Tag Archive for: #ProstateCancer

You are here: / #ProstateCancer

Posts

Editorial: Statins and biochemical recurrence after radical prostatectomy – who benefits?

/by

In the present issue of the BJUI Allott et al. [1] report results from a study where they used the Shared Equal Access Regional Cancer Hospital (SEARCH) database to explore the risk of biochemical recurrence (BCR) after radical prostatectomy (RP) among men who used statins after RP. They report improved BCR-free survival among statin users, especially among men with high-risk disease at baseline. The results provide some new insights into the current discussion on statins and prostate cancer outcomes.

Statins have recently shown promise as chemotherapeutic agents against prostate cancer. There is conflicting evidence on the effect on overall prostate cancer risk, but most studies able to evaluate the risk by tumour stage have reported lowered risk of advanced prostate cancer among statin users compared with the non-users [2], and lowered prostate cancer-specific mortality [3].

Taken together, these epidemiological findings suggest that statins may not strongly lower the risk of initiation of prostate cancer, but may be able to slow down the progression of the most dangerous form of the disease. In vitro studies support this by reporting growth inhibition and lower metastatic activity of prostate cancer cells after statin treatment [4].

Despite this, there has been recent controversy on statins’ effect on BCR of prostate cancer after radical treatment. A recent meta-analysis concluded that statin users may have a lower risk of BCR after external beam radiation therapy, but not after RP [5]. This could be due to statins acting as radiation sensitizers. Reports of improved BCR-free survival in statin users after brachytherapy would support this [6].

However, there are also differences in the characteristics of patients managed with RP or radiation therapy. Men undergoing RP have localised disease, which usually means low- to medium-grade tumours (Gleason ≤7), as high-grade disease (Gleason 8–10) progresses early and is more often locally advanced or already metastatic at diagnosis, leading to the choice of radiation therapy with neoadjuvant androgen deprivation instead of RP if curative treatment is still deemed possible.

This leads to the question whether the differing association between statins and BCR by treatment method is explained by patient selection, and whether statins are most effective against progression of high-grade disease. The study reported by Allott et al. [1] in this issue of the BJUI certainly suggests so. They report lowered risk of BCR among men who used statins after RP. They were able to study the effect of statin usage occurring after RP, not just usage at the time of RP. When the analysis was stratified by tumour characteristics, the improvement in relapse-free survival was strongest among men with high-risk disease (Gleason score ≥4 + 3; positive surgical margins).

The present study [1] supports the notion that statins could target a mechanism that is essential for progression of high-risk prostate cancer. This would be in concordance with the previously reported lowered risk of advanced prostate cancer and decreased prostate cancer mortality among statin users, as high-grade/high-risk cancer is the type progressing into advanced and fatal stages. On the other hand, if statins do not affect low-grade prostate cancer, this could explain why many RP series have not observed differences in biochemical relapses by statin use, as patients in these studies often have low-grade disease.

As always, statins’ benefits against prostate cancer are not really proven until verified in randomised clinical trials properly designed and powered to detect a difference in cancer endpoints. Designers of such trials should consider targeting the statin intervention to men with high-grade and/or high-risk prostate cancer for efficient study design.

Read the full article

Teemu J. Murtola*†

*School of Medicine, University of Tampere, and † Department of Urology, Tampere University Hospital, Tampere, Finland

References

1 Allott EH, Howard LE, Cooperberg MR et al. Postoperative statin use and risk of biochemical recurrence following radical prostatectomy: results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database. BJU Int 2014; 114: 661–6

2 Bansal D, Undela K, D’Cruz S, Schifano F. Statin use and risk of prostate cancer: a meta-analysis of observational studies. PLoS ONE 2012; 7:e46691

3 Yu O, Eberg M, Benayoun S et al. Use of statins and the risk of death in patients with prostate cancer. J Clin Oncol 2014; 32: 5–11

4 Brown M, Hart C, Tawadros T et al. The differential effects of statins on the metastatic behaviour of prostate cancer. Br J Cancer 2012; 106: 1689–96

5 Park HS, Schoenfeld JD, Mailhot RB et al. Statins and prostate cancer recurrence following radical prostatectomy or radiotherapy: a systematic review and meta-analysis. Ann Oncol 2013; 24: 1427–34

6 Moyad MA, Merrick GS, Butler WM et al. Statins, especially atorvastatin, may improve survival following brachytherapy for clinically localized prostate cancer. Urol Nurs 2006; 26: 298–303

 

Editorial: Extent of lymph node metastases

/by

The role of prostatectomy in lymph node metastasized prostate cancer has been subject to changing opinions. Classically, a nodal dissection was performed as the initial step in the procedure and prostatectomy was avoided in men with cryosection-proven metastases. Biochemical recurrence during the first 3 years occurs in the majority of men with pN1 disease [1]. Early data from randomized trials shows only a 50% prostate cancer-specific survival 12 years after prostatectomy and nodal metastases without immediate adjuvant treatment [2]. Recently, Passoni et al. [3] showed a higher 10-year overall survival of 82.8% in men with nodal metastases, of whom the majority were treated with adjuvant androgen ablation and/or radiotherapy. This percentage is remarkably similar to the treatment arm of the earlier-mentioned study reported by Messing et al. [2], which showed a 10-year disease-specific survival of >80%. At 10 years about half the patients who died, did so from prostate cancer; therefore, although reasonable intermediate range survival can be obtained in men with nodal metastases of prostate cancer, the major cause of death remains prostate cancer when surgery is applied at the age of 65 years. Although adjuvant androgen ablation may improve survival, as suggested by the above-mentioned observations, some men may not experience recurrence after resection of nodal metastases and would experience the toxicity of androgen ablation unnecessarily. The identification of these men would reduce costs and toxicity.

