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Prostate Cancer Foundation (PCF) 2019 Guide

Every year, the PCF publishes an electronic guide providing information on all aspects of prostate cancer. The chapters covered are as follows.

General information including diagnosis, symptoms, risk factors, and medical basics.
Information for the newly diagnosed, including detection, diagnosis and treatment selection.
Treatment options for localized or locally advanced prostate cancer. These include active surveillance, surgery, various radiation modalities, and other experimental therapies for localized prostate cancer.
Living with and after prostate cancer including sections on quality of life, recurrence, urinary, bowel and sexual function, diet, exercise and lifestyle changes.
What to do if one’s PSA starts to rise. Topics include local treatments for recurrent cancer, therapies for advanced recurrent or metastatic cancer, hormone-resistant cancer, non-hormonal therapy options and side effects from various treatments for advanced prostate cancer.
Cutting edge developments in prostate cancer research including precision medicine, PARP inhibitors, immune checkpoint inhibitors, CAR T cells and vaccines.
Information for families of prostate cancer patients including future risk, genetic testing and screening and prevention.
Here is a link to the most recent edition of the annual PCF prostate cancer guide.

Prostate Cancer Resources

At a recent meeting of a prostate cancer support group, a list of internet informational resources were listed. Upon checking each one, I have found the following to be most informative and current. For a complete listing, see the section entitled Medical Resources on this website.

The National Cancer Institute (NCI) of the National Institutes of Health (NIH) in Bethesda and Frederick, Maryland have a site entitled cancer.gov.

2. For a searchable compilation of active and recruiting clinical trials, see clinicaltrials.gov.

3. The Prostate Cancer Foundation is a valuable source of information about all aspects of prostate cancer. See pcf.org.

4. Likewise, the Prostate Cancer Research Institute is also a valuable source. See prci.org.

5. I had never seen the following before, but it deserves a listing. See yananow.net.

Pyl Imaging Agent Accurately Detects Recurrent Prostate Cancer Lesions

Progenics Pharmaceuticals’ PyL, a new imaging agent for positron emission tomography (PET) scans, can accurately detect the location of recurrent prostate cancer lesions, according to data from the Phase 3 CONDOR clinical trial.

“There is a need for improved diagnostics for prostate cancer to replace conventional imaging tests that have limited performance characteristics, especially in men with biochemical recurrence of their disease,” said Barry Siegel, MD, CONDOR’s principal investigator at the Mallinckrodt Institute of Radiology at Washington University School of Medicine clinical site.

PyL (18F-DCFPyl) is a tracing agent composed of DCFPyL, a small molecule that specifically targets the prostate specific membrane antigen (PSMA) protein — present at high levels in prostate cancer cells — coupled with a radioactive compound labelled with fluorine 18. After PyL is injected intravenously into the patient, it travels through the blood and accumulates at prostate cancer sites, making them “light up” during PET scans. PyL has the potential to allow clinicians to detect very small lesions that are currently missed with conventional imaging methods, so can they determine if the disease has returned or spread to distant organs and adjust treatment plans accordingly.

The open-label CONDOR study (NCT03739684) evaluated whether PyL could safely, successfully, and accurately detect new prostate cancer lesions in 208 men suspected of prostate cancer relapse. These suspicions, which were based on biochemical relapse — rising levels of prostate-specific antigen (PSA), a biomarker of the disease — were accompanied by negative or ambiguous findings on conventional imaging scans.

Participants were recruited, dosed, and imaged with PyL at 14 sites in the U.S. and Canada. CONDOR’s primary goal was to assess the predictive value of PyL in detecting the right location of new cancer lesions that confirmed the disease had returned. For that, three blinded, independent researchers compared the results of PyL PET scans with those of confirmatory biopsy or surgery, conventional imaging, and/or changes in PSA levels following radiation therapy of PyL-suspected lesions, performed within 60 days after PyL imaging. The study’s secondary goal was determining the percentage of patients whose treatment plan was changed based on PyL imaging results.

