Lisette Hilton

Transperineal targeted biopsy with electromagnetic-tracking fusion technology is low risk and detects clinically significant prostate cancer as well as the transrectal fusion-guided approach, Icahn School of Medicine at Mount Sinai investigators reported in a study published in 

 “This is of particular importance in the context of rising rates of bacterial resistance, greater calls for antibiotic stewardship, and cumulative infectious risks for patients on active surveillance or focal therapy protocols undergoing multiple repeat biopsies,” the investigators wrote.

The study helps to dispel the dogma suggesting the transperineal approach is better for anterior tumors when using a fusion biopsy approach, according to the study’s senior author, Art R. Rastinehad, DO, associate professor of urology and radiology at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell in East Garden City, New York, and vice chairman of urology at Lenox Hill Hospital, and system director for prostate cancer at Northwell Health, both in New York, New York.

“We found no difference in the biopsy techniques, even in subgroup analyses stratifying for lesion suspicion, size, and location with magnetic resonance ultrasound fusion biopsy, whether using transrectal or the transperineal approach,” Rastinehad said. “But [the paper] does support the dogma that standard transrectal ultrasound biopsy approach does undersample the anterior of the prostate compared with a standard transperineal biopsy.”

The current gold-standard technique for diagnosing prostate cancer in at-risk men, systematic 10- to 12-core prostate biopsy using transrectal ultrasound has a 20% to 30% false-negative rate and lacks specificity for detecting clinically significant disease, according to the paper. Advances in multiparametric magnetic resonance imaging (mpMRI) and magnetic resonance ultrasound have improved clinicians’ ability to visualize and target suspicious lesions. But there is no consensus about the optimal targeted prostate biopsy approach or platform.

The investigators conducted a prospective nonrandomized single-surgeon series of magnetic resonance ultrasound comparing transperineal and transrectal prostate biopsy, using the same electromagnetic tracking platform, UroNav.

“I believe this is the first paper to compare the transrectal approach or transperineal approach using the same fusion biopsy platform, allowing for a direct comparison of the transrectal versus transperineal approaches with respect to the targeted and nontargeted biopsy cores,” Rastinehad said.

The investigators studied 379 men considered at risk of prostate cancer because of a higher than 2.5-ng/mL prostate-specific antigen (PSA) level or abnormal digital rectal exam result. Among those patients, 168 underwent transperineal systematic 12-core biopsy and transperineal targeted prostate biopsy with electromagnetic tracking. The investigators compared those results with those of 211 patients who had a similar procedure with a transrectal approach.

They found the rate of clinically significant disease detection was 59% by transperineal targeted biopsy versus 54% for transrectal targeted prostate biopsy.

They also found no significant difference in the likelihood of detecting prostate cancer or clinically significant disease when they adjusted for PSA level, previous biopsy status, prostate volume, Prostate Imaging Reporting and Data System version 2 score, lesion volume, and lesion location.

The investigators reported no serious complications post biopsy in both the transperineal and transrectal groups. Six patients in the transperineal group had urinary retention compared with 1 patient in the transrectal group. One patient in the transrectal group developed sepsis that resolved with intravenous and oral antibiotics.

“We found that regardless of fusion biopsy approach, you are able to adequately sample the suspicious area detected on mpMRI,” Rastinehad said. “The urologic dogma that the transperineal approach helps sample the anterior of the prostate is only applicable to the nontargeted approach. The fusion biopsy targeting is the great equalizer between the transperineal and transrectal approaches, and if you can see it on mpMRI, you can sample it adequately regardless of the approach.”

This is good news as urologists move toward a transperineal approach, in part because of rising rates of infectious complications associated with transrectal biopsies, according to Rastinehad.

“This study does demonstrate that the transition to a transperineal from a transrectal approach will not decrease the diagnostic accuracy of your patients with an elevated PSA [level] and a suspicious mpMRI [finding],” he said.

