BERKELEY, CA (UroToday.com) - The optimal management of men with post-prostatectomy biochemical failure remains unclear, but emerging data from Johns Hopkins[1] and Duke Universities[2] have recently provided some of the earliest evidence that salvage radiotherapy may prolong overall survival versus delay of intervention until time of symptomatic progression. Nonetheless, results with salvage radiotherapy remain sub-optimal, and investigations of treatment intensification strategies are indicated, including consideration of elective targeting of the pelvic lymph nodes.
It is important to note, the majority of published trials to date of post-prostatectomy salvage radiotherapy involved treatment limited to the prostate bed. Whether or not expansion of radiation fields to include the pelvic lymph nodes can improve outcomes is unknown. Currently, the phase III RTOG 0534 trial is prospectively randomizing patients to small versus large field radiotherapy, in addition to evaluating the role of a short course of androgen deprivation therapy. This study continues to accrue, and has enrolled over 1 000 out of a target of 1 764 patients with post-prostatectomy biochemical failure. However, it may be many more years before we learn if larger fields improve outcomes and if the potential risks of increased pelvic toxicity is warranted.
The data published from our inter-institutional study[3] which included 247 patients, compared the experience of two academic radiation oncology departments with an almost 100% preference for either targeting only the prostate bed (Duke University) or including the pelvic lymph nodes (Virginia Commonwealth University). The IRB-approved study was designed with the goal of comparing disparate treatment paradigms with an analysis that may be devoid of selection bias because of institutional preferences.
The analysis showed no significant improvement in biochemical PSA control rates with larger field radiotherapy in men treated with a pre-radiotherapy PSA <0.4 ng/mL. However, in patients for whom salvage radiotherapy was initiated with a PSA ≥0.4 ng/mL (n=139), the post-radiotherapy PSA progression rates were cut in half if the pelvic lymph nodes were included (HR 0.47, 0.24-0.93, p=0.03). As demonstrated in numerous prior studies, the analysis also demonstrated outcomes with salvage radiotherapy were best when treatment was initiated at the lowest pre-radiotherapy PSA levels, and in men with Gleason scores of ≤7.
Important caveats are noted in the manuscript, including an unbalanced group of patients at each of the two institutions, largely an influence of upstream referral patterns from two different urology departments. Unfortunately, there were not enough patients available for a propensity score matched-pair analysis, and the limitations of adjusting unbalanced groups with the Cox model is highlighted in the discussion.
While these data are intriguing, at our center we continue recruiting patients for enrollment on the phase III RTOG 0534 study that may one day provide level I evidence to justify elective pelvic lymph node irradiation in this setting.
These findings are scheduled for additional presentation at the American Society of Radiation Oncology Annual Meeting in Boston this October, 2012.
References:
- Trock BJ, Han M, Freedland SJ, et al. Prostate cancer-specific survival following salvage radiotherapy vs observation in men with biochemical recurrence after radical prostatectomy. JAMA. 2008;299: 2760-2769.
- Cotter SE, Chen MH, Moul JW, et al. Salvage radiation in men after prostate-specific antigen failure and the risk of death. J Cancer. 2011;117:3925-3932.
- Moghanaki D, Koontz BF, Karlin JD, et al. Elective Irradiation of Pelvic Lymph Nodes During Postprostatectomy Salvage Radiotherapy. J Cancer. 2012; Epub ahead of print
Written by:
Drew Moghanaki, MD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia USA and,
Radiation Oncology Service, Hunter Holmes McGuire Veterans Affairs Medical Center, Richmond, Virginia USA
Elective irradiation of pelvic lymph nodes during postprostatectomy salvage radiotherapy - Abstract