Results showed that the trial met its primary goal, with PyL imaging detecting at least one posteriorly confirmed new lesion in 84.8% to 87% of the cases. This exceeded by far the 20% threshold established by the FDA “for the trial to be deemed a success,” reflecting “the impactful clinical utility of PyL imaging.”

As far as safety, the imaging agent was well-tolerated, consistent with data from the previous Phase 2/3 OSPREY clinical trial (NCT02981368). The most frequently reported adverse side effect (in 1.9% of patients) was headache, and one man had a serious immune reaction (hypersensitivity) to PyL.

“The high positive predictive value demonstrated in this study reflects the clinical utility of PSMA-targeted PET imaging agents providing actionable information to physicians to guide treatment plans and improve disease management of one of the most prevalent cancers in the U.S.,” Siegel said.

“The positive results of our Phase 3 CONDOR trial reinforce our belief in the potential of PyL to enable better physician treatment decisions and, ultimately, improve patient outcomes,” David Mims, Progenics’ interim CEO, said in a press release. The company plans to submit a new drug application for PyL to the U.S. Food and Drug Administration in the second half of this year, according to Mims.

Material cited above was received on January 13th in the Prostate Cancer News Today Weekly Digest to which I recommend a subscription.

Higher Radiation Therapy Doses Over Shorter Time Show No Added Side Effects in Men with Prostate Cancer.

Delivering higher doses of radiation therapy over a shorter time period — an approach called stereotactic body radiation therapy (SBRT) — does not worsen side effects in men with localized prostate cancer, compared to conventional radiation therapy, a Phase 3 trial shows. The study also suggests that SBRT delivered through the CyberKnife System is less toxic for the genitourinary system than conventional linear accelerators used for this kind of radiation therapy. The research was published in an article in the journal The Lancet Oncology.

Accuray’s CyberKnife is a robotic system that delivers SBRT to the prostate and other organs. This approach involves very high doses of radiation over a smaller number of treatment sessions compared to conventional radiation therapy. As the prostate can move unpredictably during the course of treatment, tracking its position and correcting the radiation delivery site are key. CyberKnife offers continual imaging and automatic beam delivery corrections through its Synchrony technology, which helps increase treatment efficacy and spare healthy tissue, according to the company.

The international, Accuray-funded PACE-B Phase 3 trial (NCT01584258) was designed to compare SBRT to conventional radiation therapy in men who were ineligible for surgery, had low or intermediate risk cancer, and to determine if the CyberKnife system provided any benefits over other SBRT delivery systems. Patients assigned to SBRT received five sessions over one or two weeks, while those on conventional radiotherapy had either 39 sessions over eight weeks, or 20 sessions over four weeks. The trial included 874 men and took place in the U.K., Ireland, and Canada. In both groups, 90% of the patients had intermediate-risk prostate cancer.

Clinical assessments and patient-completed questionnaires showed that SBRT and conventional radiation therapy resulted in similar levels of acute gastrointestinal and genitourinary side effects over three months. No treatment-related deaths occurred in either group. The researchers also found that moderate or worse genitourinary side effects were less common in CyberKnife users (12%) than in non-users (31%). Gastrointestinal side effects were similar in both groups. In a news release, researchers said the results are “promising, and for the first time show in a large patient group that giving five large doses of SBRT is safe in the short term.” Of note, eight of the study’s authors received grants and/or personal fees from Accuray.

The above information first appeared in the Oct. 3rd e mail edition of Prostate Cancer News Today, by Jose Marques Lopes, Ph.D.

Part 2. Why Am I Writing This Website?

This post is Part 2 following “Prostate Cancer Is My Assignment” posted Oct. 16th. Since 1995, I had been treated for prostate cancer at Johns Hopkins in Baltimore, MD. My excellent urologist, who knew me well, was aware I had kept a “prostate diary” over the course of my condition and urged me to write a book describing my cancer experiences. Upon considering and praying about the issue, I was clearly led to create this website, Godandprostate.net. My rationale was that books about prostate cancer necessarily have endings whereas a website can be continuous as long as there are new developments and personal experiences to relate. This site also enables me to incorporate my career knowledge in organic and medicinal chemistry and personal interactions with medical researchers coupled with the spiritual experiences and lessons God has been teaching me during these years. Anne Graham Lotz, Billy Graham’s daughter, also kept an e book detailing her experiences. She is now writing a book and embarking on speaking tours. Like her, I can also unequivocally say that cancer also continues to be my assignment.

