Contents
The Next IPCSG Meeting
NOVEMBER 17 - Dr. Richard Lam
NEW ADVANCES - A board-certified internist and
oncologist, Richard Lam, MD is the director of clinical research has been
specializing full time at Prostate Oncology Specialists in the treatment of
prostate cancer since 2001.
Dr. Lam has written numerous articles based on his
research and is an active member of the American Society of Clinical Oncology
and the American Society of Hematology. Dr. Lam continues to promote prostate
cancer awareness and education by giving lectures at various medical
conferences and prostate support groups throughout the country. He is
particularly interested in utilizing state-of-the-art therapeutics for advanced
prostate cancer.
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www.medscape.com
Radiotherapy Gives Long-Term Disease Control in Prostate Cancer
Pam
Harrison
October
29, 2018
SAN
ANTONIO — Long-term outcomes from a series of separate studies all support the
continued efficacy and tolerability of different forms of radiation therapy
(RT) in the treatment of localized, mostly low- and intermediate-risk prostate
cancer. This is the message of a session here at the American Society for
Radiation Oncology (ASTRO) 2018 annual meeting (abstracts 59-63).
"The
reason some people don't adopt new types of radiation is the fear that there
could be more toxicity beyond 5 years," session co-chair Daniel Spratt,
MD, associate professor of radiation oncology, University of Michigan, Ann
Arbor, told Medscape Medical News.
"But
from trials of stereotactic body radiation therapy (SBRT) to ones on
hypofractionation or the use of hormone therapy, there really wasn't any
increase in toxicity — they all appear to be safe," he commented. "So
I think it will all come down to patient convenience, fewer treatments, and
lower cost, as fewer treatments are less costly, so the trials that are still
on-going are all trying to shorten sessions down to five treatments in total
and we await those trials with interest," he added.
As
Amar Kishan, MD, University of California, Los Angeles, discussed in a news
briefing, traditional conventional RT for low- and intermediate-risk prostate
cancer involved the delivery of small daily doses of radiation over an extended
timeframe, typically 8 to 9 weeks.
"The
so-called fractionation of radiation is thought to help preferentially kill
tumor cells and minimize chronic tissue damage," Kishan explained.
Somewhat
uniquely, prostate cancer appears to be more sensitive to higher doses of
radiation per treatment session, "suggesting that shorter radiation
courses — in other words, higher doses per treatment in fewer total treatments
— could be efficacious," he added.
SBRT
pushes this hypothesis to the limits by condensing the treatment course to four
and five sessions — which explains why SBRT is alternatively known as
"extreme hypofractionation" or "stereotactic ablative
radiotherapy," Kishan observed.
What
radiation oncologists have been waiting for is confirmation that long-term
results of SBRT are not, indeed, accompanied by higher late toxicity rates
compared with other types of RT.
Now
They Have the Answer, and That Answer Is No
As
presented by Alan Katz, MD, Flushing Radiology Services, New York, at a median
follow-up of 108 months, 515 patients with prostate cancer, most of whom were
low- and intermediate-risk, were treated with robotic SBRT at doses ranging
from 35 to 36.25 Gy in 5 fractions on consecutive days. Approximately 100
patients received androgen deprivation therapy (ADT) as well as SBRT.
"For
the entire cohort, the 10-year biochemical recurrence-free survival (bRFS) was
93%, 81%, and 66% for low-, intermediate-, and high-risk patients,
respectively," Katz reported, "while biopsy-proven local failure was
found in 2%, 6%, and 10% in the same three risk groups, respectively," he
added.
Results
were even better for favorable, intermediate-risk patients among whom
disease-free survival (DFS) rates at 10 years were highly comparable, at 89%,
to rates in low-risk patients, at 93%, Katz noted.
Conversely,
intermediate-risk patients with unfavorable features had outcomes that were
similar to high-risk patients: DFS rates at 10 years were only 63% in
intermediate-risk patients and 66% in high-risk patients.
Grades
2 and 3 late genitourinary (GU) toxicity was higher with the higher
fractionation dose, at 14.6%, compared with 8.2% for the lower fractionation
dose, but there were no differences in grade 2 gastrointestinal (GI) toxicity
between the two schedules.
"For
sexual scores, there was a significant drop off of approximately 35% to
40%," Katz observed.
"But
this is in a group of men with a median age of 70 years, so there is going to
be some significant drop off in sexual function anyway, so it's hard to tell
exactly how much comes from the treatment or just from the aging process,"
he noted.
Interestingly,
the use of ADT in higher-risk patients did not appear to improve long-term
disease control.
