Is There an Opportunity to De-Escalate Treatments in Selected Patients with Metastatic Hormone-Sensitive Prostate Cancer?

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.

Vitamin D and prostate cancer prevention.

Vitamin D is a hot topic nowadays, especially its relationship with cancer prevention. Normally, vitamin D is associated with bone health principally, but the new research has discovered an impact on immune function and cellular signaling, even in same studies talk about a hormone, however, the most important relationship is its implication in cellular processes, inhibiting cancer growth. For now, the recent studies are oriented about a benefit and a cause-effect relationship between prostate cancer and normal levels of vitamin D. This premise opens a lot of questions in this scenario. This editorial highlighted the most important studies in this area.

Current status of anaplastic thyroid carcinoma.

In this editorial we comment on the article by Pavlidis et al, published in the recent issue of the World Journal of Oncology. We focus on the recent contributions in the management of anaplastic thyroid carcinoma, highlighting the importance of surgery and radiotherapy as first line therapies in its management and the introduction of new systemic therapies beyond chemotherapy, focused on molecular alterations, an essential step in the diagnosis and included in clinical guidelines for the selection of the ideal treatment. In contrast to other neoplasms, immunotherapy, is still beginning in studies of this pathology with encouraging results. Therefore, multimodal management of the pathology together with new drugs seems to be the logical step to increase the survival of this neoplasm.

Pembrolizumab autoimmune related diabetes: Moving forward, keep learning.

Immune checkpoint inhibitors (and more specifically programmed cell death 1/programmed cell death ligand 1 inhibitors as Pembrolizumab) initiated a revolution in the field of melanoma and have now expanded to several tumor subtypes and in increasingly broader clinical contexts, including the adjuvant and neoadjuvant setting, with potentially curable patients and prolonged survival. The side effects related to these drugs include a wide spectrum of manifestations, with endocrinological adverse events being some of the most frequent. Pembrolizumab-induced type 1 diabetes mellitus is an infrequent but potentially serious and not clearly reversible side effect that possesses characteristic clinical features and has high morbidity and mortality, with a chronic impact on quality of life. The etiopathogenesis of this phenomenom needs to be further investigated and a collaborative effort through the involvement of oncologists and other medical specialists is necessary for the correct identification and management of patients at risk.

Liquid biopsy to personalize treatment for metastatic prostate cancer.

Liquid biopsy is an innovative approach that provides a more complete understanding of treatment response and prognosis in monitoring metastatic prostate cancer. It complements invasive tissue biopsy and involves the assessment of various biomarkers in body fluids such as blood, semen, and urine. Liquid biopsy analyzes circulating tumor cells, extracellular vesicles, circulating tumor DNA, and the secretome. This is particularly important given the heterogeneity of prostate cancer and the need for better prognostic biomarkers. Liquid biopsy can personalize the treatment of homonosensitive and castration-resistant metastatic prostate cancer by acting as a predictive and prognostic tool. This review discusses various biomarkers, assay techniques, and potential applications in daily clinical practice, highlighting the exciting possibilities that this emerging field holds for improving patient outcomes.

Management of lateral pelvic lymph nodes in rectal cancer: Is it time to reach an Agreement?

In this editorial, we proceed to comment on the article by Chua et al, addressing the management of metastatic lateral pelvic lymph nodes (mLLN) in stage II/III rectal cancer patients below the peritoneal reflection. The treatment of this nodal area sparks significant controversy due to the strategic differences followed by Eastern and Western physicians, albeit with a higher degree of convergence in recent years. The dissection of lateral pelvic lymph nodes without neoadjuvant therapy is a standard practice in Eastern countries. In contrast, in the West, preference leans towards opting for neoadjuvant therapy with chemoradiotherapy or radiotherapy, that would cover the treatment of this area without the need to add the dissection of these nodes to the total mesorectal excision. In the presence of high-risk nodal characteristics for mLLN related to radiological imaging and lack of response to neoadjuvant therapy, the risk of lateral local recurrence increases, suggesting the appropriate selection of strategies to reduce the risk of recurrence in each patient profile. Despite the heterogeneous and retrospective nature of studies addressing this area, an international consensus is necessary to approach this clinical scenario uniformly.

Feasibility and Acute Toxicity of Hypo-Fractionated Radiotherapy on 0.35T MR-LINAC: The First Prospective Study in Spain.

