Despite the best efforts of surgeons and radiation oncologists, it is nearly impossible for a man to retain his ability to father children through sexual intercourse after initial treatment for prostate cancer.

During a prostatectomy, both the prostate and the nearby seminal vesicles are removed. The seminal vesicles are two small structures that lie at the base of the bladder. Together with the prostate, they provide semen that carries the sperm down the urethra and out the penis during ejaculation. The loss of semen following surgery makes ejaculation impossible, so the sperm cannot physically make it out of the body to reach the woman’s egg for fertilization.

With radiation therapy, fertility is nearly always impaired. Radiated prostate cells and seminal vesicles tend to produce semen that cannot transport the sperm well. In addition, the sperm, which is made and housed in the testicles, can be damaged, but this is seen far less frequently with more accurate dose planning.

Fertility Options After Treatment for Prostate Cancer

For men who wish to father children after treatment for prostate cancer, the best chance for fertility is sperm banking. Semen containing sperm is frozen in liquid nitrogen and, although the cells are technically still alive, all cellular activity ceases. After thawing, up to 50% of sperm will regenerate and can be used for artificial insemination.

As an alternative to banking sperm, extracting sperm directly from the testicles might be an option. After harvesting sperm from testicular tissue, a single microscopic sperm is injected into a single microscopic egg. If an embryo forms, it is implanted into the woman’s uterine wall and allowed to grow.
Although technical advances in assisted reproduction have dramatically improved the conception rates, the success rates for the two procedures combined—sperm extraction followed by injection of the sperm into the egg—is less than 50%.

The FDA has approved a supplemental New Drug Application (sNDA) for apalutamide (Erleada) for the treatment of patients with metastatic castration-sensitive prostate cancer (mCSPC).1

The sNDA was processed through the Real-Time Oncology Review Program after the application received a priority review designation when it was submitted in April 2019. Results of the phase III TITAN trial, which were presented at the 2019 ASCO Annual Meeting, were the basis for the sNDA.

“Prostate cancer is more difficult to treat once it spreads, and for patients with castration-sensitive disease, it is clear that androgen deprivation therapy [ADT] alone, is often not enough,” Kim Chi, MD, a medical oncologist at BC Cancer – Vancouver and principal investigator of the TITAN study, said in a statement. “Results from the TITAN study showed that, regardless of the extent of disease, patients with metastatic castration-sensitive prostate cancer have the potential to benefit from treatment with apalutamide in addition to ADT.”

The FDA has noted that the recommended dose for apalutamide is 240 mg or 4 tablets of 60 mg each, given orally once daily with or without food. Additionally, the agency recommends that patients also receive a gonadotropin-releasing hormone analog concurrently with apalutamide or should have received a bilateral orchiectomy.2

The international, randomized, double-blind phase III TITAN trial included 1052 patients with metastatic castration-sensitive prostate cancer across 260 sites, regardless of prior localized therapy, docetaxel treatment, or the extent of their disease. Patients were randomized 1:1 to receive either 240 mg oral apalutamide once daily plus ADT (n = 525) or placebo plus ADT (n = 527). Treatment was given until disease progression, unacceptable toxicity, or the end of treatment was reached.

Patients had a median age of 68 years and 62.7% had high-volume disease whereas the other 37.3% had low-volume disease. A total of 16.4% of patients had undergone a prostatectomy or had received radiotherapy for localized therapy. Previous docetaxel therapy was noted in 10.7% of patients.

The coprimary endpoints of the trial were radiographic progression-free survival (rPFS) and overall survival (OS).

Apalutamide with ADT demonstrated an improvement in OS compared with ADT alone, resulting in a 33% reduction in the risk of death (HR, 0.67; 95% CI, 0.51-0.89; P = .0053). The combination also demonstrated a 52% reduction in the risk of radiographic progression or death (HR, 0.48; 95% CI, 0.39-0.60; P <.0001).1

According to findings presented at the 2019 ASCO Annual Meeting and subsequently published in the New England Journal of Medicine, at 2 years, the rate of OS was 82.4% with apalutamide and ADT compared with 73.5% in the ADT and placebo group (HR, 0.67; 95% CI, 0.51-0.89; P = .005). The 2-year rate of rPFS was 68.2% with the combination versus 47.5% with ADT alone.3,4

Both the median times to prostate-specific antigen (PSA) progression (HR, 0.26; 95% CI, 0.21-0.32) and cytotoxic chemotherapy (HR, 0.39; 95% CI, 0.27-0.56; P <.001) were improved with the addition of apalutamide. In the combination arm, 68.4% of patients demonstrated significant PSA declines to undetectable levels compared with 28.7% in the ADT and placebo group.

