Depending on sextant biopsy for tumor localization is problematic, given the inherent localization error and the lack of zonal landmarks in the irradiated prostate. Even when step-section radical prostatectomy specimens are available, tumor localization and definition of a true positive versus a false positive result is not straightforward (18
). Our study helps clinicians to choose the correct unit of anatomic analysis in this setting. We found no statistically significant difference in the correctness of detection of tumor recurrence using the sextant, hemi-prostate, or whole-gland analyses.
Our results suggest that one co-registration approach should not be routinely favored over the others; and that perhaps the choice for one or other method should be driven by the reasons the correlation between imaging and biopsy results is needed. For instance, one may argue in favor of a sextant analysis if the goal is to use imaging to identify and target disease for focal therapy. Alternatively, another clinician may be interested in identification of tumor anywhere in the prostate, if the intention is to use one of the most common salvage therapies in which the entire gland becomes the focus of treatment once recurrence is detected (usually salvage brachytherapy or salvage radical prostatectomy). Finally, MR imaging may provide sufficient evidence of recurrent disease to allow for targeted hemi-prostate biopsy instead of more extensive protocols. In summary, the increased labor of performing sextant analysis does not lead to a significant gain and may not be necessary in all situations. We hope the results of our study will provide a measure of security to clinicians and researchers who opt for these alternative approaches.
At some institutions the need for salvage therapy is not determined by imaging, but simply by rising PSA and a positive biopsy; and patients are treated with local salvage therapy or systemic agents when there is evidence of metastatic disease on bone scan or cross-sectional imaging. A rising PSA, however, is not synonymous of local recurrence. Patients may present with benign PSA bounces (19
) and a transrectal ultrasound-guided biopsy may be unnecessary. Imaging results may help clinicians and patients to decide on subsequent evaluation. When confirming disease is required, positive findings may allow for a limited and targeted biopsy protocol. It is also possible that a patient with clearly positive multiparametric imaging could skip biopsy and proceed to treatment. Alternatively, negative results may provide enough security to allow for continuous PSA follow-up.
The goal of this study was not to determine the accuracy of T2-weigthed MR imaging, but the compare different units of analysis or methods of dividing the prostate gland to localize disease. Yet, our results agree with prior studies in that T2-weighted MR imaging has at best moderate accuracy in detecting locally recurrent prostate cancer after radiation therapy, irrespective of the approach used (2
). It is important to note that we do not suggest using T2-weigthed MR imaging to detect local recurrence. Prior studies have shown that combining T2-weigthed MR imaging with other MR modalities improve detection of local recurrence (2
The greatest improvement in accuracy over T2-weighted MR imaging seems to come from the addition of diffusion-weighted MR imaging. Kim et al. have shown that the technique is significantly better than T2-weighted MR imaging alone to discriminate patients with or without local recurrence (area under the ROC curve 88% versus 61%) (21
). MR spectroscopic imaging has also shown to be promising in this clinical setting. The results of the studies suggest that the area under the ROC curve for detection of recurrent cancer after external beam radiation therapy is around 80% (2
) The studies that investigated dynamic contrast enhanced MR imaging have conflicting results. Haider et al. showed that it is more sensitive than T2-weighted MR imaging (72% versus 38%) and also that it is a very specific technique (85%) with a high negative predictive value (95%) (20
). The positive predictive value however, was only 46%. The results of Yakar et al., on the contrary, suggest that DCE-guided biopsies had a positive predictive value of about 68% to 75% (6
A full multiparametric approach–i.e. an MR protocol that includes T2-weighted MR imaging, dynamic contrast enhanced MR imaging, diffusion-weighted MR imaging, and MR spectroscopic imaging–after radiation therapy has not yet been investigated, but one would expect that this would result in improved detection of recurrent disease. Because the amount of data available from such imaging protocol can be overwhelming, future research should focus not only in determining if additional sequences increase the diagnostic accuracy of MR imaging, but also on determining that best way of interpreting various sequences in combination.
Our study has limitations. First, this was a retrospective, single institution study; therefore our results may not be generalizable, as expertise and imaging acquisition vary among institutions. Also, it is unclear if our conclusion can be extrapolated to other MR imaging modalities, e.g. diffusion-weighted MR imaging or dynamically contrast-enhanced MR imaging. Second, because only one radiologist reviewed the MR images, we cannot assess reproducibility of our findings, i.e. interobserver agreement. Also, if the results of a second reader were comparable, our conclusions would be more robust. Third, the time interval between imaging and biopsy is a potential limitation of our study. Although 75% of patients had biopsy performed within 82 days of imaging, some patients had an interval approaching 180 days. Another potential criticism is the small number of patients in our study, leading to relatively wide 95% confidence intervals. Again, our goal was not to determine the accuracy of each modality, but rather to assess how they compare. As with any analysis, with a large enough sample size, and therefore narrower 95% confidence intervals, we would find statistically significant differences in the area under the ROC curve when comparing the various interpretative approaches. A statistically significant result, however, is not synonymous of a clinically relevant result, as small differences may not be important. Last, some may view as a limitation the fact we did not include in our analysis a “cranial-caudal approach,” i.e., localizing abnormalities to the apex, midgland, and base of the prostate, irrespective of the side of the gland. Our decision to discard this option was based on the results of a study by De Laet et al. (7
) which demonstrated that a positive transrectal ultrasound-guided biopsy corresponds to tumor in the same region, rather than in the exact same location in prostatectomy specimens. The latter also found that the greatest variability in agreement occurred within sextants of one or the other side of the gland (i.e., right apex, right midgland, and right base), rather than within adjacent sextants located on different sides of the prostate (i.e., right midgland and left midgland).
As expected, the point estimate was higher for the whole-gland approach, but not significantly. Reliable assessment of locally recurrent prostate cancer after external beam radiotherapy by endorectal MR imaging may be made using a sextant, hemi-prostate, or whole gland approach. The option for one or other approach should not be based solely on estimations of imaging accuracy, but on the purpose of the procedure.