There were no reductions in any sperm parameters, including semen volume, sperm concentration, sperm motility, and total motile sperm count.

Study shows COVID-19 vaccines do not affect male fertility

 study, “Systematic Evaluation of Smartphone Applications for the Medical Management of Nephrolithiasis,” for which he served as a study author. Winoker is assistant professor of urology at Johns Hopkins University in Baltimore, Maryland.

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“While patient facing apps hold great potential to support self-management behaviors, particularly in stone disease, thoughtful consideration across an array of domains should really be taken prior to supporting or even recommending one of these apps to a patient,” says Jared S. Winoker, MD.

Stone management apps compared

 COVID, I think, hit our whole country, and really turned the way we practice medicine. We saw an explosion happen in telehealth, and these patients did not want to come into the office, but they still wanted to see their physicians. And the beauty of the Exosome test, which really is just a – It's a urine test that I kind of think of like little tweets. The exosomes are tweets of RNA and DNA and proteins that give us some insight on, what is that risk of cancer, of prostate cancer, and of high-grade prostate cancer 7 and above? And the urine test was quite nice. I think that really kind of changed the playing field a little bit. You did not have to do the massage. You could do a tele visit. If the patient had an elevated PSA you would say, "Well, you're in perhaps a gray zone. Let us do a test that may give us a little more insight." You mail them the kit, you get the results back in seven to ten days and then you can say, "I think you should get a biopsy," or "No, I think we're fine. Let us continue to monitor yourself." And bringing them in. Obviously, you did not need to do a rectal exam. I think that that really was a significant boon for us because it allowed us to still diagnose prostate cancer with patients that had elevated PSA's [prostate-specific antigen].

 I just want to make a comment about telehealth and just your experience. COVID [coronavirus disease of 2019] has been a terrible situation for the world and our country, so I do not want to downplay, it's been overall very bad time for us. But out of badness comes some good things and we really forced our profession to really embrace telehealth and so the advances that we had just at our hospital in the technical ability to make telehealth work was amazing. What I have found is it's pretty easy for me to develop a good therapeutic relationship with a patient. My clinic is primarily in a cancer center. It is intimidating. And I have these guys coming in with an elevated PSA into the cancer center, they are uncomfortable, many of them are out of their element and they are nervous, their blood pressure's up. I found that telehealth for an elevated PSA, at least a first-time visit, they are at home, they are more relaxed. They can open to me more; they are not as freaked out. And, as you said, they do not like the rectal exam anyway so they can do potentially a lab. We have set up lab and leave so patients can even go to a remote location – four sites in our health system – and do not even need an appointment. They just call from their car when they are in the parking lot and the lab just go ahead and do it. But with exosome, the mail-order test has been really, nice and we can get those results back. And compliance. It blew me away when we started this initiative with Duke Primary Care, really embracing working with primary care on getting these younger guys in, how non-compliant patients are. Sometimes the patients who had the highest PSA's or seem to be at the highest risk are the ones that were most likely to no show. Not only for their PSA appointment but no show for their biopsy. I guess you do not get that that much in private practice. You used to work at Duke Cancer Center, and you know you might have a CEO in one exam room and someone who is low socioeconomic status or low health literacy in the next exam room. The point is that tests like exosome and/or pHi, more data increases the patient's compliance. Some of my embrace of these tests was to try to convince some of these guys that they need to come in for the procedure and that they should not no-show. I do not know if you have seen that in Syracuse.

 I agree completely with you. Again, we are talking about more sophisticated patients that know a lot about prostate cancer. I am sure many of them have had relatives or family members that have had it so they are really keen on these tests and they know these tests now, which is really a change. The educational level of patients is significantly higher I think than it was 10 years ago. When I was at Duke Cancer Center, I think my active surveillance rate was around 10%. It is now close to 40%. As clinicians, we are seeing, once we diagnose prostate cancer, if they have a Gleason 6, we may do some genomic testing on these individuals. And if they have an Oncotype or a Polaris or a Decipher score that's low risk we are going to follow those patients. Those patients for the most part do quite well, and that is another significant contribution that we've learned over the years to change the way we practice.

David Albala, MD and Judd W. Moul, MD consider the impact that COVID-19 has had on the clinical experience of patients with prostate cancer and share personal insights regarding telehealth and patient compliance.

COVID-19: Telehealth and Compliance in Prostate Cancer

, Robert A. Figlin, MD, deputy director, Cedars-Sinai Cancer, shared his expertise on trends in the treatment of patients with genitourinary cancers.