Treatment with apalutamide and ADT also resulted in a 34% risk reduction in the median time to second PFS (HR, 0.66; 95% CI, 0.50-0.87).

Grade 3/4 adverse events (AEs) occurred in 42.2% of patients in the apalutamide arm compared with 40.8% in the control arm. Serious AEs occurred in 19.8% of patients versus 20.3% in the 2 arms, respectively. Discontinuations due to AEs occurred in 8% of the apalutamide arm compared with 5.3% in the group receiving ADT alone. There were 10 AE-related deaths in the apalutamide arm versus 16 in the placebo arm.

Grade ≥3 AEs of special interest included rash (6.3% in the apalutamide arm vs 0.6% in the ADT-alone arm), fatigue (1.5% vs 1.1%, respectively), fall (0.8% in each arm), fracture (1.3% vs 0.8%), and seizure (0.2% vs 0).

“Erleada has the potential to change how patients with prostate cancer are treated, regardless of the extent of the disease or prior docetaxel treatment history, by delaying disease progression and prolonging survival,” Margaret Yu, MD, vice president, prostate cancer disease area leader, Janssen Research & Development, LLC, said in a statement. “This milestone highlights Janssen’s commitment to improve the standard of care for patients with prostate cancer as we continue to develop innovative treatments across the disease continuum.”

Apalutamide previously received FDA approval in February 2018 for the treatment of patients with nonmetastatic castration-resistant prostate cancer.
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The diagnosis of prostate cancer could be significantly improved with a new blood test that looks for circulating tumor cells. Unnecessary biopsies and treatments could also be avoided.

According to a recent study, combining the new test with prostate specific antigen (PSA) results can yield a diagnosis of aggressive prostate cancer that is more than 90% accurate.

This level of accuracy is higher than that of any other biomarker for prostate cancer, according to the study author, who says it could lead to a paradigm shift in the way prostate cancer is diagnosed.

PSA test not enough to diagnose cancer

The prostate produces a protein called PSA. When there is cancer in the prostate, the gland releases more PSA into the blood, and therefore, raised levels of PSA in the blood can be a sign of prostate cancer.

Unfortunately, other prostate conditions, such as inflammation or noncancerous enlargement of the gland, can also raise PSA levels.

In order to confirm the presence of cancer, the patient undergoes a biopsy, which is an uncomfortable procedure where the surgeon removes pieces of the prostate and sends them for tissue analysis.

A biopsy of the prostate is not only invasive but can also have risks such as infection and a high chance of bleeding. And the biopsy results of most men with raised PSA levels come back saying that they do not have cancer.

And when prostate biopsies do reveal the presence of cancer, in most cases, the tumor is not aggressive and will not be fatal if doctors leave it untreated.

Experts say that the first genetically targeted drug for fighting prostate cancer could become a become a revolutionary treatment.

Olaparib is a precision medicine already used by the NHS for ovarian cancer and has been called a game-changer by cancer doctors.

In trials the drug has slowed tumor growth in men with advanced prostate cancer. Researchers hope that this could improve survival for some men. Experts say the drug could be made available to patients in the next couple of years.

Precision medicine

Olaparib, also called Lynparza, works by targeting and killing cancer cells with faulty genetic code, while at the same time sparing normal cells with healthy DNA.

Researchers say that the drug won’t work for everyone with prostate cancer, but it is effective for some men with the disease.

Patients can be tested to see if they have the genetic errors that the drug can attack – faulty DNA repair genes including BRCA1 and BRCA2. This precision approach means that the patients most likely to benefit will be treated, avoiding potential side-effects from other drugs that may not work as well for them.