This observational, descriptive, longitudinal, and prospective basket-type study (Registry #5289) prospectively evaluated the feasibility and acute toxicity of hypo-fractionated radiotherapy on the first 0.35T MR-LINAC in Spain. A total of 37 patients were included between August and December 2023, primarily with prostate tumors (59.46%), followed by pancreatic tumors (32.44%). Treatment regimens typically involved extreme hypo-fractionated radiotherapy, with precise dose delivery verified through quality assurance measures. Acute toxicity assessment at treatment completion revealed manageable cystitis, with one case persisting at the three-month follow-up. Gastrointestinal toxicity was minimal. For pancreatic tumors, daily adaptation of organ-at-risk (OAR) and gross tumor volume (GTV) was practiced, with median doses to OAR within acceptable limits. Three patients experienced gastrointestinal toxicity, mainly nausea. Overall, the study demonstrates the feasibility and safety of extreme hypo-fractionated radiotherapy on a 0.35T MR-LINAC, especially for challenging anatomical sites like prostate and pancreatic tumors. These findings support the feasibility of MR-LINAC-based radiotherapy in delivering precise treatments with minimal toxicity, highlighting its potential for optimizing cancer treatment strategies.

Bridging the gap: Predicting brain metastasis in breast cancer.

Chen et al explored clinicopathological features and prognostic factors, revealing advanced tumor stage, lung metastases, HER-2 overexpression, and triple-negative status as key contributors. Recent research connects astrocytes' role in brain metastasis with signaling pathways and the impact of Trastuzumab on HER-2 tumor survival. Factors such as positive HER2 status, lack of estrogen receptor expression, and liver metastasis are identified as additional risk factors. The routine use of magnetic resonance imaging, insights into gene mutations associated with metastasis, and the role of radiotherapy, including prophylaxis possibilities, is controversial in clinical practice. Understanding these risk factors in a multidisciplinary collaboration is precise for local treatments and targeted therapies, particularly for HER2+ tumors, impacting directly on longer survival.

MR-LINAC, a New Partner in Radiation Oncology: Current Landscape.

Technological advances in radiation oncology are oriented towards improving treatment precision and tumor control. Among these advances, magnetic-resonance-image-guided radiation therapy (MRgRT) stands out, with technological advances to deliver targeted treatments adapted to a tumor's anatomy on the day while minimizing incidental exposure to organs at risk, offering an unprecedented therapeutic advantage compared to X-ray-based IGRT delivery systems. This new technology changes the traditional workflow in radiation oncology and requires an evolution in team coordination to administer more precise treatments. Once implemented, it paves the way for newer indication for radiation therapy to safely deliver higher doses than ever before, with better preservation of healthy tissues to optimize patient outcomes. In this narrative review, we assess the technical aspects of the novel linear accelerators that can deliver MRgRT and summarize the available published experience to date, focusing on oncological results and future challenges.

Docetaxel Provides Oncological Benefits in the Era of New-Generation Androgen Receptor Inhibitors - or Is Three a Crowd?

In recent years, several systemic therapies have been introduced for metastatic hormone-sensitive prostate cancer, including androgen deprivation therapy (ADT) combined with docetaxel (Doc) and/or new-generation androgen receptor signaling inhibitors (ARSI). Trials evaluating ADT + ARSI have consistently demonstrated an overall survival (OS) benefit for doublet therapy over ADT alone. Similarly, the STOPCaP meta-analysis showed an OS benefit in favor of ADT + Doc versus ADT alone. ARSI, Doc, and ADT have different antitumor mechanisms, thus potentiating the effect of combination therapy. Two randomized trials showed that the addition of ARSI to ADT + Doc improves OS, especially for synchronous high-volume disease. However, the real question about triplet therapy remains unanswered: whether combining Doc with ARSI improves outcomes compared to ADT + ARSI. As there are no head-to-head comparisons, this narrative review aims to summarize the current evidence regarding triplet therapy versus doublet therapy including ADT+ ARSI.