In an interview conducted during the 2021 ASCO Annual Meeting, Robert A. Figlin, MD, deputy director, Cedars-Sinai Cancer, shared his expertise on trends in the treatment of patients with genitourinary cancers. 

Dr. Figlin on trends in genitourinary cancer care

The first patient has been dosed in the phase 3 TALAPRO-3 study evaluating the combination of the PARP inhibitor talazoparib and the antiandrogen agent enzalutamide (Xtandi) in patients with DNA damage response (DDR)-deficient metastatic castration-sensitive prostate cancer (mCSPC).

The global, double-blind TALAPRO-3 trial will randomize approximately 550 men to enzalutamide plus either talazoparib or placebo. The study is being conducted at nearly 300 clinical sites spanning 28 countries. The initial patient dose was administered at a study location in Glendale, California.

“With the introduction of PARP inhibitors in the metastatic castration-resistant prostate cancer (mCRPC) setting, it is important to explore how a combination approach may impact outcomes for men with metastatic castration-sensitive disease,” Neeraj Agarwal, MD, professor of Oncology at the University of Utah School of Medicine, senior director for Clinical Research Innovation at Huntsman Cancer Institute, and member of the TALAPRO-3 steering committee, stated in a press release. “It’s exciting to be at the forefront of landmark studies like TALAPRO-3, which are helping to further our understanding of how different approaches may advance care for these men.”

To enroll on the trial, patients must have an ECOG performance status of 0 to 1 and confirmed DDR mutation status through liquid biopsy and/or 

 or archival tumor tissue. Prior therapy is allowed. Patients with brain metastases are not eligible for enrollment. Radiographic progression-free survival is the primary end point of the study, and overall survival is a secondary end point. The estimated primary completion date for the trial is the end of 2024.

“The prognosis for men with advanced prostate cancer has significantly improved since the introduction of novel hormone therapies, but additional therapeutic options are needed for the approximately 25 percent of men with tumors harboring DDR gene mutations, who may have poorer outcomes,” Chris Boshoff, MD, PhD, chief development officer, Oncology, Pfizer Global Product Development, stated in the press release. “By combining enzalutamide, which has a proven clinical benefit in men with metastatic castration-sensitive prostate cancer, with talazoparib, our PARP inhibitor that is active in DDR-mutated cancer, we may be able to offer a new treatment option that targets the underlying genetic mechanisms associated with DDR-mutated mCSPC.”

Beyond TALAPRO-3, the combination of talazoparib and enzalutamide is also being explored in the ongoing phase 3 randomized, double-blind, placebo-controlled TALAPRO-2 trial in patients with mCRPC. DDR defects are not required to enroll.

Enzalutamide has FDA-approved indications for the treatment of patients with mCSPC and mCRPC.

Talazoparib does not have an FDA approval in prostate cancer. The PARP inhibitor is currently approved by the FDA for the treatment of patients with deleterious or suspected deleterious germline 

-mutated, HER2‑negative locally advanced or metastatic breast cancer.

There are currently 2 PARP inhibitors—rucaparib (Rubraca) and olaparib (Lynparza)—approved in the prostate cancer space, both for the treatment of patients with metastatic castration-resistant disease.

1. First Participant Dosed In Pfizer’s Pivotal Phase 3 Talapro-3 Combination Study Of Talazoparib And Enzalutamide In Metastatic Castration-Sensitive Prostate Cancer (MCSPC). Published online June 23, 2021. Accessed June 23, 2021. https://bit.ly/3gVirn3

Articles

The study is enrolling patients with DNA damage response–deficient metastatic castration-sensitive disease. 

TALAPRO-3 study launches exploring talazoparib plus enzalutamide in mCSPC

discusses a clinical trial at his institution evaluating the nasal testosterone gel Nastesto. Ramasamy is an associate professor of urology and director of male reproductive medicine and surgery at the University of Miami Miller School of Medicine.

“It's quick to act and it's quick to leave the system,” says Ranjith Ramasamy, MD, of the nasal testosterone gel Natesto.

Dr. Ramasamy discusses clinical trial of nasal testosterone gel

Neal D. Shore, MD, discusses the phase 3 VISION trial, in which adding the targeted radioligand therapy 

Lu-PSMA-617 to standard of care (SOC) led to a nearly 40% reduction in the risk of death versus SOC alone in patients with progressive PSMA-positive metastatic castration-resistant prostate cancer. Shore, who is medical director of the Carolina Urologic Research Center, also provides insight on the next steps with PSMA-targeted agents in prostate cancer.

