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Video: Four-year outcomes from a multiparametric MRI based active surveillance programme

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Four‐year outcomes from a multiparametric magnetic resonance imaging (MRI)‐based active surveillance programme: PSA dynamics and serial MRI scans allow omission of protocol biopsies

 

Abstract

Objectives

To report outcomes from a multiparametric (mp) magnetic resonance imaging (MRI)‐based active surveillance programme that did not include performing protocol biopsies after the first confirmatory biopsy.

Patients and Methods

All patients diagnosed with Gleason 3 + 3 prostate cancer because of a raised PSA level who underwent mpMRI after diagnosis were included. Patients were recorded in a prospective clinical database and followed up with PSA monitoring and repeat MRI. In patients who remained on active surveillance after the first MRI (with or without confirmatory biopsy), we investigated PSA dynamics for association with subsequent progression. Comparison between first and second MRI scans was undertaken. Outcomes assessed were: progression to radical therapy at first MRI/confirmatory biopsy and progression to radical therapy in those who remained on active surveillance after first MRI.

Results

A total of 211 patients were included, with a median of 4.2 years of follow‐up. The rate of progression to radical therapy was significantly greater at all stages among patients with visible lesions than in those with initially negative MRI (47/125 (37.6%) vs 11/86 (12.8%); odds ratio 4.1 (95% CI 2.0–8.5), P < 0.001). Only 1/56 patients (1.8%) with negative initial MRI scans who underwent a confirmatory systematic biopsy had upgrading to Gleason 3 + 4 disease. PSA velocity was significantly associated with subsequent progression in patients with negative initial MRI (area under the curve 0.85 [95% CI 0.75–0.94]; P <0.001). Patients with high‐risk visible lesions on first MRI who remained on active surveillance had a high risk of subsequent progression 19/76 (25.0%) vs 9/84 (10.7%) for patients with no visible lesions, despite reassuring targeted and systematic confirmatory biopsies and regardless of PSA dynamics.

Conclusion

Men with low‐risk Gleason 3 + 3 prostate cancer on active surveillance can forgo protocol biopsies in favour of MRI and PSA monitoring with selective re‐biopsy.

 

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Video: Does the robot have a role in radical cystectomy?

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Does the robot have a role in radical cystectomy

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Abstract

Between 2014 and 2015, 3742 radical cystectomies (RCs) were performed in the UK. The majority of these were open RCs (ORCs), and only 25% were performed with robot assistance. These data contrast starkly with the picture in radical prostatectomy (RP), for which most operations are robot assisted (79.4% of the 7673 in 2016). Given that most pelvic surgeons have access to robotic facilities (as shown by the RP trends) and urologists are typically early adopters, one must question why many surgeons have yet to be convinced by robot‐assisted RC (RARC). This question is particularly perplexing given that RC is a more morbid operation than RP and most patients with bladder cancer are considerably less fit than the average man with prostate cancer, and therefore, reductions in morbidity are especially rewarding in this cohort.

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Video: Immediate versus delayed exercise in men initiating androgen deprivation

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Immediate versus delayed exercise in men initiating androgen deprivation: effects on bone density and soft tissue composition

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Abstract

Objectives

To examine whether it is more efficacious to commence exercise medicine in men with prostate cancer at the onset of androgen‐deprivation therapy (ADT) rather than later on during treatment to preserve bone and soft‐tissue composition, as ADT results in adverse effects including: reduced bone mineral density (BMD), loss of muscle mass, and increased fat mass (FM).

Patients and methods

In all, 104 patients with prostate cancer, aged 48–84 years initiating ADT, were randomised to immediate exercise (IMEX, n = 54) or delayed exercise (DEL, n = 50) conditions. The former consisted of 6 months of supervised resistance/aerobic/impact exercise and the latter comprised 6 months of usual care followed by 6 months of the identical exercise programme. Regional and whole body BMD, lean mass (LM), whole body FM and trunk FM, and appendicular skeletal muscle (ASM) were assessed by dual X‐ray absorptiometry, and muscle density by peripheral quantitative computed tomography at baseline, and at 6 and 12 months.

