Consensus statements on ablative radiotherapy for oligometastatic prostate cancer: A position paper of Italian Association of Radiotherapy and Clinical Oncology (AIRO)

doi:10.1016/j.critrevonc.2019.03.014

Critical Reviews in Oncology/Hematology

Volume 138, June 2019, Pages 24-28

https://doi.org/10.1016/j.critrevonc.2019.03.014 Get rights and content

Highlights

•
Ablative radiotherapy is an effective treatment for oligometastatic prostate cancer.
•
The lack of randomized phase III trials hampers the generalization of this therapy.
•
In clinical practice, ablative radiotherapy should be adopted in some cases only.
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This position paper explores available literature and proposes some recommendations.

Abstract

Oligometastatic prostate cancer comprises a wide spectrum of conditions, ranging from de novo oligometastatic cancer at diagnosis to oligometastatic castration-resistant disease, which are distinct entities in terms of biology and prognosis.

In order to clarify and standardize the clinical role of ablative radiotherapy in oligometastatic prostate cancer, the Italian Association of Radiotherapy and Clinical Oncology (AIRO) formed an expert panel to review the current literature and develop a formal consensus.

Oligometastatic prostate cancer was defined as the presence of up to three metastatic lesions involving bones or nodes outside pelvis. Thereafter, four clinical scenarios were explored: metastatic castration-sensitive disease at diagnosis and after primary treatment, and metastatic castration-resistant disease at diagnosis and during treatment, where the role of ablative radiotherapy was defined either in conjunction with systemic therapy or as the only treatment in selected cases.

This paper summarizes the current literature about these issues and the proposed recommendations.

Introduction

The ‘oligometastatic’ concept was initially proposed by Hellman and Weichselbaum in 1995 (Hellman and Weichselbaum, 1995), to identify patients with an intermediate stage of cancer disease, between localized and widespread metastatic. More recently, the same authors (Weichselbaum and Hellman, 2011) underlined the promising role of local treatments as potentially curative in strictly selected subgroups of patients with limited burden of metastatic disease. This supported the assumption that oligometastatic disease could be defined as a distinct clinical entity.

Since 2015, more than 600 papers have been published about oligometastatic cancer, and one out of five specifically focused on prostate cancer patients. In 2015, the St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) (Gillessen et al., 2015) stated that ‘the presence of ≤3 synchronous metastases (bone and/or lymph nodes) is the most meaningful definition of oligometastatic prostate cancer’. However, in 2017 the APCCC (Gillessen et al., 2018) thoroughly explored the oligometastatic concept highlighting several topics of debate, including number and site of lesions, castration-sensitive or castration-resistant setting, synchronous versus metachronous metastases and imaging modality used to identify metastases.

Indeed, oligometastatic prostate cancer comprises a spectrum of numerous conditions, ranging from de novo oligometastatic cancer at diagnosis to oligometastatic castration-resistant disease, which differ widely. These distinct settings entail wide variations in terms of biology, benefit from treatments and prognosis (Francini et al., 2018; Gravis et al., 2018).

The emerging interest for oligometastatic prostate cancer, the increasing adoption of metastasis direct therapy (MDT, either surgery or ablative radiotherapy [RT]) (Ost et al., 2015), and the recent availability of prospective studies (Ost et al., 2018; Palma et al., 2012; Siva et al., 2018) even in the absence of data from randomized phase III trials encouraged the Italian Association of Radiotherapy and Clinical Oncology (AIRO) to form an expert panel to review the current literature and develop a formal consensus about the use of ablative RT in oligometastatic patients.

We herein report the results of this expert-opinion consensus from AIRO.

Section snippets

Methods

The statements formulated refer to four clinical scenarios: metastatic castration-sensitive disease at diagnosis and metastatic castration-sensitive disease after primary treatment (controlled primary), newly diagnosed metastatic castration-resistant disease (mCRPC) and, finally, mCRPC on therapy. In all cases, the sites of metastases are lymph nodes outside pelvis or bone; visceral metastasis are excluded for their poor prognosis (Gandaglia et al., 2015). The number of metastases was defined

First clinical scenario: oligometastatic prostate cancer at diagnosis

In this scenario, patients have been diagnosed with de novo oligometastatic disease and have not yet received any treatment for their prostate cancer.

