Recommendations on the Treatment of Metastatic Hormone-Sensitive Prostate Cancer: Patient Selection.

The standard treatment for metastatic hormone-sensitive prostate cancer (mHSPC) is now a combination of androgen deprivation therapy plus an androgen receptor-targeted therapy (abiraterone, apalutamide, enzalutamide or darolutamide), with or without chemotherapy (docetaxel). The selection of suitable patients for each therapeutic approach has become a determining factor to ensure efficacy and minimize side effects. This article combines recent clinical evidence with the accumulated experience of experts in medical oncology, radiation oncology and urology, to provide a comprehensive view and therapeutic recommendations for mHSPC.

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.

Prospective study of HDR brachytherapy (BT), external beam radiotherapy (EBRT) and androgen deprivation therapy (ADT): 10-years experience of an MRI-guided approach.

OBJECTIVES: To evaluate the predictive factors for biochemical failure and distant metastases in a prospective cohort of patients with localized prostate cancer treated with the combination of HDR BT and EBRT. METHODS AND MATERIALS: Patients with intermediate (IR) or high-risk (HR) prostate adenocarcinoma received a single fraction of HDR of 15 Gy combined with RT of 37.5 Gy in 15 fractions. ADT duration was used depending on risk-group. Descriptive analyses were performed. Univariate and multivariate Hazard Ratios were obtained. Finally, the Kaplan-Meier model was used to describe the survival of the events of interest. RESULTS: 309 patients were treated prospectively (199 were IR and 110 HR). Median age was 72 years; 58.3 % were MRI stage ≤ T2c, 34.1 % T3a and 7.6 % T3b; ISUP-grade 1-3 in 78.9 % and ISUP 4-5 in 21.1 %. 71.8 % of patients had ≤ 50 % positive-cores in biopsy and 28.2 % had > 50 %. Median pre-treatment PSA was 9.9 ng/mL. After a median follow-up of 88 months, 41 patients presented biochemical failure and 18 developed distant metastases. Multivariate cox-regression analyses found that MR-T3b Stage (HR 3.88, p = 0.001) and ADT use (HR 3.99, p = 0.03) were the only predictive factors for biochemical failure and the number of positive cores (>50 %) the only independent predictive factor of distant metastases (HR 4.36, p = 0.002). CONCLUSIONS: Patients with mpMRI evidence of invasion of the SV and involvement of more than 50% of the cores in the prostate biopsy are patients with a higher risk of presenting a biochemical recurrence or developing metastasis due to their prostate cancer, respectively.

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.

Stereotactic body radiotherapy for early-stage non-small cell lung cancer: a multicentre study by the Oncologic Group for the Study of Lung Cancer (Spanish Radiation Oncology Society).

PURPOSE/OBJECTIVE(S): Stereotactic body radiotherapy (SBRT) has become the standard of care for patients with medically inoperable early-stage non-small cell lung cancer (NSCLC) and for patients who refuse surgery. The aim of this study was to evaluate the effectiveness and safety of primary SBRT in patients with early-stage NSCLC. MATERIALS/METHODS: Retrospective multicenter study of 397 patients (416 primary lung tumours) treated with SBRT at 18 centres in Spain. 83.2% were men. The median age was 74.4 years. In 94.4% of cases, the tumour was inoperable. The pathological report was available in 54.6% of cases. SPSS vs 22.0. was used to perform all statistical analyses. RESULTS: Complete response was obtained in 53.6% of cases. Significant prognostic factors were standard CT planning (p = 0.014) and 4D cone beam CT (p = 0.000). Acute and chronic toxicity ≥ grade 3 was observed in 1.2% of cases. At a median follow-up of 30 months, local relapse was 9.6%, lymph node relapse 12.8%, distant metastasis 16.6%, and another lung tumour 11.5%. Complete response was the only significant prognostic factor for local relapse (p = 0.012) and distant metastasis (p = 0.001). The local relapse-free survival was 88.7%. The overall survival was 75.7%. The cancer-specific survival was 92.7%. The disease-free survival was 78.7%. CONCLUSION: SBRT is an effective and well-tolerated treatment option for patients with early-stage lung cancer who are not suitable for surgery. The most important prognostic factor for local and distant recurrence was complete response, which in our sample depended on the type of CT planning and the IGRT technique.

MRI detected extaprostatic extension (EPE) in prostate cancer: Do all T3a patients have the same outcomes?

MRI-detected T3a prostate cancer is a heterogeneous disease. This post-hoc analysis of a prospective trial found that patients with T3a disease presenting obliteration of the recto-prostatic angle, contact-asymmetry of neuro-vascular bundle and periprostatic fat invasion, may be at higher risk of biochemical failure and metastases.

PEACE V - Salvage Treatment of OligoRecurrent nodal prostate cancer Metastases (STORM): a study protocol for a randomized controlled phase II trial.

