The Prostate Cancer Foundation (PCF) has released its comprehensive Prostate Cancer Patient Guide with the latest in diagnosis, research, treatments, and lifestyle factors for patients and caregivers. With contributions from leading physicians and scientists, the free guide is aimed at patients who have recently been diagnosed, are in treatment, or are concerned about rising prostate-specific antigen levels.
It also contains updated information for caregivers and family members who want to learn more about how genetics affect disease risk.
“We at PCF work daily on the front lines of science to find treatments and cures for prostate cancer, and because of our investments over the past 25 years, we are in a remarkable period where progress for patients is taking place more rapidly than ever before,” Christine Jones, the foundation’s chief operating officer, said in a news release.
“It is our duty to provide patients with the most comprehensive information available about prostate cancer so that they may have highly informed discussions with their doctors, and make the best choices based on state-of-the-art medical research,” she said.
Go here to get the 2019 Prostate Cancer Patient Guide, first published in 2017. The online version is continuously updated to reflect the latest advances in research and treatment.
A new resource, “Additional Facts for African-American Men and Their Families,” is also available for downloading. Compared with other ethnic groups, African-Americans are 76% more likely to be diagnosed with prostate cancer and more than twice as likely to die from the disease. The guide, which includes commentary from black celebrities, features the foundation’s investigations into identifying and overcoming healthcare disparities.
Xtandi (enzalutamide), an androgen receptor inhibitor, significantly delays disease progression — as assessed through radiological imaging — or death in metastatic hormone-sensitive prostate cancer (mHSPC) patients, a Phase 3 clinical trial shows.
The benefits were seen independently of patients’ initial PSA levels, suggesting that, contrary to prior beliefs, PSA levels are not an accurate predictive factor of responses to Xtandi in these patients.
Xtandi, developed by Pfizer and Astellas, is an approved treatment for men whose prostate cancer no longer responds to medical or surgical treatment that lowers testosterone, a condition called castration-resistant prostate cancer.
Aiming to determine if the therapy also could be used in men with metastatic disease who responded to their last testosterone-lowering treatment, researchers designed the multinational ARCHES Phase 3 trial (NCT02677896). It included a total of 1,150 mHSPC patients from the U.S., Canada, Europe, South America, and Asia-Pacific region.
Participants were assigned randomly to Xtandi or placebo, both given in combination with androgen deprivation therapy (ADT), except if they had had a bilateral orchiectomy (surgery to remove the testicles).
The trial’s main goal was radiographic progression-free survival — defined as the time patients lived without evidence of radiographic disease progression, or death, within 24 weeks of discontinuing treatment.
In a prior presentation, researchers had reported that ARCHES met its primary goal, with Xtandi lowering the risk radiographic progression or death by 61% compared to placebo, with a similar proportion of patients experiencing severe adverse side effects.
Now, researchers examined PSA-related effectiveness measures, including radiographic progression-free survival classified by initial PSA levels, time to PSA progression (a pre-specified rise in PSA levels), time to hormone treatment resistance, the rate of patients achieving undetectable PSA levels, and how much PSA had dropped from initial levels.
After a median follow-up of 14.4 months, researchers confirmed their initial findings that Xtandi lowers the risk of radiographic disease progression or death. But they also found that these benefits were seen regardless of a patient’s PSA level at beginning of treatment.
The treatment also reduced the risk of PSA progression by 81% and the chance of resistance to hormone treatment by 72%, compared to ADT alone.
Also, more patients on Xtandi saw their PSA levels drop by more than half (92.9% versus 56.8% for those taking placebo), by more than 90% (72.8% versus 30%), or reach undetectable levels (68.1% versus 17.6%).
In general, a similar proportion of patients in both groups experienced severe adverse effects, with those in ARCHES being similar to the ones seen in other Xtandi trials.
Overall, these results support the long-term effectiveness of Xtandi at delaying disease progression or death in mHSPC patients, and suggest that initial PSA levels are not predictive of responses to Xtandi, at least for patients who have received prior treatment with ADT.
