INTRODUCTION: Prostate bed radiotherapy (RT) is a major affecter of patients' long-term quality of life (QoL). To ensure the best possible outcome of these patients, dose constraints are key for optimal RT planning and delivery. However, establishing refined dose constraints requires access to patient-level data. Therefore, we aimed to provide such data on the relationship between OAR and gastrointestinal (GI) as well as genitourinary (GU) QoL outcomes of a homogenous patient cohort who received dose-intensified post-operative RT to the prostate bed. Furthermore, we aimed to conduct an exploratory analysis of the resulting data. METHODS: Patients who were treated with prostate bed RT between 2010 and 2020 were inquired about their QoL based on the Expanded Prostate Cancer Index Composite (EPIC). Those (n = 99) who received volumetric arc therapy (VMAT) of at least 70 Gy to the prostate bed were included. Dose-volume histogram (DVH) parameters were gathered and correlated with the EPIC scores. RESULTS: The median age at the time of prostate bed RT was 68.9 years, and patients were inquired about their QoL in the median 2.3 years after RT. The median pre-RT prostate-specific antigen (PSA) serum level was 0.35 ng/mL. The median duration between surgery and RT was 1.5 years. The median prescribed dose to the prostate bed was 72 Gy. A total of 61.6% received prostate bed RT only. For the bladder, the highest level of statistical correlation (p < 0.01) was seen for V10-20Gy, Dmean and Dmedian with urinary QoL. For bladder wall, the highest level of statistically significant correlation (p < 0.01) was seen for V5-25Gy, Dmean and Dmedian with urinary QoL. Penile bulb V70Gy was statistically significantly correlated with sexual QoL (p < 0.05). A larger rectal volume was significantly correlated with improved bowel QoL (p < 0.05). Sigmoid and urethral DVH parameters as well as the surgical approach were not statistically significantly correlated with QoL. CONCLUSION: Specific dose constraints for bladder volumes receiving low doses seem desirable for the further optimization of prostate bed RT. This may be particularly relevant in the context of the aspiration of establishing focal RT of prostate cancer and its local recurrences. Our comprehensive dataset may aid future researchers in achieving these goals.
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Próstata , Neoplasias de la Próstata , Masculino , Humanos , Ácido Hialurónico , Recto , Pelvis , Neoplasias de la Próstata/radioterapiaRESUMEN
BACKGROUND/PURPOSE: The present study aimed to assess whether SRT to the prostatic fossa should be initiated in a timely manner after detecting biochemical recurrence (BR) in patients with prostate cancer, when no correlate was identified with prostate-specific membrane antigen positron emission tomography (PSMA-PET). MATERIALS AND METHODS: This retrospective, multicenter analysis included 1222 patients referred for PSMA-PET after a radical prostatectomy due to BR. Exclusion criteria were: pathological lymph node metastases, prostate-specific antigen (PSA) persistence, distant or lymph node metastases, nodal irradiation, and androgen deprivation therapy (ADT). This led to a cohort of 341 patients. Biochemical progression-free survival (BPFS) was the primary study endpoint. RESULTS: The median follow-up was 28.0 months. The 3-year BPFS was 71.6% in PET-negative cases and 80.8% in locally PET-positive cases. This difference was significant in univariate (p = 0.019), but not multivariate analyses (p = 0.366, HR: 1.46, 95%CI: 0.64-3.32). The 3-year BPFS in PET-negative cases was significantly influenced by age (p = 0.005), initial pT3/4 (p < 0.001), pathology scores (ISUP) ≥ 3 (p = 0.026), and doses to fossa > 70 Gy (p = 0.027) in univariate analyses. In multivariate analyses, only age (HR: 1.096, 95%CI: 1.023-1.175, p = 0.009) and PSA-doubling time (HR: 0.339, 95%CI: 0.139-0.826, p = 0.017) remained significant. CONCLUSION: To our best knowledge, this study provided the largest SRT analysis in patients without ADT that were lymph node-negative on PSMA-PET. A multivariate analysis showed no significant difference in BPFS between locally PET-positive and PET-negative cases. These results supported the current EAU recommendation to initiate SRT in a timely manner after detecting BR in PET negative patients.
