Monday, November 12, 2018

#ProstateCancer News 2018-11


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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Send comments and news tips to news@medscape.net.
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:

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) ...
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…
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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