"Prostate
SBRT continues to demonstrate excellent local control and excellent quality of
life now out to 10 years," Katz concluded.
"And
given that most failures were not local, we hypothesize that dose escalation
will not translate into improved bRFS," he added.
Moderately
Hypofractionated Therapy
Long-term
outcomes evaluating the effect of hypofractionated RT for prostate cancer are
also limited, commented Ibrahim Abu-Gheida, MD, Cleveland Clinic Foundation,
Ohio. Hence, the 10-year outcomes of a study in which investigators treated 854
patients with a moderately hypofractionated scheme (70 Gy in 28 fractions at
2.5 Gy per fraction) are of particular interest.
Patients
again had localized prostate cancer spanning the whole risk spectrum: the study
included both favorable intermediate-risk patients and unfavorable
intermediate-risk patients as well as low- and high-risk participants.
At
10 years, the bRFS rates were 88% for low-risk patients, 78% for favorable
intermediate-risk patients, 71% for unfavorable intermediate-risk patients, and
42% for those with high-risk disease.
Prostate
cancer-specific mortality rates were actually low at 10 years ranging from 2%
in the low-risk group to a high of 15% in the high-risk group, and 5% in both
groups of intermediate-risk patients.
The
cumulative incidence of late grade 3 and higher GU toxicity was low, at 2%, as
was the incidence of late grade 3 and higher GI toxicity, at 1%.
"This
fractionation schedule appears to be acceptable for patients across all risk
groups," Abu-Gheida observed.
"High-dose
moderately hypofractionated RT for localized prostate cancer continues to show
excellent oncological outcomes with a low incidence of toxicity over long-term
follow-up," he concluded.
Both
ASTRO and its sister organization in Europe have recently endorsed
hypofractionation as the standard approach to the treatment of localized
prostate cancer, as published data are now strong enough to support this
approach, Kishan noted.
Dose
Escalation at 20 Years
However,
Dario Pasalic, MD, University of Texas MD Anderson Cancer Center, Houston, would
tend to disagree with Katz's hypothesis (as above) that dose escalation will
not translate into improved bRFS, as he presented a study which found that dose
escalation does make a difference.
Conducted
between 1993 and 1998, that study involved 301 patients with low- to high-risk
prostate cancer randomized to external beam radiation at doses of 70 Gy or 78
Gy with no accompanying neoadjuvant or adjuvant hormone therapy.
At
a median follow-up of 14.3 years, freedom from failure rates were 53.8% for
those who received 70 Gy, compared with 74.3% for those who received 78 Gy (P =
.0018).
The
significant difference between the two groups was largely driven by
improvements in both biochemical and distant failure, as Pasalic observed.
For
example, biochemical failure rates were 24.4% in the lower-dose group compared
with 13.5% in the higher-dose group (P = .05), and distant failure rates were
17.4% in the lower-dose group compared with only 5.3% in the higher-dose group
(P = .020), he noted.
This group of patients offers unique insight into the impact of increased
radiation dose. Dario Pasalic, MD
The
higher-dose fractionation group was also associated with a lower rate of
distant metastases, at 5%, compared with 11% for the lower-dose fractionation
group.
"Death
from prostate cancer was trending toward significance and was nearly halved by
dose escalation," Pasalic concluded.
"This
group of patients offers unique insight into the impact of increased radiation
dose," he added.
Standard
Versus Hypofractionated RT
Although
shortened, higher-dose hypofractionated RT is gaining the upper hand for the
treatment of localized prostate cancer, the standard approach can still hold
its own.
This
finding comes from a 10-year, head-to-head comparison of conventionally fractionated
intensity-modulated radiation (C-IMRT) therapy with hypofractionated IMRT
(H-IMRT) for localized prostate cancer.
C-IMRT
was delivered at a total dose of 78 Gy in 38 fractions at 2 Gy per fraction and
H-IMRT was delivered a total dose of 70.2 Gy in 26 fractions at 2.7 Gy per
fraction.
"High-risk
patients were scheduled to receive 24 months of ADT, and some intermediate-risk
patients were offered up to 4 months of ADT," Vladimir Avkshtol, MD, Fox
Chase Cancer Center, Philadelphia, Pennsylvania, told delegates. Equal numbers
of men in both groups took ADT.
Approximately
150 men were randomized to each group and close to 30% of the cohort were
high-risk.
At
a median follow-up of 130 months, biochemical failure rates were similar in
both groups at 21.2% in the C-IMRT group versus 25.4% in the H-IMRT group. The
incidence of biochemical and/or clinical disease failure was also similar in
both groups at 25.9% for patients treated with C-IMRT compared with 30.6% of
those treated with H-IMRT.
