Randomized phase II trial in prostate cancer with hormone-sensitive OligometaSTatic relapse: Combining stereotactic ablative radiotherapy and durvalumab (POSTCARD GETUG P13): Study protocol

Rogé, Maximilien; Pointreau, Y.; Sargos, P.; Meyer, E.; Schick, Ulrike; Hasbini, Ali; Rio, E.; Béra, G.; Ruffier, A.; Quivrin, Magali; Chasseray, Mathieu; Latorzeff, I.; Martin, Étienne; Guimas, V.; Pommier, P.; Lee, Thomas; Ronchin, P.; Lepinoy, A.; Grand, Audrey; Cartier, L.; Didas, O.; Denis, Fabrice; Libois, V.; Blanc-Lapierre, Audrey; Supiot, S.

doi:10.1016/j.ctro.2023.100613

Cited by 4 publications

(4 citation statements)

References 22 publications

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“…Indeed, PD-1 + CD4 + and CD8 + T cells were enriched in all three urogenital tissues analyzed (Figure 5C), indicating that this PD-1 + T cell aging signature is likely not specific to the prostate. Nevertheless, our demonstration of increased PD-1 + T cells in the aging mouse prostate may still be useful information given the recent interest in developing immunotherapies targeting the PD-1/PD-L1 axis in prostate cancer [55][56][57].…”

Section: Discussionmentioning

confidence: 92%

Highly multiplexed immune profiling throughout adulthood reveals kinetics of lymphocyte infiltration in the aging mouse prostate

Fox

Hashimoto

Navarro

et al. 2023

Aging

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Aging is a significant risk factor for disease in several tissues, including the prostate. Defining the kinetics of age-related changes in these tissues is critical for identifying regulators of aging and evaluating interventions to slow the aging process and reduce disease risk. An altered immune microenvironment is characteristic of prostatic aging in mice, but whether features of aging in the prostate emerge predominantly in old age or earlier in adulthood has not previously been established. Using highly multiplexed immune profiling and time-course analysis, we tracked the abundance of 29 immune cell clusters in the aging mouse prostate. Early in adulthood, myeloid cells comprise the vast majority of immune cells in the 3-month-old mouse prostate. Between 6 and 12 months of age, there is a profound shift towards a T and B lymphocyte-dominant mouse prostate immune microenvironment. Comparing the prostate to other urogenital tissues, we found similar features of age-related inflammation in the mouse bladder but not the kidney. In summary, our study offers new insight into the kinetics of prostatic inflammaging and the window when interventions to slow down age-related changes may be most effective.

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Section: Discussionmentioning

confidence: 92%

Highly multiplexed immune profiling throughout adulthood reveals kinetics of lymphocyte infiltration in the aging mouse prostate

Fox

Hashimoto

Navarro

et al. 2023

Aging

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“…Nevertheless, a recent European Society for Radiotherapy and Oncology panel reached 80% agreement, but not consensus, to recommend metastasis-directed radiotherapy to a maximum of five lesions, 20 a recommendation supported by the findings of this study. Further, many randomised controlled trials investigating MDT for PCa are now recruiting participants with up to five metastases, [24][25][26] with some studies of MDT, such as SABR-COMET-10, 27 including up to 10 metastases amenable to SBRT. MDT with SBRT is associated with very low rates of treatmentrelated toxicity, with grade three or higher toxicity typically reported in less than 5% of cases; however, most published toxicity data is limited to a median follow-up time of less than 2-3 years.…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, a recent European Society for Radiotherapy and Oncology panel reached 80% agreement, but not consensus, to recommend metastasis‐directed radiotherapy to a maximum of five lesions, 20 a recommendation supported by the findings of this study. Further, many randomised controlled trials investigating MDT for PCa are now recruiting participants with up to five metastases, 24–26 with some studies of MDT, such as SABR‐COMET‐10, 27 including up to 10 metastases amenable to SBRT.…”

Section: Discussionmentioning

confidence: 99%

Five‐year outcomes of fractionated stereotactic body radiotherapy for oligometastatic prostate cancer from the TRANSFORM phase II trial

