Impact of Adjuvant Radiotherapy in Node-positive Prostate Cancer Patients: The Importance of Patient Selection

Abdollah, Firas; Dalela, Deepansh; Sood, Akshay; Keeley, Jacob; Alanee, Shaheen; Briganti, Alberto; Montorsi, Francesco; Peabody, James O.; Menon, Mani

doi:10.1016/j.eururo.2018.04.017

Cited by 58 publications

(40 citation statements)

References 7 publications

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“…Integration of existing evidence is further hampered by differing patient characteristics, diagnostic modalities and therapy sequences [4]. Overall, it is hypothesized that MDT to lymph node recurrences optimizes the locoregional control, possibly limits the risk of distant progression and thereby might improve cancer-specific survival, as has been described by mainly retrospective data [22][23][24][25][26].…”

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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Section: Discussionmentioning

confidence: 99%

PSMA-positive nodal recurrence in prostate cancer

et al. 2020

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“…Larger series (38) and a subpopulation analysis of STAMPEDE (39) have suggested benefit with pelvic radiotherapy in pathological or clinical node positive patients. 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).…”

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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“…Indeed, even if there is a lack of randomized evidence, retrospective studies suggest that radiotherapy may improve survival for the subgroup of patients [53–57]. Furthermore, among men with pN1 PCa (at radical prostatectomy), the subgroup benefiting from radiotherapy is the one with one to two positive nodes, pathological Gleason score 7–10, and pT3b/4 disease or positive surgical margins [58].…”

Section: Discussionmentioning

confidence: 99%

Intensity-modulated radiotherapy for prostate cancer with seminal vesicle involvement (T3b): A multicentric retrospective analysis

et al. 2019

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ObjectivesNo study has reported clinical results of external-beam radiotherapy specifically for T3b prostate cancer. The possibility of escalating the dose to the involved seminal vesicles (ISV) while respecting the dose constraints in the organs at risk is thus so far not clearly demonstrated. The objective of the study was to analyze the dose distribution and the clinical outcome in a large series of patients who received IMRT for T3b prostate cancer.Materials and methodsThis retrospective analysis included all patients who received IMRT and androgen deprivation therapy for T3b prostate cancer, between 2008 and 2017, in six French institutions, with available MRI images and dosimetric data.ResultsA total of 276 T3b patients were included. The median follow-up was 26 months. The median (range) prescribed doses (Gy) to the prostate and to the ISV were 77 (70–80) and 76 (46–80), respectively. The dose constraint recommendations were exceeded in less than 12% of patients for the rectum and the bladder. The 5-year risks of biochemical and clinical recurrences and cancer-specific death were 24.8%, 21.7%, and 10.3%, respectively. The 5-year risks of local, pelvic lymph node, and metastatic recurrences were 6.4%, 11.3%, and 15%, respectively. The number of involved lymph nodes (≤ 2 or ≥ 3) on MRI was the only significant prognostic factor in clinical recurrence (HR 9.86) and death (HR 2.78). Grade ≥ 2 acute and 5-year late toxicity rates were 13.2% and 12% for digestive toxicity, and 34% and 31.5% for urinary toxicity, respectively. The dose to the pelvic lymph node and the age were predictive of late digestive toxicity.ConclusionIMRT for T3b prostate cancer allows delivery of a curative dose in the ISV, with a moderate digestive toxicity but a higher urinary toxicity. Lymph node involvement increases the risk of recurrence and death.

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Impact of Adjuvant Radiotherapy in Node-positive Prostate Cancer Patients: The Importance of Patient Selection

Cited by 58 publications

References 7 publications

PSMA-positive nodal recurrence in prostate cancer

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

Intensity-modulated radiotherapy for prostate cancer with seminal vesicle involvement (T3b): A multicentric retrospective analysis

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