Jeni Williams

Recent research shows contemporary imaging and biopsy techniques often fail to identify contralateral tumors in men presumed to have unilateral prostate cancer-and the results have significant implications for identifying candidates for hemiablation.

A study by researchers at UCLA Health David Geffen School of Medicine found a substantial percentage of patients diagnosed with unilateral prostate cancer based on contemporary imaging and biopsy techniques harbor undetected, clinically significant contralateral disease.

Among 665 patients studied, 92 met primary criteria for hemiablation based on a review of imaging and biopsy results. However, 44 patients (47.8%) were later discovered to have contralateral prostate cancer tumors of Grade Group 2 and above on final pathology. The rate of undetected contralateral disease in candidates for hemiablation ranged from 40.8% to 47.8% depending on the inclusion criteria used.

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“We were surprised by the rate of missed tumors based on the mpMRI [multiparametric magnetic resonance imaging] results,” David Johnson, MD, MPH, who was with UCLA Health at the time of the study, told 

. “We were also surprised by how robust the results were regardless of the inclusion criteria.”

Men with anterior index tumors were 2.4 times more likely to harbor undetected significant contralateral prostate cancer than men with posterior lesions, the authors found.

“It’s something we need to counsel patients on-not just that hemiablation may not treat [their cancer] completely, but also that it may not contain the cancer to begin with,” said Dr. Johnson, currently with Blue Cross NC and the University of North Carolina, Chapel Hill.

The study, presented at the 2019 AUA annual meeting in Chicago, was conducted under the direction of Robert E. Reiter, MD, of UCLA's Jonsson Cancer Center. The authors conducted a retrospective analysis of patients undergoing mpMRI with MRI-fusion prostate biopsy prior to radical prostatectomy at a single tertiary institution from June 2010 to November 2017. They identified theoretical hemiablation candidates and a range of inclusion criteria in sensitivity analyses. They also evaluated preoperative predictors of undetected contralateral disease using multivariable analysis.

“We considered a wide variety of inclusion criteria in six trials,” Dr. Johnson said.

The authors then worked to identify hemiablation candidates who were discovered to have contralateral, clinically significant prostate cancer, based on whole-mount prostatectomy pathology, and/or ipsilateral high-risk disease.

The results point to the limitations of MRI in spotting prostate tumors, Dr. Johnson said, given that nearly half the candidates for hemiablation had contralateral tumors that weren’t spotted during imaging.

“There is still sampling error from repeat biopsy and MRI that exists,” he said.

It’s important to note that one constraint of the study is the unknown clinical significance of missed contralateral disease.

Given the findings, those considering hemiablation must weigh the risk of inadequate treatment due to undetected contralateral disease against the functional benefits of hemiablation, which include less exposure of healthy tissue to treatment. Further investigation to improve patient selection for focal therapy is necessary.

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Prostate imaging, biopsy often miss contralateral tumors

A study of kidney stone patients who were treated using ureteral access sheaths found no evidence of ureteral strictures an average of 4 years following ureteroscopy.

The results are intriguing, given that some urologists believe there are too little data to ascertain whether the use of ureteral access sheaths puts patients at risk of ureteral injury 

 Also notable: The results held true regardless of the diameter of the sheath used, the size of the stone, length of operating time, or gender.

However, given the small sample size-157 patients-“This is an area where more study is needed,” Jose Eduardo Castro Matheus Rodrigues, a research student at the Massachusetts General Hospital department of urology, Boston and a medical student at University of SÃ£o Paulo-Brazil, told AUA 2019 attendees.

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The study was conducted under Brian Eisner, MD, of the Massachusetts General Hospital department of urology and Harvard Medical School, Boston.

Results from the study are based on a retrospective review of patients who have undergone ureteroscopy procedures that involved use of a ureteral access sheath. Patients included in the study also had a follow-up visit 1 year or more after the procedure and received an abdominal imaging scan.

