Development of castration resistance in prostate cancer patients treated with luteinizing hormone-releasing hormone analogues (LHRHa): results of the ANARESISTANCE study.

PURPOSE: Evaluate the percentage of patients with prostate cancer treated with luteinizing hormone-releasing hormone analogues (LHRHa) that develop castration resistance after a follow-up period of 3 years. The secondary objective is to evaluate the variables potentially related to the progression to castration resistant prostate cancer (CRPC). METHODS: A post-authorization, nation-wide, multicenter, prospective, observational, and longitudinal study that included 416 patients treated with LHRHa between 2012 and 2017 is presented. Patients were followed for 3 years or until development of CRPC, thus completing a per-protocol population of 350 patients. A Cox regression analysis was carried out to evaluate factors involved in progression to CRPC. RESULTS: After 3 years of treatment with LHRHa 18.2% of patients developed CRPC. In contrast, in the subgroup analysis, 39.6% of the metastatic patients developed CRPC, compared with 8.8% of the non-metastatic patients. The patients with the highest risk of developing CRPC were those with a nadir prostate-specific antigen (PSA) > 2 ng/ml (HR 21.6; 95% CI 11.7-39.8; p < 0.001) and those receiving concomitant medication, most commonly bicalutamide (HR 1.8; 95% CI 1-3.1, p = 0.0431). CONCLUSIONS: The proportion of metastatic patients developing CRPC after 3 years of treatment with LHRHa is consistent with what has been previously described in the literature. In addition, this study provides new findings on CRPC in non-metastatic patients. Concomitant medication and nadir PSA are statistically significant predictive factors for the time to diagnosis of CRPC, the nadir PSA being the strongest predictor.

Controversies in prostate cancer management: Consensus recommendations from experts in northern Spain.

In recent years, various aspects of prostate cancer (PC) management have undergone significant changes, including the implementation of therapeutic strategies such as the use of new hormonal agents like abiraterone, apalutamide, enzalutamide or darolutamide and the incorporation of next generation imaging techniques (NGI). However, the evidence regarding the role of NGI and the therapeutic decision-making based on their findings is not solid. Following the methodology of the Advanced Prostate Cancer Consensus Conference (APCCC), a multidisciplinary expert consensus was developed to address controversial questions concerning the use of NGI and clinical management in four priority scenarios: localized PC, PC after radical prostatectomy, PC after radiotherapy with curative intent, and metastatic hormone-sensitive PC. This consensus represents the opinions of medical oncology, radiation oncology and urology physicians and provides useful recommendations for clinical practice.

Usefulness of bone turnover markers as predictors of mortality risk, disease progression and skeletal-related events appearance in patients with prostate cancer with bone metastases following treatment with zoledronic acid: TUGAMO study.

BACKGROUND: Owing to the limited validity of clinical data on the treatment of prostate cancer (PCa) and bone metastases, biochemical markers are a promising tool for predicting survival, disease progression and skeletal-related events (SREs) in these patients. The aim of this study was to evaluate the predictive capacity of biochemical markers of bone turnover for mortality risk, disease progression and SREs in patients with PCa and bone metastases undergoing treatment with zoledronic acid (ZA). METHODS: This was an observational, prospective and multicenter study in which ninety-eight patients were included. Patients were treated with ZA (4 mg every 4 weeks for 18 months). Data were collected at baseline and 3, 6, 9, 12, 15 and 18 months after the beginning of treatment. Serum levels of bone alkaline phosphtase (BALP), aminoterminal propeptide of procollagen type I (P1NP) and beta-isomer of carboxiterminal telopeptide of collagen I (ß-CTX) were analysed at all points in the study. Data on disease progression, SREs development and survival were recorded. RESULTS: Cox regression models with clinical data and bone markers showed that the levels of the three markers studied were predictive of survival time, with ß-CTX being especially powerful, in which a lack of normalisation in visit 1 (3 months after the beginning of treatment) showed a 6.3-times more risk for death than in normalised patients. Levels of these markers were also predictive for SREs, although in this case BALP and P1NP proved to be better predictors. We did not find any relationship between bone markers and disease progression. CONCLUSION: In patients with PCa and bone metastases treated with ZA, ß-CTX and P1NP can be considered suitable predictors for mortality risk, while BALP and P1NP are appropriate for SREs. The levels of these biomarkers 3 months after the beginning of treatment are especially important.

[Prognostic factors and functional imaging in rectal cancer]. / Factores pronósticos e imagen funcional del cáncer de recto.