Passoni et al. [3] presented a multicentre study on prognostic factors after prostatectomy for node-positive disease. The number of removed nodes (median 10) seems relatively low compared with the 17 reported in their earlier single-centre study, but may be a good reflection of urological practice in general. By comparison, the percentage of men who underwent adjuvant radiotherapy in the multicentre study was low (16%). Data from da Pozzo et al. [4] suggest that adjuvant radiotherapy may be of benefit in men with limited nodal metastases. It would be of interest to study whether men with a later biochemical recurrence would be those that did experience recurrence only locally and therefore would be those most likely to benefit from adjuvant (or salvage) radiotherapy.

In the current study by Passoni et al. [1] in the BJUI, the follow-up was relatively short (16 months). Earlier data from this author group showed that number of positive nodes and lymph node density were good predictors of cancer-specific survival after prostatectomy. This earlier observation is now confirmed in a multicentre analysis with a different endpoint: biochemical recurrence. What is notable is the fact that this confirmation was obtained in a series of patients with fewer nodes removed. The value of the marker ≤2 positive nodes becomes limited with the observation that this group contained 85% of men in their series. The second marker found, the size of the node, showed a more general distribution but as a single marker had no predictive value. The differences in Harrel’s c values from the base model containing other clinical characteristics are limited and reproducibility of measures needs attention. Still, the observation that extent of nodal metastases is of prognostic value after surgery is notable.

Ideally, markers could predict the absence of further disease progression in men after prostatectomy for nodal metastasized prostate cancer. None of the studied characteristics fulfill this need because at 36 months after prostatectomy the majority of men, even those in the best prognostic group, do experience biochemical recurrence that will result in prostate cancer-related death. Gleason score is a strong predictor of the presence of nodal metastases [5], and some have suggested that nodal Gleason grade is of prognostic value in men with pN+ disease. Until these markers have been further evaluated, it remains important to address the fact that reported cancer-specific survival in most men with pN+ disease is >10 years [6]. Although tempting to speculate that prostatectomy and (extended) lymph node dissection plays a role in this, the almost inevitable development of biochemical recurrence reported in the current study by Passoni et al. [1], even in patients in the best prognostic group, stresses the systemic nature of this disease which will require a multimodality approach in most men at some point.

Read the full article

Henk G. van der Poel

Department of Urology, Netherlands Cancer Institute, Amsterdam, The Netherlands

References

1 Passoni N, Fajkovic H, Xylinas E. Prognosis of patients with pelvic lymph node metastasis following radical prostatectomy: value of extranodal extension and size of the largest lymph node metastasis. BJU Int 2014; 114: 503–10

2 Messing EM, Manola J, Yao J et al. Immediate versus deferred androgen deprivation treatment in patients with node-positive prostate cancer after radical prostatectomy and pelvic lymphadenectomy. Lancet Oncol 2006; 7: 472–9

3 Passoni NM, Abdollah F, Suardi N et al. Head-to-head comparison of lymph node density and number of positive lymph nodes in stratifying the outcome of patients with lymph node-positive prostate cancer submitted to radical prostatectomy and extended lymph node dissection. Urol Oncol 2013; 29: 29.e21–8

4 Da Pozzo LF, Cozzarini C, Briganti A et al. Long-term follow-up of patients with prostate cancer and nodal metastases treated by pelvic lymphadenectomy and radical prostatectomy: the positive impact of adjuvant radiotherapy. Eur Urol 2009; 55: 1003–11

5 Ross HM, Kryvenko ON, Cowan JE, Simko JP, Wheeler TM, Epstein JI. Do adenocarcinomas of the prostate with Gleason score (GS)</=6 have the potential to metastasize to lymph nodes? Am J Surg Pathol 2012; 36: 1346–52

6 Touijer KA, Mazzola CR, Sjoberg DD, Scardino PT, Eastham JA. Long-term outcomes of patients with lymph node metastasis treated with radical prostatectomy without adjuvant androgen-deprivation therapy. Eur Urol 2013; 65: 20–5

Are You Teaming Up for Movember?

/2 Comments/by

Urology, Social Media, and Prostate Cancer Controversies

The past couple of years have witnessed a rapid rise in the number of urologists engaging in conversation using social media. Urologists across the globe are now participating in the International Urology Journal Club on Twitter (#UROJC), tweeting at conferences, and using social media to build personal and professional relationships. As a result, providers with a passion for men’s health, who may never previously met in real life, are sharing ideas and experience with respect to issues in urology and patient care.

This uptick in the use of social media comes at a time when when prostate cancer screening and the optimal care of the prostate cancer patient are being hotly debated.  More research is clearly needed to settle many of the debates currently taking place both in traditional media and on social media. It, therefore, makes sense for the global urology community to partner with organizations that have a similar passion for advancing and promoting men’s health through scientific research.

Movember – Raising Awareness and Funding for Men’s Health Initiatives

Movember is a movement that began in Melbourne, Australia, in 2003. Since that time, it has spread to more than 20 other countries around the world. Each November, participants raise awareness and money for men’s health by growing a moustache. As the month goes on, and the mustache takes shape, these men become walking and talking men’s health billboards. Participants use their mustache to facilitate conversations about a wide variety of men’s health issues including prostate cancer, testicular cancer, and men’s mental health. They also actively raise money for the Movember Foundation by asking family and friends to donate to their efforts.