Rates
of prostate cancer-specific mortality were also similar at 2.7% for C-IMRT and
4% for H-IMRT. At 10 years, 78.4% of men in the C-IMRT group were still alive
compared with 71.1% in the H-IMRT group.
The
main difference between the two treatments was rates of metastatic disease,
which were lower at 5.3% for those treated with the standard approach compared
with 12.7% for those treated with the hypofractionated approach (P = .06).
"Previously
published work showed that long-term quality of life changes were similar in
both groups," Avkshtol concluded.
"This
phase 3 trial supports utilization of moderate hypofractionation in
intermediate- and high-risk prostate cancer," he suggested.
Upfront
or Delayed RT
Timing
of RT has not been widely explored, making noteworthy the results of a phase 3
trial evaluating the optimal sequencing of dose escalated RT given either 4
months after initiating ADT or concurrently on day 1 with ADT. The ADT used in
this particular study consisted of goserelin plus bicalutamide.
A
total of 438 intermediate- and high-risk prostate cancer patients — but not
low-risk patients — were included in the trial, noted Shawn Malone, MD,
University of Ottawa, Ontario, Canada.
At
a median follow-up in excess of 12 years, there were no significant differences
between the two treatment groups in terms of DFS, at 81% for the delayed RT
group and 86% for the upfront group.
Local
control rates were also very high and similar in both groups, at 96% for the
delayed group and 94% for the upfront group, and distant DFS rates were
similarly high, at 99% and 96% for the delayed versus upfront RT group,
respectively.
Late
grade 3 and higher GI toxicity rates were higher in the upfront group, at 4.5%,
compared with 2.8% for the delayed sequencing group, as was late grade 3 GU
toxicity, at 5.1% versus 1.9%.
Nevertheless,
Malone concluded that the sequencing of RT given in combination with ADT did
not influence clinical outcomes. In addition, the durable outcomes seen in both
groups support the benefit of treating this group of prostate cancer patients
with ADT in combination with dose-escalated RT regardless of when RT is given.
ADT
With and Without RT
A
previous report of the RTOG 9408 study (N Engl J Med. 2011;365:107-118)
demonstrated that at 10 years the addition of 4 months of ADT before and during
RT improved all relevant endpoints in early localized prostate cancer.
At
the ASTRO meeting, Christopher Jones, MD, Sutter Medical Group and Cancer
Center, Sacramento, California, gave a long-term update on the results. They
show that the addition of short-term ADT to radiotherapy, given at a dose of
66.6 Gy in 1.8 Gy fractions, continued to provide superior disease control at a
median follow-up of 18 years, although the earlier overall survival advantage
seen at 10 years in favor of additional ADT was no longer apparent.
At
a median follow-up of 18 years, rates of biochemical failure were slightly
higher than they were at 10 years, occurring in 37% of patients in the RT plus
ADT group and 51% of the RT alone group (P < .01), Jones noted.
Similarly,
rates of distant metastases at a median of 18 years were again slightly higher
than they were at 10 years, occurring in 8% of the RT plus ADT group and 12% of
the RT alone group (P = .01), Jones added.
Patients
in the RT plus ADT group also were less likely to experience local progression,
at 12%, compared with 18% for those receiving RT alone (P < .01).
Late
grade 3 GU toxicity rates, at 6.2% in the additional ADT group versus 5.3% in
the RT alone group, were similar between the two groups, as were rates of grade
4 GU toxicity, at 1.4% and 0.1% in the two groups, respectively. Rates of late
grade 3 and 4 GI toxicity were very low in both groups.
"Survival
differences at 10 years are still important as all survival curves go to zero
at some point," Jones said.
"But
these results continue to support the conclusion that the addition of
short-term ADT benefits men with intermediate-risk, though not low-risk,
adenocarcinoma of the prostate," he concluded.
Malone
has reported receiving honoraria from AbbVie, Amgen, Astellas, AstraZeneca,
Janssen, and Sanofi, and travel expenses from TerSera. The other presenters
have reported no relevant financial relationships.
American
Society for Radiation Oncology (ASTRO) 2018. Abstracts 59-63. Presented October
22.
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Medical News © 2018 WebMD, LLC
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Cite
this article: Radiotherapy Gives Long-Term Disease Control in Prostate Cancer -
Medscape - Oct 29, 2018.
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Prostate cancer surgery and radiation tied to antidepressant use
Health
November
1, 2018 / 2:33 PM / a day ago
Lisa
Rapaport
(Reuters
Health) - Men with prostate cancer who get surgery or radiation are also more
likely start taking antidepressants than their counterparts who don’t get
aggressive treatment, a recent study suggests.