Disclosures: Philips Healthcare funded the study, and Rastinehad is a consultant for Philips Healthcare.

1. Winoker JS, Wajswol E, Falagario U, et al. Transperineal versus transrectal targeted biopsy with use of electromagnetically tracked MR/US fusion guidance platform for the detection of clinically significant prostate cancer. 

 Published online September 18, 2020. doi:10.1016/j.urology.2020.07.072

Articles

Transperineal targeted biopsy with electromagnetic-tracking fusion technology is low risk and detects clinically significant prostate cancer as well as the transrectal fusion-guided approach, investigators report.

Transperineal targeted prostate biopsy comparable to transrectal fusion-guided approach 

Cancer-related pain is indicative of a poor prognosis in metastatic castration-sensitive prostate cancer (mCSPC) patients, according to a paper published in 

Some distinguish mCSPC prognostic classes based on disease burden and other clinical features. Researchers have used the presence of visceral metastasis, extent of bone metastasis, and Gleason score to classify these patients prognostically.

However, without direct comparisons among therapeutic options and given the absence of a reliable molecular and clinical prognostic stratification of mCSPC, it’s difficult to optimally select treatment, according to the study results.

“Being able to distinguish different prognostic ‘classes’ of mCSPC so as to tailor the treatment for each patient is one of the greatest future challenges,” the investigators wrote.

A group of French researchers analyzed data from about 370 de novo metastatic patients. Pain data were included for 365 of those patients, and pain was present in about a third (34.8%) of cases. According to the paper, pain was associated primarily with high value of prostate-specific antigen, greater bone extension of disease, and lymph node involvement. Pain was not associated with visceral metastases.

They found that while patients without pain had an overall survival of 56 months, patients with pain had an overall survival of only 27 months. Patients with pain in the study also had significantly lower progression-free survival at 10.1 months, versus 17.4 months among patients who did not report cancer-related pain.

When it does metastasize, prostate cancer most often spreads to bone, which often results in debilitating pain and limited function. Many associate cancer-related pain to be a key prognostic indicator that men with castration-resistant prostate cancer have a poorer prognosis than patients without pain.

But more work is needed to determine cancer pain’s true prognostic value in mCSPC.

“External prospective validation of CSPC patient cohorts is required to establish if cancer-related pain can help in guiding the treatment decision process,” the investigators concluded.

Urologists should consider 2 important takeaway points from this paper, according to urologist and urologic oncologist Christopher Filson, MD, MS, assistant professor of urology at Emory University School of Medicine in Atlanta, Georgia.

“One is understanding the importance of being thorough and assessing the degree of pain that an advanced cancer patient may be experiencing,” Filson said. “The second point is ensuring that, should a patient develop pain, not only is it a sign that it may be more advanced disease from a prognostic standpoint, but also that the issue of pain should be addressed.”

It’s becoming increasingly clear that palliative care is critical for patients who have advanced cancer, according to Filson, who was not involved with the research.

“There’s a presumption that palliative care is reserved for patients who have end-of-life issues or are within the last 30 days of their lives. But the data suggest that palliative care has a role for any patient with advanced cancer who may be experiencing symptoms like pain,” he said. “For me, reading the article reinforced my belief that, first of all, assessing patients’ cancer pain is critical, and should there be pain present, to consider addressing their needs with palliative care whether they have weeks, months, or even years to live.”

1. Iacovelli R, Ciccarese C, Caffo O, et al. The prognostic value of pain in castration-sensitive prostate cancer. 

 Published online July 10, 2020. https://doi.org/10.1038/s41391-020-0255-x

Investigators found that while patients without pain had an overall survival of 56 months, patients with pain had an overall survival of only 27 months.

Cancer-related pain indicative of poor prognosis for metastatic CSPC

Enzalutamide (XTANDI) treatment reduced risk of death in patients with nonmetastatic castration-resistant 

 and rapidly rising prostate-specific antigen (PSA) by 27% compared to placebo, according to research presented at the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program.