So why am I writing this website?

1. From my experience, it seems that men are more reluctant to discuss their personal health issues with one another than are women. So perhaps sharing some of my experiences via a website could initiate more dialog.

2. Many men have shared with me that when first diagnosed with prostate cancer, they were quietly fearful, some forseeing negative outcomes and side effects. Their first reaction was the “get rid of it now syndrome.” They often quickly jumped at the first recommendation given by a urologist without seeking 2nd and 3rd opinions. I know several men who regretted not seeking more advice. They should have taken the time to research out the possibilities and options before committing to a treatment plan, given the array of therapeutic choices. Men should also know how to interact with medical personnel, asking the right questions, receiving the clearest answers. A website such as this could provide considerable information addressing cancer screening, diagnostics, genetics, therapeutic options and their effects, linked references to manuals published by prostate cancer organizations, as well as spiritual encouragement.

3. Looking back to my own first experiences in 1995, I can now see that many more options have become available over time. The concept of “watchful waiting” or “active surveillance” was not as universally accepted then as it is now. Modes of therapy such as forms of radiation have been vastly refined and provide more targeted treatment while minimizing collateral damage to other organs. Men should be made aware of new therapeutic modalities as late stage clinical trial data become available.

4. I have also written this website to provide hope to men at any stage of their cancer. Hope certainly is fostered through access to excellent physicians but even more so, it is available to all through a personal and interactive relationship with God and Jesus Christ. After all, who better to care for our bodies other than the One who made them. According to Psalm 139:13-14, “For You (God) formed my inward parts; You did ‘weave’ me in my mother’s womb. I will give thanks to You because I am fearfully and wonderfully made.” The use of the word “weave” seems especially significant when one considers the intricate, coiled, double-helical structure of DNA, the molecular basis of life. It seems God literally “wove” our genetic material and bodies together in the most beautiful and intricate pattern. Therefore, it is not surprising that God wants to have a central role in our health. We are instructed to “present our bodies, a living and holy sacrifice, acceptable to God which is our spiritual (translated ‘rational’) service of worship (Romans 12:1).

5. Another purpose of this website is to share Biblical truths with men. We grow spiritually and mentally when we are “stretched” as in times of crises. In my own life, I can become complacant in times of “calm seas”. Having cancer has helped me to learn to pray and trust in my total dependance on God and the wisdom of the physicians to whom He has directed me. I have experienced God’s closeness in times of anxiety like none other. Testing of our faith produces endurance resulting in the fact that we can be perfect and complete lacking in nothing (see James 1:3-4). Christ’s unique gift of peace can also rule in our hearts and minds according to John 14:27. “Peace I give to you not as the world gives. Let not your heart be troubled nor let it be fearful.”

6. I have written this website to encourage men spiritually. God wants to be glorified in all aspects of our lives regardless of disease. Jesus, upon healing a blind man in John 9:1-3, proclaimed that the man’s blindness was not a result of some sinful action, but that the “works of God may be displayed in him.” Such can be the case for us as well. Jesus also raised his friend Lazarus from the dead even after a delay of three days, for the glory of God, that the Son of God (Jesus) may be glorified by it. (John 11:4).

