Metastasis-directed Therapy in Treating Nodal Oligorecurrent Prostate Cancer: A Multi-institutional Analysis Comparing the Outcome and Toxicity of Stereotactic Body Radiotherapy and Elective Nodal Radiotherapy

Bleser, Elise De; Jereczek‐Fossa, Barbara Alicja; Pasquier, David; Zilli, Thomas; As, Nicholas van; Siva, Shankar; Fodor, Andrei; Dirix, Piet; Gómez-Iturriaga, A.; Trippa, Fabio; Detti, Beatrice; Ingrosso, Gianluca; Triggiani, Luca; Bruni, Alessio; Alongi, Filippo; Reynders, Dries; Meerleer, Gert De; Surgo, A.; Loukili, Kaoutar; Miralbell, Raymond; Silva, Pedro; Chander, Sarat; Muzio, N.G. Di; Maranzano, Ernesto; Francolini, Giulio; Lancia, Andrea; Tree, A.; Deantoni, C.L.; Ponti, Elisabetta; Marvaso, Giulia; Goetghebeur, Els; Ost, Piet

doi:10.1016/j.eururo.2019.07.009

Cited by 119 publications

(77 citation statements)

References 30 publications

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“…This proportionally lower bRFS rate of the current patient cohort with SLND is comparable to a recent retrospective, multicentre analysis on SBRT vs. ENRT [31]: ENRT was associated with significantly better 3-year metastasisfree survival (77% vs. 68%) and significantly fewer individuals with local progression (9 vs. 50 patients) compared to SBRT. Like non-extensive SLND, SBRT treats only the PET-positive lymph nodes, whereas ENRT, as it was performed in the current cohort, not only treats the PET-positive, affected nodes, but the whole lymphatic drainage, for instance the entire pelvic lymphatic pathway as well as in general the prostatic fossa especially in patients with locally advanced disease or positive surgical margins.…”

Section: Discussionsupporting

confidence: 79%

PSMA-positive nodal recurrence in prostate cancer

et al. 2020

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Purpose This analysis compares salvage lymph node dissection (SLND) to salvage lymph node radiotherapy (SLNRT) of 68 Ga-PSMA PET-positive nodal recurrences after radical prostatectomy (RPE). Methods A total of 67 SLNRT and 33 SLND consecutive patients with pelvic and/or para-aortic nodal recurrences after RPE were retrospectively analyzed. Biochemical recurrence-free survival rates (bRFS; PSA <0.2 ng/mL) were calculated according to Kaplan-Meier and survival curves were compared using the log rank test. For multivariable analysis, binary logistic regression analysis was performed (p < 0.05). Results Median follow-up was 17 months (range, 6-53 months) in SLND patients and 31 months (range, 3-56 months) in SLNRT patients (p = 0.027). SLNRT patients had significantly more tumours of pT3 and pT4 category (82% vs. 67%; p = 0.006), pathologically involved lymph nodes (45% vs. 27%; p = 0.001) and positive surgical margins (54% vs. 12%; p = 0.001) at time of RPE than SLND patients. PSA persistence after RPE was significantly more frequently observed in the SLNRT cohort (73% vs. 27%; p = 0.001). There was no significant difference in the distribution of PET-positive lymph nodes. Median PSA before SLND was higher than before SLNRT (3.07 ng/ml vs. 1.3 ng/ml; p = 0.393). The 2-year bRFS was significantly higher in the SLNRT vs. the SLND cohort (92% vs. 30%; p = 0.001) with lower rates of distant metastases (21% vs. 52%; p = 0.002) and secondary treatments (5% vs. 39%; p = 0.011) irrespective of ongoing androgen deprivation therapy at last contact. In multivariable analysis, SLNRT was significantly associated with prolonged bRFS (regression coefficient 1.436, hazard ratio 4.204, 95% CI 1.789-9.878; p = 0.001). Conclusion Based on this retrospective study SLNRT might be the preferred treatment option for patients with nodal recurrence after previous RPE.

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Section: Discussionsupporting

confidence: 79%

PSMA-positive nodal recurrence in prostate cancer

et al. 2020

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“…Therefore, an alternative to HT monotherapy has long been sought. Among the alternative treatment methods, both MDT via SBRT and the surgical dissection of metastatic nodes have been tested for efficacy and feasibility in many prospective studies and retrospective series [ 3–5 , 15 ]. In the current study, treatment with sPRT combined with long-term HT resulted in a 5-year BF-free rate of 62.3%.…”

Section: Discussionmentioning

confidence: 99%

“…conducted a retrospective analysis of failure patterns following MDT (SBRT for recurrent nodes alone or elective nodal radiation therapy) in patients with nodal oligo-recurrent hormone-sensitive PCa (N1 and/or M1a). They reported that further lymph nodal progression occurred less frequently in the group treated with elective nodal radiation therapy than in the group treated with SBRT for recurrent nodes alone ( P < 0.001), especially in the pelvic region (4% vs 31%, respectively, P < 0.001) [ 3 ]. In our patients, treatment with sPRT resulted in 100% regional control, which was consistent with the findings in previous reports regarding regional irradiation [ 3 , 5 ].…”

Section: Discussionmentioning

confidence: 99%

“…A randomized phase 2 SABR-COMET trial suggested a survival benefit for patients with oligo-recurrent tumors whose metastatic lesions were treated by the addition of stereotactic body radiation therapy (SBRT) [ 2 ]. In patients with PCa, salvage treatments for recurrent metastasis via high-dose EBRT or surgical resection, referred to as metastasis-directed therapy (MDT), have been used mainly in patients with oligo-recurrent or oligo-progressive PCa; these treatments are a promising alternative to conventional lifelong HT [ 3–6 ]. However, in most studies of MDT, the cohort included both patients with recurrent distant metastasis and those with PeNR alone.…”