In the phase 3 VISION trial, adding the targeted radioligand therapy 177Lu-PSMA-617 to standard of care led to a nearly 40% reduction in the risk of death.

Dr. Shore on VISION trial and future of PSMA-targeted agents in prostate cancer

Dr. Gregg Eure, MD, FACS, Urology of Virginia, discusses a survey of approximately 1000 men aged ≥45 years with BPH (≥1 voiding symptom) who answered questions about their urinary symptoms. Over 45% of the surveyed men reported that urinary symptoms led them to avoid events or activities they enjoy. Many men reported nocturia, with 70% of respondents overall indicating that nocturia has affected their energy level. Almost one-fourth (about 22%) of the men reported sleeping in another room than their spouse/partner/significant other to avoid disturbing them with their nighttime bathroom use. Teleflex Incorporated conducted the survey.

Nearly half of the surveyed men reported that urinary symptoms led them to avoid events or activities they enjoy. 

Dr. Eure discusses survey results of BPH impact on patient QOL

Corporoplasty with plaque incision and buccal mucosa graft achieved strong structural and functional outcomes with high patient satisfaction among individuals with stable-phase Peyronie's disease, according to a prospective study published in the 

Buccal mucosa grafting had a 95% success rate at 3 months post-procedure and 90% at 24-months’ follow-up. No significant penile shortening occurred.

At the baseline preoperative evaluation, the mean International Index of Erectile Function Questionnaire (IIEF-5) score was 17.5 ± 2.2. At 3-months’ follow-up, the median IIEF-5 score was 20.1 ± 2.2, and at 24-months’ follow-up, the median IIEF-5 score was 21.3 ± 2.2 (

 <.0001). No de novo erectile dysfunction occurred, and no serious complications occurred during or following the surgical procedure.

Overall, 22 patients enrolled in the study between September 2013 and May 2020. The single-site study was conducted at the Department of Urology and Andrology, Astana Medical University, Kazakhstan. Of the 22 patients, 20 completed the study, with 2 patients lost to follow-up. At baseline, all patients reported that they were unable to have painless and satisfactory intercourse for a minimum time period of the previous 12 months. All patients had previously received unsuccessful medical/conservative treatments for Peyronie’s disease.

The median patient age was 46.5 years, the median duration of Peyronie's disease was 17 months (range 12-36 months), and the median preoperative curvature was 45° (range, 40°-90°). The of the curvature was dorsal (n = 9), ventral (n = 2), lateral (n = 4), dorsolateral (n = 3), ventrolateral (n = 2).

The median plaque length was 21.8 mm, the median operative time was 145.75 minutes, and the median lengthy of postoperative hospital stay was 8 days (range, 7-18).

After patients received treatment with plaque incision and buccal mucosa grafting, penile length and residual curvature were measured at the 3- and 24-month follow-up sessions. Penile Doppler ultrasound and completion of IIEF5 questionnaires also occurred at these visits. At the 24-month session the investigators assessed the satisfaction of the patient and their sexual partner.

“Our study contributes to the current state of knowledge regarding the safety and efficacy of buccal mucosa grafting in Peyronie's disease. Our study confirmed the results of the previous studies and showed that corporoplasty with buccal mucosa led to excellent structural, functional, and patient satisfaction results,” the investigators wrote in their conclusion.

“We think, based on our and previous studies’ results, that plaque incision and buccal mucosa grafting seems as an effective and safe correction procedure in patients with Peyronie's disease, which is worthy of further research. The success of this surgical approach in terms of erectile dysfunction should be further evaluated with dedicated questionnaires validated for use in patients with Peyronie’s disease,” the investigators added.

1. Ainayev Y, Zhanbyrbekuly U, Gaipov A, et al. Surgical reconstruction of penile curvature due to Peyronie’s disease by plaque incision and buccal mucosa graft [published online ahead of print June 17, 2021]. 

No serious complications occurred during or following the surgical procedure. 

Plaque incision and buccal mucosa graft hits high success rate in Peyronie’s disease

The Chinese National Medical Products Administration has issued a conditional approval of the PARP inhibitor olaparib (Lynparza) for the treatment of adult patients with germline or somatic

-mutated metastatic castration-resistant prostate cancer (mCRPC) who have progressed following prior treatment that included a novel hormonal agent (abiraterone acetate [Zytiga], enzalutamide [Xtandi]).