While therapies that lower male sex hormones — required for prostate cancer to survive and grow — are a mainstay of therapy for advanced prostate cancer, most patients will acquire resistance to such approaches.
This often happens because the receptor for these hormones, called the androgen receptor, becomes constantly active, even in the absence of androgens.
Therapies that inhibit the androgen receptor — such as Pfizer and Astellas‘ Xtandi and Janssen‘s Zytiga — have largely improved the overall survival of prostate cancer patients, and are now approved for mCRPC patients in the U.S. and Europe.
However, which treatment brings the most benefits or the lowest healthcare costs has not been addressed.
In this study, researchers performed a retrospective study to compare the overall survival and healthcare costs associated with these two second-generation androgen receptor inhibitors.
They examined data from 3,174 adult men with mCRPC who had not received chemotherapy for at least one year before starting treatment with either Xtandi or Zytiga. Patients had been treated between April 2014 and March 2017, and their data were recovered from the Veterans Health Administration (VHA) database.
Overall, 1,945 patients, mean age 73, received Zytiga, while Xtandi was administered to the remaining 1,229 patients, mean age 74.
After examining outcomes of these patients, researchers found that those on Xtandi lived for a median of 30 months, compared to 26 months for Zytiga. This represented a significant 17% reduction in mortality risk with Xtandi.
Xtandi-treated patients also required fewer outpatient visits — both overall and cancer-related — than those treated with Zytiga, indicating that Xtandi led to a reduced use of medical resources.
In line with this, Xtandi patients had fewer healthcare costs than Zytiga patients. In total, a patient treated with Xtandi would have a monthly healthcare cost of $8,085, compared to $9,092 for Zytiga. Prostate cancer-related costs were also lower for Xtandi — $6,321 versus $7,280.
Thus, “chemotherapy-naive mCRPC patients treated with [Xtandi] had better survival, significantly lower resource use and healthcare costs than patients treated with [Zytiga],” researchers concluded.
Cumulative evidence to date supports the implementation of stereotactic body radiotherapy — a highly precise radiation therapy delivered in shorter periods of time — as a standard treatment for people with localized prostate cancer, a study shows.
Prostate cancer is the most common cancer diagnosed in men in the U.S.and is a big component of the yearly healthcare expenditure.
External beam radiotherapy, a method that involves delivering radiation beams to a patient’s tumor, is an effective treatment for men with localized prostate cancer. Traditionally, this type of radiotherapy was delivered in small daily doses over eight to nine weeks to spare the healthy tissues adjacent to the tumor.
However, a serious drawback to this approach is the number of times the person has to undergo radiotherapy. That not only increases healthcare costs, but also creates a greater burden and challenge for patients.
Over the last 20 years, with technological advances, treatments have significantly improved. In particular, the emergence of a type of radiotherapy known as stereotactic body radiotherapy (SBRT), allows treatment in just four to seven sessions.
SBRT works by giving radiotherapy from many different angles around the body. The beams meet at the tumor, hitting it with a high dose of radiation, while the tissues around it receive a much lower dose.
Optimization of this technique over the last few decades has led to the incorporation of SBRT into routine clinical practice. In fact, SBRT is now a standard of care treatment option for many different types of tumors.
Despite the plethora of clinical trials that support SBRT, however, some organizations have yet to update their guidelines to support the adoption of SBRT for treating prostate cancer.
That led researchers to conduct a systematic review and meta-analysis of all published prospective studies to assess the outcomes following prostate cancer SBRT.
The team found 38 unique prospective studies that included a total 6,116 patients — 92% low risk, 78% intermediate risk, and 38% were high risk. The median follow-up for all patients was 39 months.
Investigators examined the time it took for participants to experience a biochemical recurrence — deemed as a rise in PSA levels — after SBRT. They found that, after five years, 95.3% of patients remained without any signs of cancer recurrence, and 93.7% reached the seven-year mark free of cancer recurrence.