While recent studies have shown that placement of ureteral access sheaths during ureteroscopy can cause ureteral lesions, such as when too much force is applied 

 the long-term consequences of deploying ureteral access sheaths are not yet known. This study sought to determine the impact of using ureteral access sheaths on the patient’s chances of developing a ureteral stricture in the first year or more after surgery.

Among the 157 patients who met these criteria, 56% were men and 44% were women, the average age of patients was 61 years (range, 27 to 96 years), and the average follow-up time was 4.1 years (range, 1 to 8 years).

The authors recorded the diameter of the ureteral access sheath used, with 95% of patients being treated with a sheath that had a diameter of 11/13 Fr or larger. The mean diameter of the largest stone removed during ureteroscopy was 6.9 mm (range, 2 to 26 mm), and the average operating time was 31 minutes (range, 10.5 to 108 minutes). Leakage of contrast material was noted in 5% of patients (eight patients).

The authors also noted the types of follow-up imaging used to examine whether use of a ureteral access sheath had caused a ureteral stricture to form. These included renal ultrasound (104 patients), computerized tomography (45 patients), and magnetic resonance imaging (seven patients).

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The results showed that during the patients’ most recent follow-up visit, none of the patients demonstrated persistent hydronephrosis, and no patients had undergone treatment for a ureteral stricture or displayed radiographic evidence of a stricture.

Previous studies on this topic have lacked long-term follow-up data, Rodrigues said. The availability of medium-term follow-up data is critical to advancing discussion around this controversial approach.

Sheath use not linked with strictures

A multicenter study in the United Kingdom found 5-year prostate cancer control rates following treatment with focal therapy are similar to those of patients who have undergone radical prostatectomy, even when accounting for variation in tumor location, size, and risk.

The study, presented at the 2019 AUA annual meeting in Chicago, showed no significant difference in failure-free survival-defined as the absence of a relapse, non-relapse mortality, or addition of another systemic therapy-between focal therapy and radical prostatectomy 5 years after either procedure.

It points to comparable medium-term results between focal therapy, which has fewer side effects and jeopardizes less healthy tissue, and radical prostatectomy.

Based on the results, “We should be talking about the harm aspects of surgery,” Deepika Reddy, MD, a urology surgeon for NHS in London, told 2019 AUA attendees.

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While focal therapy has a low side-effect profile, there has been uncertainty regarding its medium-length potential to control prostate cancer compared with radical approaches. In the United Kingdom, focal therapy for prostate cancer comprises high-intensity frequency ultrasound (HIFU) and focal cryotherapy based on cancer characteristics and location. The authors aimed to compare cancer control rates from this approach with those of radical prostatectomy.

Following National Institute for Health and Care Excellence guidance, the authors reviewed multicenter prospective cancer registries to identify men who underwent either HIFU (625 men) or cryotherapy (122) and laparoscopic radical prostatectomy (571) from 2007 to 2017.

“Up to two focal therapy sessions were allowed,” Dr. Reddy said.

From there, the authors used propensity scoring to match men who underwent focal therapy (either HIFU or cryotherapy) with their nearest radical prostatectomy patient match. Among the inclusion criteria were PSA <20 ng/mL; Gleason score £7, and T-stage £T2c. Exclusion criteria were missing matched variables and early adjuvant therapy within 1 year. The authors then matched patients by age, PSA, grade, maximum cancer core length, unilateral/bilateral disease, neoadjuvant hormone use, and treatment year.

After accounting for inclusion and exclusion criteria, the group included 420 HIFU patients, 81 cryotherapy patients, and 346 localized radical prostatectomy patients. Matching of patients led to 183 men in each cohort.

“This led to a well-matched cohort,” Dr. Reddy said.

During each of the time frames studied, the authors found no difference in failure-free survival rates between the HIFU/cryotherapy and localized radical prostatectomy groups. Focal therapy demonstrated an 88% failure-free survival rate over 5 years, while the 5-year failure-free survival rate for localized radical prostatectomy was 85%.