The approval is based on a subgroup analysis of the pivotal phase 3 PROfound trial, in which olaparib reduced the risk of death by 37% (HR, 0.63) versus abiraterone or enzalutamide in men with mCRPC harboring 

1/2 mutations. The PARP inhibitor also reduced the risk of disease progression or death by 78% (HR = 0.22; 

The continued approval of olaparib in China is contingent on the treatment demonstrating a clinical benefit in Chinese patients enrolled in a planned bridging trial.

“The approval underscores the critical importance of 

 testing in men with prostate cancer. We are proud to provide a new personalized treatment option for men with this devastating disease in China, and we will continue to collaborate with the Chinese government and healthcare organizations to bring Lynparza to patients who need it,” Roy Baynes, MD, PhD,

senior vice president and head of global clinical development, chief medical officer, Merck, which codevelops olaparib with AstraZeneca, stated in a press release.

Overall, the PROfound trial enrolled patients with mCRPC who had alterations in at least 1 of 15 prespecified genes with a direct or indirect role in homologous recombination repair (HRR) and whose disease had progressed during previous treatment with a next-generation hormonal agents.

Cohort A (n = 245) consisted of patients with at least 1 alteration in 

, while cohort B (n = 142) comprised patients with at least one alteration in any of the other 12 prespecified genes.

Patients were randomly assigned 2:1 to receive either olaparib or the physician’s choice of enzalutamide or abiraterone. In cohort A, 162 patients received olaparib and 83 patients were assigned to control therapy. In cohort B, 94 patients received olaparib while 48 patients were in the control arm.

In the subgroup analysis of patients with 

1/2 mutations, the median overall survival (OS) was 20.1 months with olaparib versus 14.4 months with abiraterone or enzalutamide. The median radiographic progression-free survival (rPFS) was 9.8 versus 3 months, respectively.

In the previously reported primary study analysis, the median OS was superior with olaparib compared with control therapy in cohort A (19.1 months vs 14.7 months; HR, 0.69; 

 = .02) and cohort B (14.1 months vs 11.5 months; HR, 0.96).

 Also of note, in cohort A the median PFS was 7.4 months with olaparib compared with 3.6 months in the control arm (HR, 0.34; 

Regarding safety, adverse reactions across all grades occurring in at least 10% of patients receiving olaparib included anemia (46% vs 15% with abiraterone/enzalutamide), nausea (41% vs 19%, respectively), fatigue (41% vs 32%), decreased appetite (30% vs 18%), diarrhea (21% vs 7%), vomiting (18% vs 12%), thrombocytopenia (12% vs 3%), cough (11% vs 2%) and dyspnea (10% vs 3%). Eighteen percent of patients receiving olaparib discontinued treatment due to adverse reactions.

In the United States, the FDA approved olaparib in May 2020 for the treatment of adult patients with deleterious or suspected deleterious germline or somatic HRR gene-mutated metastatic mCRPC who have progressed following prior treatment with enzalutamide or abiraterone.

1. LYNPARZA® (olaparib) Approved in China for the Treatment of Certain Patients with BRCA-Mutated Metastatic Castration-Resistant Prostate Cancer. Published online June 24, 2021. Accessed June 24, 2021. https://bit.ly/3dcxtDN.

2. Hussain M, Mateo J, Fizazi K, et al. Survival with olaparib in metastatic castration-resistant prostate cancer [published online September 20, 2020]. 

The approval is based on a subgroup analysis of the pivotal phase 3 PROfound trial.

Olaparib approved in China for BRCA-positive mCRPC

 I am trying to get a practical little algorithm developed for the audience. Obviously, almost everybody around the country does PSA [prostate cancer antigen] testing in some form, maybe regular to total PSA or free to total PSA or looks at PSA velocity. Then would you go to the blood test, or would you go to the urine-based test? I am curious on how you put that together and then I will tell you what my algorithm is, and we'll see if we're similar.

 Sure. There may be patients who only get a PSA and a rectal exam. For example, a patient with a PSA more than 20 and an abnormal digital rectal exam.

 We need a biopsy. We have been seeing quite a number of those guys seem more as we have gone through COVID. I do not know if it is just more or the fact that this primary care initiative that we have has just been bringing these guys out of the woodworks.

 Or maybe the after-effects as well of the task force were stuck. Several papers have shown that when prostate screening and PSA testing got a de-rating, we started to see an uptake in metastatic disease then they reduced it to a C rating a couple of years later. I do not think we have caught up completely. You are exactly right. I think that patient that has a PSA of 20 or you find an abnormality on the rectal exam, that is a no-brainer. We are going to biopsy those guys and that's the standard of care. Let us take a guy that comes in, his PSA is abnormal, maybe it's between 4 and 10, you don't feel anything which is many of the patients that we examine. How do you work that patient up and what do you do? Do you do the urine-based test first or do you do the blood test?

