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Spectroscopy in Prostate Cancer: Hope or Hype?

Spectroscopy in Prostate Cancer: Hope or Hype?

Roach and associates have extensive and unique experience in prostate imaging—with magnetic resonance imaging (MRI) and magnetic resonance spectroscopic imaging (MRSI); with the complex delivery of a radiation dose through three-dimensional conformal radiation therapy (3D CRT) and intensity-modulated radiation therapy (IMRT); and with productive interaction among the specialties of radiation oncology, diagnostic imaging, and urologic surgery.

The authors clearly show that magnetic resonance spectroscopy can provide measures of the site and volume of cancer within the prostate gland, and perhaps indicate grade as well when in the hands of academic experts in this technology. They also suggest that combining MRSI with MRI allows a more accurate estimate of the existence of extracapsular disease extension. If proven reproducible and clinically significant, the combined tests could become an important factor in directing patient treatment.

When used to determine extracapsular disease, MRI failed two prospective randomized trials, and enthusiasm for the approach never recovered from those negative studies.[1,2] With changes in time and technology, these older results probably are not currently applicable to patient care in the best institutions, although they may still apply in nonexpert imaging centers. Proper studies must prove whether the new technology of MRI/MRSI will be broadly useful in imaging departments throughout the United States—an issue that seems to contain more hope than hype.

During the 1990s, the most important technical advance in the treatment of prostate cancer was adjusting the radiation treatment volume to more accurately coincide to the target volume (or cancer). When the dose is conformed to the target in three dimensions, the margins of surrounding normal tissues are maximally excluded. The obvious benefit of this technique is less normal tissue toxicity that allows very significant dose escalation in the prostate gland. Its bottom line is cure—when we compare all prostate cancer patients treated with radiation to high-dose (78 Gy) vs standard-dose (68 Gy) recipients, we see a significant number (25% more) cured of their cancers with the high doses.[3]

Improving Local Cancer Control

The original direct Eppendorf oximeter measurements recently taken from in vivo prostate cancers by Movsas and colleagues at Fox Chase Cancer Center demonstrated a stage-related increase in hypoxia.[4] These data suggest an associated decrease in radiation sensitivity in the part of the gland with the highest hypoxia levels and support boosting the dose delivered to identified gross tumor volumes as a means of improving local cancer control. Such clinical investigations also point up the importance of remembering that prostate cancer serves as an indicator for technology that can be applied in other sites.

Will knowing the geographic distribution of cancer within the prostate help radiation oncologists use advanced treatment technology and provide sophisticated boost treatments, as illustrated by the University of California, San Francisco, investigators? Dose sculpting (ie, the generation of irregular distributions of dose throughout the organ based on where the bulk of tumor is located) is an initial and logical approach to addressing the issue of improving local control. This approach will have particular relevance in a patient with a potentially resistant tumor identified by hypoxia measurements or by other molecular biological indicators.

There are other imaging methods for identifying hypoxia and, thereby, resistant subpopulations within a cancer-bearing organ. Radiolabeling of hypoxic adducts, as extensively developed and discussed by Chapman and colleagues, may offer the ability to identify and directly treat hypoxic areas.[5] A labeled hypoxic adduct or a labeled gene product antibody that can indicate resistance might have much broader clinical application than the interpretation of layers of imaging technology.

Evolving Technology

Diagnostic imaging and nuclear medicine technologies offer us this unique opportunity to combine layers of anatomic and functional observations that will accurately define where gross tumor exists, where resistant tumor may exist, and their relation to adjacent normal tissues that may restrict our ability to deliver the dose. Technologic developments including stereotactic treatment delivery, 3D CRT, and IMRT allow us to deliver almost any dose anywhere, while excluding even closely adjacent, irregular, normal tissues. The article by Dr. Roach and colleagues incorporates early efforts at this delivery and describes the evolving technology that allows us to achieve these goals. The authors clearly state that technology is improving and will continue to improve to the point where it will be broadly useful within only a few years.

I, too, believe that advances in integrating anatomic and functional images will better define the site and nature of bulk and resistant tumor populations and that this technologic progress will be unstoppable. As the authors point out, the final benefit of new technology must be shown by prospective clinical trials, but those who deny the progress and hope of the last 10 years of technologic advancement will miss the next 10 years of progress.

References

1. Rifkin MD, Zerhouni EA, Gatsonis CA, et al: Comparison of magnetic resonance imaging and ultrasonography in staging early prostate cancer. N Engl J Med 323:621-626, 1990.

2. Tempany CM, Zhou X, Zerhouni EA, et al: Staging of prostate cancer: Results of Radiology Diagnostic Oncology Group project comparison of three MR imaging techniques. Radiology 192:47-54, 1994.

3. Hanks G: Conformal radiotherapy for prostate cancer. Ann Med 32:57-63, 2000.

4. Movsas B, Chapman J, Greenberg R, et al: Increasing levels of hypoxia in prostate carcinoma correlate significantly with increasing clinical stage and patient age. Cancer 89:2018-2024, 2000.

5. Chapman J, Schneider R, Urbain J, et al: Single-photon emission computed tomography and position-emission tomography assays for tissue oxygenation. Semin Radiat Oncol 11:47-57, 2001.

 
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