Metastases-directed radiotherapy in castration resistant oligo metastatic prostate cancer: A multicentric retrospective study from the French group COLib.

Oligometastases are defined as a number of detectable metastases less or equal to 5. In castrate-resistant oligo metastatic prostate Cancer (CR oligoM PC), Metastases-Directed Ablative radiotherapy (MDRT) is poorly investigated. Our study retrospectively reviewed the cases of CR oligoM PC treated with MDRT in 8 French high-volume radiotherapy centers. OS and PFS are defined as the delay between the first day of MDRT and death (OS) or progression according to PCWG criteria (PFS). OS and PFS are evaluated according to Kaplan Meyer, curves are compared with log rank test. Logistic regression was used to identify predictive factors for outcome: bone versus node metastasis, ISUP grade, PSA doubling Time (PSADT) at the time of MDRT, time to castration resistance. 107 patients were included in the study, among those 197 metastases received MDRT. For the overall population, the median follow-up was 25.2 months (1,4-145). OS was 93 % at 2 years and 81,4% at 3 years. At 2 years, 100 % of patients with node-only metastasis were alive versus 88,7% among those who have bone metastases (p = 0,72). The median PFS was 12,6 months (IC 95 % [9,6; 17]), with no difference among patients with node only disease versus the rest of the cohort. The PFS was 18,2 months (10,0; 32,4) in patients with PSADT >6 months versus 10,7 months (8,9; 14,3) when PSADT was inferior to 6 months. However, this difference did not reach significant. We did not find a correlation neither between ISUP grade (1-2 versus 3-4-5) and PFS, nor between hormone-sensitivity duration and PFS. Patients receiving MDRT for CR oligoM PC have a good prognosis with 81,6% OS at 3 years. PSA DT longer than 6 months could be related to better PFS. MDRT strategy could postpone the onset of new systemic treatment with median PFS >1 year.

The role of radiation therapy for de novo metastatic bladder and renal cancers.

Metastatic bladder and renal cancers account respectively for 2.1% and 1.8% of cancer deaths worldwide. The advent of immune checkpoint inhibitors has revolutionized the management of metastatic disease, by demonstrating considerable improvements in overall survival. However, despite initial sensitivity to immune checkpoint inhibitors for most patients, both bladder and renal cancer are associated with short progression-free survival and overall survival, raising the need for further strategies to improve their efficacy. Combining systemic therapies with local approaches is a longstanding concept in urological oncology, in clinical settings including both oligometastatic and polymetastatic disease. Radiation therapy has been increasingly studied with either cytoreductive, consolidative, ablative or immune boosting purposes, but the long-term impact of this strategy remains unclear. This review intends to address the impact of radiation therapy with either curative or palliative intent, for synchronous de novo metastatic bladder and renal cancers.

Role of radiotherapy in the management of brain oligometastases.

The management of patients with brain oligometastases is complex and relies on specific reasoning compared to extracranial oligometastases. The levels of evidence are still low because patients with brain oligometastases are frequently excluded from randomized clinical trials. Stereotactic radiotherapy should be preferred in this indication over whole brain irradiation, both for patients with metastases in place and for those who have undergone surgery. The decision of local treatment and its timing must be a multidisciplinary reflection taking into account the histological and molecular characteristics of the tumor as well as the intracranial efficacy of the prescribed systemic treatments. Great caution must be observed when using stereotactic radiotherapy and concomitant systemic treatments because interactions are still poorly documented. We present the recommendations of the French society of radiation oncology on the management of brain oligometastatic patients with radiotherapy.

Indication and perspectives of radiation therapy in the setting of de-novo metastatic prostate cancer.

