Patterns of Lymph Node Failure in Patients With Recurrent Prostate Cancer Postradical Prostatectomy and Implications for Salvage Therapies

Abstract

Purpose There is increasing use of radical prostatectomy to treat patients with high-risk prostate cancer. This has contributed toward a pathologic stage migration, and a greater number of patients are subsequently being diagnosed with biochemical failure. There is increasing use of advanced imaging techniques in the setting of biochemical failure, including positron emission tomography-computed tomography (PET-CT). Methods and Materials This critical literature review highlights the evidence for PET-CT in postprostatectomy biochemical failure and identifies sites of pelvic lymph node relapse in the setting of biochemical failure and the potential implications that the locations of these relapses may have for salvage therapies. Potential future directions are then considered. Results The optimal PET-CT tracer remains uncertain but there is increasing use of prostate-specific membrane antigen PET-CT for investigating sites of nodal metastasis at low prostate-specific antigen levels, and this is leading to a blurring of the biochemical and radiologic recurrence phases. The optimal therapeutic approach remains undefined, with current trials investigating postoperative radiation therapy to the whole pelvis in addition to the prostatic fossa, the use of PET-CT in the setting of biochemical recurrence to guide delivery of salvage radiation therapy, and, for patients with node-only relapsed prostate cancer, the addition of whole pelvis radiation therapy to metastasis-directed therapies such as stereotactic ablative radiotherapy. Conclusions The most appropriate target volume for salvage radiation therapy remains uncertain, and the findings of studies using PET-CT to map nodal recurrences suggest that there could be a role for extending whole pelvis radiation therapy volumes to increase coverage of superior nodal regions. The emerging fields of radiomics and radiogenomics could provide important prognostic information and aid decision making for patients with relapsed prostate cancer.

Elective nodal radiotherapy in prostate cancer

“…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. 16,54 This increasing knowledge also led to an adaptation in the RTOG delineation guidelines 55 for pelvic nodal areas. These guidelines stress the importance of the upper (should include common iliac arteries and veins) and lower delineation limits (should include presacral nodes to the bottom of the third sacral vertebra).…”

“…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.…”

Salvage Reirradiation Options for Locally Recurrent Prostate Cancer: A Systematic Review

“…The recent proPSMA randomised study reported that PSMA PET-CT had a greater accuracy compared to conventional imaging with CT and bone scan in the primary setting (92% vs 65%) ( 81 ). PSMA PET-CT also has superior performance characteristics for the detection of distant metastasis in the setting of biochemical failure compared to other PET tracers ( 82 ). Nevertheless, the clinical significance of detecting and treating small volume local recurrence at low PSA levels remains uncertain and may risk additional toxicity.…”

Value of PET imaging for radiation therapy

“…Through improved characterization of recurrent prostate cancer, PSMA-targeted PET/CT has shown significant impact on management decisions, such as by identifying patients with recurrence confined to the prostate or pelvic nodes [179,180]. At a PSA value of less than 0.5 ng/mL, PSMA-PET/CT detects lymph node metastases in approximately 20 % of patients [181].…”