Editorial
Are we at the end of adjuvant radiotherapy for prostate cancer?
¿Estamos ante el final de la radioterapia adyuvante en cáncer de próstata?
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"tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "521" "paginaFinal" => "523" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "F. Couñago, M. Alvarez-Maestro" "autores" => array:2 [ 0 => array:3 [ "nombre" => "F." "apellidos" => "Couñago" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 1 => array:4 [ "nombre" => "M." "apellidos" => "Alvarez-Maestro" "email" => array:1 [ 0 => "malvarezmaestro@hotmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Departamento de Radiología Oncológica, Hospital Universitario Quirón Salud, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Hospital La Luz, Universidad Europea, Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Departamento de Urología, Hospital Universitario La Paz, Madrid, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "¿Estamos ante el final de la radioterapia adyuvante en cáncer de próstata?" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Few issues regarding the management of prostate cancer have been as widely analyzed and debated as the optimal timing for the administration of radiotherapy following radical prostatectomy. The concept of “adjuvant” radiotherapy refers to the administration of treatment when there is no evidence of residual disease after surgery, and “salvage” radiotherapy refers to the administration of treatment when there is already recurrence of disease. The potential advantage of adjuvant radiotherapy versus salvage radiotherapy is the early management of the disease, when there is little or no disease burden and, therefore, there is a higher chance of obtaining curative results. However, it also has its drawbacks: overtreatment of patients who will be cured by surgery alone and who are therefore exposed to unnecessary toxicity, especially gastrointestinal and genitourinary toxicity.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Currently, treatments should demonstrate clinical benefit for the patient (in terms of metastasis-free survival, cancer-specific survival or overall survival) in one or more randomized trials, in order to change clinical practice in prostate cancer. In addition, these should be shown to be safe, with acceptable side effect profiles. Finally, these treatments should be used considering the inclusion and exclusion criteria of the corresponding pivotal clinical trials.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Having said that, there are 7 randomized phase III studies that have analyzed the best timing to administer postoperative radiotherapy to the prostate bed after radical prostatectomy. Four “former” studies: ARO 96-02/AUO AP 09/95, SWOG 8794, EORTC 22911, and the Finnish FinnProstate Group trial,<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1–4</span></a> which included patients undergoing surgery for prostate cancer and randomized to observation or adjuvant radiotherapy. These 4 studies concluded that adjuvant radiotherapy is superior to observation in terms of biochemical control. Furthermore, the SWOG study demonstrated increased metastasis-free survival and overall survival rates. Consequently, the indication for adjuvant radiotherapy in patients with extracapsular involvement (pT3) or with positive surgical margins was implemented in the clinical guidelines worldwide. However, and despite this recommendation, few patients went on to receive adjuvant radiotherapy within the real clinical practice.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> On the other hand, contemporary studies show that less than 30% of patients who relapse after surgery receive salvage radiotherapy,<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> which is, as we know, the only curative treatment in this clinical scenario. Of these patients, only half of them receive early radiotherapy (with PSA < 0.5 ng/mL), at which time, curative results may be greater.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Three new phase 3 trials (GETUG-17,<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> RADICALS-RT,<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> RAVES<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a>) and a meta-analysis, ARTISTIC,<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> based on these 3 studies, have been published during 2020. These trials compared adjuvant versus early salvage radiotherapy (PSA < 0.5 ng/mL).<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6–9</span></a> None of these studies demonstrated that adjuvant radiotherapy was beneficial in terms of progression-free survival and, predictably, adjuvant radiotherapy was associated with increased urinary and gastrointestinal toxicity. Despite the relatively short follow-up (about 5 years) of these 3 studies, a long-term benefit from adjuvant radiotherapy greater than the one obtained in the “former” studies (in which observation or late radiotherapy (PSA > 0.5 ng/mL figures) were compared), should not be expected.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Following the publication of these studies, several authors (D’Amico, Spratt and Parker) have published 3 editorials analyzing the results and their implications.<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10–12</span></a> The conclusions of these editorials were:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">-</span><p id="par0030" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">D’Amico</span>: while we await the long-term results of the RADICALS-RT study to evaluate metastasis-free survival in the subgroup of high risk patients, in these patients (pT3b-4 and Gleason ≥ 8), who account for less than 20% of the patients included in the 3 “new” trials, it is prudent to consider adjuvant radiotherapy after the clinical assessment performed by a multidisciplinary team.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">-</span><p id="par0035" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Spratt</span>: we may abandon adjuvant radiotherapy as long as we increase the use of early salvage radiotherapy (PSA < 0.5 ng/mL; 0.2 ng/mL, ideally) in clinical practice. Patients who may still benefit from adjuvant radiotherapy are those who are underrepresented in “new” trials: pelvic lymph node-positive patients or patients with multiple adverse pathologic factors (Gleason = 9–10; pT3b; positive margin; with very high Decipher score [>0.8]).<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">-</span><p id="par0040" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Parker</span>: adjuvant radiotherapy after radical prostatectomy increases gastrointestinal and genitourinary toxicity without demonstrating any benefit. Salvage radiotherapy should be the current standard of care in this clinical scenario.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> Parker’s argument for not recommending adjuvant radiotherapy in very high-risk patients is that the RADICALS-RT<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> study already included 436 patients with Gleason = 8–10 or pT3b/T4 or both.</p></li></ul></p><p id="par0045" class="elsevierStylePara elsevierViewall">Therefore, while some authors (D’Amico and Spratt)<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10,11</span></a> consider that adjuvant radiotherapy might still play a small role in selected patients (pelvic lymph node-positive or patients with high-risk pathological factors), other authors (Parker)<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> believe that we are facing the end of adjuvant radiotherapy and that, therefore, salvage treatment should be the standard of care.</p><p id="par0050" class="elsevierStylePara elsevierViewall">In conclusion, based on the 3 randomized trials published in 2020, early salvage radiotherapy (PSA < 0.5 ng/mL) should be the current standard of care for patients who have previously undergone radical prostatectomy, since it has been shown to have the same clinical benefit as adjuvant radiotherapy, and decreased bowel and urinary toxicity. However, to date, and despite the existent controversy, we believe that adjuvant radiotherapy could still be considered in the subgroup of patients who were underrepresented or excluded from these clinical trials: patients with positive pelvic nodes or patients at high risk of recurrence (pT3b-4; Gleason ≥ 8).</p><p id="par0055" class="elsevierStylePara elsevierViewall">Future indications in the management of these patients who are to receive early salvage radiotherapy are the implementation of advanced molecular imaging (multiparametric MRI and positron emission tomography) when PSA levels are below 0.5 ng/mL. In this clinical scenario, the utility of imaging tests remains moderate (30%–40% tumor detection), and their clinical benefit remains unclear.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> In this sense, considering the poor clinical benefit of adjuvant radiotherapy versus late radiotherapy or observation shown in the “former” studies, a strategy of molecular imaging-guided late radiotherapy would be an option to explore in upcoming clinical trials.</p><p id="par0060" class="elsevierStylePara elsevierViewall">On the other hand, we still have pending the challenge of transferring the use of molecular biomarkers (e.g., Decipher) into routine clinical practice; this will allow us to select those patients who will benefit most from salvage radiotherapy or associated hormone therapy.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Couñago F, Alvarez-Maestro M. ¿Estamos ante el final de la radioterapia adyuvante en cáncer de próstata? 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| 2023 March | 2 | 3 | 5 |
| 2021 December | 1 | 0 | 1 |