Movember is not just for men. Women (Mo Sistas), through encouragement, conversation, fundraising, and, in some cases, sheer tolerance, are a critical part of Movember’s success. Mo Sistas do everything Mo Bros do – they just don’t grow a moustache. Since Movember started, more than 4 million Mo Bros and Mo Sistas around the world have participated. In the process over $556 million dollars has been raised for the Movember Foundation.

Funding Cancer Research in Urology

 

Since its very inception, the Movember Foundation has supported ongoing research in men’s health. Currently the Movember Foundation is funding more than 832 men’s health programs worldwide. In 2010, Movember created a Global Action Plan to improve the clinical tests and treatments used for men with prostate and testicular cancer. Currently, Movember is funding prostate cancer research in four areas:

1. Developing more accurate blood, urine and tissue tests to differentiate between low risk and aggressive forms of prostate cancer.

2. Developing new imaging techniques that enable the earlier detection of metastatic prostate cancer.

3. Optimizing the management of men with low risk prostate cancer.

4. Understanding how increasing physical activity might improve the quality of life and survival of prostate cancer patients.

Movember’s criteria for research support encourages national and international collaboration. Working collaboratively, research groups are able to pool experience, streamline cost, and avoid duplication, in an effort to accelerate the  bench-to-bedside development of new investigations and treatments.

Disrupting the Status Quo

In the past, many different men’s health initiatives have come and gone. Movember’s innovative approach is unique in that each year, for a full month, the movement puts important men’s health issues – such as prostate cancer, testicular cancer and men’s mental health – back into the public spotlight.  The effect of the movement has been to not only energize men, but also healthcare, and even government.

One great example of this is the Prostate Cancer of Australia Specialist Nurse Program. The program, initially funded by Movember in 2011 with AU $3.6m, placed full time specialty nurses in every Australian state to help fill a gap in prostate cancer support and delivery. The pilot program was so successful that the Australian government invested AU $7.2m to allow the program to further expand. Movember has also created a variety of unexpected domino effects in the men’s health community. This year, our American colleagues, Dr. Jamin Brahmbhatt and Dr. Sijo Parekattil, inspired in part by the success of the Movember movement, started the Drive for Men’s Health. There are likely many others who, if asked, would tip their hats in the direction of Movember for their inspiration.

When Urologists Participate, Patients Benefit

Urologists by their very nature are both competitive and cooperative. The Movember movement is a unique opportunity for urologists across continents to join with other individuals and organizations that are passionate about improving the health and quality of life of men.  Movember is also an opportunity for colleagues, who may have only met via social media, to cooperate and/or compete all in an effort to raise awareness and money for men’s health research.  Last year, for example, Canadian urologist Dr. Rajiv Singal, assembled an international Movember team of Canadian and American urologists, patient advocates, and other healthcare providers to raise money and awareness for men’s health. Working together, the team raised nearly CA $50,000 dollars for the Movember Foundation.

An Invitation to Team Up

In the spirit of collaboration and friendly competition, this November we invite our urology colleagues from around the world to start their own local Movember Team, or to join our international team as we attempt to better our fundraising performance from last year.

 

sLND for Prostate Cancer Nodal Recurrence: #urojc September 2014 summary

/by

The September 2014 edition of the International Urology Journal Club (#urojc) returned to familiar territory – prostate cancer. In particular, the discussion focused on salvage lymph node dissection following radical prostatectomy. For the second time (first in July 2014), two journal articles were selected. Both were kindly made available to open access by The Journal of Urology (@JUrology).

The first paper from the Mayo Clinic by Karnes et al., titled ‘Salvage Lymph Node Dissection (sLND) for Prostate Cancer Nodal Recurrence Detected by 11C-Choline Positron Emission Tomography/Computed Tomography (PET/CT)’, reported on a retrospective single-surgeon series of 52 men who underwent salvage lymph node dissection for nodal recurrence post radical prostatectomy. Median follow-up was 20 months. Three-year Biochemical recurrence (BCR)-free survival rate was 45.5% (PSA <0.2). Metastatic/systemic progression-free and cancer-specific survival rates were 46.9% and 92.5% respectively. They concluded that sLND may delay further progression of disease but highlighted the need for randomised controlled trials.

The second paper from German group Tilki et al., titled ‘Salvage Lymph Node Dissection for nodal recurrence of prostate cancer after Radical Prostatectomy’, also reported on a retrospective series of 58 patients who underwent sLND for nodal recurrence on PET/CT post radical prostatectomy. Median follow-up was 39 months. All but 1 patient had BCR. Five-year clinical recurrence-free and cancer-specific survival rates were 35.9% and 71% respectively.  Tilki et al. concluded that while most patients had BCR, sLND may delay ADT and clinical recurrence in selected cases.

A common sentiment shared during the discussion related to the lack of randomised evidence for sLND:

There were some serious concerns about the methodology and results from the two articles:

Discussions quickly shifted away from the two articles to the actual clinical question of sLND in oligometastatic disease and delay to ADT. Matthew Katz provided useful links to the use of stereotactic radiation therapy.

Issues surrounding sLND training and the paradigm shift in recent years were also highlighted:

Opinions were divided on the question of surgical morbidity versus the potential increase in time to ADT:

Pop culture references were in vogue this month. An article by the Mayo Clinic on the 11C-Choline PET scan sparked the linked exchange:

Some take home messages pertained to the uncertainty regarding patient selection and the role of sLND in the broader multidisciplinary arena of prostate cancer treatment:

The winner of the Best Tweet Prize is Brian Chapin (@ChapinMD) for his tweet above.  We thank the Journal of Clinical Urology for supporting this month’s prize by way of a one year electronic subscription to their journal.  We also thank the Journal of Urology for supporting this month’s discussion by way of allowing time limited open access of both articles.

