Correspondence
Radiotherapy for Prostate Cancer
N Engl J Med 2007; 356:308-311January 18, 2007
- Article
To the Editor:
In the Clinical Therapeutics article by Pisansky (Oct. 12 issue),1 intensity-modulated radiotherapy with photons and proton therapy2 are mentioned, but intensity-modulated proton therapy3 and tomotherapy are not.4 With proton therapy, intensity-modulated proton therapy, and tomotherapy, the dose of radiation delivered to nontargeted tissue is reduced,2-4 and intensity-modulated proton therapy even permits a reduction in the dose delivered to targeted tissue in order to spare critical structures.5 We agree with Pisansky that external-beam radiotherapy with photons is recommended for the patient in the vignette and that patients with localized prostate cancer should enroll in clinical trials. Advances in treatment methods require careful studies to show that they offer therapeutic gain.
We have assessed the feasibility of high-definition intensity-modulated proton therapy to restrict doses at the surface of, and within, a small-volume target, such as the prostate (Figure 1Figure 1
A Planning Study Showing Relative Doses of High-Definition Intensity-Modulated Proton Therapy Overlaid on a Computed Tomographic (CT) Scan in a Patient with Localized Prostate Cancer.). High-definition intensity-modulated proton therapy might be exploited for treating target volumes that are complex in shape and for target-specific dose intensification — that is, to deliver a dose equivalent to 2 Gy (photons) or less per fraction to critical structures within the target (e.g., the urethra) and close to the target (e.g., the rectum), while escalating the dose levels elsewhere within the target. Clinical studies will be necessary to evaluate the therapeutic benefit.5 ReferencesHans Peter Rutz, M.D.
Antony J. Lomax, Ph.D.
Paul Scherrer Institute, 5232 Villigen, Switzerland
hanspeter.rutz@psi. ch 1
Pisansky TM . External-beam radiotherapy for localized prostate cancer. N Engl J Med 2006;355:1583-1591
Full Text | Web of Science | Medline2
Slater JD ,Rossi CJ Jr ,Yonemoto LT , et al. Proton therapy for prostate cancer: the initial Loma Linda University experience. Int J Radiat Oncol Biol Phys 2004;59:348-352
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Cella L ,Lomax A ,Miralbell R . Potential role of intensity modulated proton beams in prostate cancer radiotherapy. Int J Radiat Oncol Biol Phys 2001;49:217-223
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Rodrigues G ,Yartsev S ,Chen J , et al. A comparison of prostate IMRT and helical tomotherapy class solutions. Radiother Oncol 2006;80:374-377
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Rutz HP ,Lomax AJ . Donut-shaped high-dose configuration for proton beam radiation therapy. Strahlenther Onkol 2005;181:49-53
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To the Editor:
Pisansky's article does not mention urethral strictures with bilateral obstructive nephropathy. This is an uncommon and symptomless late complication that usually goes undetected until an advanced stage of chronic renal failure is reached. (During the past 5 years, all three patients at our institution in whom this complication was diagnosed began dialysis within 3 months after the diagnosis of advanced renal failure.) Given this observation, it seems reasonable to recommend long-term renal ultrasonographic monitoring for all patients undergoing radiotherapy for prostate cancer and to avoid radiotherapy in patients who have preexisting renal impairment.
Andrea Campo, M.D.
S. Lazzaro Hospital, 12052 Alba, Italy
andrea_campo@hotmail.com To the Editor:
Pisansky withholds androgen suppression from a patient who has prostate cancer, a 7-ml prostate gland, and a serum prostate-specific antigen (PSA) level of 11 ng per milliliter, stating that there are no data establishing that androgen suppression provides an additional benefit in patients with intermediate-risk prostate cancer who are treated with high-dose external-beam radiation and that it increases toxic effects.
D'Amico et al. showed that 6 months of androgen suppression plus radiotherapy decreased the risk of PSA recurrence, as compared with radiotherapy alone, in men in whom the rate of PSA velocity before treatment was more than 2 ng per milliliter per year.1 Other data cited in Pisansky's article also support androgen suppression plus radiotherapy (at a dose of approximately 70 Gy), showing a prolonged interval to PSA recurrence.
Furthermore, androgen suppression has been shown to reduce the prostate volume by 30%.2,3 This shrinkage of the target lessens the exposure of normal tissue to radiation, thereby reducing the toxic effects of the radiation. This benefit must be weighed against the deleterious effects of androgen-suppression therapy. Given that androgen suppression before and during radiotherapy (in the 70-Gy range) has been shown to improve the outcome and to provide a mechanism for directly reducing the toxic effects of radiation, its use would seem to be warranted, even with the higher radiation doses recommended for the patient in the vignette.