Prostate cancer is the most common cancer and the third leading cause of cancer mortality in men. Each year, approximately 10% of prostate cancers are diagnosed metastatic at initial presentation. The standard treatment option for de-novo metastatic prostate cancer is androgen deprivation therapy with novel hormonal agent or with chemotherapy. Recently, PEACE-1 trial highlighted the benefit of triplet therapy resulting in the combination of androgen deprivation therapy combined with docetaxel and abiraterone. Radiotherapy can be proposed in a curative intent or to treat local symptomatic disease. Nowadays, radiotherapy of the primary disease is only recommended for de novo low-burden/low-volume metastatic prostate cancer, as defined in the CHAARTED criteria. However, studies on stereotactic radiotherapy on oligometastases have shown that this therapeutic approach is feasible and well tolerated. Prospective research currently focuses on the benefit of intensification by combining treatment of the metastatic sites and the primary all together. The contribution of metabolic imaging to better define the target volumes and specify the oligometastatic character allows a better selection of patients. This article aims to define indications of radiotherapy and perspectives of this therapeutic option for de-novo metastatic prostate cancer.

Recommendations for stereotactic body radiation therapy for spine and non-spine bone metastases. A GETUG (French society of urological radiation oncolgists) consensus using a national two-round modified Delphi survey.

Background and purpose: The relevance of metastasis-directed stereotactic body radiation therapy (SBRT) remains to be demonstrated through phase III trials. Multiple SBRT procedures have been published potentially resulting in a disparity of practices. Therefore, the french society of urological radiation oncolgists (GETUG) recognized the need for joint expert consensus guidelines for metastasis-directed SBRT in order to standardize practice in trials carried out by the group. Materials and methods: After a comprehensive literature review, 97 recommendation statements were created regarding planning and delivery of spine bone (SBM) and non-spine bone metastases (NSBM) SBRT. These statements were then submitted to a national online two-round modified Delphi survey among main GETUG investigators. Consensus was achieved if a statement received ≥ 75 % agreements, a trend to consensus being defined as 65-74 % agreements. Any statement without consensus at round one was re-submitted in round two. Results: Twenty-one out of 29 (72.4%) surveyed experts responded to both rounds. Seventy-five statements achieved consensus at round one leaving 22 statements needing a revote of which 16 achieved consensus and 5 a trend to consensus. The final rate of consensus was 91/97 (93.8%). Statements with no consensus concerned patient selection (3/19), dose and fractionation (1/11), prescription and dose objectives (1/9) and organs at risk delineation (1/15). The voting resulted in the writing of step-by-step consensus guidelines. Conclusion: Consensus guidelines for SBM and NSBM SBRT were agreed upon using a validated modified Delphi approach. These guidelines will be used as per-protocole recommendations in ongoing and further GETUG clinical trials.

[What do we need to deliver "online" adapted radiotherapy treatment plans?] / Que faut-il pour faire de la radiothérapie adaptative « online ¼ ?

During the joint SFRO/SFPM session of the 2019 congress, a state of the art of adaptive radiotherapy announced a strong impact in our clinical practice, in particular with the availability of treatment devices coupled to an MRI system. Three years later, it seems relevant to take stock of adaptive radiotherapy in practice, and especially the "online" strategy because it is indeed more and more accessible with recent hardware and software developments, such as coupled accelerators to a three-dimensional imaging device and algorithms based on artificial intelligence. However, the deployment of this promising strategy is complex because it contracts the usual time scale and upsets the usual organizations. So what do we need to deliver adapted treatment plans with an "online" strategy?

[Clinical research in radiotherapy oncology in private sector: A reality with a possible future?] / Recherche clinique en oncologie radiothérapie dans le secteur libéral : une réalité avec un avenir possible ?

Clinical research is one of the activities of medical practice, particularly in oncology including radiotherapy. It was developed in the public sector and then in the liberal sector, in compliance with regulatory institutions, resulting in a doubling of inclusions over the last decade. Setting up and developing clinical research in the liberal sector are major axes in terms of interests: improving the proposition of care, access to innovation, to keep patients, intellectual stimulation, encouraging recruitment, activity of scientific publications, financial valorisation, quality of visibility… An inventory on French national territory via the national union of iadiotherapists oncologists (SNRO) and the club of liberal oncologists (Colib) is reported in this article, as well as examples of structuring and organization.