Very few patients experienced acute severe side effects (fewer than 1%) or long-term severe side effects (2% for genitourinary and 1.1% for gastrointestinal toxicity rates).
While treatment worsened the patients’ bowel and urinary functions, these returned to baseline levels within a 2-year period. Sexual function, however, continued to worsen with time, reaching a statistically significant difference three years after treatment.
Researchers lastly showed that, while increasing the dose of SBRT increased the time patients lived without a biochemical recurrence, it also increased the rates of late severe genitourinary toxicity.
“We herein demonstrate that there is considerable evidence that prostate SBRT is an effective treatment for localized prostate cancer, with a very favorable toxicity profile that has minimal impact on long-term urinary and bowel quality of life,” the investigators said.
“Our findings support that SBRT could be considered a standard radiotherapeutic strategy for localized prostate cancer, while ongoing trials assess its potential superiority to other treatment methods,” they concluded.
Men with low-risk prostate cancer can safely receive a single high dose of brachytherapy — a type of radiation therapy delivered directly into the tumor within a few minutes — as an alternative treatment for their condition, a study shows.
Brachytherapy is a cancer treatment that places small radioactive sources directly into a patient’s tumor, ensuring that the radiation is delivered specifically to cancer cells while it spares healthy surrounding tissues.
Usually, this treatment involves the placement of a radioactive seed inside the tumor, which delivers low doses of radiation over time. But prostate cancer patients have another option: a high-dose rate brachytherapy that places the radioactive material temporarily and for shorter periods, while delivering high doses of radiation during that time.
The latter approach “usually means patients make four to six visits to the hospital for a series of lower-dose treatments,” Tharmalingam said in a press release. Thus, “we wanted to see whether we could get similar results but with just one high-dose treatment, saving time for the patient and the hospital.”
The study included 441 men with localized prostate cancer who received a high-dose rate brachytherapy in a single 19 Gy dose (a measure of radiation). Among them, 44 men had low-risk disease, 285 medium risk, and 112 men had high-risk prostate cancer.
None of the patients received surgery or chemotherapy, but 37% were also given androgen deprivation therapy (ADT) — a treatment that lowers testosterone levels to prevent prostate cancer growth.
For an average of 26 months, researchers monitored patients through their prostate specific antigen (PSA) levels, a biomarker that indicates prostate cancer recurrence.
Overall, 94% and 88% of men had no signs of cancer recurrence after two and three years, respectively. However, men with low-risk disease fared better than medium- or high-risk patients, researchers found.
At two years, 100% of these men remained free of cancer, compared to 95% among those with medium-risk disease, and 92% for high risk. Similarly, at three years after treatment, all low-risk prostate cancer patients had no signs of the cancer returning, while 86% and 75% of medium- and high-risk patients, respectively, achieved the same outcome.
Of the 27 patients who experienced biochemical recurrence — a rise in PSA levels — 25 had their relapse confirmed on radiological analysis. Among those, 10 had their cancer spread to distant organs, while 15 had their cancer return in the prostate only.
The treatment was generally safe, with only 12% and 13% of the patients experiencing moderate genitourinary and gastrointestinal problems, which eventually resolved.
“[High-dose rate] monotherapy delivered in a single dose of 19Gy is a safe and effective treatment for localized prostate cancer that is well-tolerated over the first two years with very good early biochemical control,” researchers said.
Additional studies are now warranted to evaluate the long-term effects of single, high-dose rate brachytherapy in localized prostate cancer, especially in high-risk patients who are more likely to experience a recurrence. Given the low risk of side effects, Tharmalingam believes that doses could be increased for these patients to achieve better outcomes.
“The technology and expertise needed to deliver this treatment is not yet available in all cancer centers. However, given that it may offer time and money savings for hospitals as well as benefits to patients, there is a good argument for investing in this type of radiotherapy,” said Bradley Pieters, MD, PhD, chair of ESTRO’s brachytherapy committee and a radiation oncologist at the Academic University Medical Centers in the Netherlands.