There are limitations to the study, Dr. Reddy said. For example, certain variables, such as tumor volume, were not captured, although maximum cancer core length as a surrogate marker of tumor volume was used.

While long-term data around the efficacy of focal therapy compared with radical prostatectomy are still needed, the results provide the basis for conversations with patients around treatment options, she said.

5-year cancer control comparable for focal therapy, RP

Chronic opioid use is rare following radical prostatectomy (RP) in Europe. Slightly more than half of men undergoing RP in Sweden between 2007 and 2017 were found to have filled an opioid prescription, but the proportion who became chronic opioid users was less than 1%.

Using data from nationwide Swedish registries, Walter Cazzaniga, MD, and colleagues found that preoperative opioid use was the strongest predictor of chronic postoperative use following RP. They presented their findings at the 2019 AUA annual meeting in Chicago and also published research on this topic in the 

“Additional study is warranted to optimize the use of opioid and minimize risk of chronic use, particularly for high-risk patients, in the continued efforts to combat the opioid epidemic,” concluded Dr. Cazzaniga, visiting researcher, department of surgical sciences, Uppsala University, Uppsala, Sweden.

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Previous data suggest that up to 7% of opioid-naÃ¯ve patients who receive an opioid prescription after surgical procedures become chronic opioid users, he said. Among a random sample of 10% of patient records from a large U.S. commercial health plan, the probability of continued opioid use was 6.0% at 1 year and 2.9% at 3 years after an opioid prescription following a surgical procedure.

To examine the risk of chronic opioid use following RP, the investigators used data from the Prostate Cancer Data Base Sweden linked to the Prescribed Drug Register to assess opioid prescriptions for 25,703 men who underwent RP from 2007 to 2017. The median age at RP was 64 years. Most men had clinical stage T1c disease, and most were categorized as intermediate risk. Sixty percent of the men underwent robot-assisted RP, 36% had open RP, and 4% had laparoscopic surgery.

The authors examined opioid use 1 year prior to RP and 1 year following RP. At least one prescription for an opioid was filled by 16,368 (64%) of the men.

The proportion of men undergoing RP who received a prescription for an opioid increased from 40% in 2007 to 59% in 2017. The pattern of opioid prescription changed from a preponderance of prescriptions for strong opioids (eg, morphine, fentanyl, oxycodone, buprenorphine, hydromorphone) in 2007 to nearly all opioid prescriptions being weak opioids (eg, tramadol, dihydrocodeine, codeine) by 2017.

Baseline consumption of opioids prior to RP was related to other comorbidities, with 1.9% of men having filled an opioid prescription in the preoperative period. There was a strong peak in opioid use in the first 6 weeks after the procedure, to 59%, which decreased after 2 months to a level (2.3%) that was only slightly higher than that at baseline.

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“This is true for the overall opioids and also for the strong and weak opioids, with the biggest peak for the strong opioids,” said Dr. Cazzaniga.

On a multivariable model, the following factors predicted new chronic opioid users after RP: intermediate- (OR=3.30, 

=.004); a Charlson Comorbidity Index of 1 (OR=1.94, p=.0004), 2 (OR=2.51, 

=.05). Undergoing a robot-assisted RP was associated with a lower risk of conversion to chronic opioid use (OR=0.71, 

“Our results report the first nationwide investigation in Europe about the opioid issue,” Dr. Cazzaniga said. “Even if we cannot conclude anything on pain management strategies to avoid chronic opioid consumption, physicians and patients should be aware of our results in order to tailor the postoperative pain management strategy in order to minimize potential abuse.”

Chronic opioid use is rare following radical prostatectomy in Europe. Slightly more than half of men undergoing RP in Sweden between 2007 and 2017 were found to have filled an opioid prescription, but the proportion who became chronic opioid users was less than 1%.

Jeni Williams

Articles

Prostate imaging, biopsy often miss contralateral tumors

Sheath use not linked with strictures

5-year cancer control comparable for focal therapy, RP

Risk of chronic opioid use low after RP