Staying true to form, this month’s edition of #urojc provided a forum for lively international discussion. We look forward to next month’s installment and especially encourage trainees to make use of this excellent educational opportunity.

 

Isaac Thangasamy is a second year Urology Trainee currently working at the Royal Brisbane and Women’s Hospital, Brisbane, Australia. He is passionate about education and social media. Follow him on Twitter @iThangasamy

 

Editorial: Perioperative aspirin: To give or not to give?

/by

As the population ages and life expectancy increases, one may safely assume that more men will be diagnosed with diseases of the elderly such as prostate cancer. In the USA, it is estimated that the number of older adults (≥65 years old) will double between 2010 and 2030, contributing to a 45% increase in cancer incidence [1]. Also, it is likely that these older patients will present with multiple comorbidities, commonly described as ‘multimorbidity’ in the contemporary medical literature, including chronic cardiac and pulmonary conditions requiring multidisciplinary medical management.

Hence, the present study by Leyh-Bannurah et al. [2] examining the peri-operative use of aspirin in patients undergoing radical prostatectomy (RP) is a timely and important contribution, and may very well influence our clinical decision-making regarding the perioperative management of the anti-coagulated patient. Their results show that perioperative continuation of aspirin made no difference in peri and postoperative outcomes following RP. Previous studies have assessed the effect of aspirin continuation in patients undergoing minimally invasive RP, but the present study is the first to evaluate the effect of aspirin continuation in patients undergoing minimally invasive and open RP at a high-volume tertiary centre. Studies from other surgical specialties evaluating the role of anti-platelet therapy and its timing before surgery have shown conflicting results. The study by Park et al. [3], looking at discontinuation of aspirin for ≥7 days vs <7 days before surgery in patients undergoing lumbar spinal fusion, found that aspirin discontinued only 3–7 days before surgery significantly increased the risk of intraoperative bleeding. Alghamdi et al. [4] found similar results in patients undergoing coronary artery bypass grafting. In contrast, the study by Wolf et al. [5] showed that continuation of aspirin up to the day of the surgery did not increase the risk of bleeding, transfusion or other adverse outcomes in patients undergoing pancreatectomy. Similarly, Khudairy et al. [6] assessed the use of clopidogrel and its discontinuation time in hip fracture repair, and found that whether it was stopped ≥1 week or <1 week before surgery did not make any difference to the risk of bleeding or peri-operative complications. Nonetheless, the evidence provided by the present study by Leyh-Bannurah et al. is important, as the risk of bleeding seems to be procedure-specific, depending on the nature and source of potential bleeding (primarily arterial vs primarily venous). The lack of information, however, regarding cardiovascular morbidities in their patient population is an important limitation of their study; as such factors may influence perioperative decision-making, including the threshold for transfusion.

Read the full article

Akshay Sood and Quoc-Dien Trinh*
VUI Center for Outcomes Research, Analytics and Evaluation, Henry Ford Health System, Detroit, MI, and *Division of Urologic Surgery and Center for Surgery and Public Health, Brigham and Women’s Hospital/Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA

References

  1. Lamb A. Fast Facts: prostate cancer, seventh edition. BJU Int 2012; 110: E157
  3. Park JH, Ahn Y, Choi BS et al. Antithrombotic effects of aspirin on 1- or 2-level lumbar spinal fusion surgery: a comparison between 2 groups discontinuing aspirin use before and after 7 days prior to surgery. Spine 2013; 38: 1561–1565
  4. Alghamdi AA, Moussa F, Fremes SE. Does the use of preoperative aspirin increase the risk of bleeding in patients undergoing coronary artery bypass grafting surgery? Systematic review and meta-analysis. J Cardiac Surg 2007; 22: 247–256
  5. Wolf AM, Pucci MJ, Gabale SD et al. Safety of perioperative aspirin therapy in pancreatic operations. Surgery 2014; 155: 39–46
  6. Al Khudairy A, Al-Hadeedi O, Sayana MK, Galvin R, Quinlan JF. Withholding clopidogrel for 3 to 6 versus 7 days or more before surgery in hip fracture patients. J Orthop Surg 2013; 21: 146–150
Read more articles of the week

15th Asia-Pacific Prostate Cancer Conference 2014

/by

Blog author Dr Sarah Wilkinson enjoys lunchtime entertainment at APCC in Melbourne.

The 15th Asia-Pacific Prostate Cancer Conference 2014 (#apcc14; prostatecancerconference.org.au/) is the largest prostate cancer educational event in the region and attracts over 800 multidisciplinary delegates every year. The world’s leading experts in prostate cancer have featured on the Faculty at this conference in recent year’s and this year’s Faculty was again a great team-sheet for leaders in this field:

The Confernece kicked off on Sun 31st August with a series of Masterclasses including the very popular da Vinci© Prostatectomy Masterclass (featuring Dr Henk Van Der Poel, Dr John Davis, Dr Markus Graefen and Dr Paul Cathcart), along with new master classes focusing on Prostate MRI scanning (led by Dr Jelle Barentsz), and LDR Brachytherapy (led by Dr Juanita Crook).

