Stereotactic radiotherapy of nodal oligometastases from prostate cancer: a prisma-compliant systematic review

Clinical & Experimental Metastasis https://doi.org/10.1007/s10585-022-10183-6 REVIEW Stereotactic radiotherapy of nodal oligometastases from prostate cancer: a prisma‑compliant systematic review Alice Zamagni1 · Mattia Bonetti1 · Milly Buwenge1 · Gabriella Macchia2 · Francesco Deodato2,3 · Savino Cilla4 · Erika Galietta1 · Lidia Strigari5 · Francesco Cellini6,7 · Luca Tagliaferri6 · Silvia Cammelli1,8 · Alessio Giuseppe Morganti1,8 Received: 16 April 2022 / Accepted: 4 August 2022 © The Author(s) 2022 Abstract Androgen deprivation therapy (ADT) is the standard treatment of metastatic prostate cancer (PCa). However, metastasesdirected therapies can delay the initiation or switch of systemic treatments and allow local control (LC) and prolonged progression-free survival (PFS), particularly in patients with lymph nodes (LN) oligometastases. We performed a systematic review on stereotactic body radiotherapy (SBRT) in this setting. Papers reporting LC and/or PFS were selected. Data on ADT-free survival, overall survival, and toxicity were also collected from the selected studies. Fifteen studies were eligible (414 patients), 14 of them were retrospective analyses. A high heterogeneity was observed in terms of patient selection and treatment. In one study SBRT was delivered as a single 20 Gy fraction, while in the others the median total dose ranged between 24 and 40 Gy delivered in 3–6 fractions. LC and PFS were reported in 15 and 12 papers, respectively. LC was reported as a crude percentage in 13 studies, with 100% rate in seven and 63.2–98.0% in six reports. Five studies reported actuarial LC (2-year LC: 70.0–100%). PFS was reported as a crude rate in 11 studies (range 27.3–68.8%). Actuarial 2-year PFS was reported in four studies (range 30.0–50.0%). SBRT tolerability was excellent, with only two patients with grade 3 acute toxicity and two patients with grade 3 late toxicity. SBRT for LN oligorecurrences from PCa in safe and provides optimal LC. However, the long-term effect on PFS and OS is still unclear as well as which patients are the best candidate for this approach. Keywords Prostate cancer · Lymph node metastasis · Stereotactic radiotherapy · Systematic review Introduction Prostate cancer (PCa) is the second most frequent cancer and the fifth leading cause of cancer death in men worldwide [1]. In Developed Countries, one out of eight men will be diagnosed with PCa during their lifetime [2]. PCa incidence * Alice Zamagni 1 Department of Experimental Diagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum - Bologna University, Bologna, Italy 2 Radiation Oncology Unit, Gemelli Molise Hospital - Università Cattolica del Sacro Cuore, Campobasso, Italy 3 Istituto di Radiologia, Università Cattolica del Sacro Cuore, Rome, Italy 4 Medical Physics Unit, Gemelli Molise Hospital - Università Cattolica del Sacro Cuore, Campobasso, Italy and death rates are strictly related to the widespread use of PSA screening since it allows early tumor detection but also increases the identification of latent PCa [1]. Moreover, advances in imaging techniques in recent years led to increased detection of oligometastatic PCa and thus to a growing interest in metastases-directed therapies (MDT) [3]. 5 Medical Physics Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy 6 Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Radioterapia Oncologica ed Ematologia, Rome, Italy 7 Dipartimento Universitario Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Università Cattolica del Sacro Cuore, Rome, Italy 8 Radiation Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy 13 Vol.:(0123456789) Clinical & Experimental Metastasis The optimal treatment in this setting is still under debate due to a lack of strong evidence. Moreover, based on international guidelines [4, 5], the current treatment standard for metastatic PCa is still androgen deprivation therapy (ADT) (± other systemic therapies), without specific indications for the subset of oligometastatic patients. However, increasing evidence suggests that a more targeted management of oligometastatic PCa could play a role as a “curative” option in the multimodal treatment approach [6] with high local control (LC) rate and delay of systemic treatments. As a result, 75% of the Advanced Prostate Cancer Consensus Conference (APCCC, 2019) panelists recommended systemic therapy plus local treatment of all lesions for most patients with oligorecurrent PCa [7] due to better tolerability of MDT [7–11] compared to chemotherapy or ADT [12, 13]. Even though publications in this setting have increased in the last years, at least two questions are still open, namely, what is the impact of MDT on overall survival (OS) and cancer-specific survival and how to select patients suitable for this approach. For patient stratification, following the recent classification proposed by the European Society for Radiotherapy and Oncology (ESTRO) and Radiation Therapy Oncology Group (RTOG) consensus [14], a first distinction should be made between synchronous and metachronous oligometastatic PCa [15, 16]. In fact, metachronous nodal oligometastases should be considered as a potentially different entity compared to bones or visceral oligometastases (or at least as a different step of disease progression) [17, 18] being lymph nodes (LN) oligometastases a favorable subset in terms of disease progression [17, 19, 20]. However, clear evidence (especially from randomized phase III trials) in this setting is lacking. Therefore, we performed a systematic review to summarize the available results on stereotactic body radiotherapy (SBRT) as MDT in nodal oligometastases from PCa. Materials and methods The protocol of this systematic review was submitted to the PROSPERO international prospective register of systematic review on August 25th, 2020 [21]. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed to perform the analysis [22]. We searched for articles reporting on the outcome of metachronous oligometastatic PCa patients treated with SBRT for LN metastases. The primary objectives of the review were LC and progression-free survival (PFS). We also collected data on the biochemical response (BRes), biochemical relapse, clinical response (CRes), androgen deprivation therapy-free survival (ADT-FS), OS, and toxicity when reported with at least one of the primary endpoints. 13 Bibliographic search A literature search for relevant studies was conducted in PubMed, Scopus, and Cochrane library up to July 1st, 2021, using the combination of several terms like: “lymph node”, “metastases”, “stereotactic body radiotherapy”. The term “prostat*” was not included in the search criteria to allow the identification of papers reporting data on mixed primary tumors. The complet (...truncated)