The outcome of treatment for rectal cancer in recent years has been improved by diverse advances in the field of surgery and in neoadjuvant oncologic therapies. Heald's introduction of the concept of the mesorectum as an anatomical unit (total mesorectal excision) in 1982 and the generalization of preoperative radiochemotherapy have improved the prognosis in a significant number of patients. Owing to these advances, it has become necessary for imaging studies to define a series of prognostic factors for tumors, both before and after neoadjuvant treatment, to make it possible to tailor treatment for individual patients with rectal tumors. On the other hand, the advent of functional and molecular imaging techniques has provided a way to study a series of distinctive tumor characteristics in vivo, including the angiogenesis, metabolism, or cellularity of rectal tumors, and these techniques are making a growing contribution to the prognosis, staging, treatment planning, and evaluation of the response to therapy in patients with rectal cancer.

Quality indicators and excellence requirements for a multidisciplinary lung cancer tumor board by the Spanish Lung Cancer Group.

Multidisciplinary care is needed to decide the best therapeutic approach and to provide optimal care to patients with lung cancer (LC). Multidisciplinary teams (MDTs) are optimal strategies for the management of patients with LC and have been associated with better outcomes, such as an increase in quality of life and survival. The Spanish Lung Cancer Group has promoted this review about the current situation of the existing national LC-MDTs, which also offers a set of excellence requirements and quality indicators to achieve the best care in any patient with LC. Time and sufficient resources; leadership; administrative and institutional support; and recording of activity are key factors for the success of LC-MDTs. A set of excellence requirements in terms of staff, resources and organization of the LC-MDT have been proposed. At last, a list of quality indicators has been agreed to achieve and measure the performance of current LC-MDTs.

RENORT: a project to analyze patterns of care in radiation oncology in Spain.

PURPOSE: RENORT is an application (app) developed to assess the role of radiotherapy in the treatment of cancer using the oncology information systems (OIS). METHODS/PATIENTS: The RENORT app was used to analyze the data for all patients seen and/or treated at six radiation oncology departments in Spain in 2019. This app can be used to extract the demographic data, treatment sequence, disease status, and radiotherapy treatments from the ARIA and Mosaiq OIS. RESULTS: A total of 6564 treatments were performed at these six centers in 2019. Most patients (56.9%) were males (females 43.1%). The mean patient age was 64.9 years. The most common treatment types and sites were as follows: metastases/palliative care (25.9%), followed by breast (19.0%), genitourinary (13.7%), lung (10.1%), head and neck (6.0%), rectal (6.0%), gynecological (4.9%), and other (< 4%) cancers. Distribution by disease stage was as follows: breast cancer: 75.5% early stage (stages 0, I, and II); lung: 63.1% advanced stage (III and IV); and head and neck: 72.1% advanced. Treatment intent was curative in 76.5% of cases and palliative in 23.5%. The most common techniques were intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) (41.4%), followed by three-dimensional conformal radiation therapy (3D-CRT) (39.2%); stereotactic body radiotherapy (SBRT) (8.1%); brachytherapy (5.5%); radiosurgery (2.1%); fractionated stereotactic radiotherapy to the brain (1.4%); and intraoperative radiotherapy (1.4%). Hypofractionation was used in 62.3% of curative treatments (mean number of fractions = 16.5). CONCLUSIONS: RENORT is a free app that is available for the two main oncology information systems used in most radiation oncology departments. This app has demonstrated the capacity to extract data from these systems, which in turns allows for a comprehensive analysis and better understanding of the role of radiotherapy in the treatment of cancer.

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.

Consensus on management of castration-resistant prostate cancer on behalf of the Urological Tumours Working Group (URONCOR) of the Spanish Society of Radiation Oncology.

BACKGROUND: The knowledge in the field of castration-resistant prostate cancer (CRPC) is developing rapidly, with emerging new therapies and advances in imaging. Nonetheless, in multiple areas there is still a lack of or very limited evidence, and clear guidance from clinicians regarding optimal strategy is required. METHODS: A modified Delphi method, with 116 relevant questions divided into 7 different CRPC management topics, was used to develop a consensus statement by the URONCOR group. RESULTS: A strong consensus or unanimity was reached on 93% of the proposed questions. The seven topics addressed were: CRPC definition, symptomatic patients, diagnosis of metastasis, CRPC progression, M0 management, M1 management and sequencing therapy, and treatment monitoring. CONCLUSIONS: The recommendations based on the radiation oncology experts' opinions are intended to provide cancer specialists with expert guidance and to standardise CRPC patient management in Spain, facilitating decision-making in different clinically relevant issues regarding CRPC patients.

Survival after biochemical failure in prostate cancer treated with radiotherapy: Spanish Registry of Prostate Cancer (RECAP) database outcomes.

