Pelvic Proton Radiotherapy for High-Risk Prostate Cancer
Reviewer: Christine Hill, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: May 23, 2008
Presenter: Bhishamjit S. Chera, M.D. Presenter's Affiliation: University of Florida Department of Radiation Oncology, Gainesville, FL Type of Session: Scientific
Treatment options for prostate cancer in the current era are largely based on risk assessment and stratification.
Patients with clinical stage T3 – T4 disease, Gleason stage 8 – 10, and/ or PSA of 20 ng/ ml or greater are classified as having high-risk disease. This disease classification is associated with an 11 – 50% risk of pelvic lymph node involvement (Partin, 2001).
Although the topic of pelvic radiation is relatively controversial among radiation oncologists, many clinicians endorse radiotherapeutic treatment of the pelvic nodes in patients with high-risk disease.
This is generally carried out with either a “four-field box” technique, employing opposed lateral and anterior-posterior beams to treat the entire true pelvis, or an intensity-modulated radiotherapy (IMRT) technique, with dose delivery planned to the common iliac nodes as well as the proximal internal/ external iliac nodes.
Treatment of the pelvic nodes is acknowledged to increase risk of acute and late genitourinary and gastrointestinal complication when compared to treatment to the prostate/ seminal vesicles alone.
This toxicity is reduced with use of IMRT versus conventional radiotherapy (Zelefsky, 2008).
Proton beam radiotherapy may offer dose distribution benefits by allowing greater limitation of dose to normal tissues. This may be possible as a result of the physical properties of protons which provide steep dose fall off beyond the Bragg peak.
This study was carried out to compare dose distribution to volumes of targeted tissue (prostate, seminal vesicles, and pelvic lymph nodes) as well as normal tissue with IMRT versus forward-planned, double-scattered, 3-dimensional proton radiotherapy.
Materials and Methods
Treatment planning was considered for 5 high-risk prostate cancer patients.
Cases for each of the five patients were planned prescribing 46 cobalt gray equlivalents (CGE)/ Grays (Gy) to the whole pelvis, followed by conedown to the prostate and seminal vesicles to a total dose of 78 CGE/ Gy.
Prostate PTV was defined as the GTV (prostate and seminal vesicles as delineated based on planning CT scan) expanded 3 mm.
Nodal CTV was defined as the distal common and proximal internal/ external iliac nodes with a 7 mm expansion.
Nodal PTV was defined as CTV expanded 3 mm in the superior and inferior directions.
Organs at risk were defined as the bladder, rectum, small bowel, femoral heads, and non-CTV pelvis.
The authors note that volumes used during this study were similar to those described by Taylor et al in 2005.
Plans were created using IMRT for the entire 78 Gy, proton radiotherapy for the entire 78 CGE, and IMRT to deliver 46 Gy to the whole pelvis followed by proton boost to the prostate/ seminal vesicles to total dose of 78 Gy/ CGE.
With use of all techniques, doses were prescribed such that 95% of the PTV received 100% of the prescribed dose.
Plans to deliver dose to the whole pelvis and prostate with proton radiotherapy involved the use of 6 fields and 3 isocenters. Two nodal volumes (right and left) were each treated with lateral and posterior oblique fields. These four fields were abutted to two opposed lateral, lower, fields used to deliver dose to the prostate/ seminal vesicles.
Dosimetric endpoints between IMRT plans, proton radiotherapy plans (3DCPRT), and combined (IMRT + 3DCPRT) were compared.
Coverage of the prostate and nodal PTVs were similar between all three techniques, with the PTV receiving at least 95% of the prescribed dose. Mean, maximum, and minimum PTV doses were also similar.
Dose to most organs at risk was decreased with use of 3DCPRT:
3DCPRT reduced the mean rectal dose by 60% (24 CGE).
The rectal volume receiving 5 CGE (V5) was reduced by 35-53% with use of 3DCPRT versus photon-based plans (p < 0.05). Rectal V40 was also significantly reduced.
3DCPRT reduced the mean bladder dose by 50% (21 CGE).
The bladder V5 was reduced by 46-50% with 3DCPRT when compared to plans utilizing IMRT (p < 0.05). Bladder V40 was also significantly reduced.
3DCPRT reduced the mean small bowel dose by 62% (17 CGE).
The volume of small bowel receiving 5 – 30 Gy/CGE was reduced 56 – 62% with 3DCPRT when compared to plans using IMRT (p < 0.05).
Dose to the whole non-CTV pelvis was reduced by 38 – 50% with use of 3DCPRT.
Femoral head doses were increased with use of 3DCPRT: Mean dose to femoral heads was 22 Gy with IMRT alone, 25 Gy/ CGE with IMRT + 3DCPRT, and 30.6 CGE with 3DCPRT alone.
The authors conclude that proton therapy may significantly reduce dose to the normal tissues of the pelvis, while maintaining adequate coverage of the prostate, proximal seminal vesicles, and pelvic lymph nodes when compared to IMRT alone and IMRT + 3DCPRT.
They note that significant uncertainties with regards to treatment planning and set-up exist with regard to 3DCPRT planning, which in their center requires use of three isocenters and abutting superior and inferior fields.
They note also that the practicality of delivering this treating with 3DCPRT alone is limited by the greater than 60 minute treatment time required per patient.
They do mention that further developments in proton radiotherapy technologies including, but not limited to, scanning beams, may help to reduce the uncertainties and logistic complications of use of proton radiotherapy in treatment of prostate cancer.
This dosimetric study demonstrates that proton radiotherapy may reduce dose to normal pelvic structures, namely the bladder, rectum, and small bowel, when compared to photon-based techniques.
These dose reductions may or may not prove to be clinically significant.
The authors’ discussion of logistic difficulties with delivery of 3DCPRT alone is well taken, particularly as proton radiotherapy remains a very limited resource. The use of proton beam to deliver prostate cancer treatment requiring over an hour of treatment time per patient may certainly not be the best use of this scarce resource. Additionally, long treatment times may be quite unappealing to patients, and may not be warranted in the absence of known clinical benefit.
As the authors point out, however, improvements in technology will hopefully reduce the logistical problems of proton beam delivery. Additionally, with increased sparing of normal tissues with proton-based treatment, dose escalation may be possible. Dose escalation in photon treatment has been demonstrated to provide biochemical relapse-free survival benefit (Zelefsky, 2008), and this would be expected to potentially improve outcomes in the setting of proton radiotherapy as well.
The use of proton radiotherapy for prostate cancer remains an interesting topic, and the authors demonstrate that it may well offer the opportunity to deliver adequate PTV dose with improved sparing of normal tissues. Further investigation of the clinical impact of these changes, as well as use of newer technologies, is certainly warranted.