Many
men with early-stage prostate cancer may not need treatment right away, or
ever, because these tumors often don’t grow fast enough to cause symptoms or
prove fatal. In the absence of symptoms or tests that suggest tumors are
growing quickly, doctors may advise men to put off immediate treatments like
surgery or radiation and instead get regular screenings to reassess whether the
cancer is dangerous enough to warrant intervention.
For
the current study, researchers examined data on men with early-stage prostate
cancer, including 4,952 people who had surgery, 4,994 who got radiation and
2,136 who opted instead for surveillance, or “watchful waiting.” In the year
before their cancer diagnosis, 7.7 percent of the men were prescribed
antidepressants, and this climbed to 10.5 percent in the first year after
diagnosis.
Compared
to a control group of men in the general population without a prostate cancer
diagnosis, men with prostate cancer were 49 percent more likely to be taking
antidepressants five years after surgery and 33 percent more likely to take
antidepressants five years after radiation treatment, the study found.
But
watchful waiting wasn’t linked to any increase in the odds of men taking
antidepressants.
“Prostate
cancer patients often fit the demographic profile (white, older age, and male)
of someone at risk for depression,” said senior study author Dr. Robert Nam of
Sunnybrook Health Sciences Centre in Toronto.
“Once
they receive treatment for prostate cancer, whether that is surgery or radiation,
they may experience treatment-related side effects, such as erectile
dysfunction, incontinence, and bowel dysfunction, which can significantly
worsen quality of life,” Nam said by email.
Roughly
half of men diagnosed with prostate cancer receive treatment known as androgen
deprivation therapy, which suppresses production of the male sex hormone
testosterone and contributes to mood disorders, Nam added.
Men
in the study who received surveillance tended to be older and were more likely
to have multiple chronic health problems than the patients who got surgery or
radiation.
The
study wasn’t a controlled experiment designed to prove whether or how different
approaches to prostate cancer treatment might directly impact mental health.
Another limitation is the potential for factors not measured in the study to
have influenced both the treatment decisions men made and their mental health,
researchers note in European Urology.
A
separate study in the same journal, however, looked at trends in management of
erectile function after prostate cancer surgery and offered fresh evidence that
many men may be missing out on interventions that could improve their sexual
health and quality of life.
The
study examined data on 2,364 patients who had prostate cancer surgery at one
U.S. academic medical center between 2008 and 2015.
Researchers
didn’t find any meaningful changes in the proportion of men who had erectile
dysfunction up to two years after surgery, despite advances in surgical care
and postoperative penile rehabilitation during the study period.
This
study also wasn’t a controlled experiment, and it’s possible that results from
a single medical center might not reflect outcomes for men who got prostate
cancer treatment elsewhere.
The
study also didn’t examine how any use of antidepressants might have played a
role in men’s sexual health after prostate cancer surgery.
“Sexual
dysfunction is a common adverse effect of antidepressants,” Nam said.
“Identifying
the cause of the sexual dysfunction can be complicated as these symptoms are
also associated with depression and can be improved once the patient’s
depression is treated,” Nam added. “A healthy lifestyle, consisting of a
well-balanced diet and exercise, is an important way to promote good sexual function,
regardless of underlying medical conditions.”
SOURCE:
bit.ly/2Jw28vO
and bit.ly/2JvtphP
European Urology, online September 18 and 17, 2018.
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ADT Plus Docetaxel and Estramustine vs. ADT In High-Risk Localized Prostate Cancer
October
30, 2018
Advanced
Prostate Cancer
Hormone
Therapy (ADT) along with the chemotherapy drug Taxotere (docetaxel) and
Estramustine improves survival in men with high risk, localized
castration-resistant prostate cancer over ADT alone.
In
a randomized phase III trial performed at 26 hospitals in France, a phase III
trial enrolled men with treatment-naive prostate cancer and at least one risk
factor (i.e., stage T3-T4 disease, Gleason score of ≥8, prostate-specific antigen
concentration >20 ng/mL, or pathological node-positive). All men had a staging
pelvic lymph node dissection.
The
men were randomly assigned (1:1) to either androgen deprivation therapy (ADT;
with goserelin) plus four cycles of docetaxel and Estramustine or ADT
only. The primary endpoint was
relapse-free survival. Follow-up for other endpoints is ongoing.
The
trial randomly assigned 207 men to the ADT plus docetaxel and Estramustine
group and 206 to the ADT only group. Median follow-up was 8.8 years.