MRI Prostate Masterclass led by Jelle Barentsz was a sell-out

The Nursing & Allied Health streams also opened their plenary sessions to a busy auditorium. The official Poster and Welcome Session was held on Sunday evening on what was an unseasonally warm and to Winter in Australia. Whilst enjoying the range of lovely canapés and beverages on offer via Melbourne’s premier conference and catering venue (https://mcec.com.au/), delegates caught up with their long lost urology colleagues and perused the high quality posters on display. Poster prizes were awarded for each of the three conference streams; Clinical Urology, Nursing & Allied Health, and Translational Science, as judged by experts in the respective fields. The task of picking just one winner for the Clinical Urology category proved too difficult for judges A/Prof Henry Woo (@DrHWoo) and Dr Phil Dundee (@phildundee), so a dual prize was awarded to both Dr Fairleigh Reeves (@DrFairleighR) and A/Prof Jeremy Millar (@jeremymillar). Rob McDowell took out the poster prize for the Nursing & Allied Health stream with his poster on baseline characteristics of participants in a telephone-delivered mindfulness intervention for men with advanced prostate cancer. The Translational Science winner was Saeid Alinezhad, who presented; ACSM1, CACNA1D and LMNB1 as three novel prostate cancer biomarker candidates.

Monday morning saw the Official Conference Opening given by conference President Prof Tony Costello (@proftcostello) who announced the opening of a new Royal Men’s Hospital to specifically address the needs of men’s health in Australia. The life expectancy of Australian males is currently 5 yrs less than women, and cancer mortality is a third higher for prostate cancer compared to breast. Rates of alcohol, tobacco and drug abuse, as well as suicide, are all 4x higher in men compared to women. 66% Australian men are overweight or obese, and men are also far less likely to visit their GP for a check-up. Next we were lucky enough to have Federal Minister for Health and Sport, the Hon. Peter Dutton MP (@PeterDutton_MP), take leave from Parliament to give the Ministerial Address. Mr Dutton expressed his support for the conference and the forthcoming opening of the new “Royal Men’s Hospital”, a clinic focussed on Men’s Health in Australia’s premier health science precinct, and spoke of how he hopes the recently proposed $20 billion Medical Research Future Fund will further help advances in this area.

Conference President Prof Tony Costello with Australia’s Minister for Health, Hon Peter Dutton MP

The 2nd Patrick C Walsh Lecture was given by Dr Peter Carroll from the Department of Urology, UCSF, USA. Dr Carroll discussed how we can refine current risk assessments for patients with prostate cancer, and in the process give them refined treatment options. Dr Caroll and his team (including Dr Matthew Cooperberg who was also present), have led the way in risk stratification for men with localised prostate cancer and continue to find ways to best select men at higher risk of adverse outcomes.

This year’s point-counter point debate focused on the preferred method of prostate cancer biopsy. In the left side of the ring we had Mr Jeremy Grummet (@jgrummet) who argued the case for a transperineal biopsy due to multi-drug resistant rectal flora. On the right side we had Mr Shomik Sengupta (@shomik_s) who was in favour of sticking with the well-established TRUS. Following a very close audience vote, session chair A/Prof Nathan Lawrentschuk (@lawrentschuk) declared the winner, “Close, but transfecal by an organism.”

The Conference dinner was held on Monday evening at the Mural Hall, Myer Building. 18th century style mirrored commodes and Parisian inspired parquet flooring transported guests to another world, whilst some fine whisky and entertainment was enjoyed.

And for those who hadn’t partied too hard, the Clinical Urology and Translational Science Breakfast sessions were back by popular demand beginning promptly at 6:45 am the next morning. Both sessions focused on genomics and its implications in diagnosis and treatment planning in what is now coined ‘The Genomic Era’.

Later in the morning we remembered renowned British urologist Prof John Fitzpatrick, who sadly passed away aged 65 on May 14th 2014, suffering from a massive subarachnoid haemorrhage. His close colleague and friend, Prof Roger Kirby, delivered the remembrance speech “Life in the Fast Lane”, along with a musically accompanied slide show. Prof Kirby’s tribute can also be read here at Blogs@BJUI (https://www.bjuinternational.com/bjui-blog/professor-john-fitzpatrick-1948-2014/).

The urology Twitterati were again out in full force at #apcc14. During peri-conference period (including the 5 day lead up period, the actual conference dates, and 2 days post-conference), almost 400,000 impressions were generated in cyperspace from 424 tweets, by 111 participants. There was an average of 2 tweets per hr over the peri-conference period and each participant averaged 4 tweets each.

The conference ended with the exciting news of a 2nd Prostate Cancer World Congress, to be held August 18-21st 2015 in beautiful Cairns, Queensland Australia. See you there!

 

 

 

Sarah Wilkinson completed her PhD in prostate cancer research and is now working as a Medical Science Liaison for Oncology and Haematology at GSK. Twitter: @wilko3040

 

Editorial: The importance of knowing testosterone levels in patients with prostate cancer

/by

The paper by San Francisco et al. [1] in this issue of BJUI, reviews 154 patients with prostate cancer who were included in an active surveillance cohort. In all, 54 (35%) progressed to active treatment. Men who had disease reclassification had significantly lower free testosterone than those who were not reclassified. They concluded that on multivariate analysis, free testosterone and a family history of prostate cancer were independent predictors of disease reclassification. The authors acknowledge that this was a retrospective study of small size and the data was missing in some of the men, sex hormone-binding globulin (SHBG), luteinizing hormone and oestradiol were not measured. Nevertheless, this review adds to the increasing evidence that it is important to measure testosterone levels in men with prostate cancer.