Asunto(s)
Antígeno Prostático Específico , Neoplasias de la Próstata , Masculino , Humanos , Estudios Retrospectivos , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/patología , Metástasis Linfática , Antagonistas de Andrógenos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Radioisótopos de Galio , Recurrencia Local de Neoplasia/patología , Tomografía de Emisión de Positrones , Prostatectomía/métodos , Terapia Recuperativa/métodosRESUMEN
Importance: Prostate-specific antigen membrane positron-emission tomography (PSMA-PET) is increasingly used to guide salvage radiotherapy (sRT) after radical prostatectomy for patients with recurrent or persistent prostate cancer. Objective: To develop and validate a nomogram for prediction of freedom from biochemical failure (FFBF) after PSMA-PET-based sRT. Design, Setting, and Participants: This retrospective cohort study included 1029 patients with prostate cancer treated between July 1, 2013, and June 30, 2020, at 11 centers from 5 countries. The initial database consisted of 1221 patients. All patients had a PSMA-PET scan prior to sRT. Data were analyzed in November 2022. Exposures: Patients with a detectable post-radical prostatectomy prostate-specific antigen (PSA) level treated with sRT to the prostatic fossa with or without additional sRT to pelvic lymphatics or concurrent androgen deprivation therapy (ADT) were eligible. Main Outcomes and Measures: The FFBF rate was estimated, and a predictive nomogram was generated and validated. Biochemical relapse was defined as a PSA nadir of 0.2 ng/mL after sRT. Results: In the nomogram creation and validation process, 1029 patients (median age at sRT, 70 years [IQR, 64-74 years]) were included and further divided into a training set (n = 708), internal validation set (n = 271), and external outlier validation set (n = 50). The median follow-up was 32 months (IQR, 21-45 months). Based on the PSMA-PET scan prior to sRT, 437 patients (42.5%) had local recurrences and 313 patients (30.4%) had nodal recurrences. Pelvic lymphatics were electively irradiated for 395 patients (38.4%). All patients received sRT to the prostatic fossa: 103 (10.0%) received a dose of less than 66 Gy, 551 (53.5%) received a dose of 66 to 70 Gy, and 375 (36.5%) received a dose of more than 70 Gy. Androgen deprivation therapy was given to 325 (31.6%) patients. On multivariable Cox proportional hazards regression analysis, pre-sRT PSA level (hazard ratio [HR], 1.80 [95% CI, 1.41-2.31]), International Society of Urological Pathology grade in surgery specimen (grade 5 vs 1+2: HR, 2.39 [95% CI, 1.63-3.50], pT stage (pT3b+pT4 vs pT2: HR, 1.91 [95% CI, 1.39-2.67]), surgical margins (R0 vs R1+R2+Rx: HR, 0.60 [95% CI, 0.48-0.78]), ADT use (HR, 0.49 [95% CI, 0.37-0.65]), sRT dose (>70 vs ≤66 Gy: HR, 0.44 [95% CI, 0.29-0.67]), and nodal recurrence detected on PSMA-PET scans (HR, 1.42 [95% CI, 1.09-1.85]) were associated with FFBF. The mean (SD) nomogram concordance index for FFBF was 0.72 (0.06) for the internal validation cohort and 0.67 (0.11) in the external outlier validation cohort. Conclusions and Relevance: This cohort study of patients with prostate cancer presents an internally and externally validated nomogram that estimated individual patient outcomes after PSMA-PET-guided sRT.
Asunto(s)
Neoplasias de la Próstata , Masculino , Humanos , Antígeno Prostático Específico , Antagonistas de Andrógenos , Andrógenos , Estudios de Cohortes , Nomogramas , Estudios Retrospectivos , Enfermedad Crónica , RecurrenciaRESUMEN
BACKGROUND: Management of local recurrence of prostate cancer (PCa) in the prostatic bed after radical prostatectomy (RP) and radiotherapy remains challenging. OBJECTIVE: To assess the efficacy and safety of salvage stereotactic body radiotherapy (SBRT) reirradiation in this setting and evaluate prognostic factors. DESIGN, SETTING, AND PARTICIPANTS: We conducted a large multicenter retrospective series that included 117 patients who were treated with salvage SBRT for local recurrence in the prostatic bed after RP and radiotherapy in 11 centers across three countries. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Progression-free survival (PFS; biochemical, clinical, or both) was estimated using the Kaplan-Meier method. Biochemical recurrence was defined as prostate-specific antigen nadir +0.2 ng/ml, confirmed by a second increasing measure. The cumulative incidence of late toxicities was estimated using the Kalbfleisch-Prentice method by considering recurrence or death as a competing event. RESULTS AND LIMITATIONS: The median follow-up was 19.5 mo. The median SBRT dose was 35 Gy. The median PFS was 23.5 mo (95% confidence interval [95% CI], 17.6-33.2). In the multivariable models, the volume of the recurrence and its contact with the urethrovesical anastomosis were significantly associated with PFS (hazard ratio [HR]/10 cm3 = 1.46; 95% CI, 1.08-1.96; p = 0.01 and HR = 3.35; 95% CI, 1.38-8.16; p = 0.008, respectively). The 3-yr cumulative incidence of grade ≥2 late GU or GI toxicity was 18% (95% CI, 10-26). In the multivariable analysis, a recurrence in contact with the urethrovesical anastomosis and D2% of the bladder were significantly associated with late toxicities of any grade (HR = 3.65; 95% CI, 1.61-8.24; p = 0.002 and HR/10 Gy = 1.88; 95% CI, 1.12-3.16; p = 0.02, respectively). CONCLUSIONS: Salvage SBRT for local recurrence in the prostate bed may offer encouraging control and acceptable toxicity. Therefore, further prospective studies are warranted. PATIENT SUMMARY: We found that salvage stereotactic body radiotherapy after surgery and radiotherapy allows for encouraging control and acceptable toxicity in locally relapsed prostate cancer.