Results

There was a significant time effect (P < 0.001) for whole body, spine and hip BMD with a progressive loss in the IMEX and DEL groups, although lumbar spine BMD was largely preserved in the IMEX group at 6 months compared with the DEL group (−0.4% vs −1.6%). LM, ASM, and muscle density were preserved in the IMEX group at 6 months, declined in the DEL group at 6 months (−1.4% to −2.5%) and then recovered at 12 months after training. FM and trunk FM increased (P < 0.001) over the 12‐month period in the IMEX (7.8% and 4.5%, respectively) and DEL groups (6.5% and 4.3%, respectively).

Conclusions

Commencing exercise at the onset of ADT preserves lumbar spine BMD, muscle mass, and muscle density. To avoid treatment‐related adverse musculoskeletal effects, exercise medicine should be prescribed and commenced at the onset of ADT.

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Video: APAC APCCC 2018

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Management of patients with advanced prostate cancer in the Asia Pacific region: ‘real‐world’ consideration of results from the Advanced Prostate Cancer Consensus Conference 2017

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Abstract

Objective

The Asia Pacific Advanced Prostate Cancer Consensus Conference (APAC APCCC 2018) brought together 20 experts from 15 APAC countries to discuss the real‐world application of consensus statements from the second APCCC held in St Gallen in 2017 (APCCC 2017).

Findings

Differences in genetics, environment, lifestyle, diet and culture are all likely to influence the management of advanced prostate cancer in the APAC region when compared with the rest of the world. When considering the strong APCCC 2017 recommendation for the use of upfront docetaxel in metastatic castration‐naïve prostate cancer, the panel noted possible increased toxicity in Asian men receiving docetaxel, which would affect this recommendation in the APAC region. Although androgen receptor‐targeting agents appear to be well tolerated in Asian men with metastatic castration‐resistant prostate cancer, access to these drugs is very limited for financial reasons across the region. The meeting highlighted that cost and access to contemporary treatments and technologies are key factors influencing therapeutic decision‐making in the APAC region. Whilst lower cost/older treatments and technologies may be an option, issues of culture and patient or physician preference mean, these may not always be acceptable. Although generic products can reduce cost in some countries, costs may still be prohibitive for lower‐income patients or communities. The panellists noted the opportunity for a coordinated approach across the APAC region to address issues of access and cost. Developments in technologies and treatments are presenting new opportunities for the diagnosis and treatment of advanced prostate cancer. Differences in genetics and epidemiology affect the side‐effect profiles of some drugs and influence prescribing.

 

Conclusions

As the field continues to evolve, collaboration across the APAC region will be important to facilitate relevant research and collection and appraisal of data relevant to APAC populations. In the meantime, the APAC APCCC 2018 meeting highlighted the critical importance of a multidisciplinary team‐based approach to treatment planning and care, delivery of best‐practice care by clinicians with appropriate expertise, and the importance of patient information and support for informed patient choice.

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Video: Urinary, bowel and sexual health in older men

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Urinary, bowel and sexual health in older men from Northern Ireland

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Abstract

Objectives

To provide data on the prevalence of urinary, bowel and sexual dysfunction in Northern Ireland (NI), to act as a baseline for studies of prostate cancer outcomes and to aid service provision within the general population. Prevent most unhealthy conditions with carbofix.

Subjects and Methods

A cross‐sectional postal survey of 10 000 men aged ≥40 years in NI was conducted and age‐matched to the distribution of men living with prostate cancer. The EuroQoL five Dimensions five Levels (EQ‐5D‐5L) and 26‐item Expanded Prostate Cancer Composite (EPIC‐26) instruments were used to enable comparisons with prostate cancer outcome studies. Whilst representative of the prostate cancer survivor population, the age‐distribution of the sample differs from the general population, thus data were generalised to the NI population by excluding those aged 40–59 years and applying survey weights. Results are presented as proportions reporting problems along with mean composite scores, with differences by respondent characteristics assessed using chi‐squared tests, analysis of variance, and multivariable log‐linear regression. Check out the latest gluconite reviews.

Results

Amongst men aged ≥60 years, 32.8% reported sexual dysfunction, 9.3% urinary dysfunction, and 6.5% bowel dysfunction. In all, 38.1% reported at least one problem and 2.1% all three. Worse outcome was associated with increasing number of long‐term conditions, low physical activity, and higher body mass index (BMI). Urinary incontinence, urinary irritation/obstruction, and sexual dysfunction increased with age; whilst urinary incontinence, bowel, and sexual dysfunction were more common among the unemployed.