7. Finally and most importantly, I am writing this website to share how we all can have a personal relationship with God, our Father, by placing our faith in His Son, Jesus, who paid the penalty for all our sins and mistakes via His death and, in addition by His resurrection, offers us the gift of eternal life in a new heaven and a new earth with new, perfect bodies. “For God so loved the world (us), that He gave His only begotten Son, that whosoever believes (trusts) in Him, should not perish but have eternal life.” (John 3:16.) Hopefully, we who are concerned about prostate cancer will live for many years. But as we age we wonder what comes after this current life? Do we just cease to exist? We begin to focus on eternal values. We are eternal beings created to have fellowship with God forever. But we need to be sure where we will spend eternity and never be separated from God. Just after citing the famous golden rule, Jesus Himself said “for the gate is small and the way is narrow that leads to life and few are those who find it” (Matthew 7:14). Jesus has also promised when He said “I came that we may have life and have it abundantly” (John 10:10.) My sincere wish in writing this site is one day to meet many of you men who may have read this website and enjoy your fellowship forever in perfect bodies with no concern about prostate cancer or any other condition.

From Prostvac to Fear Then to Faith

Early 12th century Viking Christian chapel near Larvik, Norway; photo: Bjarne Gabrielsen

As many of you readers know, I have earlystage, asymptomatic but advanced prostate cancer. After treatment with Provenge, I was informed (perhaps divinely through a former colleague) of a National Cancer Institute (NCI) clinical trial currently recruiting patients like myself. The protocol involves treatment with the vaccine Prostvac and the antibody therapy, Opdivo. I had written about this in earlier posts. Since that time, Yervoy (ipilimumab) has been removed from the trial and most recently a large Phase 3 trial of Prostvac has been discontinued. Independently, I had been informed about the potential toxicity of Yervoy which reinforced my anticipation of the trial; but then the news of Prostvac’s lack of success seriously dampened my enthusiasm. It was just at that time when a devotional (August 13th) from Our Daily Bread Ministries placated my fears and inflated my faith that I was indeed pursuing the right track in my treatment.

The message was from an Old Testament prophet named Habakkuk who served as an inspiring example of someone who argued with God yet came to the point of trusting Him regardless of the impending circumstances. Habakkuk states (Hab. 3:16-19), “I heard and my heart pounded, my lips quivered at the sound; decay crept into my bones and my legs trembled.” However in contrast, “though the fig tree does not bud and there are no grapes on the vines, though the olive crop fails and the fields produce no food, though there are no sheep in the pen and no cattle in the stalls, yet I will rejoice in the Lord, I will be joyful in God my Savior.”

What do we do when circumstances are beyond our control or when the outlook seems hopeless? The prophet Habakkuk’s situation was out of his control and the fear that he felt terrified him. The coming judgment could be catastrophic. Yet, in the midst of the impending chaos, Habakkuk made a choice to live by his faith and rejoice in God. He did not place his confidence and his faith in his circumstances, ability or resources but in the goodness and greatness of God. His trust in God compelled him to proclaim: “The Sovereign Lord is my strength; he makes my feet like the feet of a deer, he enables me to treat on the heights.”

When we are faced with difficult or unknown circumstances, we too have only to place our faith and trust in God to be our strength. He is with us in everything we face.

Are you unsure of whether or not you have a personal relationship with God? See the following.

1. Prostate Cancer Is My Assignment.

This blog is Part One. Part Two, entitled “Why Do I Write This Website?’ will be forthcoming.

I am sure most of you have heard about the Rev. Billy Graham. In 2018, his daughter, Anne Graham Lotz, also a noted speaker and teacher, was diagnosed with breast cancer. She writes about enduring surgery, “seven brutal chemotherapy infusions” as well as radiation. When asked what she thought God was teaching her through her ordeal, she wrote as follows in the June, 2019 Decision magazine. “Many people who are diagnosed with something like this wonder, ‘why did this happen to me? Why didn’t God protect me? Does He not love me? What did I do to deserve this?'” She states “this cancer is not any indication that I have been bad or that He doesn’t love me or that He hasn’t blessed me. It’s just my assignment. It’s what He’s given me so I can use it to glorify Him.”