During the trial, doctors compared Olaparib with two other commonly prescribed prostate drugs (hormone treatments called Abiraterone and Enzalutamide).

It appeared that Olaparib delayed cancer growth by months, which researchers say hopefully means men can survive for longer even when their disease is advanced. The researchers will be monitoring patients to confirm this.

About prostate cancer

One in eight men will be diagnosed with prostate cancer in their lifetime. It mainly affects men over the age of 50 and the risk increases with age.

Not all of these tumors need immediate treatment. If the cancer is at an early stage and not causing symptoms, doctors may instead suggest careful monitoring.

Some cases are more aggressive and need treatment but can be cured if caught early enough.

Other cases may only be diagnosed at a late stage when the cancer has spread and cannot be cured.

All treatments, including Olaparib, can have side-effects. Doctors can talk advise patients about what might be the best treatment for them.

A team of medical researchers led by University of Michigan doctors wanted to answer the question of whether black race associated with worse prostate cancer outcomes after controlling for variables such as access to care.

This question of racial disparity in regard to prostate cancer is important because African American men in the United States are more than twice as likely to die from prostate cancer as Caucasian men. The reason for the disparity, in black and white men with similar stages of prostate cancer disease, is still unclear, especially in regard to the contribution of biological versus non-biological differences.

The University of Michigan conducted an extensive study which concluded that the reason for the prostate cancer outcome disparity isn’t that black men intrinsically and biologically harbor more aggressive disease. The study stated that when provided the same access to treatment and care, black and white men have very similar cure rates.

However, black men get fewer prostate cancer screenings, and are more likely to be diagnosed with later-stage cancer. They are also less likely to have health insurance.

The study from the University of Michigan also suggests that when it comes to African American prostate cancer, health care, and socioeconomic factors play a larger role than genetics.

This study is very important to African American men and also for the physicians who treat them. The key takeaway is that now, more than ever, it is important for African American men to be proactive about their prostate health, and that a good first step in that direction is to initiate a discussion with a primary care physician or a urologist about the benefit of prostate cancer screening.

The University of Michigan study reviewed data on 306,100 men — 54,840 black men — ages 59 to 71 from the Veterans Affairs system and four other clinical trials.

Thanks to this study from the University of Michigan, urologists and other physicians now have evidence that prostate cancer outcomes in African Americans are substantially linked to access to care rather than genetic factors.

According to the results of a recent study, there was no difference in disease recurrence among men with prostate cancer when they were given radiation after surgery or not.

The results from the study could mean that men with prostate cancer could be spared having to undergo radiation after surgery. The study found no difference in disease recurrence at five years between those who did and did not utilize the adjuvant therapy.

As an added benefit for patients, these findings could lead to patients experiencing far fewer side effects. The good news could be that in future, many men will avoid the side-effects of radiotherapy. These side effects can include urinary leakage and narrowing of the urethra, which can make urination difficult. Both are still potential complications after surgery alone, but the risk is increased if radiotherapy is used as well.

In the trial, researchers enrolled 1,396 patients after surgery for prostate cancer, and randomized them to receive either postoperative radiotherapy or the standard approach of observation only (in this particular group radiotherapy was only kept as an option if the disease recurred).

After five years at a median follow-up, progression free survival (the time from treatment to disease progression or worsening) was 85% in the radiotherapy group, compared with 88% in the standard care group.

After one year post-surgery, self-reported urinary incontinence was worse in the radiotherapy group (5.3%), compared with those who underwent observation (2.7%).

There is a strong case to be made that observation could be the standard approach after surgery and radiotherapy should only be used if the cancer comes back.

These same findings were also confirmed in a collaborative meta-analysis that included three randomized trials comparing adjuvant radiotherapy with early salvage radiotherapy following prostatectomy for men with localized prostate cancer.

The analysis was comprised of 2,151 men, including 1,074 who were randomized to adjuvant radiotherapy and 1,077 men were randomized to early salvage radiotherapy. Of those randomized to early salvage radiotherapy, only 37% started salvage treatment to date.

