Radiotherapy in oligometastatic prostate cancer—a pattern of care survey among members of the German Society for Radiation Oncology (DEGRO)

Rogowski, Paul; Trapp, Christian; Bestenbostel, Rieke von; Konnerth, Dinah; Marschner, Sebastian; Hegemann, Nina-Sophie; Belka, Claus; Li, Minglun

doi:10.1007/s00066-022-01925-2

Cited by 5 publications

(7 citation statements)

References 30 publications

(33 reference statements)

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“…In other studies, there was a lack of prospective data regarding the influence of these factors on outcomes in patients with oligometastatic prostate cancer. Owing to multiple studies of prostate cancer and other diseases, there has been a drive for use of MDT for prostate cancer based primarily on the number of metastatic sites, as noted by expert consensus opinions, surveys, and national guidelines . Our inclusion criteria were designed for generalizability to reflect the clinical setting in which patients present to clinics predominantly based on the number of metastases.…”

Section: Discussionmentioning

confidence: 99%

“…Owing to multiple studies of prostate cancer and other diseases, 17,35,36 there has been a drive for use of MDT for prostate cancer based primarily on the number of metastatic sites, as noted by expert consensus opinions, surveys, and national guidelines. 6,7,16,37,38 Our inclusion criteria were designed for generalizability to reflect the clinical setting in which patients present to clinics predominantly based on the number of metastases. Ultimately, the findings from this study are consistent with those of prior studies [8][9][10] in highlighting the benefit of MDT in a more generalizable clinical population and in combination with hormone therapy.…”

Section: Discussionmentioning

confidence: 99%

“…[8][9][10] There also exists significant preclinical and clinical evidence of synergy between hormone therapy and radiation therapy, the predominate form of MDT. 11-14 However, despite this rationale and that hormone therapy is often combined with MDT to treat oligometastatic prostate cancer in clinical practice, 6,15,16 combining these modalities, to our knowledge, has not been tested in a randomized clinical trial.…”

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confidence: 99%

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Addition of Metastasis-Directed Therapy to Intermittent Hormone Therapy for Oligometastatic Prostate Cancer

et al. 2023

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ImportanceDespite evidence demonstrating an overall survival benefit with up-front hormone therapy in addition to established synergy between hormone therapy and radiation, the addition of metastasis-directed therapy (MDT) to hormone therapy for oligometastatic prostate cancer, to date, has not been evaluated in a randomized clinical trial.ObjectiveTo determine in men with oligometastatic prostate cancer whether the addition of MDT to intermittent hormone therapy improves oncologic outcomes and preserves time with eugonadal testosterone compared with intermittent hormone therapy alone.Design, Setting, ParticipantsThe External Beam Radiation to Eliminate Nominal Metastatic Disease (EXTEND) trial is a phase 2, basket randomized clinical trial for multiple solid tumors testing the addition of MDT to standard-of-care systemic therapy. Men aged 18 years or older with oligometastatic prostate cancer who had 5 or fewer metastases and were treated with hormone therapy for 2 or more months were enrolled to the prostate intermittent hormone therapy basket at multicenter tertiary cancer centers from September 2018 to November 2020. The cutoff date for the primary analysis was January 7, 2022.InterventionsPatients were randomized 1:1 to MDT, consisting of definitive radiation therapy to all sites of disease and intermittent hormone therapy (combined therapy arm; n = 43) or to hormone therapy only (n = 44). A planned break in hormone therapy occurred 6 months after enrollment, after which hormone therapy was withheld until progression.Main Outcomes and MeasuresThe primary end point was disease progression, defined as death or radiographic, clinical, or biochemical progression. A key predefined secondary end point was eugonadal progression-free survival (PFS), defined as the time from achieving a eugonadal testosterone level (≥150 ng/dL; to convert to nanomoles per liter, multiply by 0.0347) until progression. Exploratory measures included quality of life and systemic immune evaluation using flow cytometry and T-cell receptor sequencing.ResultsThe study included 87 men (median age, 67 years [IQR, 63-72 years]). Median follow-up was 22.0 months (range, 11.6-39.2 months). Progression-free survival was improved in the combined therapy arm (median not reached) compared with the hormone therapy only arm (median, 15.8 months; 95% CI, 13.6-21.2 months) (hazard ratio, 0.25; 95% CI, 0.12-0.55; P &lt; .001). Eugonadal PFS was also improved with MDT (median not reached) compared with the hormone therapy only (6.1 months; 95% CI, 3.7 months to not estimable) (hazard ratio, 0.32; 95% CI, 0.11-0.91; P = .03). Flow cytometry and T-cell receptor sequencing demonstrated increased markers of T-cell activation, proliferation, and clonal expansion limited to the combined therapy arm.Conclusions and RelevanceIn this randomized clinical trial, PFS and eugonadal PFS were significantly improved with combination treatment compared with hormone treatment only in men with oligometastatic prostate cancer. Combination of MDT with intermittent hormone therapy may allow for excellent disease control while facilitating prolonged eugonadal testosterone intervals.Trial RegistrationClinicalTrials.gov Identifier: NCT03599765

