Patient registries are potentially a rich source of
information with which to evaluate outcomes. They often include patient
characteristics, details of the therapies they received, and outcomes tracked
over time. They provide full population data of all patients treated at
participating centers, and can provide very large amounts of data over time.
Like a clinical trial, there are specific and uniform
definitions used in capturing patient and treatment data, allowing for
comparability on a variety of variables. Registries and clinical trials are
internal review board (IRB) approved for ethical standards and must comply with
HIPAA laws (patients must consent, and patient names are not entered in). In
the US, they both have an insurance advantage as well: Medicare, Medicaid and insurance
companies may cover the costs of clinical trials and registries for treatments
that they would not ordinarily cover. In some situations, they will only
provide coverage if the patient is enrolled in a registry or clinical trial.
Unlike a clinical trial, there are usually no detailed
patient inclusion and exclusion criteria, and the treatments may vary from
center to center and from patient to patient. Because patients are not excluded
from the database, registries are capable of providing very large databases for
analysis. There is no randomization, so there is selection bias –
patients who received different treatments may have been selected for specific
reasons. The quality of the data is only as reliable as the clinician entering
it, and it is not necessarily subject to peer review as publication of clinical
trial results are. As with other large database analyses, it may be possible to
find matched cases for control, but that is not the same as randomization. While
clinical trials have a hypothesis to be proved or disproved, a registry
provides data for quality improvement and for generating hypotheses.
Registries are difficult and expensive to establish and
maintain. The American Board of Radiology attempted to create a
national brachytherapy registry, but abandoned those efforts in 2015 when issues in
its development and implementation “proved to be more daunting and costly than
initially anticipated.” In 2012, the American Society of Radiation Oncologists
(ASTRO)
announced plans to implement a National Radiation Oncology Registry (NROR) with
Prostate Cancer as its first focus. A pilot was completed in June 2015, and
there are
plans for expansion.
The Registry for Prostate Cancer Radiosurgery (RPCR) was
established in 2010. There are 45 participating sites in the US, and the
database included nearly 2000 men as of 2014. They collect three kinds of data
for each patient: screening, treatment, and follow-up.
Screening data include age, performance status, rationale for
radiosurgery, initial TNM stage, Gleason score, number of positive biopsy
cores, use of hormonal therapy, and several baseline measures, including
pre-treatment PSA, IPSS, International Index of Erectile Function (IIEF-5)
score, Bowel Health Inventory score, and Visual Analog pain score.
Treatment data include radiation delivery device details,
treatment dates, dosimetry (e.g., doses, schedules, targets, margins, including
doses to specific organs at risk: rectum, bladder, penile bulb, and testicles),
and how image tracking was performed.
Follow-up data include periodic
tracking of the baseline data collected at screening, as well as
physician-reported toxicity. RPCR encourages sites to record follow-up data every 3 months for the first 2 years
following SBRT treatment and every 6–12 months
thereafter, for a minimum of 5 years.
Some interim findings have been published by Freeman et al. So far, they have only reported 2-year data on 1,743 patients.
Oncological control was reported as biochemical disease-feee survival:
· Low
Risk: 99% (n=111)
· Favorable
Intermediate Risk: 97% (n=435)
· Unfavorable
Intermediate Risk: 85% (n=184)
· High
Risk: 87% (n=168)
There was no severe late-term urinary toxicity, and
one patient developed severe late-term rectal bleeding. Erectile function was
preserved in 80% of men under 70 years of age, and 55% of men over 70.
The other SBRT registry is called the
Radiosurgery Society Search Registry (RSSearch Registry) and includes data from 17 community centers
treating prostate cancer patients. There were 437 prostate cancer patients
enrolled between 2006 and 2015. The data collected is similar to the RPCR
Registry. All patients in their first report were treated using the CyberKnife
platform (this registry was originated by Accuray, the manufacturer of
CyberKnife), although they allowed other platforms in later enrollments.
Davis et al.
recently reported their interim findings. Oncological control was reported as 2-year
biochemical disease-fee survival:
· Low
Risk: 99.0% (n=189)
· Intermediate
Risk: 94.5% (n=215)
· High
Risk: 89.8% (n=33)
There was no severe (grade 3) acute urinary or rectal
toxicity, and very little grade 2. There was no severe (grade 3) late-term
urinary or rectal toxicity. The highest incidence of grade 2 late term symptoms
was 8% with urinary frequency, They did not collect baseline data on sexual
function.
Both of these registries are administered by Advertek.
The results of the RSSearch Registry were reported in Cureus, which is their
own publication. RPCR results were published in Frontiers in Oncology, which is
an independently peer-reviewed journal. It is important to note this because
questions about the reliability of the data may arise.
If these data look a little too good to be true… well,
let’s dig a little deeper. The biochemical disease-free survival figures only
reflect 2 years of follow-up. In that short amount of time, many patients have
not yet reached their nadir PSA let alone had time to rise 2 points above that
nadir. Most of the low-risk patients and many of the intermediate-risk patients
would not have had a rise of 2 points in their PSA even if they’d had no
treatment.
The toxicity data are very suspect. Unlike a clinical
trial where experienced researchers are carefully evaluating patients on a
regular schedule, patient evaluations by community clinicians are haphazard.
The clinicians may introduce affirmation bias into their assessments – they
have incentive to make their numbers look good. The best way to evaluate toxicity
is with patient-reported outcomes on validated, guided-response questionnaires,
like EPIC. This was not done in either of these registries.
I think SBRT is actually quite a good therapy (I chose
it for myself!), but we have to look to other sources for more reliable data.
With longer term follow-up, the cancer control data from these registries may
become more reliable, and may help us generate better hypotheses about which treatment
variants work best and on which patient groups.