In early 2004, my wife Marie and I attended a small, country church in Maryland. I had been raised to believe in the practice of prayer accompanied by anointing the sick with oil according to James 5:14-16. “Is anyone among you sick? Let him call for the elders of the church, and let them pray over him, anointing him with oil in the name of the Lord. And the prayer offered in faith will restore the one who is sick, and the Lord will raise him up, and if he has committed sins, they will be forgiven him.” Anointing with oil had been a practice in every church I had ever attended. My pastor and the elders had planned to anoint me with oil and pray over me but we hadn’t scheduled a time to do this. I have first-hand knowledge of several individuals who have been healed from cancer as attested to by their physicians after being prayed for and anointed.

God often speaks to us when we least expect it. January 11th, 2004 was to be the 25th anniversary service of our church. In dressing for church that morning, my mood was anything but confident, trusting, worshipful or joyful. I was still asking God why He had allowed this cancer to recur after successful surgery in 1995. I was not in any celebratory mood at all and could have just as well stayed home that morning. But I was part of the music program and choir at church so I put on my best face and with a doubtful attitude, asked God to show me something, anything in answers to my questions. There was a guest speaker that morning whose sermon was about the characteristics of an ideal church. During the sermon, I sat in the choir loft and frankly, paid little attention. However, as the sermon progressed in one ear and out the other, the still small inner voice I know to be that of the Holy Spirit started to tell me to go forward and ask to be anointed with oil. An opposing inner voice urged me to postpone it until a more opportune time. The inner debate raged like a tennis match. Our service ended with a pastoral invitation for anyone who desired prayer to come forward to an altar. I decided it is now or never. At the invitation, I looked for two elders in the congregation and asked them to anoint me with oil and pray over me right there and now. Several other men joined them. I knelt at a simple altar railing and these men prayed for my healing while laying hands on my head and shoulders. I am not an emotional person and do not shed tears readily. But the feeling I experienced can only be described as being in a shower fully clothed. “Water” seemed to be pouring over me. Tears were rolling down my cheeks. I had never sensed the Holy Spirit in such an amazingly strong way. I heard the distinct command to “reach out and touch the hem of my (Jesus’) garment” reminiscent of the words a woman, plagued by years of suffering, had uttered upon seeing Jesus when she proclaimed “if I just touch His garments, I shall get well”, (Mark 5:28). I remember thinking that I cannot do this in reality since Jesus is not physically present but I reached out my hand anyway. Tears flowed from all of us men. I also heard the distinct words, “go and show yourself to the priests,” a term Jesus often cited after healing someone in the New Testament. But He is applying it to me to mean “go and show yourself to physicians especially where I had been treated”. I was confident that I had been touched in some way. As the service ended, I stood to my feet with a dazed look on my face. My wife Marie had been watching and could see something very unusual was taking place. In short, I had never in my 62 years experienced God’s (or Jesus’) presence through the Holy Spirit as I did that Sunday. Was I physically healed? No. What did this all mean? I had been given an assignment. I had many lessons to learn in the process and this was just the beginning. (For more information, see the My Story portion of this website, for the years 2004-5.)

PSMA PET-CT Offers Best Detection Rates in Recurrent Prostate Cancer.

In a recent study, investigators reported the findings of a clinical trial designed to compare the rates for detecting recurrent cancer sites using the prostate-specific membrane antigen (PSMA) PET-CT imaging agent (68Ga-PSMA-11) to those of 18F-fluciclovine in a group of men with recurrent prostate cancer who had already undergone prostatectomy and had very low levels of PSA (less than 2.0 ng/mL).

Whole-body positron emission tomography–computed tomography (PET-CT) scans are necessary to determine the location and extent of disease in men whose prostate cancer has returned, to select the best course of treatment. However, there is no consensus among different health authorities as to which specific PET-CT imaging agent should be used to identify suspected sites of prostate cancer recurrence in these patients.

Guidelines defined by the National Comprehensive Cancer Network (NCNN) have established that 18F-fluciclovine is the most suitable imaging agent for these cases, while the European Association of Urology (EAU) recommends the use of prostate-specific membrane antigen (PSMA) PET-CT imaging agents. 18F-fluciclovine labels prostate cancer cells by exploiting their increased amino acid (the building blocks of proteins) transport, whereas PSMA PET-CT agents label prostate cancer cells containing high amounts of PSMA, a marker of disease. Preliminary reports suggest superior detection rates of PSMA PET-CT compared with 18F-fluciclovine PET-CT. However, these imaging tests have not been compared prospectively and directly.