Enzalutamide, an androgen receptor inhibitor, is indicated for the treatment of men with castration-resistant prostate cancer and metastatic castration-sensitive prostate cancer. This final analysis of the phase 3 PROSPER study supports enzalutamide and androgen deprivation therapy as the standard of care to improve overall survival in prostate cancer patients before the onset of detectable metastasis.

“This is great news for urologists who see patients with this type of disease. The data are reassuring that patients with nonmetastatic castration-resistant prostate cancer and a rapidly rising PSA have a safe and effective option that improves overall survival by almost 1 year,” according to the study’s lead author Cora N. Sternberg, MD, of Weill Cornell Medicine, New York-Presbyterian in New York City.

The Safety and Efficacy Study of Enzalutamide in Patients With Nonmetastatic Castration-Resistant Prostate Cancer, or PROSPER, is a randomized, double-blind, placebo-controlled, multinational trial of about 1400 men with nonmetastatic castration-resistant prostate cancer. Patients had no evidence of metastatic disease, but their prostate cancer had progressed based on a rising PSA.

Researchers evaluated treating patients with once-daily 160 mg oral enzalutamide and androgen deprivation therapy vs placebo and androgen deprivation therapy.

PROSPER had previously shown enzalutamide resulted in a significant and clinically meaningful lower risk of radiographic progression or death, improvement in metastasis-free survival, of 71% compared to placebo. Overall survival data were immature when the investigators first reported their findings.

In this final overall survival analysis, median overall survival was 67.0 months among men who received enzalutamide compared to 56.3 months in the placebo arm. Sternberg and colleagues reported a median follow up of 48 months. Of 466 deaths, 288, or 30.9%, were in the enzalutamide arm vs 178, or 38.0%, in the placebo group.

Enzalutamide treatment resulted in 11 months of additional survival benefit for patients, according to Sternberg.

“Subsequent antineoplastic therapies were initiated after treatment discontinuation by 310 (33%) men in the enzalutamide arm vs 390 (84%) in the [placebo] arm. This includes patients who crossed over to receive enzalutamide. Median duration of treatment was 33.9 mo vs 14.2 mo with enzalutamide vs [placebo], respectively,” according to the presentation.

Forty-eight percent of men in the enzalutamide arm and 27% in the placebo arm reported grade 3 or higher adverse events, including falls, fatigue, and hypertension. In the enzalutamide arm, 16% of adverse events were drug-related vs 6% in the placebo arm.

“The safety profile was consistent with the established safety profile of enzalutamide. These data should be reassuring to colleagues who are interested in overall survival data and this is a confirmation of metastasis-free survival results,” Sternberg said.

Disclosure: Pfizer and Astellas Pharma funded the trial. Dr. Sternberg has been a consultant to Astellas Pharma, AstraZeneca, Bayer, Incyte, Merck, MSD, Pfizer, Roche, Roche-Genentech, Clovis and Sanofi-Genzyme. For full disclosures, 

This final analysis of the phase 3 PROSPER study supports enzalutamide and androgen deprivation therapy as the standard of care to improve overall survival in prostate cancer patients before the onset of detectable metastasis.

Enzalutamide reduces risk of death in men with nmCRPC by 27% vs placebo

Apalutamide (ERLEADA) combined with androgen deprivation therapy improves overall survival more than androgen deprivation therapy alone in men with non-metastatic castration-resistant prostate cancer at high risk of metastases, according to results from investigators’ final analysis of the phase 3 Study of Apalutamide in Men With Non-Metastatic Castration-Resistant Prostate Cancer (SPARTAN) trial.

Apalutamide, an androgen receptor inhibitor, became the first FDA-approved therapy for non-metastatic castration-resistant prostate cancer in February 2018. In September 2019, the FDA approved apalutamide for the treatment of patients with metastatic castration-sensitive prostate cancer.

Investigators enrolled 1207 patients in the SPARTAN study, who were randomized 2:1 to receive either 240 mg apalutamide orally once daily in combination with androgen deprivation therapy or placebo once daily in combination with androgen deprivation therapy.