Eighty-eight (88 or 43%) of 207 men in the ADT plus docetaxel and Estramustine
group had an event (relapse or death) versus one hundred and eleven (111 or
54%) of 206 in the ADT only group.
Eight
(8) year relapse-free survival was 62% in the ADT plus docetaxel and
Estramustine group versus 50% in the ADT only group.
This
study has demonstrated that docetaxel-based chemotherapy improves relapse-free
survival in men with high-risk localized prostate cancer. Longer follow-up is
needed to assess whether this benefit translates into improved metastasis-free
survival and overall survival.
However,
the study does not tell us if the addition of the Estramustine to the docetaxel
is superior to the current standard of care of Early Chemotherapy with
docetaxel alone.
This
study is registered with ClinicalTrials.gov, number NCT00055731
Ligue Contre le Cancer,
Sanofi-Aventis, AstraZeneca, Institut National du Cancer.
Lancet
Oncol. 2015 Jul;16(7):787-94. doi: 10.1016/S1470-2045(15)00011-X. Epub 2015 May
28.
Joel
T Nowak, MA, MSW
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Lutetium-177 PSMA-617 in Phase III (VISION) trial for treatment of mCRPC
Posted
on October 25, 2018 by Sitemaster
We
have just been appraised of a randomized, double-blind, multi-center, Phase III
clinical trial of the targeted, radiolabeled agent 177Lu-PSMA-617 (a form of
“radioligand” therapy) in the treatment of metastatic, castration-resistant
prostate cancer (mCRPC). Details about this trial can be found on the
ClinicalTrials.gov web site. Details
about this trial can be found on the ClinicalTrials.gov web site.
Some basic information for patients is also available on a
study-specific web site. https://visionclinicaltrial.com/
·
Contacts
o
Contact:
Richard Messmann, MD 765-476-1070
rmessmann@endocyte.com
o
Contact:
Wendy Perez 317-608-0590 wperez@endocyte.com
·
Locations
o
United
States, California
o
UCLA
Recruiting
o
Los
Angeles, California, United States, 90095-7370
o
Contact:
Jeannine Gartmann
JGartmann@mednet.ucla.edu
o
Principal
Investigator: Johannes Czernin, MD
o
Sub-Investigator:
Jeremie Calais, MD
The trial (also
known as the VISION study) is nominally being sponsored by Endocyte (the
developer of 177Lu-PSMA-617), but Endocyte recently agreed to being acquired by
Novartis, and so — to all practical intents and purposes — Novartis is now the
effective sponsor of this trial (unless the deal falls through).
The
primary endpoint of this study is overall survival (OS) among patients with
progressive, PSMA-positive mCRPC randomized to treatment with either
177Lu-PSMA-617 + best supportive/best
standard of care or
Best supportive/best standard of care alone
Best
supportive/best standard of care for each individual patient is as defined by
the local investigator at each study center.
The
eligibility criteria for enrollment into this study are a little complex but,
basically:
Patients must have metastatic,
castration-resistant prostate cancer.
They must have disease that has progressed
after
An orchiectiomy or treatment with
standard androgen deprivation therapy (ADT) and
Treatment with at least one drug like
enzalutamide (Xtandi) or abiraterone acetate (Zytiga) and
Either one or two prior taxane
chemotherapy regimens, e.g., docetaxel (Taxotere) and/or cabazitaxel (Jevtana)
They must not have received any prior
treatment with any other form of radiolabeled therapy, e.g., radium-223
(Xofigo)
Patients
will require careful evaluation to ensure that they meet all relevant criteria
for inclusion in this trial.
The
study protocol indicates that this trial may have been open since late May this
year at as many as eight different sites in the US, but this is the first time
we have heard about it. The trial expects to enroll a total of 750 patients,
and the estimated study completion date is listed as August 2020.
We
note that the trial is also said to be an international trial, but no ex-US
study sites are currently listed on the ClinicalTrials.gov web site
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Prostate cancer: Scientists reveal new way to target stubborn cells
Published
Thursday 25 October 2018
By
Monica Beyer
Fact
checked by Jasmin Collier
A
new compound that targets hard-to-treat prostate cancer cells may pave the way
for a new, more successful treatment in the future, a new study reports.
two
researchers in lab
Researchers
find a new compound that is more able to target stubborn prostate cancer cells.
The
study, which is now published in Nature Communications, notes that this
particular compound targets areas that lead to the multiplication of prostate
cancer cells.
The
researchers, at the New York University (NYU) School of Medicine in New York
City, created a compound called cyclic peptoids.
Cyclic
peptoids specifically seek targets that current prostate cancer treatments
cannot.
The
scientists were able to develop a compound that reduced prostate cancer cell
growth (in cultures) by 95 percent, when compared with untreated cells.
