Anthony Noah

November saw the return of the International Urology Journal Club #urojc on Twitter. The annual meetings of the World Congress for Endourology (#WCE2015) and Société Internationale D’Urologie (#SIU15) led to an October break for #urojc. This month’s discussion was based around a recent editorial in the New England Journal of Medicine by Welch et al on the effects of screening on the incidences of metastatic-at-diagnosis prostate and breast cancers. In the three days prior to the start of the discussion the editorial and it’s now well-known graph had been trending amongst medical Twitter users.

The issue of PSA screening for prostate cancer has been a topic of debate amongst urologists for a number of years. PSA and DRE are first line for early detection of prostate cancer. Supporters of PSA screening argue that it leads to a significant fall in prostate cancer specific mortality. Many others believe there is insufficient evidence to support universal PSA screening given the risks of prostate biopsy and potential overtreatment of low risk prostate cancer.

The editorial presented data showing a significant fall in the number of patients first presenting with metastatic prostate cancer (advanced stage incidence) following the introduction of universal screening. However no effect was shown on similar data for breast cancer. Variations in disease dynamics were suggested to play a role.

The conversation started on Sunday 1st November at 20:00 (GMT), marking the beginning of the fourth year of #urojc. The first questions centred around the reasons behind the trends seen in the graph. Being a urology journal club the conversation was based almost exclusively on the prostate cancer aspect of the editorial.

One suggestion for the discrepancy between the two cancers is that PSA is a better detector of metastatic disease, whilst mammography can only detect localised disease.

Based on incidence of metastatic prostate cancer, the article makes a convincing statement in support of universal PSA screening. However, a successful screening programme should result in a reduction in the incidence of advanced cancers, decreased advanced-stage incidence and reduced mortality. Leading to the question of whether looking solely at advanced-stage incidence is useful.

The importance of responsible treatment and active surveillance was mentioned early on.

One of the most important questions of the discussion: What impact and relevance does the image have? Views were polarised. Some contributors were cautious about drawing conclusions from the graph whilst others were satisfied that it justified PSA screening.

The article drew comparison between Halsted’s and Fisher’s descriptions of cancer progression. Halsted suggested cancer originates from a single site and spreads, whereas Fisher’s paradigm proposed that breast cancer is a systemic disease by the time it is detectable.

The United States Preventive Services Task Force (USPSTF) has recommended against universal screening of prostate cancer, suggesting the risks of testing outweighed the benefits. However, many believe this to be based on outdated evidence.

The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial results showed a 12% higher incidence of prostate in the screening arm versus control, with no difference in mortality. Yet, the European Randomized Study of Screening for Prostate Cancer (ERSPC) has shown screening to result in a 1.6 fold increase in prostate cancer with a 21% reduction in mortality.

The debate briefly discussed the morbidity and cost of metastatic disease.

The editorial certainly raised a number of interesting points. It seems the topic of universal PSA screening will continue to be debated. There is a significant benefit to screening in the prevention of metastatic prostate cancer. Whether this is due to differing disease dynamics or PSA being a better screening tool than mammography is as yet unclear.

One point we can all agree on is that increasing utilisation of active surveillance with timely biopsies is important in preventing overtreatment of low risk disease and identifying those at risk of disease progression for curative treatment.

Anthony Noah Urology Speciality Trainee, West Midlands, UK
Twitter: @antnoah

The month of May 2015 saw the International Urology Journal Club #urojc Twitter discussion move away from a cancer topic to a benign one. The discussion centred on the recent Journal of Urology paper entitled ‘Transarterial Embolization of Angiomyolipoma – A Systematic Review’. In this paper Murray et al presented a review of 524 cases of transarterial embolization (TAE) for AML in 31 studies (published between 1986 and 2013) with a mean follow up of 39 months.

The authors reported technical success of the procedure in 93.3% of cases with a mean AML size reduction of 3.4cm (38.3%). Post-procedural mortality was reported in 6.9% and unplanned repeat procedures in 20.9%.

The conversation kicked off on Sunday 3rd May at 22:00 (BST) with a flurry of tweets from around the world. Initially there were brief questions about the sample size and clarity of the results in the paper.

A few contributors were not convinced by the overall efficacy of embolisation in the study.

Post-procedure embolisation-related morbidity was reported in 6.9% of patients.

The suggestion of low morbidity moved the conversation away from the paper itself and on to the risks of AMLs if left untreated. The most significant risk of renal AML is bleeding.

There is also the important issue of misdiagnosis

Oesterling et al (1986) published a key paper suggesting that 82% of patients with symptoms had AMLs >4cm. This and other similar papers from the 1980s and 1990s form the basis of treatment protocols for renal AML. The lack of further literary knowledge regarding the natural history of AML became a key sticking point.

Cue the introduction of some more recent literature, suggestive that <2cm AMLs can be ignored (https://www.ncbi.nlm.nih.gov/m/pubmed/24837696/).

This caused further debate about the appropriate screening and management of AMLs. It became apparent that opinions on surveillance vary.

Growth is the important factor. Rate of growth is perhaps more important than actual size in small AMLs.

However there will be data published further supporting this approach to small AMLs.

Are we being overcautious?

Or are we shifting our anxieties to the patient?

There was the inevitable discussion of surgical treatment (partial nephrectomy preferred) instead of embolization. The reasoning for embolization versus surgery was sought out.

Partial nephrectomy allows for definitive treatment of the AML with preservation of renal function and acceptable complication rates.

Embolisation is less invasive without the risks of major surgery and so provides first line treatment for many.

Therefore local complication rates are important to consider, especially when considering nephron-sparing surgery.

CT angiography findings may aide in treatment choice if the vascular supply is amenable to a successful embolisation with minimal non-target embolisation.

Mammalian target of rapamycin (mTOR) is a protein which regulates cell growth, proliferation and survival. Everolimus, an oral mTOR inhibitor, has been shown to reduce the size and growth rate of Tuberous Sclerosis related AML.

As AMLs are benign tumours with significant potential complications, there may be wider variations in management protocols than would be seen with a malignant tumour. Perhaps patient preference, or urologist preference plays much more of a role in individual cases.

As always the debate was interesting and raised a number of key points. Discussion focussed more on overall issues around the management of angiomyolipoma following a brief discussion of the paper itself. The literature is lacking recent high level evidence for treatment of angiomyolipoma. Whilst most follow classical teaching of intervening in symptomatic and larger tumours (>4cm), there is wide variation in the follow up and surveillance of small tumours.

More recent data suggests smaller tumours may not require close follow up. Perhaps rate of growth, much like PSA dynamics in prostate cancer, is more important than the actual size of the tumour. There is also evidence lacking in the direct comparison of embolization versus nephron-sparing surgery for angiomyolipoma.

This draws to a conclusion the summary of the May #urojc summary blog. Please follow @iurojc on Twitter for updates and to get involved on the first Sunday/Monday of each month.

Anthony Noah

Urology Speciality Trainee, West Midlands, UK

Twitter: @antnoah

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Does presentation with metastatic prostate cancer matter?

Transarterial Embolisation of Angiomyolipomas – Not so Cut and Dry

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