Cost-effectiveness of hypofractionated versus conventional radiotherapy in patients with intermediate-risk prostate cancer: An ancillary study of the PROstate fractionated irradiation trial - PROFIT.

PURPOSE: To evaluate the cost-effectiveness of moderate Hypofractionated Radiotherapy (H-RT) compared to Conventional Radiotherapy (C-RT) for intermediate-risk prostate caner (PCa). METHODS: A prospective randomized clinical trial including 222 patients from six French cancer centers was conducted as an ancillary study of the international PROstate Fractionated Irradiation Trial (PROFIT). We carried-out a cost-effectiveness analysis (CEA) from the payer's perspective, with a time horizon of 48 months. Patients assigned to the H-RT arm received 6000 cGy in 20 fractions over 4 weeks, or 7800 cGy in 39 fractions over 7 to 8 weeks in the C-RT arm. Patients completed quality of life (QoL) questionnaire: Expanded Prostate Cancer Index Composite (EPIC) at baseline, 24 and 48 months, which were mapped to obtain a EuroQol five-dimensional questionnaire (EQ-5D) equivalent to generate Quality Adjusted Life Years (QALY). We assessed differences in QALYs and costs between the two arms with Generalized Linear Models (GLMs). Costs, estimated in euro (€) 2020, were combined with QALYs to estimate the Incremental Cost-effectiveness ratio (ICER) with non-parametric bootstrap. RESULTS: Total costs per patien were lower in the H-RT arm compared to the C-RT arm €3,062 (95 % CI: 2,368 to 3,754) versus €4,285 (95 % CI: 3,355 to 5,215), (p < 0.05). QALY were marginally higher in the H-RT arm, however this difference was not significant: 0.044 (95 % CI: - 0.016 to 0.099). CONCLUSIONS: Treating localized prostate cancer with moderate H-RT could reduce national health insurance spending. Adopting such a treatment with an updated reimbursement tariff would result in improving resource allocation in RT management.

[Intermediate-risk prostate cancer treated with exclusive external irradiation: Focus on anatomical sites of recurrence in two French trials]. / Cancer de la prostate de risque intermédiaire traité par irradiation externe exclusive : focus sur les sites anatomiques de récidive dans deux essais français.

PURPOSE: Retrospective description of anatomical sites of relapse based on (18F)-choline PET-CT, (68Ga)-prostatic specific-membrane antigen PET-CT, bone scan, and prostate magnetic resonance imaging (MRI) data. MATERIALS AND METHODS: From two French prospective cohorts, patients treated with exclusive radiotherapy for an intermediate-risk cancer were identified during their follow-ups. They were included if they presented a rising of the prostate-specific antigen (PSA) associated with the realization of an imaging showing the sites of recurrences. RESULTS: Two hundred and sixty-three patients were included. After a median follow-up of 76 months (interquartile range [IQR] 67-95), 65 patients had biochemical recurrence and positive imaging. The median nadir PSA was 0.6ng/mL and the median PSA at recurrence was 3.4ng/mL. A single lesion was found in 48% of cases, 2 to 4 lesions in 43% of cases and more than 4 lesions in 9% of cases. The sites of relapse identified were prostate (37/65), prostate only (19/65), seminal vesicles (9/65) Pelvic nodes (35/65), extrapelvic nodes (15/65) and bone (13/65). CONCLUSIONS: The majority of relapses presented as a single lesion localized in the pelvis.

Management of patients with a persistently elevated PSA after radical prostatectomy: a narrative review.