The treatment of metastatic disease at diagnosis has suddenly changed in recent years: indeed, the STAMPEDE (James et al., 2016, 2017), CHAARTED (Kyriakopoulos et al., 2018) and LATITUDE (Fizazi et al., 2017) trials have recorded impressive survival benefit adding docetaxel (DOC) or abiraterone acetate + prednisone (AAP) to standard androgen

Discussion

In the absence of high-quality, level I evidence, two possibilities are available to meet clinical needs: phase III randomized trials or expert opinions. Randomized trials are the best way to evaluate the impact, and its magnitude, of a treatment or diagnostic intervention. However, this approach is not always feasible, especially in a widely heterogeneous population, such as oligometastatic prostate cancer patients.

Besides, if conflicting data, or their controversial interpretation, are

Funding

The preparation of the present article was supported by an unconditioned contribution from Janssen-Cilag SpA. The funding source had no role in study design, collection, analysis and interpretation of data, in writing of the report or in the decision to submit the article for publication.

Conflict of interest statement

Authors declared no conflict of interest.

Acknowledgement

Editorial assistance was provided by EDRA SpA (Milan, Italy)

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Currently, when nodal pelvic oligorecurrent disease is detected, no standard treatment option is recommended. One possible salvage option is nodal stereotactic body radiotherapy (SBRT). Here we analysed recurrence patterns after nodal SBRT in patients affected by pelvic oligometastatic relapse after radical prostatectomy, and androgen deprivation therapy (ADT)-free survival in this population.
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Nodal SBRT yielded encouraging DFS and ADT-free survival in this population. Only a minority of patients developed prostate bed recurrence, suggesting that local treatment may be safely avoided. A consistent percentage of patients could be managed with a second SBRT course.
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<3 metastases on PET-CT or magnetic resonance imaging (any site) [10,11]. <3 metastases on PET-CT (excluding visceral) [6-8]. <5 metastases (any site, conventional imaging or PET-CT) [9].
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We obtained 119 responses (response rate of 12.6%) after sending the questionnaire twice with one month apart. Most of them being staff/faculty (89%) practicing in the United States of America (84.87%). Most of the responders referred that a significant proportion of their practice comes from PC patients. Most defined OMPC <3 bone/lymph node metastasis seen with conventional imaging, only 26.9% of the responders used positron emission tomography. Regarding the clinical benefit of metastasis-oriented treatment, a curing rate >10% or an increase in 1 year of androgen deprivation therapy-free survival would make the treatment worthwhile. We present examples of sample size calculations for future clinical trials using these parameters as an expected “clinically-significant” benefit.
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Consensus statements on ablative radiotherapy for oligometastatic prostate cancer: A position paper of Italian Association of Radiotherapy and Clinical Oncology (AIRO)

Highlights

Abstract

Introduction

Section snippets

Methods

First clinical scenario: oligometastatic prostate cancer at diagnosis

Discussion

Funding

Conflict of interest statement

Acknowledgement

Lung Cancer

Eur. Urol.

Eur. Urol.

Eur. Urol.

Lancet Oncol.

Eur. Urol.

Eur. J. Cancer

Ann. Oncol.

Eur. Urol.

Eur. Urol.

Lancet

Eur. Urol.

Lancet Oncol.

Eur. Urol.

Int. J. Radiat. Oncol. Biol. Phys.

Eur. Urol.

Lancet

J. Urol.

Lancet Oncol.

Eur. Urol.

Enzalutamide in metastatic prostate cancer before chemotherapy

N. Engl. J. Med.

Evaluation of prostate Cancer with 11C-Choline PET/CT for treatment planning, response assessment, and prognosis

J. Nucl. Med.

Combining abiraterone and radiotherapy in prostate cancer patients who progressed during abiraterone therapy

Anticancer Res.