Section: Introductionmentioning

confidence: 99%

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Long-term clinical outcomes of salvage pelvic radiation therapy for oligo-recurrent pelvic lymph nodes after definitive external-beam radiation therapy for non-metastatic prostate cancer

Sato

Aizawa

Nakamura

et al. 2020

Journal of Radiation Research

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Abstract Although salvage external-beam radiation therapy (EBRT) is an attractive treatment option for pelvic lymph nodal recurrence (PeNR) in patients with prostate cancer (PCa), limited data are available regarding its long-term efficacy. This study examined the long-term clinical outcomes of patients who underwent salvage pelvic radiation therapy (sPRT) for oligo-recurrent pelvic lymph nodes after definitive EBRT for non-metastatic PCa. Patients who developed PeNR after definitive EBRT and were subsequently treated with sPRT at our institution between November 2007 and December 2015 were retrospectively analyzed. The prescribed dose was 45–50.4 Gy (1.8–2 Gy per fraction) to the upper pelvis, with up to 54–66 Gy (1.8–2 Gy per fraction) for recurrent nodes. Long-term hormonal therapy was used as neoadjuvant and/or adjuvant therapy. The study population consisted of 12 consecutive patients with PeNR after definitive EBRT (median age: 73 years). The median follow-up period was 58.9 months. The 5-year overall survival, PCa-specific survival, biochemical failure-free, clinical failure-free, and castration-resistant PCa-free rates were 82.5, 100.0, 62.3, 81.8, and 81.8%, respectively. No grade 2 or higher sPRT-related late toxicities occurred. In conclusion, more than half of the study patients treated with sPRT had a long-term disease-free status with acceptable morbidities. Moreover, most of the patients maintained hormonal sensitivity. Therefore, this approach may be a promising treatment method for oligo-recurrent pelvic lymph nodes.

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“…Therefore, current guidelines recommend prostate-specific membrane antigen ligand positron emission tomography (PSMA-PET)-imaging if the outcome will affect treatment planning (1). Promising efficacy of metastasesdirected therapy such as salvage lymph node dissection (SLND) or salvage radiotherapy (S-RT) has been reported in several studies (2,3), but evidence on the long-term oncological impact is missing. In patients with longer PSA doubling times, lower RP specimen pathological ISUP grades and disease recurrence confined to lymph nodes, metastases-directed therapy aims at decreased risk of distant progression, later onset of ADT and potential improvement of cancer-specific survival.…”

Section: Introductionmentioning

confidence: 99%

Mapping Prostate Cancer Lesions Before and After Unsuccessful Salvage Lymph Node Dissection Using Repeat PSMA PET

et al. 2019

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Introduction: The aim of this study was to analyze patterns of persistent versus recurrent or new PET lesions in a selected patient cohort with PSA persistence following salvage lymph node dissection (SLND) and pre/post procedure prostate-specific membrane antigen ligand positron emission tomography (PSMA-PET). Material and Methods: 16 patients were included in this multicenter study. Inclusion criteria were: a) PSMA-PET performed for biochemical recurrence before SLND (pre-SLND PET) and b) repeat PSMA-PET performed for persistently elevated PSA level (≥0.1 ng/mL) ≥6 weeks after SLND (post-SLND PET). Image analysis was performed by three independent nuclear medicine physicians applying the molecular imaging TNM system PROMISE. Lesions were confirmed by histopathology, presence on correlative CT/MRI/bone scan or PSA response after focal therapy. Results: post-SLND PET identified PCa-lesions in 88% (14/16) of patients with PSA persistence after SLND. Median PSA was 1.2 ng/mL (IQR, 0.6-2.8 ng/mL). Disease was confined to the pelvis in 56% of patients (9/16) and most of these men had common iliac (6/16, 38%) and internal iliac lymph node metastases (6/16, 38%). Extrapelvic disease was detected in 31% of patients (5/16). In pre-and post-SLND PET comparison, 10/16 had at least one lesion already detected at baseline (63% PET persistence); 4/16 had new lesions only (25% PET recurrence); 2 had no disease on post-SLND PET. All validated regions (11 regions in 9 patients) were true positive. 9/14 (64%) patients underwent repeat local therapies after SLND (7/14 radiotherapy, 2/14 surgery). Conclusions: SLND of pelvic nodal metastases was often not complete according to PSMA-PET. About two thirds of patients had PET positive nodal disease after SLND already seen on pre-SLND PSMA-PET. Notably, about one quarter of patients had new lesions, not detected by presurgical PSMA-PET.

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Metastasis-directed Therapy in Treating Nodal Oligorecurrent Prostate Cancer: A Multi-institutional Analysis Comparing the Outcome and Toxicity of Stereotactic Body Radiotherapy and Elective Nodal Radiotherapy

Cited by 119 publications

References 30 publications

PSMA-positive nodal recurrence in prostate cancer

PSMA-positive nodal recurrence in prostate cancer

Long-term clinical outcomes of salvage pelvic radiation therapy for oligo-recurrent pelvic lymph nodes after definitive external-beam radiation therapy for non-metastatic prostate cancer

Mapping Prostate Cancer Lesions Before and After Unsuccessful Salvage Lymph Node Dissection Using Repeat PSMA PET

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