INTRODUCTION: The clinical course in patients with prostate cancer (PCa) after biochemical failure (BF) has received limited attention. This study analyzes survival time from recurrence, patterns of progression, and the efficacy of salvage therapies in patients treated with radical or postoperative radiotherapy (RT). METHODS: This is a multicenter retrospective comparative study of 1135 patients diagnosed with BF and treated with either radical (882) or postoperative (253) RT. Data correspond to the RECAP database. Clinical, tumor, and therapeutic characteristics were collected. Descriptive statistics, survival estimates, and comparisons of survival rates were calculated. RESULTS: Time to BF from initial treatment (RT or surgery) was higher in irradiated patients (51 vs 37 months). At a median follow-up of 102 months (14-254), the 8-year cause-specific survival (CSS) was 80.5%, without significant differences between the radical (80.1%) and postoperative (83.4%) RT groups. The 8-year metastasis-free survival rate was 57%. 173 patients (15%) died of PCa and 29 (2.5%) of a second cancer. No salvage therapy was given in 15% of pts. Only 5.5% of pts who underwent radical RT had local salvage treatment and 71% received androgen deprivation (AD) ± chemotherapy. The worst outcomes were in patients who developed metastases after BF (302 pts; 26.5%) and in cases with a Gleason > 7. CONCLUSIONS: In PCa treated with radiotherapy, median survival after BF is relatively long. In this sample, no differences in survival rates at 8-years have been found, regardless of the time of radiotherapy administered. AD was the most common treatment after BF. Metastases and high Gleason score are adverse variables. To our knowledge, this is the first study to compare outcomes after BF among patients treated with primary RT vs. those treated with postoperative RT and to evaluate recurrence patterns, treatments administered, and causes of death. The results allow avoiding overtreatment, improving quality of life, without negatively affecting survival.

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.

Adjuvant versus salvage radiotherapy in prostate cancer: multi-institutional retrospective analysis of the Spanish RECAP database.

PURPOSE: To compare adjuvant radiotherapy (ART) to salvage radiotherapy (SRT) after radical prostatectomy (RP) in a cohort of prostate cancer (PCa) patients. The primary aim was to comparatively assess 2- and 5-year biochemical relapse-free survival (BRFS). A secondary aim was to identify predictors of survival. PATIENTS AND METHODS: Data were acquired from the RECAP database, a population-based prostate cancer registry in Spain. Inclusion criteria included RP (with or without lymphadenectomy) followed by ART or SRT. A total of 702 patients were analyzed. Pre-RT PSA values (>0.5 vs. ≤0.5 ng/ml), pathological stage (T1-2 vs. T3-4), post-surgical Gleason score (≤7 vs. 8-10), margin status (positive vs. negative), hormonal treatment (yes vs. no), and RT dose (≤66 Gy vs. >66 Gy) were evaluated to assess their impact on BRFS. RESULTS: The mean patient age in the ART and SRT groups, respectively, was 64 years (range 42-82) and 64.8 years (range 42-82). Median follow-up after RT in the whole sample was 34 months (range 3-141). A total of 702 patients were included: 223 (31.8%) received ART and 479 (68.2%) SRT. BRFS rates (95% CI) in the ART and SRT groups at months 24 and 60 were, respectively: 98.1% (95.9-100.0%) vs. 91.2% (88.2-94.2%) and 84.5% (76.4-92.6%) vs. 74.0% (67.4-80.7%) (p = 0.004). No significant differences in OS were observed (p = 0.053). The following variables were significant predictors of biochemical recurrence in the SRT group: (1) positive surgical margin status (p = 0.049); (2) no hormonotherapy (p = 0.03); (3) total prostate dose ≤66 Gy (p = 0.004); and pre-RT PSA ≥0.5 ng/ml (p = 0.013). CONCLUSIONS: This is the first nationwide study in Spain to evaluate a large cohort of PCa patients treated with RP followed by postoperative RT. ART yielded better 2- and 5-year BRFS rates, although OS was equivalent. These findings are consistent with most other published studies and support ART in patients with adverse prognostic characteristics after radical prostatectomy. Prospective trials are needed to compare immediate ART to early SRT to better determine their relative benefits.

Demand for radiotherapy in Spain.

AIM: Assessing the demand for radiotherapy in Spain based on existing evidence to estimate the human resources and equipment needed so that every person in Spain has access to high-quality radiotherapy when they need it. MATERIAL AND METHODS: We used data from the European Cancer Observatory on the estimated incidence of cancer in Spain in 2012, along with the evidence-based indications for radiotherapy developed by the Australian CCORE project, to obtain an optimal radiotherapy utilisation proportion (OUP) for each tumour. RESULTS: About 50.5 % of new cancers in Spain require radiotherapy at least once over the course of the disease. Additional demand for these services comes from reradiation therapy and non-melanoma skin cancer. Approximately, 25-30 % of cancer patients with an indication for radiotherapy do not receive it due to factors that include access, patient preference, familiarity with the treatment among physicians, and especially resource shortages, all of which contribute to its underutilisation. CONCLUSIONS: Radiotherapy is underused in Spain. The increasing incidence of cancer expected over the next decade and the greater frequency of reradiations necessitate the incorporation of radiotherapy demand into need-based calculations for cancer services planning.

