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Letters to the Editor |
Department of Vascular and Genitourinary Radiology, Hopital E. Herriot, Pavillon P Radio, 5 place d'Arsonval, Lyon, Rhone 69003, France
e-mail: olivier.rouviere{at}netcourrier.com
I read with great interest the article by Dr Sala and colleagues (1), published in the January 2006 issue of Radiology, in which the authors reported the results of endorectal T2-weighted magnetic resonance (MR) imaging performed before salvage prostatectomy in patients initially treated with radiation therapy.
The management of locally recurrent prostate cancer after radiation therapy is difficult. Further irradiation of the prostate is hazardous and risks serious injury to the urethra, bladder, or rectum. Hormonal therapy provides tumor control that is effective but of limited duration. Salvage prostatectomy is technically difficult but, as mentioned by the authors, can be associated with prolonged survival when performed by highly trained surgeons (2). Other treatment options exist, and promising results have been obtained with new minimally invasive ablative techniques such as cryosurgery (3) or transrectal high-intensity focused ultrasound (4). However, all these therapies have higher risks of complication in patients with history of radiation therapy than in patients with no such history.
Therefore, I agree with the authors that there is a need for a precise preoperative assessment of the local extent of the recurrence to aid in patient selection, to guide surgery, or to improve the targeting of minimally invasive ablative techniques. In addition, accurate mapping of the tumor distribution within the gland could improve biopsy accuracy, which would allow earlier detection and, presumably, easier treatment.
I also agree with the authors that endorectal T2-weighted MR imaging can depict local recurrences and provide valuable information about the local staging of the tumor. However, like others (5), I found T2-weighted MR images to be difficult to interpret in most patients because of the treatment-related diffuse low T2 signal intensity in the gland. Dr Sala and colleagues state that their findings suggest that the accuracy of endorectal T2-weighted MR imaging in tumor evaluation (tumor localization and staging) prior to salvage prostatectomy is similar to the accuracy of endorectal T2-weighted MR imaging in patients with no history of radiation therapy. I do not think that the data in the study by Dr Sala and colleagues support such a conclusion.
Indeed, the staging performance of endorectal T2-weighted MR imaging in untreated patients remains controversial, with a reported accuracy ranging from 54% to 88% (6). I do not think that any solid conclusion can be drawn from the fact that the accuracy of endorectal T2-weighted MR imaging in patients with a history of radiation therapy falls within this wide range.
The same comment applies to the tumor detection capability with endorectal T2-weighted MR imaging that has also been diversely evaluated in the literature, with detection rates ranging from 37% to 76% (6). Moreover, the high tumor detection rate obtained in the study by Dr Sala and colleagues could be explained by two factors. First, the authors divided the prostate into four quadrants, which is less challenging than the usual division into sextants. Second, the volumes of the tumors are not reported. However, it seems that in this series, tumors were quite large (23 of 45 patients had tumors that invaded three or four quadrants). On the contrary, because of the downward stage migration induced by prostate-specific antigen (PSA) screening, patients who are referred for prostatectomy usually have small tumor volumes.
Hence, I think it is difficult to compare the results of this study with those reported in the literature for patients who are not treated with radiation therapy.
The authors also failed to discuss two alternative imaging techniques that might be accurate in patients with history of radiation therapy: MR spectroscopy and dynamic contrast material–enhanced MR imaging. MR spectroscopy takes advantage of the radiation-induced metabolic atrophy to depict tumor recurrences, and results of a limited preliminary study (5) showed that biopsy results were much better correlated with spectroscopic than with endorectal T2-weighted MR imaging findings. Similarly, dynamic contrast-enhanced MR imaging offers a favorable contrast between the early enhancing recurrence and the slowly enhancing postradiation fibrosis. Dynamic contrast-enhanced MR imaging has recently been shown to provide excellent interobserver agreement and a significantly better correlation with biopsy findings than nonendorectal T2-weighted imaging (7). These preliminary data require further confirmation. However, because of the risks of salvage therapies and the need for a careful selection of the most appropriate treatment option, I think that MR spectroscopy and/or dynamic contrast-enhanced MR imaging should be considered as potentially useful adjuncts to endorectal T2-weighted MR imaging in the local assessment of tumor recurrence after radiation therapy.
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Department of Radiology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021
e-mail: es220{at}radiol.cam.ac.uk
Many thanks to Dr Rouvière for his interest in our article, "Endorectal MR Imaging Prior to Salvage Prostatectomy: Tumor Localization and Staging" (1).