3 ReferencesJoel H. Elconin, M.D.
New Mexico Oncology Hematology Consultants, Albuquerque, NM 871091
D'Amico AV ,Loffredo M ,Renshaw AA ,Loffredo B ,Chen MH . Six-month androgen suppression plus radiation therapy compared with radiation therapy alone for men with prostate cancer and a rapidly increasing pretreatment prostate-specific antigen level. J Clin Oncol 2006;24:4190-4195
CrossRef | Web of Science | Medline2
Solhjem MC ,Davis BJ ,Pisansky TM , et al. Prostate volume before and after permanent prostate brachytherapy in patients receiving neoadjuvant androgen suppression. Cancer J 2004;10:343-348
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Kucway R ,Vicini F ,Huang R ,Stromberg J ,Gonzalez J ,Martinez A . Prostate volume reduction with androgen deprivation therapy before interstitial brachytherapy. J Urol 2002;167:2443-2447
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Author/Editor Response
I agree with Rutz and Lomax that intensity-modulated particle-beam radiotherapy is an appealing alternative to photon radiotherapy, as recently described. I hope investigators will heed their call for careful clinical studies to compare particle-beam radiotherapy with photon radiotherapy as this technology develops and becomes more broadly available.
Campo describes obstructive uropathy attributed to radiotherapy. This complication is decidedly uncommon and rarely reported in the literature. In my review, I mention that radiotherapy-induced “bladder-neck or urethral stricture may cause retention,” but one must also consider benign prostatic hypertrophy and cancer recurrence as alternative causes. Approximately 4% of patients have urethral stricture requiring dilation after external radiotherapy,1 but the risk is substantially reduced among those who have not also undergone transurethral resection of the prostate. I favor obtaining a detailed medical history of urinary function and selectively obtaining studies of the urinary flow rate and ultrasonographic studies of bladder volume after voiding. This strategy reduces diagnostic testing and directs the investigation to the root cause of the secondary condition that Campo describes.
Elconin suggests that the combination of androgen suppression and high-dose external-beam radiotherapy seems warranted for the patient in the vignette, citing the recent retrospective series by D'Amico et al.2 I agree that radiotherapy with short-term androgen suppression is a reasonable alternative to radiotherapy alone for patients with intermediate-risk prostate cancer. The strongest evidence supporting androgen suppression, however, comes from its use with lower-dose (approximately 67-Gy) radiotherapy.2 Studies similar to that by D'Amico et al. have not shown a benefit when high-dose radiotherapy is used. I must therefore agree with D'Amico et al. that “only a randomized study can provide proof”2 of this assertion, and I suggest that this is an area of uncertainty that warrants more definitive research.
I agree with Elconin that androgen suppression given before radiotherapy reduces the prostate volume, and this reduction may improve urinary obstruction in affected patients. However, the reduction does not often result in a similar decrease in the irradiated volume of the surrounding organs when highly conformal approaches are used. This finding may explain why radiotherapy-related adverse effects remain largely unaltered by androgen suppression.3 Androgen suppression has its own array of adverse effects,4 which include hot flashes, erectile dysfunction, osteopenia with bone fracture, metabolic alterations, and changes in libido, cognition, and mood. These effects must be weighed carefully when considering the use of androgen suppression with high-dose image-guided radiotherapy.
4 ReferencesThomas M. Pisansky, M.D.
Mayo Clinic, Rochester, MN 559051
Lawton CA ,Won M ,Pilepich MV , et al. Long-term treatment sequelae following external beam irradiation for adenocarcinoma of the prostate: analysis of RTOG studies 7506 and 7706. Int J Radiat Oncol Biol Phys 1991;21:935-939
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D'Amico AV ,Loffredo M ,Renshaw AA ,Loffredo B ,Chen MH . Six-month androgen suppression plus radiation therapy compared with radiation therapy alone for men with prostate cancer and a rapidly increasing pretreatment prostate-specific antigen level. J Clin Oncol 2006;24:4190-4195
CrossRef | Web of Science | Medline3
Valicenti RK ,Winter K ,Cox JD , et al. RTOG 94-06: is the addition of neoadjuvant hormonal therapy to dose-escalated 3D conformal radiation therapy for prostate cancer associated with treatment toxicity? Int J Radiat Oncol Biol Phys 2003;57:614-620
CrossRef | Web of Science | Medline4
Sharifi N ,Gulley JL ,Dahut WL . Androgen deprivation therapy for prostate cancer. JAMA 2005;294:238-244
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- Citing Articles (1)
Citing Articles
1
Hans Peter Rutz, Damien C. Weber, Gudrun Goitein, Carmen Ares, Alessandra Bolsi, Antony J. Lomax, Eros Pedroni, Adolf Coray, Eugen B. Hug, Beate Timmermann. (2008) Postoperative Spot-Scanning Proton Radiation Therapy for Chordoma and Chondrosarcoma in Children and Adolescents: Initial Experience at Paul Scherrer Institute. International Journal of Radiation Oncology*Biology*Physics 71:1, 220-225
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