Prostate Cancer: Management of Biochemical Recurrence after Surgery

Radical prostatectomy (RP) is one of the primary treatment options for localised prostate cancer (PCa). Despite its curativeintent, 1/3 of patients will experience biochemical recurrence (BCR) during follow-up. Experts have devoted efforts to associatethe influence of each individual factor with the risk of BCR to select the optimal treatment for each patient. Optimal managementmust aim to find a balance between delaying the onset of metastatic disease and overtreating an indolent disease with treatmentsthat can affect quality of life of the patients. Thus far, effective treatment options for men with BCR remain controversial interms of ideal treatment timing (adjuvant vs. salvage), radiotherapy (RT) fields and doses, selection and duration of systemictherapy and potential synergies between treatments and their therapeutic sequencing. Next-generation imaging techniques, suchas Prostate-Specific Membrane Antigen Positron Emission Tomography, are used for early detection of disease progression andexact site of recurrence or progression, thereby enhancing decision making for future disease management. In this review, weevaluate available evidence of controversial topics regarding BCR after RP and explore future directions, such as prognosticand/or predictive factors of response, genetic panels, second-generation hormone treatments, ultra-hypofractionated RT andongoing clinical trials in this clinical scenario. (AU)

Jorge clinical study: 10-year outcomes of risk-adapted radiotherapy defined by multiparametric MRI for prostate cancer.

PURPOSE: To analyze the 10-year biochemical relapse-free survival (BRFS), locoregional relapse-free survival (LRFS), metastasis-free survival (MFS), and overall survival (OS) in patients diagnosed with localized prostate adenocarcinoma treated with radiotherapy (RT) ± androgen deprivation therapy (ADT), according to the risk groups based on multiparametric magnetic resonance imaging (mpMRI) instead of digital rectal exam (DRE). METHODS: We retrospectively evaluated 140 consecutive patients diagnosed with localized prostate adenocarcinoma, stratified into different risk groups-low (LR), intermediate (IR), and high (HR) by mpMRI results. RESULTS: After a median follow-up of 104 months, in LR group (n = 15), 10-year BRFS was 86.7%, 10-year LRFS was 86.7%, 10-year MFS was 93.3%, and 10-year OS was 100%. In IR group (n = 80), 10-year BRFS was 80.5%, 10-year LRFS was 86.1%, 10-year MFS was 92.6%, and 10-year OS was 76%. In HR group (n = 45), 10-year BRFS was 72.8%, 10-year LRFS was 78.7%, 10-year MFS was 82.1%, and 10-year OS was 77% (2 deaths from prostate cancer). According to mpMRI results, 36 (25.7%) patients change the risk group and 125 (89.28%) patients change the TNM stage. There was a trend for higher metastatic relapse in patients who switched from IR to HR (due to mpMRI) versus the patients who remained in the IR (20%, vs. 1.81% p = 0.059). Multivariate analysis showed that locoregional relapse was strongly associated with distant relapse (OR = 9.28; 95%CI: 2.60-33.31). There were no cases of acute grade 3 toxicity. Late grade 3 genitourinary, gastrointestinal, and sexual toxicity were 2.8%, 0.7%, and 1.2%, respectively. CONCLUSION: This is the first study with a 10-year median follow-up of patients diagnosed with localized prostate cancer treated with radiotherapy according to the risk groups established by mpMRI. Our findings show that mpMRI is a key tool to diagnose and establish risk groups in these patients, to optimize their treatment.

Total neoadjuvant therapy approach for the treatment of locally advanced rectal cancer. Where do we stand?

BACKGROUND: for the management of locally advanced rectal cancer (LARC), initial treatment with neoadjuvant chemoradiotherapy followed by surgery and chemotherapy in selected patients is considered one of the recommended options by the main international clinical guidelines. Nonetheless, the administration of all chemotherapy before definitive treatment (total neoadjuvant therapy or TNT) is an optimal alternative with a growing level of evidence that must be evaluated in multidisciplinary boards. This review summarizes the available data and controversies in this scenario. SUMMARY: we have analyzed the characteristics of the main published studies that assess the use of TNT in patients with LARC, evaluating their inclusion criteria and distinguishing between the employed radiotherapy fractionations, systemic agents, timing, and the implications of these treatments in regard to surgery and long-term oncological results. Our aim is to describe the evidence that supports the use of a specific regime in everyday clinical practice. KEY POINTS: there is solid evidence for the use of TNT in patients with LARC. There is no data indicating the superiority of one specific TNT scheme among all the existing options. International clinical guidelines leave the door open to choose the most adequate treatment based on the clinical and pathological characteristics of each patient. This review shows the different approaches to TNT and assesses the best options based on clinical evidence.

