Nodal recurrence patterns on PET/CT after RTOG-based nodal radiotherapy for prostate cancer

Abstract

Biochemical failure after external beam radiotherapy (RT) for node-positive prostate cancer (PC N+) frequently involves nodal recurrences, in most cases out of field. This raises the question if current RTOG-based elective nodal fields can still be considered optimal. Modern diagnostic tools like PSMA PET/ CT and choline PET/CT can visualize nodal recurrences with unprecedented accuracy. We evaluated recurrence patterns on PET/CT after RT for PC N+ , with the aim to explore options for improved nodal target definition. Methods and materials: Data of all patients treated with curative intent EBRT for PC N+ in NKI-AVL from 2008 to 2018 were retrospectively reviewed. EBRT comprised 70 Gy to the prostate or 66-70 Gy to the prostate bed, 60 Gy to involved nodes, and 52,5-56 Gy (46 Gy EQD2) to RTOG-based elective nodal fields, in 35 fractions. Locations of recurrences on PET/CT were noted, and nodal locations were correlated with the applied EBRT fields. Results: 42 patients received PSMA (28) or choline (14) PET/CT at biochemical recurrence. 35 patients (83%) had a positive scan. At their first positive scan 17 patients had nodal metastasis, in some cases together with a local recurrence or distant disease. In-field nodal recurrences were uncommon (n = 3). Out-field nodal recurrences occurred more frequently (n = 14), with the majority (n = 12) just above the elective nodal field. These nodes were the single area of detectable failure in 6 patients (14%). Conclusions: Current RT with RTOG-based nodal fields for PC N+ provides good in-field tumour control, but frequent out-field nodal recurrences suggest missed microscopic locations. Expanding elective fields to include the aorta bifurcation may prolong recurrence-free survival. Future research must address whether the potential benefits of this strategy outbalance additional toxicity.

Elective nodal radiotherapy in prostate cancer

“…Lymphatic drainage of the prostate is complex and lymph node metastases are found in hypogastric and internal iliac nodes (lateral pathway), obturator fossa nodes (inferior pathway), external iliac nodes (ascending pathway), presacral nodes (posterior pathway), and in the common iliac nodes. 2,5,[17][18][19] However, the proPSMA trial 42 showed that in some cases uptake in the nodes was outside the traditional boundaries of an extended pelvic Review lymph node dissection. Translating this finding to the radiation-oncology community implies the use of vascular anatomy instead of the bony anatomy and inclusion of common iliac nodes, which has also been proposed in published reviews.…”

“…51 Because the upper border excludes common iliac nodes and parts of the external iliac and presacral nodes, 7 major lymph node areas at risk were missed for the whole pelvis radiotherapy group, 5 with only 33% of these areas covered when compared with the location of lymph node metastases in patients with pelvic nodal recurrences after radical local treatment. 17,18 Even when the upper border was set at the L5-S1 interspace (same as in the RTOG 9413 trial), only 42% of patients with nodal disease would have complete coverage; hence this coverage is probably insufficient to show any benefit from whole pelvis radiotherapy. Conversely, raising the upper limit of whole pelvis radiotherapy to the L4/L5 interspace could have prevented more than 90% of the nodal recurrences after definitive radiotherapy, according to a retrospective analysis on 2694 patients at Memorial Sloan Kettering Cancer Center (New York, NY, USA).…”

“…9 An exploratory post-hoc analysis of the Medical Research Council PR07 trial 13 confirmed that there was no benefit of whole pelvis radiotherapy. Reasons for this finding might not necessarily be due to the absence of a benefit, but might be the result of incorrect patient selection (in patients with low risk and positive pelvic nodes the benefit of whole pelvis radiotherapy is often absent), [4][5][6]8,9,11,[14][15][16] inadequate treatment volume definition (not all pelvic nodal regions at risk were considered and consequently not irradiated), 2,4,5,7,[9][10][11]14,15,17,18 inappropriate technology used, 3,10,19 an insufficient dose, 4,[10][11][12]14,15,17,19,20 and inadequate use of concomitant and adjuvant androgen deprivation therapy. 9,11,17,20,21 In 2014, Dirix and colleagues 2 published a systematic review on this issue, analysing seven contemporary retrospective studies from 2006 to 2011 on elective pelvic radiotherapy.…”

Elective nodal radiotherapy with a gapless radiation field junction for oligorecurrent prostate cancer after previous radiotherapy

“…In addition, pattern of failure analyses after pelvic ENRT have shown that with current treatment field recommendations a relevant proportion of LN are inadequately covered, thus e.g. recommending extending the superior border of the treatment field [39] , [40] . However, although prophylactic pelvic RT and extending pelvic treatment fields may benefit some high-risk patients with microscopic tumour cells metastasis in lymph drainage pathways, there might be a proportion of patients who are overtreated, suffering from radiation-induced side effects unnecessarily.…”

PEARLS – A multicentre phase II/III trial of extended field radiotherapy for androgen sensitive prostate cancer patients with PSMA‐avid pelvic and/or para-aortic lymph nodes at presentation

“…On review of patterns of recurrence after pelvic radiotherapy, a predominant site for lymph node recurrence is within the para-aortic lymph node region. Sites of recurrence are rarely seen within irradiated pelvic lymph node field [11] , [12] . These findings form the basis of the hypothesis being tested in the PEARLS trial – i.e., that encompassing the para-aortic lymph nodes will have a favourable effect on metastasis free survival (MFS).…”