Roach and associates have extensive and unique experience in
prostate imagingwith 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
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 Statesan 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 curewhen 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.
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. 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. 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.
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
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
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.