Coronavirus disease 2019 and lung cancer: where are we?

Oncology patients are more susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection due to hospital contact and an immunological system that can be compromised by antineoplastic therapy and supportive treatments. Certain similarities have been described in the physiopathology of coronavirus disease 2019 (COVID-19) and lung cancer (LC) that may explain the higher probability of these patients of developing a more serious disease with more frequent hospitalizations and even death, especially with the addition of smoking, cardiovascular and respiratory comorbidities, old age and corticosteroids use. Pre-existing lesions and cancer therapies change the normal architecture of the lungs, so diagnostic scales such as COVID-19 Reporting and Data System (CO-RADS) are of vital importance for a correct diagnosis and patient homogenization, with a high inter-observer correlation. Moreover, anticancer treatments have required an adaptation to reduce the number of visits to the hospital [hypofractionated radiotherapy (RT), larger intervals between chemotherapy cycles, delay in follow-up tests, among others]. In a way, this has also caused a delay in the diagnosis of new cancers. On the other hand, vaccination has had a positive impact on the mortality of these patients, who maintain a similar seroprevalence to the rest of the population, with a similar impact in mortality.

PEACE V-Salvage Treatment of OligoRecurrent nodal prostate cancer Metastases (STORM): Acute Toxicity of a Randomized Phase 2 Trial.

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.

Stereotactic body radiation therapy after radical prostatectomy: current status and future directions.

PURPOSE: Around 40% of men with intermediate-risk or high-risk prostate cancer will experience a biochemical recurrence after radical prostatectomy (RP). The aim of this review is to describe both toxicity and oncological outcomes following stereotactic body radiation therapy (SBRT) delivered to the prostate bed (PB). METHOD: In april 2023, we performed a systematic review of studies published in MEDLINE or ClinicalTrials.gov according to Preferred Reporting Items for Systematic Reviews, using the keywords "stereotactic radiotherapy" AND "postoperative" AND "prostate cancer". RESULTS: A total of 14 studies assessing either adjuvant or salvage SBRT to the whole PB or macroscopic local recurrence (MLR) within the PB, and SBRT on radiorecurrent MLR within the PB were included. Doses delivered to either whole PB or MLR between 30 to 40 Gy are associated with a low rate of late grade ≥ 2 genitourinary (GU) toxicity, ranging from 2.2 to 15.1%. Doses above 40 Gy are associated with increased rate of late GU toxicity, raising up to 38%. Oncological outcomes should be interpreted with caution, due to both short follow-up, heterogeneous populations and androgen deprivation therapy (ADT) use. CONCLUSION: PB or MLR SBRT delivered at doses up to 40 Gy appears safe with relatively low late severe GU toxicity rates. Caution is needed with dose-escalated RT schedules above 40 Gy. Further prospective trials are eagerly awaited in this disease setting.

Total neoadjuvant therapy for locally advanced rectal cancer: a narrative review.

Locally advanced rectal cancer has traditionally been treated with chemoradiotherapy (CRT) followed by surgery and adjuvant chemotherapy. However, a new strategy, total neoadjuvant therapy, involves the administration of CRT and neoadjuvant chemotherapy with the aim of eradicating micrometastases earlier and achieving greater control of the disease. The use of total neoadjuvant therapy has shown higher rates of pathological complete response and resectability compared with CRT, including improved survival. Nevertheless, distant relapse is the main cause of morbidity and mortality in locally advanced rectal cancer. To address this, new biomarkers are being developed to predict disease response.

Novel Approaches in the Systemic Management of High-Risk Prostate Cancer.

Locally advanced prostate cancer comprises approximately 20% of new prostate cancer diagnoses. For these patients, international guidelines recommend treatment with radiotherapy (RT) to the prostate in combination with long-term (2-3 years) androgen deprivation therapy (ADT), or radical prostatectomy in combination with extended pelvic lymph node dissection (PLND) as another treatment option for selected patients as part of multimodal therapy. Improvements in overall survival with docetaxel or an androgen receptor signaling inhibitor have been achieved in patients with metastatic castration sensitive or castration resistant prostate cancer. However, the role of systemic therapy combinations for high risk and/or unfavorable prostate cancer is unclear. In this context, the aim of this review is to assess the current evidence for systemic treatment combinations as part of primary definitive therapy in patients with high-risk localized prostate cancer.