The FDA’s first approval of the drug was based on the primary SPARTAN analysis. Investigators found that in a median follow-up of 20 months, treatment with apalutamide significantly delayed development of metastases, as well as the development of symptoms, according to Eric Small, MD, of the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco.

Small, the lead SPARTAN study investigator, presented the results of this study during the 2020 American Society of Clinical Oncology Virtual Scientific Program.

“What remained unanswered was whether using a novel androgen receptor targeting agent used early before the development of metastases, as opposed to waiting until metastatic castration-resistant prostate cancer, could prolong life,” Small said. “The answer is yes.”

At their final survival analysis with a median follow-up of 52 months, Small and coauthors found that apalutamide significantly increased overall survival from 59.9 months to 73.9 months. That’s an increase of 14 months in median survival, with a hazard ratio for death of 0.78, with 

“If you correct for the benefits in survival from crossing over from placebo to apalutamide, the increase in survival goes up to 21 months,” he said.

The combination decreased the risk of death by 22%. And treatment with apalutamide and androgen deprivation therapy significantly delayed patients’ time to cytotoxic chemotherapy compared to placebo in combination with ADT, with a hazard ratio of 0.63 and 

“A fair question that is always raised about studies like this where an active agent is used early, is if overall survival is improved not because earlier is better than later, but because the placebo group ends up not getting any active therapy at all. The study ends up being a study of early treatment versus no treatment,” Small said.

That wasn’t the case in SPARTAN, according to Small.

“Over 80% of placebo patients went on to receive active, life-prolonging, FDA-approved therapy. Around 70% of placebo patients went on to receive abiraterone or other life-prolonging therapy at the time of metastases. All 19% of placebo patients who hadn’t yet progressed at the time of study unblinding went on to receive open-label apalutamide. Parenthetically, in addition to prolonging life, apalutamide also significantly delayed the time to chemotherapy use, a secondary end point of the trial,” he said.

Small said that in his estimation, the data are really important to the practicing clinician and an absolute game-changer for patients with prostate cancer.

“We already knew that apalutamide would delay time to metastases. But there was always this gnawing worry that maybe we were burning that bridge, and that it would ultimately disadvantage the patient to use this therapy early. In fact, the results in SPARTAN were exactly the opposite. Early use prolongs life, even when compared to later use. This means that we can use apalutamide in non-metastatic castration-resistant prostate cancer patients with the full confidence that we are prolonging life 

 not ‘burning a bridge’ that we will later regret,” Small said.

Apalutamide’s safety and tolerability were consistent across studies. Median treatment duration was nearly 3 times longer, at 33 months, for patients treated with apalutamide plus androgen deprivation therapy compared to 12 months in the placebo group. The most common adverse reactions in the SPARTAN study, occurring in 10% or less of patients were fatigue, hypertension, rash, diarrhea, nausea, weight decreased, arthralgia, falls, hot flush, decreased appetite, fracture, and peripheral edema.

Disclosures: Janssen Research & Development funded the phase 3 trial. Small has ties to Fortis, Harpoon Therapeutics, Janssen, Beigene, Janssen Oncology, Teon Therapeutics, Tolero Pharmaceuticals, and Merck. For full disclosures, 

Apalutamide (ERLEADA) combined with androgen deprivation therapy improves overall survival more than androgen deprivation therapy alone in men with non-metastatic castration-resistant prostate cancer at high risk of metastases, according to results from investigators’ final analysis of the phase 3 SPARTAN trial.

Author | Lisette Hilton

Articles

Transperineal targeted prostate biopsy comparable to transrectal fusion-guided approach

Cancer-related pain indicative of poor prognosis for metastatic CSPC

Enzalutamide reduces risk of death in men with nmCRPC by 27% vs placebo

Apalutamide plus ADT improves OS in men with non-metastatic castration-resistant PCa