How the
treatment differs from current drugs
Current
prostate cancer treatments target hormonal signals that encourage the growth of
prostate cancer. People who take these type of medications, known as
anti-androgen drugs, often experience a recurrence of cancer growth within
months.
This
has led to more research in hopes of developing new treatments that can work
with these "undruggable" targets.
That's
where Dr. Susan Logan, an associate professor in the Department of Urology from
the NYU School of Medicine, and study co-author Prof. Kent Kirshenbaum, also
from the NYU School of Medicine, come in.
"Rather
than continue making compounds that are just like older drugs, the focus of our
work has been to rethink the definition of what a drug-like molecule can
be," notes Dr. Logan.
Their
report highlights how their compound blocked cancer growth by hampering the
interaction between proteins that turn on the genes that make cells multiply.
This
gene activity helps the prostate grow during a person's early development, but
it does not continue to trigger cell production later in adulthood — that is,
unless there are changes that reactive them, which can lead to prostate cancer.
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Burgess Shares Insight on Evolving Prostate Cancer Paradigm
https://www.onclive.com/web-exclusives/burgess-shares-insight-on-evolving-prostate-cancer-paradigm
Brandon
Scalea
Earle
Burgess, MD
Recent
clinical trials and regulatory decisions have shifted treatment for patients
with metastatic castration-sensitive prostate cancer, but tireless research
needs to continue until curative strategies emerge, said Earle Burgess, MD.
One
of the latest advances was the February 2018 FDA approval of abiraterone
acetate (Zytiga) in combination with prednisone for patients with high-risk
disease. This approval was based on phase III findings from the LATITUDE study.
In
the trial, the combination of abiraterone acetate and androgen deprivation
therapy (ADT) led to a 38% reduction in the risk of death compared with ADT
alone. After a median follow-up of 30.4 months, median overall survival (OS)
was not yet reached with abiraterone acetate compared with 34.7 months with
placebo for patients with high-risk metastatic castration-sensitive prostate
cancer (HR, 0.62; 95% CI, 0.51-0.76; P <.001).
Additionally,
based on data from the CHAARTED and STAMPEDE studies, docetaxel has continued
to show encouraging results when combined with ADT as a frontline treatment of
this patient population.
In
an interview at the 2018 OncLive® State of the Science Summit™ on Genitourinary
Cancers, Burgess, an associate professor of medicine at Levine Cancer
Institute, Atrium Health, discussed the shifting paradigm of metastatic
castration-sensitive prostate cancer.
OncLive: What
have been some impactful trials in metastatic castration-sensitive prostate
cancer?
Burgess:
Four years ago, we learned that the addition of docetaxel to ADT for patients
with newly diagnosed castration-sensitive prostate cancer improves survival and
secondary endpoints. The CHAARTED trial was the key study here. It was a
randomized phase III study that confirmed the benefit for docetaxel. The
STAMPEDE trial was a multi-arm study run out of the United Kingdom that
included multiple different therapeutic interventions. It confirmed the
findings of CHAARTED—the survival benefit with the addition of docetaxel.
Separate
from that, abiraterone acetate has been tested in combination with ADT for this
space. The LATITUDE study was a randomized phase III trial, which showed that
abiraterone acetate improved OS.
Could you
explain the synergy between abiraterone acetate and prednisone?
Abiraterone
was first developed in the castration-resistant setting. We know that in a
castrated patient, when testicular androgen production has been stopped,
prostate cancer can still grow and progress. Abiraterone acetate essentially
shuts off adrenal steroidogenesis. It was shown to improve survival in
castration-resistant patients. For that reason, it's a natural synergy with
ADT.
Do you see a
role for immunotherapy in prostate cancer?
I
do. At the 2018 ASCO Annual Meeting, we learned that there clearly is a small
subset of patients with advanced disease that will benefit from immunotherapy.
It seems to be enriched in the population that has homologous recombination
repair defects. This is particularly true in patients with microsatellite
instability-high tumors. We are also learning about the role of CDK12 in
prostate cancer. We know from early data that CDK12 may increase sensitivity to
immunotherapy. That has not yet been tested in a large clinical trial.
How much of a
challenge is it to sequence these therapies?
This
is an important point. When patients are first diagnosed, we are trying to
learn as much as we possibly can about that particular tumor, specifically
germline status. We know which patients are starting to respond to PARP
inhibitors, as I just mentioned. It is important to track this early in the
course of the disease. The more we know about the molecular profile of the
tumor, the easier sequencing becomes.
What does a
diagnosis of prostate cancer mean today versus 5 years ago?
