Effect on Overall Survival of Locoregional Treatment in a Cohort of De Novo Metastatic Prostate Cancer Patients: A Single Institution Retrospective Analysis From the Royal Marsden Hospital

Bianchini, Diletta; Lorente, David; Rescigno, Pasquale; Psychopaida, Elena; O’Sullivan, Hazel; Alaras, Mervyn; Kolinsky, Michael; Sumanasuriya, Semini; Fontes, Mariane; Mateo, Joaquín; Pérez-López, Raquel; Tunariu, Nina; Fotiadis, Nikolaos; Kumar, Pardeep; Tree, A.; As, Nicholas van; Khoo, Vincent; Parker, Chris; Eeles, Rosalind; Thompson, Alan; Dearnaley, David P.

doi:10.1016/j.clgc.2017.04.013

Cited by 16 publications

(11 citation statements)

References 25 publications

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“…The trend for longer OS with lower NLR may also be due to the increased immunity seen in patients lower NLR, which may in turn increase the efficacy of therapy by facilitating an abscopal effect, where a response is observed in lesions that are distant from the site of treatment. This effect has been seen with both radiotherapy [ 29 , 30 ], and, more recently, studies have suggested it may occur with radium-223 [ 31 , 32 ]. Regarding prior docetaxel, the trend for OS observed in this study is similar to ALSYMPCA, in which median OS with radium-223 was numerically longer in patients without prior docetaxel (with vs without prior docetaxel: 14.4 vs 16.1 months); however, the hazard ratio of radium-223 to placebo was similar (0.70 vs 0.69) regardless of prior docetaxel [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Three-year follow-up of a phase II study of radium-223 dichloride in Japanese patients with symptomatic castration-resistant prostate cancer and bone metastases

Uemura

Nagamori

et al. 2019

Int J Clin Oncol

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Background Radium-223 is a first-in-class targeted alpha therapy to prolong overall survival (OS) in castration-resistant prostate cancer with bone metastases (mCRPC). The aim of the present analysis was to assess the long-term safety with radium-223 in Japanese patients with mCRPC. Methods Patients with symptomatic mCRPC, ≥ 2 bone metastases and no known visceral metastases received up to 6 injections of radium-223 (55 kBq/kg), one every 4 weeks. Adverse events (AEs) considered to be related to radium-223 were reported until 3 years after the first injection. Pre-specified conditions, such as acute myelogenous leukemia, myelodysplastic syndrome, aplastic anemia, primary bone cancer, or other primary malignancies, were reported regardless of causality. Results Of the 49 patients enrolled in the study, 44 (89.8%) entered the survival follow-up period and 33 (67.3%) died. Throughout the entire study, there were no reports of second primary malignancy or other pre-specified conditions. Eight patients (16.3%) experienced post-treatment drug-related AEs, which were all hematological (anemia and decreased lymphocyte, platelet, and white blood cell counts). No serious post-treatment drug-related AEs were reported. Updated median OS was 19.3 months (95% CI: 14.2, 28.5). Conclusions In Japanese patients with symptomatic mCRPC and bone metastases, radium-223 had a favorable long-term safety profile with no second primary malignancies reported. Taken together with median OS, which was comparable to that in the pivotal phase III ALSYMPCA study, these results support continued benefit from radium-223 in Japanese patients with mCRPC. Electronic supplementary material The online version of this article (10.1007/s10147-018-01389-4) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Three-year follow-up of a phase II study of radium-223 dichloride in Japanese patients with symptomatic castration-resistant prostate cancer and bone metastases

Uemura

Nagamori

et al. 2019

Int J Clin Oncol

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“…In different tumour types, these ablative doses of radiation apart from achieving high local control rates are able to produce the known systemic antitumour activity called the abscopal effect and this phenomenon could at least partially explain the benefit of MDT on the malignant disease course in general (Decaestecker et al, 2014). It is known that the local inflammatory reactions generated by RT activate immune signals and contribute to better antigen cross-presentation leading to CD8+ cytotoxic T-cell activation, converting the irradiated tumour into an immunogenic host and contribute both to the local response to RT and to a systemic elimination of metastases (Bianchini et al, 2017). Unfortunately, prostate cancer is not a very immunogenic tumour, but still, ongoing clinical trials are exploring this synergy of radiation and immunotherapy (Modena et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Outcomes after a first and/or second salvage treatment in patients with oligometastatic prostate cancer recurrence detected by (18‐F) choline PET‐CT