 First, as a urologist, I do the rectal exam. That is my first step when I'm seeing a patient because I really want to contextualize the PSA based on the size of the prostate. Rectal exams, we all know, are not perfect, and it is hard to teach a primary care physician to do a rectal exam and many of them are not that interested. But we as urologists and as urology educators, we need to make sure all our residents who we train know how to do a good rectal exam and size of prostate. If I have a gentleman who has a very robust prostate, significant BPH on DRE, and it's a smooth DRE with no nodules, sometimes I may just only do the PSA test and reassure that gentleman and schedule him back in a year. Just important to point out that the basics of what we do as urology is still there. However, if it is a borderline on rectal exam, if the patient has a borderline PSA family history, our next test usually is going to be a prostate health index and those are going to be binned in four groups. Generally, if the patient is low risk on pHi then they're going to be reassured and maybe come back in six to 12 months. If it is a high-risk pHi with a 50% greater probability of prostate cancer most of the time, we will recommend a biopsy without necessarily going to the exosome. However, as you said, sophisticated patients, many patients are reluctant, and they want more data. In those patients who want more data we will get the exosome and then if they have a combination of high-risk pHi and exosome greater than 15.6, we are going to really push for a biopsy. If the patient still does not want a biopsy and insists on an MRI, we will order the MRI counseling the patient that he might have to pay out of pocket. Where the exosome has helped me, the most is in patients who have that intermediate prostate health index – the gray zone. There is a gray zone there too. Then I like to get the exosome. Or the patient who is just reluctant and just has a no show and I am the third urologist telling him he needs a biopsy. Sometimes I am using the exosome test to try to convince him that he has a condition that needs to be taken seriously. I use it to try to increase compliance as much as anything. Also, finally I will say, our practice is employing more physician extenders, APPs. We train them the best we can, but they are not urologists, they have not been in practice 30 years like I have. Sometimes our younger APPs are using these tests because they are not quite as confident with a rectal exam. Is that right or wrong? It is a reality of needing some of those tests in our current workforce.

 I think that is terrific. We up here have adopted obviously using PSA as our primary test, much like what I did when I was at Duke. We did go to a blood test with the 4K score and then we pivoted a little bit to the urine studies. It started with SelectMDx and now, I think, with exosome, having the home kit – a couple of things. One is, for exosomes they must be over the age of 50 to do the test. Most of our patients, when they come into the urology clinic leave a urine specimen so it is hard to get them to urinate again. Then I just say, "We're going to mail this to you," and it works out well. That has been my test. When they get the exosome test, as you say, if they are hesitant about a biopsy, that is where the MRI, to me, fits in place. If the patients are concerned, then we go directly to a biopsy. I think the algorithms can be massaged depending on the area where you are and the tests that are readily available. We don't have pHi up here, so we relied on the K, which is commercially available, and it was a good starter test.

 Dave, I do not have a lot of experience or any experience with the Select urine test. What is the difference or what has been your experience when you look at those two?

 They're very comparable tests. With the Select test, you do need to do a rectal massage, so it is almost like a PCA 3 test. Maybe it is a PCA 3 on steroids, so to speak, because you do have to do a rectal exam in these patients. But when you looked at the areas under the curve and the accuracy of the test it appeared to be a little bit better than some of the blood tests and so that's why we initially pivoted a little bit to the urine test and then when exosome came out, just the ease for the physician made it a little bit easier to do. When a new test comes out, I look at the efficacy, I look at the cost, I look at the side effect profile, I look at the ease of doing the test and then the durability. Those five things, whether it's a new drug, a new procedure, or whatever, I always think of those five things in the back of my head to try to put these tests in perspective. Because when they come out, there is a lot of hype, there's a lot of excitement about these new tests, you want to bring them back down to earth and put them in their place on where they really have a place. That is how I've used things and it's served me pretty well.

Key opinion leaders in urology review factors to consider when selecting screening and risk-assessment tests for the diagnosis of prostate cancer including insurance coverage, commercial availability, and patient preference.  

Plaque incision and buccal mucosa graft hits high success rate in Peyronie’s disease

Olaparib approved in China for BRCA-positive mCRPC

Algorithms for Diagnostic Testing in Prostate Cancer