INTRODUCTION: The management of the postoperative biological relapse of prostate cancer is most often based on salvage radiotherapy (SRT) with or without the addition of a variable duration of hormone therapy (HT). The indications for SRT +/- HT are established in the setting of a rising PSA level after a period where an undetectable PSA was achieved. However, in case of detectable PSA immediately after radical prostatectomy, the treatment options and prognosis are still unclear. MATERIALS AND METHODS: We conducted a narrative review based on an analysis of the literature focusing on articles targeting the population of patients with postoperative persistently detectable PSA level. Case reports, original articles, clinical trials, and published reviews were studied for this purpose. CONCLUSION: This article will describe current management of patients with detectable PSA immediately after radical prostatectomy, notably the contribution of modern imaging and new treatment options involving the combination of RT and HT.

Radiation therapy for brain metastases.

We present the update of the recommendations of the French society for radiation oncology on radiation therapy for the management of brain metastases. It has evolved in recent years and has become more complex. As the life expectancy of patients has increased and retreatments have become more frequent, side effects must be absolutely avoided. Cognitive side effects must in particular be prevented, and the most modern radiation therapy techniques must be used systematically. New prognostic classifications specific to the primary tumour of patients, advances in imaging and radiation therapy technology and new systemic therapeutic strategies, are making treatment more relevant. Stereotactic radiation therapy has supplanted whole-brain radiation therapy both for patients with metastases in place and for those who underwent surgery. Hippocampus protection is possible with intensity-modulated radiation therapy. Its relevance in terms of cognitive functioning should be more clearly demonstrated but the requirement for its use is constantly increasing. New targeted cancer treatment therapies based on the nature of the primitive have complicated the notion of the place and timing of radiation therapy and the discussion during multidisciplinary care meeting to indicate the best sequences is becoming a challenging issue as data on the interaction between treatments remain to be documented. In the end, although aimed at patients in the palliative phase, the management of brain metastases is one of the locations for which technical reflection is the most challenging and treatment become increasingly personalized.

External radiotherapy for prostatic cancers.

We present the update of the recommendations of the French society of oncological radiotherapy on external radiotherapy of prostate cancer. External radiotherapy is intended for all localized prostate cancers, and more recently for oligometastatic prostate cancers. The irradiation techniques are detailed. Intensity-modulated radiotherapy combined with prostate image-guided radiotherapy is the recommended technique. A total dose of 74 to 80Gy is recommended in case of standard fractionation (2Gy per fraction). Moderate hypofractionation (total dose of 60Gy at a rate of 3Gy per fraction over 4 weeks) in the prostate has become a standard of therapy. Simultaneous integrated boost techniques can be used to treat lymph node areas. Extreme hypofractionation (35 to 40Gy in five fractions) using stereotactic body radiotherapy can be considered a therapeutic option to treat exclusively the prostate. The postoperative irradiation technique, indicated mainly in case of biological recurrence and lymph node involvement, is detailed.

[Salvage radiotherapy after prostatectomy - what do do in case of elevated post operative PSA or macroscopic relapse?] / Radiothérapie de rattrapage après prostatectomie radicale : que faire en cas de concentration de PSA postopératoire élevée persistante ou de récidive locale macroscopique ?

The management of the postoperative biological relapse of prostate cancer is most often based on salvage radiotherapy (RT) and a variable duration of hormone therapy (HT) in addition. The indications for RT±HT become more consensual for the adjuvant postoperative situation or in the event of a rising PSA level after a period where an undetectable PSA level was achieved. On the other hand, in the event of detectable PSA immediately postoperatively or in the event of a biological recurrence with macroscopic relapse in the prostate bed seen on conventional imaging assessment, the treatment options are still being evaluated. This article will describe these 2 situations and their current management but also will come through assessments with the contribution of modern imaging and new treatment options in terms of RT dose and RT±HT combination.

[Postoperative radiotherapy for prostate cancer: when to propose it? What is the place for androgen deprivation?] / Radiothérapie postopératoire des cancers de la prostate : à quel moment la proposer ? Quelle place pour la déprivation androgènique ?