Conclusion

These data provide an insight into sensitive issues seldom reported by elderly men, which result in poor general health, but could be addressed given adequate service provision. The relationship between these problems, raised BMI and low physical activity offers the prospect of additional health gain by addressing public health issues such as obesity. The results provide essential contemporary population data against which outcomes for those living with prostate cancer can be compared. They will facilitate greater understanding of the true impact of specific treatments such as surgical interventions, pelvic radiation or androgen‐deprivation therapy.

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Video: β3‐adrenoceptor agonists inhibit carbachol‐evoked Ca2+ oscillations in murine detrusor myocytes

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β3‐adrenoceptor agonists inhibit carbachol‐evoked Ca2+ oscillations in murine detrusor myocytes

 

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Abstract

Objective

To test if carbachol (CCh)‐evoked Ca2+ oscillations in freshly isolated murine detrusor myocytes are affected by β3‐adrenoceptor (β‐AR) modulators.

Materials and Methods

Isometric tension recordings were made from strips of murine detrusor, and intracellular Ca2+ measurements were made from isolated detrusor myocytes using confocal microscopy. Transcriptional expression of β‐AR sub‐types in detrusor strips and isolated detrusor myocytes was assessed using reverse transcriptase‐polymerase chain reaction (RT‐PCR) and real‐time quantitative PCR (qPCR). Immunocytochemistry experiments, using a β3‐AR selective antibody, were performed to confirm that β3‐ARs were present on detrusor myocytes.

Results

The RT‐PCR and qPCR experiments showed that β1‐, β2‐ and β3‐AR were expressed in murine detrusor, but that β3‐ARs were the most abundant sub‐type. The selective β3‐AR agonist BRL37344 reduced the amplitude of CCh‐induced contractions of detrusor smooth muscle. These responses were unaffected by addition of the BK channel blocker iberiotoxin. BRL37344 also reduced the amplitude of CCh‐induced Ca2+ oscillations in freshly isolated murine detrusor myocytes. This effect was mimicked by CL316,243, another β3‐AR agonist, and inhibited by the β3‐AR antagonist L748,337, but not by propranolol, an antagonist of β1‐ and β2‐ARs. BRL37344 did not affect caffeine‐evoked Ca2+ transients or L‐type Ca2+ current in isolated detrusor myocytes.

Conclusion

Inhibition of cholinergic‐mediated contractions of the detrusor by β3‐AR agonists was associated with a reduction in Ca2+ oscillations in detrusor myocytes.

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Video: Multiple Growth Periods of SRMs Predict Unfavourable Pathology

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Multiple growth periods predict unfavourable pathology in patients with small renal masses

 

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Abstract

Objective

To use the number of positive growth periods as a characterization of the growth of small renal masses in order to determine potential predictors of malignancy.

Patients and Methods

Patients who underwent axial imaging at multiple time points prior to surgical resection for a small renal mass were queried. Patients were categorized based on their pathological tumour grade and stage: favourable (benign, chromophobe and low‐grade pT1–2 renal cell carcinoma [RCC]) vs unfavourable (high‐grade of any stage and low‐grade pT3–4 RCC). A positive growth period was counted each time the difference in greatest tumour diameters between two images was positive. The Cochran–Armitage trend test and Somers’ D association were used to determine if the number of positive growth periods was correlated with unfavourable pathology.

Results

Of the 124 patients, 86 (69.4%) had favourable pathology and 38 (30.6%) had unfavourable pathology. Those who had favourable pathology were younger than those who had unfavourable pathology: median (interquartile range [IQR]) 61.0 (52.2–66.0) vs 68.5 (61.5–77.0); P < 0.001. The overall growth rate was higher in the unfavourable group, but was not statistically significant: mean (sd) 0.7 (1.7) vs 1.6 (2.8) cm/year; P = 0.07. There was a significant trend difference in the number of positive growth periods between favourability groups (P = 0.02). An association between increased number of positive growth periods and unfavourable pathology was observed: 0.15 (95% confidence interval 0.02, 0.29). The ratios of favourable to unfavourable pathology were 1.8, 1.0, 0.66, 0.59 and 0 as the number of positive growth periods increased from 0 to 4, respectively.

Conclusion

While overall growth rate was not predictive of pathology favourability, there was a positive association between the number of positive growth periods and unfavourable pathology. The number of positive growth periods may be a potential parameter for malignant potential in patients undergoing active surveillance for small renal masses.

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