Similarly, the analysis did not find a significant difference supporting the use of adjuvant therapy to improve prostaAfter Surgery May Not Be Necessary Among Men With Prostate Cancer
According to the results of a recent study, there was no difference in disease recurrence among men with prostate cancer when they were given radiation after surgery or not.

The results from the study could mean that men with prostate cancer could be spared having to undergo radiation after surgery. The study found no difference in disease recurrence at five years between those who did and did not utilize the adjuvant therapy.

As an added benefit for patients, these findings could lead to patients experiencing far fewer side effects. The good news could be that in future, many men will avoid the side-effects of radiotherapy. These side effects can include urinary leakage and narrowing of the urethra, which can make urination difficult. Both are still potential complications after surgery alone, but the risk is increased if radiotherapy is used as well.

In the trial, researchers enrolled 1,396 patients after surgery for prostate cancer, and randomized them to receive either postoperative radiotherapy or the standard approach of observation only (in this particular group radiotherapy was only kept as an option if the disease recurred).

After five years at a median follow-up, progression free survival (the time from treatment to disease progression or worsening) was 85% in the radiotherapy group, compared with 88% in the standard care group.

After one year post-surgery, self-reported urinary incontinence was worse in the radiotherapy group (5.3%), compared with those who underwent observation (2.7%).

There is a strong case to be made that observation could be the standard approach after surgery and radiotherapy should only be used if the cancer comes back.

These same findings were also confirmed in a collaborative meta-analysis that included three randomized trials comparing adjuvant radiotherapy with early salvage radiotherapy following prostatectomy for men with localized prostate cancer.

The analysis was comprised of 2,151 men, including 1,074 who were randomized to adjuvant radiotherapy and 1,077 men were randomized to early salvage radiotherapy. Of those randomized to early salvage radiotherapy, only 37% started salvage treatment to date.

Similarly, the analysis did not find a significant difference supporting the use of adjuvant therapy to improve prostate cancer from recurring, compared to early salvage radiotherapy. Based on these results, the difference in five-year event free survival is likely only to be around 1%, according to the release.

te cancer from recurring, compared to early salvage radiotherapy. Based on these results, the difference in five-year event free survival is likely only to be around 1%, according to the release.

A retrospective cohort study showed that men who used statin drugs had a lower risk of prostate cancer but only with prolonged use or higher doses.

Men who had a history of treatment with statins was associated with a 15% reduction in the relative risk of low-grade prostate cancer and a 46% lower risk of developing high-grade disease. The association, however, was limited to men who took statins for at least 11 months or who had a specific defined daily dose of ≥121. This number is based on a reference dose of 20-mg simvastatin.

According to a report, lipophilic statins appeared to be more protective against prostate cancer than did hydrophilic drugs.

Researchers believe that mechanistically, statins have been found to reduce intracellular and serum cholesterol, and therefore may affect cell membrane organogenesis, steroidogenesis, and proliferation. Growth inhibition in prostate-derived cells lines was observed at clinically relevant statin concentrations.

This study adds to numerous others that preceded it, which collectively showed that statin use is associated with a lower risk of prostate cancer. The cumulative data does suggest only a modest effect on prostate cancer diagnosis.

Statins and Prostate Cancer

Over the past 15 years, statin use has increased dramatically, and as a class, the drugs are among the most widely prescribed medications in the world. It is thought that lowering serum and tissue levels of cholesterol may disrupt cellular lipid rafts, leading to reduced raft-dependent signaling and cell proliferation. And by extension, statins may have chemopreventive effects that reduce carcinogenesis, including prostate cancer carcinogenesis.

A recent study has found that eating dairy products has been linked to a higher chance of developing prostate cancer, and a plant-based diet appears to cut the risk.

In the past, some studies have found a link between consuming dairy products; such as milk and cheese; and prostate cancer. The disease is more prevalent in Western countries with the biggest consumption of calcium. The researchers in the study cited that prostate cancer is less common in Asian countries where such foods are consumed much less.

The team of Mayo Clinic researchers examined more than 47 existing scientific journal articles published between 2006 and February 2017, and involved more than 1 million participants in total.