et al. 2019

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Objective:The primary objective of this study was to assess clinical outcomes in patients with oligometastatic prostate cancer recurrence after single or repeated salvage radiation treatment.Methods: Forty-nine consecutive prostate cancer patients diagnosed with oligometastatic recurrence on Ch-PET have been prospectively treated. Seven (23%) patients had castrate-resistant disease. Clinical outcomes were assessed using the Kaplan-Meier method. Potential prognostic factors were examined using univariate proportional hazards regression. Results:The treatments administered to the initial oligorecurrence sites were intensity-modulated radiotherapy (IMRT) ± ADT (26 patients; 53%) and stereotactic ablative radiotherapy (SABR) ± ADT (23 patients; 47%). With a median follow-up of 24 months (range 6-39), 24 patients developed a biochemical failure. Twenty out of the 24 relapsed patients underwent a second Ch-PET/CT. Seven patients presented poly-metastatic relapse and 10 oligometastatic diseases. Six of 10 patients with a second oligorecurrence were treated again with SABR. Overall, 102 lesions were treated. Local control was detected in 45 (91.8%) patients. No relevant (grade ≥ 2) toxicity was reported, and there was no grade 3 toxicity. On univariate analysis, none of the variables were significantly predicted for clinical disease-free survival. At last follow-up visit, 24 patients (40%) were free from biochemical failure and 37 (71%) patients were free from clinical disease. The 2-year OS and PCSS were 91.8% and 95.9% respectively. Conclusion: Salvage IMRT or SBRT of oligometastatic prostate cancer recurrence is associated with a prolonged cDFS. This may result in a longer time to develop castrate-resistant disease and a longer time without systemic therapies.

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“…The local inflammation involves more efficient antigen cross-presentation and immune activation leading to CD8+ cytolytic T cell responses. However, the precise underlying the mechanism of the abscopal effect, which we describe in more detail below, remains unclear (166, 167).…”

Section: A Brief Comment On the Abscopal Effect And Its Consequences mentioning

confidence: 99%

Liquid Biopsy in Oligometastatic Prostate Cancer—A Biologist's Point of View

et al. 2019

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Prostate cancer (PCa) is the main cause of cancer-related mortality in males and the diagnosis, treatment, and care of these patients places a great burden on healthcare systems globally. Clinically, PCa is highly heterogeneous, ranging from indolent tumors to highly aggressive disease. In many cases treatment—generally either radiotherapy (RT) or surgery—can be curative. Several key genetic and demographic factors such as age, family history, genetic susceptibility, and race are associated with a high incidence of PCa. While our understanding of PCa, which is mainly based on the tools of molecular biology—has improved dramatically in recent years, efforts to better understand this complex disease have led to the identification of a new type of PCa–oligometastatic PCa. Oligometastatic disease should be considered an individual, heterogeneous entity with distinct metastatic phenotypes and, consequently, wide prognostic variability. In general, patients with oligometastatic disease typically present less biologically aggressive tumors whose metastatic potential is more limited and which are slow-growing. These patients are good candidates for more aggressive treatment approaches. The main aim of the presented review was to evaluate the utility of liquid biopsy for diagnostic purposes in PCa and for use in monitoring disease progression and treatment response, particularly in patients with oligometastatic PCa. Liquid biopsies offer a rapid, non-invasive approach whose use t is expected to play an important role in routine clinical practice to benefit patients. However, more research is needed to resolve the many existing discrepancies with regard to the definition and isolation method for specific biomarkers, as well as the need to determine the most appropriate markers. Consequently, the current priority in this field is to standardize liquid biopsy-based techniques. This review will help to improve understanding of the biology of PCa, particularly the recently defined condition known as “oligometastatic PCa”. The presented review of the body of evidence suggests that additional research in molecular biology may help to establish novel treatments for oligometastatic PCa. In the near future, the treatment of PCa will require an interdisciplinary approach involving active cooperation among clinicians, physicians, and biologists.

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Effect on Overall Survival of Locoregional Treatment in a Cohort of De Novo Metastatic Prostate Cancer Patients: A Single Institution Retrospective Analysis From the Royal Marsden Hospital

Cited by 16 publications

References 25 publications

Three-year follow-up of a phase II study of radium-223 dichloride in Japanese patients with symptomatic castration-resistant prostate cancer and bone metastases

Three-year follow-up of a phase II study of radium-223 dichloride in Japanese patients with symptomatic castration-resistant prostate cancer and bone metastases

Outcomes after a first and/or second salvage treatment in patients with oligometastatic prostate cancer recurrence detected by (18‐F) choline PET‐CT

Liquid Biopsy in Oligometastatic Prostate Cancer—A Biologist's Point of View

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