BACKGROUND: Pelvic nodal recurrences are being increasingly diagnosed with the introduction of new molecular imaging techniques, like choline and PSMA PET-CT, in the restaging of recurrent prostate cancer (PCa). At this moment, there are no specific treatment recommendations for patients with limited nodal recurrences and different locoregional treatment approaches are currently being used, mostly by means of metastasis-directed therapies (MDT): salvage lymph node dissection (sLND) or stereotactic body radiotherapy (SBRT). Since the majority of patients treated with MDT relapse within 2 years in adjacent lymph node regions, with an estimated median time to progression of 12-18 months, combining MDT with whole pelvic radiotherapy (WPRT) may improve oncological outcomes in these patients. The aim of this prospective multicentre randomized controlled phase II trial is to assess the impact of the addition of WPRT to MDT and short-term androgen deprivation therapy (ADT) on metastasis-free survival (MFS) in the setting of oligorecurrent pelvic nodal recurrence. METHODS & DESIGN: Patients diagnosed with PET-detected pelvic nodal oligorecurrence (≤5 nodes) following radical local treatment for PCa, will be randomized in a 1:1 ratio between arm A: MDT and 6 months of ADT, or arm B: WPRT added to MDT and 6 months of ADT. Patients will be stratified by type of PET-tracer (choline, FACBC or PSMA) and by type of MDT (sLND or SBRT). The primary endpoint is MFS and the secondary endpoints include clinical and biochemical progression-free survival (PFS), prostate cancer specific survival, quality of life (QoL), toxicity and time to castration-resistant prostate cancer (CRPC) and to palliative ADT. Estimated study completion: December 31, 2023. DISCUSSION: This is the first prospective multicentre randomized phase II trial assessing the potential of combined WPRT and MDT as compared to MDT alone on MFS for patients with nodal oligorecurrent PCa. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03569241, registered June 14, 2018, ; Identifier on Swiss National Clinical Trials Portal (SNCTP): SNCTP000002947, registered June 14, 2018.

Prognostic factors in neoadjuvant treatment followed by surgery in stage IIIA-N2 non-small cell lung cancer: a multi-institutional study by the Oncologic Group for the Study of Lung Cancer (Spanish Radiation Oncology Society).

PURPOSE: To evaluate the prognostic factors associated with survival in patients treated with neoadjuvant treatment [chemoradiotherapy (CRT) or chemotherapy] followed by surgery (CRTS) in patients with stage IIIA-N2 non-small cell lung cancer (NSCLC). METHODS: A retrospective study was conducted of 118 patients diagnosed with stage T1-T3N2M0 NSCLC and treated with CRTS at 14 hospitals in Spain between January 2005 and December 2014. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method and compared using the log-rank test. Cox regression analysis was performed. RESULTS: Surgery consisted of lobectomy (74.5% of cases), pneumectomy (17.8%), or bilobectomy (7.6%). Neoadjuvant treatment was CRT in 62 patients (52.5%) and chemotherapy alone in 56 patients (47.5%). Median follow-up was 42.5 months (5-128 months). 5-year OS and PFS were 51.1% and 49.4%, respectively. The following variables were independently associated with worse OS and PFS: pneumonectomy (vs. lobectomy); advanced pathologic T stage (pT3 vs. pT0-pT2); and presence of persistent N2 disease (vs. ypN0-1) in the surgical specimen. CONCLUSIONS: In this sample of patients with stage IIIA-N2 NSCLC treated with CRTS, 5-year survival (both OS and PFS) was approximately 50%. After CRTS, the patients with the best prognosis were those whose primary tumour and/or mediastinal nodal metastases were downstaged after induction therapy and those who underwent lobectomy. These findings provide further support for neoadjuvant therapy followed by surgery in selected patients.

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.

Multiparametric MRI for prostate cancer: a national survey of patterns of practice among radiation oncologists in Spain.

PURPOSE: To investigate patterns of practice among Spanish radiation oncologists in the use of multiparametric magnetic resonance imaging (mpMRI) for the treatment of prostate cancer (PCa). We evaluated (1) access to mpMRI, (2) current clinical practices, and (3) physician expectations of mpMRI. METHODS: Cross-sectional survey of 118 radiation oncologists at 75 Radiation Oncology (RO) departments in Spain. RESULTS: A total of 55 radiation oncologists from 52 RO departments (52/75; 69%) completed the survey. Prostate mpMRI is performed at 94.5% of the centres that provided data. The most common indications for mpMRI in routine clinical practice were: (1) detection/localization of the tumour prior to second biopsy (82.7%), (2) cancer staging (80.8%), and (3) detection of recurrence after definitive treatment (80.8%). Most respondents (72.7%) reported modifying the primary radiotherapy treatment when mpMRI findings indicate a more advanced T stage with a resultant change in the risk group. Most respondents (90.5%) treat macroscopic local recurrence after prostatectomy with high doses, ranging from 71 to 83 Gy; in 37.7% of cases, the full dose is delivered to the entire prostate bed. In pelvic nodal recurrence, more than half (59.3%) of the respondents reported performing elective pelvic radiotherapy, including the prostate bed, with a boost to the involved nodes. CONCLUSIONS: This survey shows that prostate mpMRI is routinely used by radiation oncologists in Spain in a wide range of clinical scenarios. The findings reported here underscore the need to standardize treatment protocols for definitive and salvage radiotherapy in patients evaluated with mpMRI.