Janssen has submitted an application with the U.S. Food and Drug Administration (FDA) seeking the approval of its androgen receptor inhibitor Erleada (apalutamide) for patients with metastatic castration-sensitive prostate cancer (CSPC).
It is being reviewed under the FDA’s Real-Time Oncology Review program, a pilot program that allows the FDA to start reviewing clinical data before an official application is submitted. The new program is intended to accelerate the review process so that treatments are available for patients as soon as possible.
“This submission marks an important step in providing a potential treatment option for patients with metastatic castration-sensitive prostate cancer, regardless of prior treatment or the extent of their disease,” Craig Tendler, MD, vice president of oncology clinical development and medical affairs in Janssen’s research and development division, said in a press release.
“We look forward to closely collaborating with the FDA through the efficient Real-Time Oncology Review pilot program with the goal of bringing Erleada to an earlier population of patients with metastatic prostate cancer as soon as possible,” he added.
Erleada is an oral agent that prevents the binding of testosterone to the androgen receptor, blocking signals that prostate cancer cells require to grow and proliferate. It is already approved in the U.S. and Europe for preventing metastasis in men with castration-resistant prostate cancer.
TITAN was designed to investigate if adding Erleada to standard ADT could improve the outcomes of prostate cancer patients whose cancer had spread to distant organs but responded to prior ADT treatment before the cancer spread.
It enrolled 1,052 patients and randomly assigned them to once-daily, oral Erleada plus ADT, or a placebo plus ADT. Treatment was continued until patients experienced disease progression or unacceptable toxicity.
The study’s primary goals were overall survival and the time to disease progression or death, and secondary measures included time to chemotherapy, time to worsening of pain, time to opioid use, and time to skeletal-related event — including fractures, bone metastasis, or spinal cord compression.
“We are excited to announce the nomination of EPI-7386 as our lead clinical candidate for the treatment of mCRPC,” David Parkinson, Essa’s president and CEO, said in a press release.
Hormone therapies targeting male sex hormones, or androgens, are a mainstay in treating prostate cancer. Androgens bind to the androgen receptor activating signals that prostate cancer cells require to grow and proliferate.
However, patients often develop mutations in the androgen receptor that render it resistant to such therapies over time. New treatments that inhibit the activation of the androgen receptor through distinct mechanisms may help men with prostate cancer who no longer respond to the anti-androgen therapies.
Essa Pharma’s EPI-7386 works differently from current hormonal therapies by targeting a different region of the androgen receptor: instead of preventing androgens from binding the receptor, the candidate therapy binds to the N-terminal domain needed to activate the androgen receptor signaling cascade.
Through this novel mechanism, EPI-7386 is able to block the androgen receptor even in cells that acquired resistance to other androgen receptor inhibitors, like Xtandi (enzalutamide).
It also seems to be metabolically more stable than first-generation small molecule androgen receptor inhibitors being developed by Essa – including their EPI-506 (ralaniten acetate). EPI-7386 has a similar efficacy as Xtandi, but at double that therapy’s current dose.
“EPI-7386 represents a novel approach to targeting the androgen receptor, one of the most validated targets in oncology. We look forward to bringing this novel drug candidate to patients with mCRPC who have no other treatment options,” Parkinson said.
Essa is now conducting further studies, and expects to begin clinical trials for EPI-7386 by April 2020.
Ccheck, a new test for early cancer detection under development by Anixa Biosciences, was able to identify patients with aggressive prostate cancer, and helped decide who should be recommended for a prostate biopsy, potentially reducing the number of unnecessary biopsies, the company announced.
The test may be also used for other cancer types in the future.
Anixa’s ongoing study is evaluating if Ccheck can accurately predict if a man is at higher risk of having an aggressive form of prostate cancer (Gleason grade 4+3 or higher) — and should be recommended for biopsy — or if he is at lower or no risk for the cancer.