We agree with Dr Rouvière that T2-weighed MR images may be difficult to interpret in patients who have received radiation therapy because of treatment-related diffuse low T2 signal intensity and loss of zonal anatomy of the prostate gland. However, in our study, readings from two independent radiologists demonstrated that the accuracy of endorectal MR imaging was in fact similar to the previously reported accuracy of endorectal MR imaging for pretreatment staging. Our radiologists achieved sensitivity and specificity values of 76% and 73% (reader 1) and 55% and 65% (reader 2), respectively, for tumor detection; 86% and 84% (reader 1) and 64% and 76% (reader 2), respectively, for extracapsular extension; and 58% and 96% (reader 1) and 42% and 96% (reader 2), respectively, for seminal vesicle invasion (1). In interpreting the endorectal MR images, the radiologists in our study may have been aided by their substantial experience (each had previously read more than 500 prostate MR images), which contributed to their familiarity with the imaging features of extracapsular extension and seminal vesicle invasion and the typical appearance of the irradiated prostate gland.
For the past 2 years, endorectal MR imaging has been performed in every patient considered for salvage prostatectomy at our institution. The results of endorectal MR imaging therefore may have contributed to the decision to perform or cancel salvage prostatectomy, and it is possible that this bias led to inflated estimates of the area under the receiver operating characteristic curve, sensitivity, and specificity, as well as to better selection for organ-confined disease at surgery. We did acknowledge this limitation in our article.
We agree that tumors in our study were quite large (36 of 45 patients had tumor in more than one quadrant). We also agree with Dr Rouvière that PSA screening has caused a downward stage migration and that tumor volumes in patients referred for primary prostatectomy are usually small; however, this does not necessarily hold true for salvage prostatectomy candidates.
We also agree with Dr Rouvière that there are other, complementary MR techniques that might be used in patients who have undergone radiation therapy. In a study of patients with biochemical failure after external-beam radiation therapy (2), MR spectroscopic imaging had a sensitivity of 87% and a specificity of 72% for detection of recurrent tumor. Furthermore, in the same study, MR spectroscopic imaging had a negative predictive value of 100% for the exclusion of locally recurrent tumor when there was no metabolic activity at spectroscopy. In another study (3), findings at sextant biopsy, digital rectal examination, MR imaging, and MR spectroscopic imaging were compared in nine patients with rising PSA levels after external-beam radiation therapy who underwent salvage radical prostatectomy with step-section pathologic evaluation. MR imaging and MR spectroscopic imaging had estimated sensitivities of 68% and 77%, respectively, while the sensitivities of biopsy and digital rectal examination were 48% and 16%, respectively. However, MR spectroscopic imaging was found to have lower specificity (78%) than the other three diagnostic tests, each of which had a specificity of more than 90%. The discrepancies in the results of the two studies are likely caused by the different reference standards used, since step-section pathologic evaluation (not biopsy) was the standard of reference in the latter study (3).
Dynamic contrast-enhanced MR imaging was developed in an attempt to surpass the sensitivity and specificity of prostate cancer detection, localization, and staging offered by conventional high-spatial-resolution T2-weighted MR imaging. It has been shown that dynamic contrast-enhanced MR imaging improves interobserver agreement and produces significantly better correlation with biopsy findings than nonendorectal T2-weighted imaging in patients with recurrent prostate cancer after external-beam radiation therapy (4). In that study, however, core biopsy was used as the standard of reference rather than histologic step-section analysis of salvage prostatectomy specimens. The limitations of biopsy in prostate cancer detection for both newly diagnosed and treated prostate cancer have been extensively discussed and documented in the literature (5,6).
Another advance in MR evaluation of prostate cancer is the combination of dynamic MR imaging and MR spectroscopic imaging. It has been shown that this combined approach has excellent potential for improving the localization and characterization of prostate cancer (7). However, adequately powered studies with whole prostatectomy specimen correlation are still needed to assess the incremental value of MR spectroscopic imaging and dynamic contrast-enhanced MR imaging to endorectal T2-weighted imaging in patients considered for salvage prostatectomy. Until such results become available, evidence-based guidelines for the routine use of dynamic contrast-enhanced MR imaging or MR spectroscopic imaging cannot be developed. It is important to acknowledge that information obtained from MR should be incorporated into the diagnostic algorithm used to select patients who will likely benefit from salvage radical prostatectomy.
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