PURPOSE: While there is no high-level evidence showing superiority of surgery over radiation treatment, radical prostatectomy is the most common treatment option for patients with localized, non-metastatic disease. Nearly 30% of all patients undergoing surgery will develop a biochemical recurrence in 10 years. In fact, more than 30% of contemporary patients treated with RP will harbor aggressive disease characteristics at final pathology. MATERIAL AND MEHODS: We conducted a review of the literature evaluating the timing of radiotherapy and the place of androgen deprivation after prostatectomie totale. RESULTS: Four trials randomizing adjuvant radiotherapy and surveillance found an advantage in biochemical relapse-free survival in favor of immediate irradiation after radical prostatectomy, called adjuvant. However, in these studies, more than 40% of patients in the arm without adjuvant radiotherapy did not relapse at 10 years of follow-up. More recently, the question of the optimal time of this post-operative, adjuvant RT or during biological relapse has arisen through three trials (RADICALS-RT, RAVES, GETUG-AFU 17). These trials did not show a benefit for adjuvant radiotherapy in terms of event-free survival, a PSA-based endpoint, while confirming the toxicities observed during irradiation immediately after surgery. The optimal duration of hormonal therapy when associated with post-prostatectomy radiation therapy remains controversial. CONCLUSION: Early salvage radiotherapy is a new standard of treatment and adjuvant radiotherapy could be reserved for very selected patients. The role of hormone therapy is well defined in salvage situation, but its duration is still being studied.

[The role of radiotherapy to the primary tumor and metastases in patients with oligometastatic prostate cancer]. / Place de la radiothérapie de la tumeur primitive et/ou des métastases du cancer de la prostate oligométastatique.

Oligometastatic prostate cancer is among the most studied oligometastatic cancers in the literature. However few prospective studies have assessed stereotactic body radiotherapy (SBRT) for prostate cancer oligometastases. Two randomised phase II trials show a progression-free survival benefit compared with observation. Prospective registry data show very good local control and low toxicity too. Inclusion in ongoing trials should be strongly encouraged to define the role of SBRT in addition to systemic therapy. Radiation therapy to the primary tumour has been studied in randomised trials and provides an overall survival benefit in patients with low metastatic burden. The benefit is inversely correlated with the number of bone lesions using conventional imaging, up to three metastases. Radiotherapy to the primary tumour is recommended by the learned societies for patients with low metastatic burden. Its role in combination with second generation anti androgen therapy needs to be clarified.

Postoperative radiotherapy in prostate cancer: Dose and volumes.

Approximately thirty percent of patients experience biochemical recurrence after radical prostatectomy for prostate cancer. Early salvage radiotherapy has recently become a standard of care in this setting. The purpose of this review is first to summarize current knowledge in terms of dose to the prostate bed in light of the recent SAKK 09/10 randomized phase III trial results. The evidence on moderate hypofractionation will also be discussed whereas extreme hypofractionation remains highly investigational. Regarding target volumes, several different guidelines have been published to address the need for standardization of postoperative target delineation. The recent GFRU (Groupe Francophone de Radiothérapie Urologique) recommendations could represent an international consensus.

[Recent advances in high-risk prostate cancer surgery]. / Nouveautés dans la chirurgie des cancers de la prostate localisés de haut risque.

The management of high-risk prostate cancer has greatly evolved in recent years. Advances in imaging helps to better define the actual aggressiveness of the disease, to plan the surgical procedure, and to improve the prognostic evaluation of this high-risk of recurrence disease. The information obtained by MRI and by targeted biopsies improves management before surgery. Advances in nuclear medicine and generalization of PSMA-PET scans are beginning to improve the initial stage of diagnosis, thanks to a better detection of lymph node and distant metastases. The oncological interest of these new imaging techniques, which then influence the therapeutic plan, remains to be defined. The curative impact of an extensive lymph node dissection, as currently recommended, remains to be proved, and recently published randomized trials do not provide firm conclusions. The new hormone therapies pave the way for an intensification of perioperative systemic treatment, with a significant action on the tumor tissue, but an impact on survival, which remains to be defined in the context of ongoing randomized trials.