The prostate-specific antigen (PSA) test is the standard for detecting prostate cancer but “results in a large frequency of false positives leading to numerous men each year undergoing unnecessary prostate biopsy procedures,” the researchers said in their presentation.
Ccheck detects a type of cell that often appears early in cancer, called myeloid-derived suppressor cells (MDSCs), by combining flow cytometry — a technique that detects specific cell populations within a biological sample — and artificial intelligence (machine learning).
MDSCs are often induced by tumors of different types, after cancer cells have harassed the development and function of immature immune cells termed myeloid. Those cells are called into the tumor microenvironment and diverted to suppress the anti-tumor immune system attacks trying to fight the cancer.
A growing body of evidence indicates that MDSCs support the growth and spread of several cancer types, and enable tumors to resist immunotherapies. That is why they are emerging as novel anti-cancer therapeutic targets.
In this study, researchers used Ccheck to screen blood samples of 114 patients with biopsy-confirmed prostate cancer, 89 participants with biopsy-confirmed benign prostate enlargement, and 116 healthy subjects.
The flow cytometry part of the test detected the profile of MDSCs, and other immune cells, present in the patient’s blood (immunophenotyping), while machine learning analyzed this pattern and predicted cancer risk.
The test had 90% sensitivity for predicting whether subjects should undergo a prostate biopsy. The researchers argued that this data meant that of the 203 subjects recommended for biopsy, about 105 of them could have been spared the procedure if Ccheck had been used.
“In a clinical setting, we believe that this technology, in use with other known clinical risk factors, would allow for clinicians to have a more informed decision when recommending their patients for a prostate biopsy procedure,” the researchers wrote.
“We are pleased with the response received on our presentation from the scientific community, and look forward to the impact our technology may have on cancer treatment,” Amit Kumar, PhD, CEO of Anixa, said in a press release.
Previous studies have shown that EBRT, the most common type of radiation therapy, together with ADT, a hormone therapy that aims to slow disease progression by reducing levels of male hormones, led to significant improvements in patients’ survival compared to EBRT alone.
More recently, the Phase 3 clinical trials NCT00002633 and ISRCTN01534787, plus a third trial, have shown that a combination therapy of ADT and EBRT led to better clinical outcomes compared to ADT alone in patients with locally advanced prostate cancer — that which has spread outside the prostate, but not yet to other tissues and organs.
In this multi-center, randomized, open-label, Phase 3 clinical trial (NCT01122121), researchers aimed to confirm these findings and report the long-term effects of the combination therapy of ADT and EBRT compared to ADT alone.
The study, called TAP 32, enrolled 263 patients with locally advanced prostate cancer who were randomly assigned to receive either ADT alone or a combination of ADT and EBRT.
ADT was similar in both groups, with patients receiving 11.25 mg of leuprorelin for three years. Patients placed in the combination therapy group also received radiation therapy in the whole pelvis at a dose of 46 Gy (a measure of radiation) and 20-28 Gy specifically in the prostate.
The trial’s primary endpoint was to assess the time patients lived without the disease worsening, a measure called progression-free survival.
Secondary endpoints included overall survival, disease-specific survival, locoregional progression-free survival (the time patients lived without lesions in pelvic lymph nodes), metastasis-free survival (the time patients lived without cancer spreading) and treatment tolerability.
Patients were followed for a median of 7.3 years. Results showed that a significantly higher percentage of patients treated with the combination lived past the eight-year mark without disease worsening, compared to those on ADT alone (48% versus 7%).
Overall survival at eight years was also higher for those in the combination (65%) compared to ADT alone (57%). The risk of death from prostate cancer was significantly lower in patients from the combination therapy group compared to those on ADT only.
Although no significant differences in the time to metastasis or death were found between the two groups, patients receiving the combination therapy lived longer without developing lesions in pelvic lymph nodes.