Previous studies have indicated that a low testosterone level before treatment for prostate cancer is an independent predictor of a more aggressive high-grade cancer [2]. In addition to this, there appears to be an increased likelihood of extraprostatic disease at the time of diagnosis [3] and an unfavourable response to treatment [4].

Garcia-Cruz et al. [5] in 2012 reported that low testosterone bioavailability is related to a positive prostate cancer diagnosis in patients submitted for prostate biopsy. In a further study, he showed that low testosterone levels were related to poor prognosis factors in men with prostate cancer prior to treatment. Testosterone was inversely related to prostate cancer bilaterally and percentage of tumour in the biopsy. Higher testosterone levels were found in patients allocated to the low-risk progression group. In the multivariate analysis, older age and lower testosterone levels were related to a higher D’Amico risk of progression [5]. The researchers went on to show that higher SHBG and lower bioavailable testosterone are related to prostate cancer detection on biopsy. The study was a prospective analysis of 279 patients referred for prostate biopsy. Low bioavailable testosterone and high SHBG levels were related to a 4.9- and 3.2-fold increased risk of detection of prostate cancer on prostate biopsy taken due to an abnormal PSA result or an abnormal DRE [6].

Free testosterone accounts for about 1–2% of total testosterone and hence most circulating testosterone is bound to SHBG and as such, is inactive. Yamamoto et al. [7] had previously shown that men with a low free testosterone (<1.5 ng/dL) had an increased risk of a high Gleason score (>8) compared with men with higher free testosterone (8% vs 2%; P = 0.04). Additionally, a free testosterone level of <1.5 ng/dL was associated with increased risk of biochemical recurrence of tumour.

Morgentaler et al. [8] have been turning conventional wisdom upside down. They report on 13 symptomatic testosterone deficient men who also had untreated prostate cancer. The men received testosterone therapy while undergoing active surveillance for a median of 2.5 years. None of the men had aggressive or advanced prostate cancer and they were rigorously followed up. Despite effective treatment, neither the PSA level nor prostate volume showed any change. Follow-up biopsies were taken in all of the men at yearly intervals and none developed cancer progression.

It is intriguing to think that the decline in testosterone with age and comorbidities may contribute to tumorigenesis in the prostate. Clearly this study needs to be replicated with much larger numbers. But it seems reasonable to suggest that we ought to know about the hormonal environment existing in our patients with prostate cancer. This will of course, raise the even more controversial area of what to do about men with symptomatic hypogonadism with treated and untreated prostate cancer. There is limited data available on this issue.

Before considering testosterone therapy, the first step should be intensive lifestyle intervention; this is not only known to improve cancer survival, but raises total and free testosterone. Weight loss inhibits aromatase, and other complex cytokines, this reduces the suppression of the pituitary gonadal axis and conversion of testosterone to oestrogen, raising testosterone levels.

Read the full article

Michael Kirby*,†
*The Prostate Centre, London, and †Institute of Diabetes for Older People (IDOP), Beds & Herts Postgraduate Medical School, Puckeridge Bury Campus, Luton, UK

References

  1. San Francisco I, Rojas P, Dewolf W, Morgentaler A. Low free testosterone predicts disease reclassification in men with prostate cancer undergoing active surveillance. BJU Int 2014; 114: 229–235
  2. Massengill JC, Sun L, Moul JW et al. Pretreatment total testosterone level predicts pathological stage in patients with localized prostate cancer treated with radical prostatectomy. J Urol 2003; 169: 1670–1675
  3. Chen SS, Chen KK, Lin AT, Chang YH, Wu HH, Chang LS. The correlation between pretreatment serum hormone levels and treatment outcome for patients with prostatic cancer and bony metastasis. BJU Int 2002; 89: 710–713
  4. Ribeiro M, Ruff P, Falkson G. Low serum testosterone and a younger age predict for a poor outcome in metastatic prostate cancer. Am J Clin Oncol 1997; 20: 605–608
  5. Garcia-Cruz E, Piqueras M, Huguet J et al. Low testosterone levels are related to poor prognosis factors in men with prostate cancer prior to treatment. BJU Int 2012; 110: E541–546
  6. Garcia-Cruz E, Carrión Puig A, Garcia-Larrosa A et al. Higher sex hormone-binding globulin and lower bioavailable testosterone. Scand J Urol 2013; 47: 282–289
  7. Yamamoto S, Yonese J, Kawakame S et al. Preoperative serum testosterone level as an independent predictor of treatment failure following radical prostatectomy. Eur Urol 2007; 52: 696–701
  8. Morgentaler A, Liphultz LI, Bennett R, Sweeney M, Avila D Jr, Khera M. Testosterone therapy in men with untreated prostate cancer. J Urol 2011; 185: 1256–1260
Read more articles of the week

Editorial: Pushing the robot-assisted prostatectomy envelope – to the safety limits? Better outcomes

/by

The present article by Lim et al. [1] describing the new technique for robot-assisted radical prostatectomy is provocative. It really does highlight the dramatic improvement in outcomes of prostate cancer surgery for men over the last 25 years. What used to be a 3-week hospital stay with a 50% incontinence rate and a 100% impotence rate [2, 3] now becomes a day case with a high likelihood of excellent urinary control early after surgery and a fair potential for potency preservation. Twenty-five years ago men who underwent radical prostatectomy were truly brave patients.