To ascertain this, a prospective, single-center, open-label, single-arm trial (NCT02940262) was carried out at the University of California Los Angeles. All men enrolled in the study had PET-CT scans with both imaging agents within a period of 15 days. The study’s primary endpoint was to determine the detection rates for both imaging agents on a per-patient and per-region level. Each PET-CT scan was analyzed by three independent experts. The opinion of the majority was considered the correct interpretation of the findings. Between February, 2018 and September, 2018, 143 men suspected of having recurrent prostate cancer were screened for eligibility and 50 were enrolled into the trial for a median follow-up period of eight months.

Study findings revealed the PSMA PET-CT imaging agent had significantly higher overall detection rates per patient, compared to those of 18F-fluciclovine (56% vs. 26%). The difference remained significant regardless of PSA levels at the time of the imaging scans. In addition, on a per-region level, the detection rates of the PSMA PET-CT imaging agent were also higher than those of 18F-fluciclovine on pelvic lymph nodes (30% vs. 8%), lymph nodes in other regions (16% vs. 0%), bone (8% vs. 0%) and other organs (4% vs. 0%).

This study concluded that the imaging agent 68Ga-PSMA-11 has better detection rates than 18F-fluciclovine in men with recurrent prostate cancer who have already had radical surgery to remove the prostate and whose levels of prostate-specific antigen (PSA, a marker of disease) are very low.

“However, because the PET findings could not be validated by a gold reference standard in two-thirds of patients, neither sensitivity nor specificity could be established,” the researchers said. “Nevertheless, the results of this prospective head-to-head comparison indicate that PSMA should be the PET tracer of choice when PET-CT imaging is considered for subsequent treatment management decisions in patients with biochemical recurrence and low PSA concentrations. Further research is needed to investigate whether higher detection rates translate into improved oncological outcomes.”

The findings of the study, “18F-fluciclovine PET-CT and 68Ga-PSMA-11 PET-CT in patients with early biochemical recurrence after prostatectomy: a prospective, single-center, single-arm, comparative imaging trial,” were published in The Lancet Oncology. The information in this post originally was published in the Sept. 16th, 2019 e mail Prostate Cancer News Today by Joana Carvalho. MSc.

FDA Approves Erleada to Treat Metastatic Castration-sensitive Prostate Cancer

The U.S. Food and Drug Administration (FDA) has approved Erleada (apalutamide) for the treatment of men with metastatic, castration (hormone)-sensitive prostate cancer (mCSPC), or those whose cancer still responds to androgen deprivation (hormonal) therapy (ADT).

The decision is based on the double-blind TITAN Phase 3 trial (NCT02489318), as it showed that adding Janssen’s Erleada to ADT significantly extended both overall survival and progression-free survival (PFS) – the period without cancer progression –, which were the trial’s primary goals. Based on results from the SPARTAN clinical trial, Erleada had already been approved in 2018 as a treatment for patients with non-metastatic (localized) castration (hormone)-resistant prostate cancer in both the United States and the European Union.

Compared to ADT and a placebo, treatment with Erleada and ADT reduced the risk of death by 33%, and the likelihood of disease worsening (as assessed by radiography) or death by 52%. After a median follow-up of 22.7 months, 84% of the patients on Erleada and ADT reached the two-year mark alive, compared to 78% of those on ADT and placebo. In this indication, Earleada decreased the risk of cancer spreading or death by 72 percent compared to a placebo, and delayed the cancer’s metastasis by more than two years. The frequency of serious adverse events was 19.8% for Erleada and 20.3% for placebo.

Erleada is an oral therapy that targets the androgen receptor, blocking its activation by androgens such as testosterone. Its chemical structure and mode of action are similar to that of enzalutamide (Xtandi). In turn, ADT, a mainstay of prostate cancer treatment, reduces the amount of androgens in the body.

