Patients experiencing biochemical failure — defined as an increase in
prostate-specific antigen (PSA) level — after prostatectomy for prostate cancer
often receive salvage radiation therapy (SRT) to control the disease and
prevent metastases.
However, despite SRT, some patients still exhibit biochemical failure.
Now, a long-term, single-center study, published online
July 9 in the American Journal of Clinical Oncology, has
demonstrated that outcomes for 61 men who experienced a biochemical recurrence
after surgery, including a subset of 34 men who experienced failure twice (once
after surgery and once after SRT), are robust.
The median overall survival was 13.6 years for the men in the study who
had two biochemical recurrences and 14.7 years for the men who had just the one
recurrence after surgery, report the authors, led by D. Nathan Kim, MD,
PhD, from Texas Oncology in Waco.
Furthermore, the 10-year prostate-cancer-specific, metastasis-free, and
castration-resistant-free survival (from the time of PSA failure after SRT)
rates were all in excess of 70% for the men who had two biochemical
recurrences.
The new retrospective data might be of service to clinicians in
discussions with anxious patients because there is a "paucity" of
prospective data about this clinical scenario, the authors suggest.
The extensive follow-up period makes the study one of the longest in the
literature. Median follow-up was 126 months after SRT and 112 months after SRT
failure. Most studies have a median follow-up of less than 90 months after SRT.
"Because of our long-term follow-up, we were able to make
observations in those patients who recurred despite SRT," the authors
write.
Although their study was of a single group of men, and thus not
comparative in any way, the authors observe that another study on natural
history after PSA failure demonstrated that the median time to distant metastasis
was 8 years after PSA failure after radical prostatectomy (without SRT), and
roughly one in three patients developed distant metastases within 5 years
without radiation therapy.
"In our series, distant metastases-free survival at 5 years was 94%
for all patients, and was 75% for those who failed after SRT," the authors
report.
"The study suggests that SRT is effective in preventing
prostate-cancer-specific mortality and decreases the rate of distant
metastases," the team writes.
The new study also raises the issue of the timing of radiation therapy
after prostatectomy.
Patients with pathologic T3 disease or positive margins are candidates
for postoperative radiation therapy, said Colleen A.F. Lawton, MD, past
chair of the American Society for Radiation Oncology (ASTRO) board of
directors, who was not involved in the study.
This recommendation is based on the American Urological
Association/ASTRO guidelines on the use of adjuvant and SRT after
prostatectomy, which is endorsed by the American Society of Clinical Oncology (Int
J Radiat Oncol Biol Phys. 2013;86:822-828).
PSA levels determine what's next for these patients, Dr Lawton told Medscape
Medical News.
Patients with adverse pathologic features, such as seminal vesicle
invasion, positive surgical margins, and extraprostatic extension without
evidence of disease recurrence (i.e., undetectable PSA levels), are candidates
for adjuvant radiation therapy (ART), said Dr Lawton, who is from the Medical
College of Wisconsin in Milwaukee.
Patients who show increases in PSA at any time after surgery are
candidates for SRT, she explained.
Patients with pathologic T3a disease should see a radiation oncologist
and discuss whether they are candidates for ART or SRT, Dr Lawton said.
"The issue is that many patients do not consult with their radiation
oncologist," she told Medscape Medical News.
The new study findings do not challenge the guidelines, she suggested.
The study provides food for thought, but is not practice-changing.
"The study provides food for thought, but is not
practice-changing," said Dr Lawton.
Nevertheless, in this study, the authors indicated that 70% of their
patients would have been candidates for ART based on their pathologic stage and
margin status. They emphasize that "without concrete evidence from
randomized clinical trials, one must seriously consider the advantages and
disadvantages of ART versus SRT."
"The decision of whether to use ART or SRT remains an area of
active debate, and prospective randomized trials are currently underway to
attempt to answer this question," they add.
The authors were referring to the RAVES trial (NCT00860652), which is a
phase 3 study investigating the timing of radiation therapy for prostate
cancer with high-risk features.
Active surveillance is indicated for men with a PSA level of 10 ng/L or
less, a Gleason score below 6, and a pathologic disease stage of T2a or less,
said Dr Lawton. She explained that if patients have pathologic T3 disease and
undetectable PSA, other factors should be taken into account when deciding on
management, including the presence of comorbidities.
Study Details
The analysis involved 61 men treated at the University of Texas
Southwestern Medical Center in Dallas from 1992 to 2000 who underwent SRT
following biochemical recurrence after prostatectomy.
Biochemical recurrence of the disease after surgery was defined as a
persistently detectable PSA level of at least 0.05 ng/mL or two
consecutive PSA increases of at least 0.1 ng/mL that triggered initiation
of SRT.
Failure of SRT was defined as a single increase in PSA of at least
2 ng/mL from nadir levels, two consecutive PSA increases of at least
0.2 ng/mL, initiation of salvage treatment, or clinical disease
recurrence.
At 10 years, overall survival was 67%, freedom from PSA failure was 33%,
prostate-cancer-specific survival was 84%, and distant metastases-free survival
was 84% for the men who failed SRT.
Pathologic T-stage, Gleason score, seminal vesicle involvement, and
pre-SRT PSA were associated with freedom from PSA failure.
For patients who failed SRT, the median time to biochemical recurrence
after SRT was 30 months.
A total of 19 patients (68%) received androgen-deprivation therapy.
Early SRT failure correlated with a significant decrease in distant
metastases-free survival and prostate-cancer-specific survival. Ten-year
distant metastases-free survival from SRT was 43% (recurrence at 1 year or
sooner) versus 91% (recurrence at 1 year or beyond).
The study begs the question of whether biochemical failure is an
important surrogate for clinical care in prostate cancer. Dr Lawton indicated
that it is an important surrogate; however, there is no absolute proof about
its being associated with survival.
Am J Clin Oncol. Published online July 9, 2015.