Lim et al. report a single series by the senior author of 50 cases performed using the so-called Retzius preservation technique. Their cohort of 50 patients treated this way was compared with a retrospective cohort of the surgeon’s patients. The patients had lower-risk disease and patients who had seminal vesicle invasion or extracapsular extension noted preoperatively, presumably on MRI, were excluded from the series. The authors report a shorter operating time and an earlier return to urinary continence in the first 6 months after surgery.

I guess where surgeons are now taking us is to an attempt to remove the prostate from the hammock of neurovascular, muscular and fascial tissue surrounding it, without disturbing the anatomy [4]. If this can be achieved then radical prostatectomy with minimal morbidity is a very compelling choice for the primary treatment of prostate cancer.

The authors’ hypothesis is that preservation of the levator fascia, puboprostatic ligaments and detrusor apron will fix the bladder somewhat like a sling would, with support at the bladder neck during increased intra-abdominal pressure.

It should be noted, however, that the present paper represents a single series of patients selected after a long learning curve by a very experienced surgeon. These excellent outcomes may simply reflect the fact that the surgeon is now extremely technically capable. It is contentious to assume that a propensity score matching of a retrospective cohort would represent a true comparator to contemporary outcomes. These excellent outcomes probably reflect technical improvements achievable with more risky and innovative surgery – after many cases. The authors should be congratulated on pushing the envelope to achieve even better outcomes for patients undergoing this operation, but the exclusion of patients with high-risk disease is probably the major negative aspect of their report. It has become increasingly obvious that patients with high-risk disease are those who benefit most from radical prostatectomy surgery. Surgery for patients with very-low-risk disease (Gleason 6) is probably unnecessary. Nevertheless, with continued insights such as those provided by these surgeons, we may be able to increase the range of patients to whom Retzius-sparing surgery in higher risk cohorts can be offered.

Read the full article

Anthony J. Costello
Department of Urology, Royal Melbourne Hospital, Parkville, Victoria, Australia

References

  1. Lim SK, Kim KH, Shin T-Y et al. Retzius-sparing Robot-assisted Laparoscopic Radical Prostatectomy – combining the best of retropubic and perineal approaches. BJU Int 2014; 114: 236–244
  2. Wein AJ, Kavousi LR, Novick AC, Partin AW, Peters CA. Campbell-Walsh Urology, 10th edn. Saint Louis, MO: Saunders, 2011: 5688
  3. Catalona WJ, Carvalhal GF, Mager DE, Smith DS. Potency, continence and complication rates in 1,870 consecutive radical retropubic prostatectomies. J Urol 1999; 162: 433–438
  4. Costello AJ, Brooks M, Cole OJ. Anatomical studies of the neurovascular bundle and cavernosal nerves. BJU Int 2004; 94: 1071–1076
Read more articles of the week

Do we really need to show a survival benefit to justify ePLND in prostate cancer?

/7 Comments/by

Whilst extended pelvic lymphadenectomy has become part of standard care in select patients undergoing radical prostatectomy at some centres, it is not universally accepted or performed and remains controversial, so why is this? The most common reasons cited for not performing a node dissection, or at least an extended node dissection, include lack of proven therapeutic benefit and the increased operative time and risk of complications. But do we really need to show a survival benefit to accept the role of extended pelvic lymphadenectomy for patients undergoing radical prostatectomy? It would take a randomised trial run over at least a decade, thousands of patients and untold cost to prove or disprove. Although randomised trials can be invaluable in assessing some aspects of medical or surgical care, they are not always appropriate or even desirable for surgical outcomes as O’Brien et al eloquently illustrated. What’s more, results from RCTs in surgery can be misleading – consider the Prostate Cancer Intervention Versus Observation Trial, in which overall survival at a median follow-up of 10 years was approximately 50% in both arms. This is equivalent to the overall survival in the observation arm of Messing’s trial, in which virtually no patients died of non-prostate cancer causes and contrasts starkly with the current life expectancy of 65 year old males in Australia of 20 years. Patients in PIVOT weren’t living long enough to die from prostate cancer!

There is no doubt that for accurate nodal staging, an extended lymphadenectomy is currently the gold standard, as reflected in the EAU guidelines on prostate cancer. Two very elegant trials in recent years assessed the performance of similar templates in terms of staging accuracy and concluded that a modified extended template struck the right balance between accuracy and risk of complications. Joniau et al, showed in a prospective cohort of 74 patients, around half of whom were lymph node positive, a modified extended template including the pre-sacral nodes had a staging accuracy of 97% and removed 88% of positive nodes. Omitting the pre-sacral nodes accurately staged 94% of patients and removed 76% of positive nodes. Mattei et al concluded that their modified ePLND removed approximately 75% of “sentinel” nodes in a prospective series of 34 node negative patients. Whether a “modified” ePLND or “plain” ePLND is performed, the staging accuracy is significantly better than a “standard” PLND, which omits the nodes around the internal iliac vessels and according to Joniau et al would accurately stage 76% of patients and remove only 29% of positive nodes. A “limited” node dissection, removing only the tissue within the obturator fossa performed even worse, staging 47% and removing just 15% of positive nodes.

