Doctor's Review: Medicine on the Move

August 22, 2017

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2011 Canadian Urological Association conference

A year of real progress against prostate cancer

The year 2011 was a big one in urology, and particularly in Canadian urology. Canadian centres either led or participated heavily in several landmark studies in prostate cancer. So there was a definite feel-good factor on display at the Canadian Urological Association's 2011 conference in Montreal last June. Prostate cancer is not on the ropes yet, far from it, but it yielded ground to new therapies and combinations on several fronts, both in early and advanced-stage disease.

A Canadian-led study proved conclusively that in non-metastatic prostate cancer, intermittent androgen deprivation therapy is as good as continuous ADT in terms of overall survival, and brings fewer side effects in the form of gynecomastia and hot flushes.1

Another Canadian-led study found that radiation therapy added to androgen deprivation significantly slows progression and improves survival in high risk/locally advanced prostate cancer.2 Both of these results are already changing treatment around the world. Naturally, conference-goers had plenty to say on other issues that are currently making waves in urology, such as the ongoing search for better prostate biomarkers; the problems of bone loss and brittleness in androgen deprivation therapy; a fundamental re-examination of the causes of overactive bladder; and the role that Botulinum toxin A might play in its treatment.

PC solutions

Radiation as an adjuvant in locally-advanced prostate cancer has been a hot topic since a 2008 Swedish study found it halved cancer-specific mortality at 10 years.3 But that study used the endocrine treatment flutamide instead of the more typical LHRH agonists or bilateral orchiectomy. Using today's anti-androgens, the new study finds 10-year cancer-specific mortality of 15 percent with adjuvant radiation and 23 percent without it. That's enough benefit to make adjuvant radiation the new gold standard in locally-advanced or high-risk disease.

New options are appearing at the wrong end of the disease spectrum too. In castrate-resistant prostate cancer, where bone metastasis is a likely next stage in progression, the RANK ligand inhibitor denosumab significantly delayed appearance of skeletal tumours, by 4.2 months compared to placebo. The overall prognosis remains clouded, however, in this patient population.

Men with low-risk cancer on active surveillance were significantly less likely to progress if they took a 5-alpha reductase inhibitor, the conference heard. Multivariate analysis indicated that men who took no 5-ARI were three times as likely to experience pathological progression over an average 38 months' follow-up. That is a potent preventive effect from a cheap and relatively well-tolerated therapy, but participants were quick to raise the question about an increase in high-grade cancers in the group taking 5-ARI.

Prevention was on the mind of Dr Neil Fleshner of Toronto, head of urology at the University Health Network, who gave the distinguished lecture. We know there are opportunities to prevent prostate cancer, he said, because biological evidence of precancerous changes is similar in autopsies of young men around the world yet cancer rates differ sharply.

Obesity is clearly one factor at play. But what most intrigues Dr Fleshner's team is the tantalizing suggestion that patients taking metformin for diabetes appear to get less prostate cancer than the general population. They also appear to suffer less aggressive disease when it does strike. The researchers are currently trawling through Ontario's health records to see if the effect is real.

Cryotherapy is one treatment that hasn't fared well in the latest round of research. It was clearly outperformed by external beam radiation in locally advanced disease (T2c-T3b), though it may still have a role to play against less bulky targets.

Bladder activity

Overactive bladder is a much-debated topic in urology lately, even if no one can say precisely what it is. Urologists have settled on a broad consensus that it shouldn't be defined too closely, since its causes are surely varied. But that hasn't prevented them from trying new treatments, and one has shown great promise: Botulinum toxin A.

On the plus side, it's certainly effective, increasing bladder capacity, reducing episodes of incontinence, and improving quality-of-life scores. It's also relatively painless and safe. There is occasional minor hematuria, an infection risk similar to cystoscopy, a 5 to 21 percent risk of urinary retention, and occasional reports of temporary distal muscle weakness — though these appear limited to patients treated for neurogenic OAB, not idiopathic OAB. Among the negatives are cost — it's about $14,000 per quality of life year — and the need for frequent repeat injections.

CUA past-president and conference organizer Dr Sender Herschorn led a study using Botulinum toxin A to treat idiopathic detrusor overactivity and found significant improvements in continence and quality of life.4

These results aren't disputed, but the field is split on whether this justifies making it a first line therapy in idiopathic OAB or detrusor overactivity. There are theoretical concerns about long-term loss of efficacy with Botulinum due to antibody build-up, but its effect has been shown in practice up to 10 years. Advocates point out that most people with these conditions don't even stay on today's anticholinergic medication for six months. Failure is a foregone conclusion with anticholinergics, they argue, so why wait?

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