The
advancement and options we have are allowing patients to live longer with a
much better quality of life (QoL). With the drugs currently in development, and
with our better knowledge of the disease, we will create even more personalized
therapy. Outcomes are better, tolerability is better, and we're just moving
forward.
Are there any
specific ongoing trials or therapies you want to highlight?
There
are so many. The biggest thing right now is the PARP inhibitors. There is a lot
of ongoing research in that space and we are eagerly awaiting the results.
Those are of the most interest. Another big question is if we can build on what
we learned from CHAARTED, STAMPEDE, and LATITUDE and develop combination
therapies.
What area of
prostate cancer needs the most research?
At
the end of the day, we are not curing these patients. Therefore, there is
always going to be that unmet need until we can get there. The highest-risk
patients are the ones with advanced metastatic castration-resistant disease. We
need to come up with something that is going to prolong the survival and QoL of
these patients.
Fizazi K, Tran N, Fein LE,
et al. Abiraterone
plus prednisone in metastatic, castration-sensitive prostate cancer. N Engl J
Med. 2017;377(4):352-360. doi: 10.1056/NEJMoa1704174.
Prostate Cancer Surgery and Radiation Tied to Antidepressant Use
By Lisa Rapaport
November 05, 2018
(Reuters Health) - Men
with prostate cancer who undergo surgery or radiation therapyare also more
likely start taking antidepressants than their counterparts who don't get
aggressive treatment, research suggests.
Researchers examined
data on men with early-stage prostate cancer, including 4,952 people who had
surgery, 4,994 treated with radiation and 2,136 who opted instead for
surveillance, or "watchful waiting." In the year before their cancer
diagnosis, 7.7 percent of the men were prescribed antidepressants, and this
climbed to 10.5 percent in the first year after diagnosis.
Compared to a control
group of men in the general population without a prostate cancer diagnosis, men
with prostate cancer were 49 percent more likely to be taking antidepressants
five years after surgery and 33 percent more likely to take antidepressants
five years after radiation treatment, the study found.
But watchful waiting
wasn't linked to any increase in the odds of men taking antidepressants.
"Prostate cancer
patients often fit the demographic profile (white, older age, and male) of
someone at risk for depression," said senior study author Dr. Robert Nam
of Sunnybrook Health Sciences Centre in Toronto.
"Once they receive
treatment for prostate cancer, whether that is surgery or radiation, they may
experience treatment-related side effects, such as erectile dysfunction,
incontinence, and bowel dysfunction, which can significantly worsen quality of
life," Nam said by email.
Men in the study who
received surveillance tended to be older and were more likely to have multiple
chronic health problems than the patients who got surgery or radiation.
The study wasn't a
controlled experiment designed to prove whether or how different approaches to
prostate cancer treatment might directly impact mental health. Another
limitation is the potential for factors not measured in the study to have
influenced both the treatment decisions men made and their mental health,
researchers note in a report in European Urology.
A separate study in the
same journal, however, looked at trends in management of erectile function
after prostate cancer surgery and offered fresh evidence that many men may be
missing out on interventions that could improve their sexual health and quality
of life.
The study examined data
on 2,364 patients who had prostate cancer surgery at one U.S. academic medical
center between 2008 and 2015.
Researchers didn't find
any meaningful changes in the proportion of men who had erectile dysfunction up
to two years after surgery, despite advances in surgical care and postoperative
penile rehabilitation during the study period.
This study also wasn't
a controlled experiment, and it's possible that results from a single medical
center might not reflect outcomes for men who got prostate cancer treatment
elsewhere.
The study also didn't
examine how any use of antidepressants might have played a role in men's sexual
health after prostate cancer surgery.
"Sexual
dysfunction is a common adverse effect of antidepressants," Nam said.
"Identifying the
cause of the sexual dysfunction can be complicated as these symptoms are also
associated with depression and can be improved once the patient's depression is
treated," Nam added. "A healthy lifestyle, consisting of a
well-balanced diet and exercise, is an important way to promote good sexual
function, regardless of underlying medical conditions."
SOURCE:
https://bit.ly/2Jw28vO and https://bit.ly/2JvtphP
Eur Urol 2018.
Reuters Health
Information © 2018
Cite this article:
Prostate Cancer Surgery and Radiation Tied to Antidepressant Use - Medscape -
Nov 01, 2018.
Links:
2. Active surveillance
for prostate and thyroid cancers: evolution in clinical paradigms and lessons
learned | Nature Reviews Clinical Oncology: Review Article
3. Neutrophil, Platelets,
and Eosinophil to Lymphocyte Ratios Predict Gleason Score Upgrading in Low-Risk
Prostate Cancer Patients - Abstract - Urologia Internationalis - Karger
Publishers: Background: Several biochemical and clinical
markers have been proposed for selecting patients for active surveillance (AS).