Neoadjuvant treatment followed by surgery versus definitive chemoradiation in stage IIIA-N2 non-small-cell lung cancer: A multi-institutional study by the oncologic group for the study of lung cancer (Spanish Radiation Oncology Society).

OBJECTIVES: The role of surgery in stage IIIA-N2 non-small cell lung cancer (NSCLC) is an actively debated in oncology. To evaluate the value of surgery in this patient population, we conducted a multi-institutional retrospective study comparing neoadjuvant chemoradiotherapy or chemotherapy plus surgery (CRTS) to definitive chemoradiotherapy (dCRT). MATERIAL AND METHODS: A total of 247 patients with potentially resectable stage T1-T3N2M0 NSCLC treated with either CRTS or dCRT between January 2005 and December 2014 at 15 hospitals in Spain were identified. A centralized review was performed to ensure resectability. A propensity score matched analysis was carried out to balance patient and tumor characteristics (n = 78 per group). RESULTS: Of the 247 patients, 118 were treated with CRTS and 129 with dCRT. In the CRTS group, 62 patients (52.5%) received neoadjuvant CRT and 56 (47.4%) neoadjuvant chemotherapy. Surgery consisted of either lobectomy (97 patients; 82.2%) or pneumonectomy (21 patients; 17.8%). In the matched samples, median overall survival (OS; 56 vs 29 months, log-rank p = .002) and progression-free survival (PFS; 46 vs 15 months, log-rank p < 0.001) were significantly higher in the CRTS group. This survival advantage for CRTS was maintained in the subset comparison between the lobectomy subgroup versus dCRT (OS: 57 vs 29 months, p < 0.001; PFS: 46 vs 15 months, p < 0.001), but not in the comparison between the pneumonectomy subgroup and dCRT. CONCLUSION: The findings reported here indicate that neoadjuvant chemotherapy or chemoradiotherapy followed by surgery (preferably lobectomy) yields better OS and PFS than definitive chemoradiotherapy in patients with resectable stage IIIA-N2 NSCLC.

Recent developments in radiotherapy for small-cell lung cancer: a review by the Oncologic Group for the Study of Lung Cancer (Spanish Radiation Oncology Society).

Small-cell lung cancer (SCLC) accounts for 13% of all lung tumours. The standard treatment in patients with limited-stage disease is radiotherapy combined with chemotherapy. In extensive SCLC, the importance of consolidation thoracic radiotherapy in patients with a good treatment response has become increasingly recognized. In both limited and extensive disease, prophylactic cranial irradiation is recommended in patients who respond to treatment. New therapeutic approaches such as immunotherapy are being increasingly incorporated into the treatment of SCLC, although more slowly than in non-small cell lung cancer (NSCLC). Diverse radiation dose and fractionation schemes, administered in varying combinations with these new drugs, are being investigated. In the present study we review and update the role of radiotherapy in the treatment of SCLC. We also discuss the main clinical trials currently underway in order to identify future trends.

Targeted therapy combined with radiotherapy in non-small-cell lung cancer: a review of the Oncologic Group for the Study of Lung Cancer (Spanish Radiation Oncology Society).

In recent years, major advances in our understanding of the molecular biology of lung cancer, together with significant improvements in radiotherapy technologies, have revolutionized the treatment of non-small cell lung cancer (NSCLC). This has led to the development of new therapies that target molecular mutations specific to each tumor type, acting on the cell surface antigens or intracellular signaling pathways, or directly affecting cell survival. At the same time, ablative dose radiotherapy can be delivered safely in the context of metastatic disease. In this article, the GOECP/SEOR (Oncological Group for Study of Lung Cancer/Spanish Society of Radiation Oncology) reviews the role of new targeted therapies used in combination with radiotherapy in patients with locally advanced (stage III) NSCLC and in patients with advanced, metastatic (stage IV) NSCLC.

Evidence-based recommendations of postoperative radiotherapy in lung cancer from Oncologic Group for the Study of Lung Cancer (Spanish Radiation Oncology Society).

Locally advanced non-small cell lung cancer (NSCLC) is a diversified illness in which postoperative radiation therapy (PORT) for complete resection with positive hiliar (pN1) and/or mediastinal (pN2) lymph nodes is controversial. Although several studies have shown that PORT has beneficial effects, randomized trials are needed to demonstrate its impact on overall survival. In this review, the Spanish Radiation Oncology Group for Lung Cancer describes the most relevant literature on PORT in NSCLC patients stage pN1-2. In addition, we have outlined the current recommendations of different national and international clinical guidelines and have also specified practical issues regarding treatment volume definition, doses and fractionation.