Management of prostate cancer patients following radiation therapy after radical surgery referred from urology to radiation oncology departments in Spain.

PURPOSE: To define usual clinical management of prostate cancer (PCa) patients following postoperative radiation therapy (RT) (adjuvant or salvage) and its evolution over time in radiation oncology (RO) departments in Spain. METHODS: An epidemiological, cross-sectional, multicentre study was conducted. 567 PCa patients that had undergone radical prostatectomy (RP) and received postoperative RT between February and December of both 2006 and 2011 participated in the study. In patients from 2006, health-related quality of life (HRQoL) was assessed using the EPIC questionnaire. Investigators completed a specific survey on two clinical cases of adjuvant and salvage RT. RESULTS: 70.6 % of patients received salvage RT versus 29.4 % who received adjuvant RT; no significant differences were found in terms of frequency for each procedure between both the years. Regarding the survey, a positive surgical margin was the main criteria used in adjuvant RT decision making. In terms of salvage RT scenario, 85.7 % of the investigators stated that adjuvant RT should have been offered instead, 81.4 % of the investigators agreed on a PSA score >0.2 ng/mL as the main criteria for identifying biochemical recurrence after RP, and 67.4 % of investigators did not consider any PSA score for ruling out salvage RT treatment. CONCLUSIONS: Most patients are referred to RO departments to receive salvage RT. Despite the publication of three IA evidence level randomized clinical trials, the patterns for using adjuvant and salvage RT did not change from 2006 to 2011, although patients' profile did. A consensus regarding postoperative RT indications should be reached in order to correct this controversial situation.

Androgen deprivation and radiotherapy in patients with prostate cancer and cardiovascular risk factors: clinical controversies.

INTRODUCTION: Recent reports of an association between androgen deprivation treatment (ADT) and increased risk of cardiovascular (CV) events have generated debate on the use of ADT in patients with prostate cancer (PCa) and CV comorbidities. This study aims to describe the recommendations of radiation oncologists in the most controversial aspects of treating such patients. MATERIALS AND METHODS: The project involved 61 oncologists and comprised 4 phases: (1) selection of the most controversial aspects in the administration of ADT in patients with a history of CV disease and PCa, (2) selection of the most relevant published evidence, (3) preparation of case reports, (4) critical reading and discussion. Therapeutic procedures were classified as "highly recommendable", "recommendable in some cases", or "not recommendable/not applicable". For each item assessed, the mode of the scores given, and the percentage of experts who selected each score were calculated. RESULTS: The panel recommended that patients with high/very high-risk PCa and a history of CV disease should receive gonadotropin-releasing hormone agonists (GnRHa). ADT with GnRHa for 24-36 months + radiotherapy (RT) was also considered highly recommendable. In intermediate-risk PCa and a history of CV, ADT with GnRHa for 6-8 months + RT, and not administering ADT were considered highly recommendable. CONCLUSIONS: Studies are necessary to investigate the impact of ADT on CV mortality in patients who benefit most from adjuvant ADT in terms of survival. In the meantime, the experts believe that clinical evidence on the proven therapeutic benefits of ADT should override concerns about potential cardiac toxicity.

Infrastructures, treatment modalities, and workload of radiation oncology departments in Spain with special attention to prostate cancer.

AIM: The purpose of the study was to describe infrastructures, treatment modalities, and workload in radiation oncology (RO) in Spain, referred particularly to prostate cancer (PC). METHODS: An epidemiologic, cross-sectional study was performed during 2008-2009. A study-specific questionnaire was sent to the 108 RO-registered departments. RESULTS: One hundred and two departments answered the survey, and six were contacted by telephone. Centers operated 236 treatment units: 23 (9.7 %) cobalt machines, 37 (15.7 %) mono-energetic linear accelerators, and 176 (74.6 %) multi-energy linear accelerators. Sixty-one (56.4 %) and 33 (30.5 %) departments, respectively, reported intensity-modulated radiation therapy (IMRT) and image-guided RT (IGRT) capabilities; three-dimensional-conformal RT was used in 75.8 % of patients. Virtual simulators were present in 95 departments (88.0 %), 35 use conventional simulators. Fifty-one departments (47.2 %) have brachytherapy units, 38 (35.2 %) perform prostatic implants. Departments saw a mean of 24.9 new patients/week; the number of patients treated annually was 102,054, corresponding to 88.4 % of patients with a RT indication. In 56.5 % of the hospitals, multidisciplinary teams were available to treat PC. CONCLUSIONS: Results provide an accurate picture of current situation of RO in Spain, showing a trend toward the progressive introduction of new technologies (IMRT, IGRT, brachytherapy).