See,

Conway,

Frydenberg

et al. 2024

Intl Journal of Cancer

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Metastasis‐directed therapy (MDT) for oligometastatic prostate cancer (PCa), including stereotactic body radiotherapy (SBRT), has shown promise but is still considered investigational. This is the 5‐year analysis of the TRANSFORM trial, the largest prospective cohort of men with oligometastatic PCa treated with SBRT‐based MDT. The primary endpoint was 5‐year treatment escalation‐free survival (TE‐FS), defined as freedom from any new cancer therapy other than further SBRT. In total, 199 men received SBRT; 76.4% were hormone‐naïve at baseline. The rate of 5‐year TE‐FS was 21.7% (95% confidence interval [CI]: 15.7%–28.7%) overall and 25.4% (95% CI: 18.1%–33.9%) in the hormone‐naïve subgroup. The subgroups with International Society of Urological Pathology Grade Groups 4–5 disease (hazard ratio [HR] = 1.48, 95% CI: 1.05–2.01, p = .026), a higher baseline prostate‐specific antigen (PSA) (HR = 1.06, 95% CI: 1.03–1.09, p < .001) and those who received prior androgen deprivation therapy (ADT) (HR = 2.13, 95% CI: 1.40–3.26, p < .001), were at greater risk of treatment escalation. Outcomes for participants with four or five initial lesions were comparable to those with one to three lesions. At last follow‐up, 18.9% (95% CI: 13.2%–25.7%) of participants were free from treatment escalation (median follow‐up of 67.9 months) and two participants had an undetectable PSA level. No treatment‐related grade three or higher adverse events were reported. The findings of this study demonstrate that SBRT‐based MDT is an effective option for delaying systemic treatment escalation in the context of oligometastatic PCa. Future randomised trials comparing SBRT‐based MDT to standard‐of‐care ADT‐based approaches are required to evaluate the impact of delaying ADT on survival.

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“…Patients were randomly assigned to either SBRT + Durvalumab (anti PD-L1), or SBRT alone in oligometastatic hormone-sensitive prostate cancer patients. The primary endpoint is two-year progression-free survival and secondary endpoints encompass ADT-free survival, acute and late toxicity, prostate cancer-specific survival, quality of life, overall survival, and immune response [67].…”

Section: Rt + Immunotherapymentioning

confidence: 99%

Review of Current Treatment Intensification Strategies for Prostate Cancer Patients

Wasim,

Park,

Nam

et al. 2023

Cancers

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Prostate cancer (PCa) used to be one of the most common nondermatologic cancers in men that can be treated only with surgery. However, a revolutionary breakthrough came in the 1980s with the introduction of long-acting luteinizing hormone-releasing hormone (LHRH) agonists for the curative treatment of PCa. This paradigm shift contributed to the combined use of androgen deprivation therapy (ADT), chemotherapy, and radiotherapy for the treatment. The latest data highlight the use of treatment intensification (TI), i.e., combined use of radiotherapy (RT) and hormonal or drug treatments, for localized or locally advanced PCa. Indeed, the results of combined modality treatments have shown a reduction in disease-specific mortality and improved overall survival. Although TI seems promising, more research studies are warranted to confirm its efficacy. This review summarizes the latest available outcome results of pivotal trials and clinical studies on the efficacy of TI.

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Randomized phase II trial in prostate cancer with hormone-sensitive OligometaSTatic relapse: Combining stereotactic ablative radiotherapy and durvalumab (POSTCARD GETUG P13): Study protocol

Cited by 4 publications

References 22 publications

Highly multiplexed immune profiling throughout adulthood reveals kinetics of lymphocyte infiltration in the aging mouse prostate

Highly multiplexed immune profiling throughout adulthood reveals kinetics of lymphocyte infiltration in the aging mouse prostate

Five‐year outcomes of fractionated stereotactic body radiotherapy for oligometastatic prostate cancer from the TRANSFORM phase II trial

Review of Current Treatment Intensification Strategies for Prostate Cancer Patients

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