Nodal Oligorecurrent Prostate Cancer: Anatomic Pattern of Possible Treatment Failure in Relation to Elective Surgical and Radiotherapy Treatment Templates

Bruycker, Aurélie De; Bleser, Elise De; Decaestecker, Karel; Fonteyne, Valérie; Lumen, Nicolaas; Visschere, Pieter De; Man, Kathia De; Delrue, Louke; Lambert, Bieke; Ost, Piet

doi:10.1016/j.eururo.2018.10.044

Cited by 50 publications

(43 citation statements)

References 29 publications

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“…While NRG GU experts thoroughly discussed the inclusion of perirectal levels especially for T4 tumors, the majority of experts had opted against routinely including these lymph nodes in view of the corresponding increase in treatment volume ( 15 ). As the perirectal region has been a frequent site of nodal recurrence in multiple studies ( 12 , 14 , 26 ), it would be highly beneficial to identify reliable predictive factors for perirectal involvement to include perirectal nodes in high-risk patients but to avoid unnecessary toxicity in others.…”

Section: Discussionmentioning

confidence: 99%

“…Finally, De Bruycker et al. analyzed nodal recurrence patterns in patients with biochemical failure and ≤ 5 nodal metastases on choline-PET/CT with most patients (82.9%) having initially been treated with radical prostatectomy or a combination of radical prostatectomy and postoperative radiation ( 14 ). Most nodal metastases in the work by De Bruycker et al.…”

Section: Discussionmentioning

confidence: 99%

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The Distribution of Pelvic Nodal Metastases in Prostate Cancer Reveals Potential to Advance and Personalize Pelvic Radiotherapy

et al. 2021

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BackgroundTraditional clinical target volume (CTV) definition for pelvic radiotherapy in prostate cancer consists of large volumes being treated with homogeneous doses without fully utilizing information on the probability of microscopic involvement to guide target volume design and prescription dose distribution.MethodsWe analyzed patterns of nodal involvement in 75 patients that received RT for pelvic and paraaortic lymph node metastases (LNs) from prostate cancer in regard to the new NRG-CTV recommendation. Non-rigid registration-based LN mapping and weighted three-dimensional kernel density estimation were used to visualize the average probability distribution for nodal metastases. As independent approach, the mean relative proportion of LNs observed for each level was determined manually and NRG and non-NRG levels were evaluated for frequency of involvement. Computer-automated distance measurements were used to compare LN distances in individual patients to the spatial proximity of nodal metastases at a cohort level.Results34.7% of patients had pelvic LNs outside NRG-consensus, of which perirectal was most common (25.3% of all patients) followed by left common iliac nodes near the left psoas major (6.7%). A substantial portion of patients (13.3%) had nodes at the posterior edge of the NRG obturator level. Observer-independent mapping consistently visualized high-probability hotspots outside NRG-consensus in the perirectal and left common iliac regions. Affected nodes in individual patients occurred in highly significantly closer proximity than at cohort-level (mean distance, 6.6 cm vs. 8.7 cm, p < 0.001).ConclusionsBased on this analysis, the common iliac level should extend to the left psoas major and obturator levels should extend posteriorly 5 mm beyond the obturator internus. Incomplete coverage by the NRG-consensus was mostly because of perirectal involvement. We introduce three-dimensional kernel density estimation after non-rigid registration-based mapping for the analysis of recurrence data in radiotherapy. This technique provides an estimate of the underlying probability distribution of nodal involvement and may help in addressing institution- or subgroup-specific differences. Nodal metastases in individual patients occurred in highly significantly closer proximity than at a cohort-level, which supports that personalized target volumes could be reduced in size compared to a “one-size-fits-all” approach and is an important basis for further investigation into individualized field designs.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The Distribution of Pelvic Nodal Metastases in Prostate Cancer Reveals Potential to Advance and Personalize Pelvic Radiotherapy

et al. 2021

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“…Correspondingly, they found that with ENRT more patients were theoretically fully covered (p < 0.02) and the total number of covered lesions was higher (p < 0.001) when compared to all types of SLND, except for superextended SLND, which was comparable to ENRT. The authors concluded that limited or standard extended SLND might be insufficient as a salvage treatment approach and ENRT or superextended SLND should be preferred [33].…”