However, some of these are expensive and not easily accessibl
4. Fractionated
Docetaxel and Radium 223 in Metastatic Castration-Resistant Prostate Cancer:
Clinical Trials - clinicaltrials.gov The objective of this study is to
determine the maximum safe dose of Ra-223 in combination with fractionated
(split doses) ...
7. Circulating
tumor DNA in advanced prostate cancer: transitioning from discovery to a
clinically implemented test | Prostate Cancer and Prostatic Diseases:
Review Article
8. Is
Problem X really a side effect of ADT, or not …? | THE "NEW" PROSTATE
CANCER INFOLINK: We have long been bedeviled by questions about some of the
short- and the long-term side effects and complications of androgen deprivation
therapy (ADT) in the treatment of prostate cancer. Frankly…
9. How
accurate are gallium-68 PSMA PET/CT scans in the “real world”? | THE
"NEW" PROSTATE CANCER INFOLINK: A new article in the journal
Cancer Imaging has provided us with an interesting set of “real world” data on
the accuracy of gallium-68 PSMA PET/CT scans in the management of prostate ca…
10. 'Shared
Decision-Making': Real or Just a Feel-Good Buzzword? | Medpage Today:
Patient gets PSA test without his knowledge, then told to report for prostate
biopsy
11. Prostate Cancer
Surgery and Radiation Tied to Antidepressant Use: Men with prostate cancer
who undergo surgery or radiation therapyare also more likely start taking
antidepressants than their counterparts who don't get aggressive treatment,
research suggests.
12. First-line
treatment for prostate cancer and use of antidepressants | THE "NEW"
PROSTATE CANCER INFOLINK: According to a recently reported study in the
journal European Urology, men who received first-line surgery or radiation
therapy for non-metastatic prostate cancer were significantly more likely to…
13. Variation
and Trends in Antidepressant Prescribing for Men Undergoing Treatment for
Nonmetastatic Prostate Cancer: A Population-based Cohort Study - European
Urology: Patients treated for nonmetastatic prostate cancer with surgery or
radiation have an increased risk of receiving antidepressant prescriptions for
at least 5 yr, whereas patients undergoing surveillance do not. Thus,
psychological support after treatment is an important part of prostate cancer
care.
14. Medicare
to cover costs of new test for AR-V7 | THE "NEW" PROSTATE CANCER
INFOLINK: We have recently learned that Medicare will be covering the costs
of the Oncotype DX AR-V7 Nucleus Detect™ test for patients with metastatic,
castration-resistant prostate cancer (mCRPC) as of Dece…
16. Newest
radiopharmaceutical: thorium-227 PSMA antibody | THE "NEW" PROSTATE
CANCER INFOLINK: Bayer has announced a new clinical trial of the latest
entry in the race for radiopharmaceuticals to treat prostate cancer, joining
177Lu PSMA-617, 225Ac PSMA-617, and 131I MIP-1095. They are tryin…
17. Burgess
Shares Insight on Evolving Prostate Cancer Paradigm: Earle Burgess, MD,
discusses the shifting paradigm of metastatic castration-sensitive prostate
cancer.
18. Prostate cancer:
Scientists reveal new way to target stubborn cells: Prostate cancer is
common, so findings new ways to destroy it is very important. Now, researchers
believe that they may have found a new drug target.
19. Lutetium-177
PSMA-617 in Phase III (VISION) trial for treatment of mCRPC | THE
"NEW" PROSTATE CANCER INFOLINK: We have just been appraised of a
randomized, double-blind, multi-center, Phase III clinical trial of the
targeted, radiolabeled agent 177Lu-PSMA-617 (a form of “radioligand” therapy)
in…
20. US
court invalidates patent on Johnson & Johnson's prostate cancer drug
Zytiga - FirstWord Pharma: FirstWord Pharma -
21. ADT
Plus Docetaxel and Estramustine vs. ADT In High-Risk Localized Prostate Cancer
— Cancer ABCs: Hormone Therapy (ADT) along with the chemotherapy drug
Taxotere (docetaxel) and Estramustine improves survival in men with high risk,
localized castration-resistant prostate cancer over ADT alone.
22. Radiotherapy Gives
Long-Term Disease Control in Prostate Cancer: Long-term outcomes in prostate
cancer trials continue to support radiation therapy as a standard of care that
provides excellent local control and minimal late toxicity over many years to
come.
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