Safety analysis showed that after six months of treatment, a higher percentage of patients treated with ADT plus EBRT experienced side effects (26% versus 2%). However, these values tended to decrease gradually throughout follow-up.
“The present results show a trend in favor of combined arm in order to delay metastatic progression, reinforcing the idea that local control could impact disease’s distant spread even for patients presenting strong micro-metastatic risk,” the investigators stated.
“The long-term results of this study corroborate that standard dose-level prostate EBRT combined with prolonged hormone therapy significantly improves oncological outcomes for locally advanced prostate cancer,” they said.
But these imaging techniques may have low sensitivity, specifically when PSA levels are low. Thus, researchers have been developing tracers for positron emission tomography (PET) imaging that light up prostate cancer before it is evident on other imaging tests.
PET scans use probes called radiotracers, which are specific molecules linked to or “labeled” with a small bit of radioactive material, making them detectable on the scan. The non-radioactive part of a radiotracer is a molecule designed to accumulate in cancers or regions of inflammation, or bind specific proteins in the body.
Several studies have demonstrated that one PET probe — 68Ga-PSMA-11 — yields “unprecedented accuracy and effect on treatment,” researchers noted. It is composed of a molecule that binds the prostate specific membrane antigen (PSMA), labeled with the radioactive compound gallium (68G).
Although this technique has been used on a compassionate basis and evaluated in multiple case studies outside the U.S., there is a lack of prospective data — a study that watches for outcomes over the study period, rather than looking at data obtained in the past (retrospective study).
The studies (NCT02940262 and NCT03353740) measured the positive predictive value, detection rate, reproducibility, and safety of 68Ga-PSMA-11 PET in 635 patients, ages 44 to 95, who had biochemical recurrence of prostate cancer (evidenced by PSA tests) after prior treatment with surgery, radiation therapy, or both.
Results showed that 68Ga-PSMA-11 PET had a positive predictive value — the probability that subjects testing positive on the scan truly have the disease — ranging from 84% to 92%, depending on whether tumors were validated by biopsy or a composite assessment that also included PSA levels.
The scan detected and localized recurrent prostate cancer in 475 of 635 (75%) patients with a PSA test indicative of cancer recurrence.
PET scans were able to detect more recurrent patients, as their PSA levels were higher. Detection rates were 38%, 57%, 84%, 86%, and 97% as PSA levels ranged from less than 0.5, 0.5 to less than 1, 1 to less than 2, 2 to less than 5, and 5 or more ng/mL.
Each scan was repeated three times on different PET readers to test a reader’s reproducibility, which was considered to be “substantial.” No serious adverse events were observed with 68Ga-PSMA-11 administration.
In a small group of patients, lesions identified by PET scans were therapeutically targeted either using radiation therapy, surgery, or cryoablation. This type of PET-directed focal therapy alone led to a PSA reduction of 50% or greater in 31 out of 39 patients (80%).
“This prospective multi-center trial demonstrates high accuracy, reproducibility, and safety of 68Ga-PSMA-11 PET in patients with biochemically recurrent prostate cancer,” researchers said.
Compared with prior analysis, this study is strengthened by its large sample of patients, the blind reproducibility tests of PET readers, and independent validation of tumors.
“High rates of biochemical response (≥80%) in patients with PET-directed focal therapy indicate potential value of the PET information for treatment planning,” the researchers said. However, these results must be interpreted with caution, as a potential benefit “needs to be carefully weighed against potential morbidity and complexity of salvage procedures in clinical trials,” they said.
PET false-negative lesions were reported in few patients (17) and half of those were associated with weak uptake of the radiotracer by the tumors. These false negatives may also happen because of elimination of the tracer in urine, inflammation, or post-therapeutic remodeling, low or absent PSMA expression, or small tumor size.
Another promising PET modality for prostate cancer, 18F-fluciclovine PET, is not yet approved. Comparison between 68Ga-PSMA-11 vs 18F-fluciclovine PET for recurrent prostate cancer is underway on a clinical trial at UCLA (NCT03515577).