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Addition of Metastasis-Directed Therapy to Intermittent Hormone Therapy for Oligometastatic Prostate Cancer

et al. 2023

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“…Regardless of existing knowledge gaps, MDT has gained widespread acceptance as a treatment option across various settings of omPCa, including common use beyond clinical trials to bolster treatment in conjunction with systemic and/or interventional therapies. A recent survey conducted by the DEGRO group revealed that almost all radiation oncology respondents favored MDT for oligometastatic recurrence in PCa patients, with over half considering combining MDT with systemic therapy [ 4 ]. Notably, more than half of those surveyed did not differentiate between synchronous and metachronous disease, even though the evidence for MDT in PCa primarily stems from metachronous omPCa [ 3 ▪ ].…”

Section: General Overview Of Metastasis-directed Therapy In Context O...mentioning

confidence: 99%

Metastasis-directed therapy in oligometastatic prostate cancer

Miszczyk,

Soeterik,

Marra

et al. 2024

Current Opinion in Urology

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Purpose of review To summarize the recent findings on the subject of metastasis-directed therapy (MDT) in the treatment of oligometastatic prostate cancer (omPCa). Recent findings Evidence from two randomized clinical trials (RCTs) and a meta-analysis show favorable toxicity profiles, and the potential to delay androgen-deprivation therapy (ADT) for up to two years in nearly half of patients with metachronous hormone-sensitive omPCa. Another RCT showed promising results of MDT as treatment-escalation method combined with androgen receptor signaling inhibitors (ARSI) in first-line treatment for castration-resistant omPCa. Surveys by radiation oncologists and consensus guidelines advocate for MDT across various omPCa scenarios. Multiple single-arm trials present encouraging results; however, the evidence for the benefit of MDT is still weak requiring further investigation to assess its impact on pivotal endpoints, such as survival and quality of life. Summary MDT is a promising approach in omPCa, and can be used to defer ADT in newly diagnosed metachronous omPCa patients, or to add to ARSI treatment at first diagnosis of castration-resistance. Ongoing prospective trials are needed to guide its optimal utilization in other settings, and patients should be informed about the evolving landscape of systemic therapies with proven survival benefits alongside MDT options.

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“…Considering our evolving knowledge of tumor biology, the continuous interplay between different subclones and disease sites, introduction of anticancer therapies, and relying on aggravating the host response, utilizing strict imaging-based thresholds for the maximum number of metastases or organs involved may lead to an arbitrary classification, resulting in suboptimal treatment selection and oncologic outcomes. This issue is reflected by the results of a survey among the Members of the German Society for Radiation Oncology (DEGRO) and the omBC consensus [11 ▪▪ ,32 ▪ ]. According to 25.7% of DEGRO survey responders, the maximum number of lesions should be determined based on the ability to deliver curative treatment to the metastases [32 ▪ ].…”

Section: Conclusion and Future Challengesmentioning

confidence: 99%

Defining oligometastatic state in uro-oncological cancers

Fazekas,

Miszczyk,

Matsukawa

et al. 2024

Current Opinion in Urology

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Purpose of review Oligometastatic tumors illustrate a distinct state between localized and systematic disease and might harbor unique biologic features. Moreover, these tumors represent a different clinical entity, with a potential of long-term disease control or even cure, therefore they receive growing attention in the field of urologic oncology. Recent findings Currently, there is no consensus on the definition of oligometastatic prostate cancer, most experts limit it to a maximum of three to five lesions and involvement of no more than two organs, excluding visceral metastases. Quality data on oligometastatic bladder cancer is scarce, however, a consensus of experts defined it as a maximum of three metastatic lesions, either resectable or suitable for stereotactic therapy, without restrictions to the number of organs involved. As for kidney cancer, a maximum number of five metastases, without limitations to the location are defined as oligometastatic, with an important implication of timing of developing metastases since diagnosis of the primary tumor. Summary Defining oligometastatic state among urological tumors reflecting their distinct biological and clinical behavior is crucial to establish a sound framework for future clinical trials, and to facilitate guideline and policy formulation for improved patient care. Advancements in molecular imaging are expected to transform the field of oligometastatic urologic tumors in the future.

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Radiotherapy in oligometastatic prostate cancer—a pattern of care survey among members of the German Society for Radiation Oncology (DEGRO)

Cited by 5 publications

References 30 publications

Addition of Metastasis-Directed Therapy to Intermittent Hormone Therapy for Oligometastatic Prostate Cancer

Addition of Metastasis-Directed Therapy to Intermittent Hormone Therapy for Oligometastatic Prostate Cancer

Metastasis-directed therapy in oligometastatic prostate cancer

Defining oligometastatic state in uro-oncological cancers

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