The study results linked plant-based diets, such as vegetarian and vegan diets with a lower or unchanged risk of developing prostate cancer from the baseline.

Eating animal products, and dairy in particular, was associated with an increased or unchanged risk of being diagnosed with the disease.

Each year, approximately 175,000 new cases of prostate cancer are diagnosed, making it the most prevalent form of the disease among men other than skin cancer.

The disease is the second leading cause of cancer death in the U.S. after lung cancer, and kills around 31,620 people annually.

The study highlighted a cause for concern with high consumption of dairy products and the findings also support a growing body of evidence on the potential benefits of plant-based diets.

However, the study was limited because it included a range of different papers with varying methods. The researchers said that future research could test the validity of the findings by carrying out randomized control trials. Researchers would also like to look at the effects of other lifestyle factors like smoking and exercise.

A research team has been investigating the mechanisms driving prostate cancer progression and have been developing novel treatments and models to combat metastasis for the past 15 years. The team has mechanistically examined how cancer cells have been able to bypass immune cells and survive. The work initially started with the discovery that in advanced stages of prostate cancer, the cancer cells could not only escape immune system surveillance, but could also disable the immune system response.

The research found that the underlying mechanisms for these events came from the oncogenic stress-induced molecule called “MIC.” When found in healthy cells, MIC is not expressed on cell surfaces. However, the researchers discovered that during cancer development, and even at very early stages, prostate cells start to express MIC. MIC’s primary function is to “flag down” the immune cells, particularly the natural killer and cytotoxic T cells, to initiate their response in fighting cancer cells. However, it was found that in stages of advanced prostate cancer, the cancer cells have “chopped off” or eliminated the ability of MIC to “flag down” the immune cells.

Therefore, the cancer cells are able to bypass immune surveillance and roam free. Then, detrimentally, cancer cells release a soluble form of MIC, called sMIC, which shuts down the immune system and this allows for the cancer cells to “dodge” immune cells. When considered together, the research team reasoned that these mechanisms may explain the non-responsiveness to immunotherapy in patients with advanced prostate cancer.

The team developed a first-in-class monoclonal antibody to target sMIC. In preclinical models, the antibody has been found to “revive” immune system function and eliminate prostate cancer metastasis to solve this problem. The antibody has already shown promise in controlling metastasis of cancer cells when administered solo, and even in non-responders to immunotherapy. When it has been administered in combination with an immune checkpoint blockade, a synergistic anti-tumor effect occurred where both agents work to restore immune function.

The team is also working toward bringing this anti-sMIC antibody from preclinical to clinical use in humans. Plans are to conduct a preclinical safety assessment for clinical trials, examine how the antibody would work with current standards of care for prostate cancer, and investigate how to use the antibody to tackle neuroendocrine prostate cancer, the most lethal type prostate cancer.

After presenting the results of a new study, researchers have called for immediate action to recommend screening for prostate cancer for men with BRCA2 mutations over the age of 40.

It is widely known that BRCA mutations greatly increase the risk of breast and ovarian cancer in women with the disease. However they also increase the risk of several types of cancer in men, including prostate and breast.

Scientists have also determined that BRCA2 mutations are likely to increase the chance of a type of childhood cancer called non-Hodgkin lymphoma.

The sturdy research looked at almost 3,000 men aged 40-69, with just over half carrying inherited mutations in either BRCA1 or BRCA2, while the others were healthy controls. These men were screened with a common test for prostate cancer called the PSA (prostate-specific antigen) test.

The researchers found that the incidence of prostate cancer in men with BRCA2 mutations was significantly higher than in men with no BRCA mutations. They also determined that BRCA2 carriers were typically diagnosed when younger and had more substantial disease. However, there were no differences observed in men who carried BRCA1 mutations, compared to healthy controls.
The researchers feel that the study shows very clearly that men with the BRCA2 gene fault are at increased risk of aggressive prostate cancer and that regular PSA testing could go some way to improving early diagnosis and treatment.

The research indicates that men over the age of 40 who carry a mutation in the BRCA2 gene should undergo an annual PSA test as a way of identifying prostate cancer which in their case may be more aggressive.