TITAN included 1,052 mCSPC patients regardless of extent of disease and of being newly diagnosed or having been treated with up to six cycles of docetaxel (taxotere). It was funded by Johnson & Johnson-owned Aragon Pharmaceuticals and Janssen Research and Development (also owned by Johnson & Johnson). The study’s findings were presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting and published in The New England Journal of Medicine.

“Prostate cancer is more difficult to treat once it spreads, and for patients with castration (hormone)-sensitive disease, it is clear that androgen deprivation therapy (ADT) alone is often not enough,” Kim Chi, principal investigator in TITAN and medical oncologist at BC Cancer-Vancouver, said in a press release. “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 Erleada in addition to ADT.”

Most information in this post appeared in the September 19th, 2019 Prostate Cancer News Today by Jose Marques Lopes, Ph.D.

PSMA-Targeted Therapies Work Best in Tumors With Mutations in DNA Repair Genes.

Tumors with large numbers of prostate cancer cells with mutations in DNA repair genes (e.g. BRCA1 and 2) are easier to target using prostate-specific membrane antigen (PSMA) therapies, and patients with these tumors are more likely to respond to this potential treatment’s use, a study found and published in European Urology.

PSMA is a membrane protein often found at very high levels on the surface of prostate cancer cells, especially among those forming castration (hormone)-resistant prostate cancer (CRPC) tumors, an aggressive form of the disease that no longer responds to hormone therapy.

For that reason, PSMA has become a promising target of researchers working to develop a new class of medications that combine an anti-PSMA antibody with a radioactive moiety. Such medications, like lutetium (Lu)177-PSMA, use the anti-PSMA antibody to specifically spot and deliver the radioactive lutetium-177 conjugate to prostate cancer cells which produce PSMA in large amounts.

But this type of targeted radiation therapy does not work for all patients, and the rates of those failing to respond have amounted to about 30% in studies. Between 30% to 60% of patients with metastatic CRPC (mCRPC) treated with these therapies, however, have reported reductions of more than 50% in PSA levels (a biomarker of prostate cancer).

Prior studies used antibodies that target the intracellular (not the surface) part of PSMA, which has no clinical value for estimating PSMA levels. A team of investigators at the Institute of Cancer Research in London set out to characterize the levels of PSMA found specifically on the surface of prostate cancer cells — called membranous PSMA (mPMSA) — in a group of men with mCRPC. Because mutations in DNA repair genes lead to a high genetic variability within a single tumor, researchers also examined if these mutations affect PSMA levels and could be used to guide PSMA-directed therapies.

The study involved two groups of patients: a test group of 60 patients who provided mCRPC tissue samples, including 38 people with matched, castration (hormone)-sensitive prostate cancer (CSPC) diagnostic samples; and a confirmation group of 10 patients whose tumors contained a high number of mutations in DNA repair genes.

Despite the high degree of variability in membranous PSMA levels evident among different patients and even between samples obtained from the same patient, high levels of mPSMA at diagnosis generally associated with greater cancer aggressiveness (based on the Gleason score) and poorer patient survival.

In addition, researchers found that membranous PSMA (mPSMA) levels tended to be higher in metastatic hormone-resistant prostate cancer samples compared to hormone-sensitive samples, or samples from patients whose tumors respond to hormone therapies.

Investigators also found that mPSMA levels were more than four times higher in tumors containing numerous mutations in DNA repair genes, compared to those with no mutations. These findings were confirmed in the second group of study patients.

Testing for DNA repair defects was a good indication of which tumors had high levels of PSMA — and so would be expected to respond to these PSMA-targeted therapies like lutetium-177-PSMA. Identifying patients with DNA repair mutations could be useful in design of clinical trials to identify likely responders to PSMA treatments. (I was recently informed that genetic testing for DNA repair mutations is commercially available from the company Invitae.)

For additional details see the Aug. 22 Prostate Cancer News Today.