Section: Discussionmentioning

confidence: 99%

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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“…More extensive analyses even suggest adjuvant radiotherapy and LT-ADT alone could suffice for patients with a limited nodal burden (40). However, these studies do not consider the previously occult nodal burden that may now be detected by increasingly implemented more sensitive modern functional imaging (41,42). Ultimately, patients with involved lymph nodes are likely at an increased risk of recurrence, randomized evidence for their management is lacking, they may be detected more frequently, and the population is not included among the ongoing randomized trials (19)(20)(21)34).…”

Section: Discussionmentioning

confidence: 99%

Combined Long-Term Androgen Deprivation and Pelvic Radiotherapy in the Post-operative Management of Pathologically Defined High-Risk Prostate Cancer Patients: Results of the Prospective Phase II McGill 0913 Study

et al. 2020

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Following radical prostatectomy, prostate bed radiotherapy (PBRT) has been combined with either long-term androgen deprivation therapy (LT-ADT) or short-term ADT with pelvic lymph node radiotherapy (PLNRT) to provide an oncological benefit in randomized trials. McGill 0913 was designed to characterize the efficacy of combining PBRT, PLNRT, and LT-ADT. It is the first study to do so prospectively. Methods: In a single arm phase II trial conduced from 2010 to 2016, 46 post-prostatectomy prostate cancer patients at a high-risk for relapse (pathological Gleason 8+ or T3) were assessed for treatment with combined LT-ADT (24 months), PBRT, and PLNRT. Patients received PLNRT and PBRT (44 Gy in 22 fractions) followed by a PBRT boost (22 Gy in 11 fractions). The primary endpoint was progression-free survival (PFS). Toxicity and quality of life (QoL) were evaluated using CTCAE V3.0 and EQ-5D-3L questionnaires, respectively. Results: Among the 43 patients were treated as per protocol, median PSA was 0.30 µg/L. On surgical pathology, 51% had positive margins, 40% had Gleason 8+ disease, 42% had seminal vesicle involvement, and 19% had lymph node involvement. At a median follow-up of 5.2 years, there were no deaths or clinical progression. At 5 years, PFS was 78.0% (95% Confidence Interval 63.7-95.5%). Not including erectile dysfunction, patients experienced: 14% grade 2 endocrine toxicity while on ADT, one incident of long-term gynecomastia, 5% grade 2 acute urinary toxicity, 5% grade 2 late Kucharczyk et al. McGill 0913: Pelvic Radiotherapy and LT-ADT Urinary toxicity, and 24% long-term hypogonadism. No comparison between the average or minimum self-reported QoL at baseline, during ADT, nor after ADT demonstrated a statistically significant difference. Conclusions: Combining PBRT, PLNRT, and LT-ADT had an acceptable PFS in patients with significant post-operative risk factors for recurrence. While therapy was well-tolerated, long-term hypogonadism was a substantial risk. Further investigations are needed to determine if this combination is beneficial. Trial registration: NCT01255891.

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Nodal Oligorecurrent Prostate Cancer: Anatomic Pattern of Possible Treatment Failure in Relation to Elective Surgical and Radiotherapy Treatment Templates

Cited by 50 publications

References 29 publications

The Distribution of Pelvic Nodal Metastases in Prostate Cancer Reveals Potential to Advance and Personalize Pelvic Radiotherapy

The Distribution of Pelvic Nodal Metastases in Prostate Cancer Reveals Potential to Advance and Personalize Pelvic Radiotherapy

PSMA-positive nodal recurrence in prostate cancer

Combined Long-Term Androgen Deprivation and Pelvic Radiotherapy in the Post-operative Management of Pathologically Defined High-Risk Prostate Cancer Patients: Results of the Prospective Phase II McGill 0913 Study

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