 From Mattei et al European Urology 2008, 53:118-125

But what is the real value in accurate nodal staging? Does it change patient management? The Messing trial showed that node positive patients who received adjuvant hormone therapy had improved CSS and OS compared to node positive patients observed until clinical progression. The study, however, has limited application to current real life patient management. Whilst patients with high volume nodal disease are likely to benefit from adjuvant hormone therapy, some patients with node positive disease, particularly those with micro-metastatic disease, will not suffer biochemical progression let alone clinical progression and therefore may not warrant ADT. Furthermore, most patients will be commenced on hormone therapy according to specific PSA criteria long before clinical progression. Despite these apparent weaknesses, the CSS and OS are remarkably similar to many retrospective series of node positive patients outside trials and managed in “real life”. Bader and Schumacher presented series of 92 and 122 node positive patients respectively, none of who received adjuvant hormone therapy. Ten year CSS for both of these series was approximately 60% and 10-yr OS in the Schumacher cohort was 53%, almost identical to the 10-yr OS in the Messing trial. Conversely, a number of retrospective series of node positive patients in which all, or almost all patients received AHT, 10-yr CSS ranged between 74-86% and 10-yr OS was 60 – 67%. These outcomes are similar to the AHT arm in Messing’s trial, in which 10-yr CSS was 85% and 10-yr OS was 75%. This is far from compelling evidence in favour of AHT in node positive patients, but it is certainly food for thought.

Rather than treat all node positive patients equally, however, we should be more sophisticated in our approach. Briganti and Schumacher have shown that patients with 1 or 2 positive lymph nodes have better 10-yr CSS than patients with 3 or more positive nodes whether they receive adjuvant hormone therapy or not. In Schumacher’s series, 10-yr CSS was 72-79% for patients with 1 and 2 positive nodes, versus 33% for patients with 3 or more positive nodes, without AHT. In Briganti’s series, 10-yr CSS for patients with 3 or more positive nodes was 73% and they were almost twice as likely to die from prostate cancer than those with fewer than 3 nodes positive. All patients received AHT. Perhaps then, we should consider patients with higher volume nodal disease on extended pelvic lymphadenectomy for immediate adjuvant hormone therapy, whilst those with micro-metastatic disease may be suitable for observation until predetermined PSA criteria are reached.

Beyond the staging benefit, Jindong et al recently published a prospective, randomised trial showing a BCR free survival benefit for patients undergoing extended versus standard pelvic lymphadenectomy. With a median follow-up of just over 6 years, intermediate risk patients undergoing ePLND had a 12% absolute reduction in biochemical recurrence (73.1% v 85.7%) and high risk patients more than 20% (51.1% v 71.4%) compared to those undergoing a standard node dissection. This may eventually translate into a survival benefit, or at least a clinical progression benefit, but in this cohort of patients, a reduction in biochemical recurrence means a reduction in the numbers requiring salvage radiation therapy and salvage androgen deprivation and the consequent side-effects and complications of these treatments.

It is clear the complication rate following ePLND is higher than with sPLND or no node dissection, but a recent review revealed the difference is accounted for by an increase in the incidence of symptomatic lymphoceles, most of which resolve with conservative management. Ureteric, nerve and major vascular injuries are rare. This would appear to be a much more acceptable complication profile than that following salvage radiotherapy, or androgen deprivation. Although uncommon, membranous urethral stricture following salvage radiation often confers debilitating and enduring morbidity. Continence and potency rates also suffer, not to mention bowel toxicity. A 20% absolute reduction in biochemical recurrence may also swing the pendulum away from adjuvant radiation in high risk disease, benefiting even more patients.

Proving a survival benefit with level 1 evidence is the holy grail of medical and surgical trials, but it is not the only outcome to consider. Biochemical recurrence following radical prostatectomy carries significant psychological burden and salvage therapies can carry significant morbidity. Disease recurrence is most common in the high risk population and there is now level 1 evidence of a real benefit to these patients when ePLND is included as part of their surgical care.

 

Dr Philip E Dundee

Epworth Prostate Centre and The Royal Melbourne Hospital

T: @phildundee

 

Vasectomy causes aggressive prostate cancer – HELP!!!

/7 Comments/by

How many of you have already had a patient get in touch about this latest scare? As one expects nowadays, I first heard about this paper on Twitter within a few minutes of it being published, but it wasn’t long after that a recent patient of mine rang my rooms to challenge me about the reassurance I had given him only last week about the lack of increased risk of prostate cancer, which he had specifically asked me about. And of course since then, we have had headlines in the mass media all over the world alerting us to the results of this 24-year study that suggests that vasectomy confers an increased risk of not just prostate cancer, but high-grade prostate cancer in men undergoing vasectomy. Here are just some of the headlines:

 

So what are we to make of all this? The private vasectomy counselling has always been a challenging area due to the well documented possibilities of early and late failure, and also of the ever present issue of chronic scrotal pain. And while the area of prostate cancer risk has been raised previously, I must say I have always felt comfortable saying that on balance, the increased risk of developing significant prostate cancer following vasectomy proved to be minimal. “Don’t worry about it” was my typical blithe reassurance. Do I have cause to change my advice now?

Let’s look at this paper from Siddiqui et al. The data is taken from the well-known Health Professionals Follow-up Study (HPFUS), which originally enrolled almost 50,000 men aged between 40 and 75 back in 1986. Of these, about 12,000 (25%) underwent vasectomy and 6000 of these (12.2% of population) were subsequently diagnosed with prostate cancer over the 24-year follow-up period. Of these, 811 (1.6%) died of prostate cancer. The authors calculate that vasectomy was associated with a small overall increase in the risk of prostate cancer (RR = 1.10). However the headlines are coming from the higher relative risk of 1.22 among men subsequently diagnosed with high-grade prostate cancer (Gleason 8 to 10). Also, vasectomy appeared to confer a higher relative risk (1.19) of actually dying of prostate cancer or developing distant metastases compared to men who did not undergo vasectomy. It is these findings that vasectomy appears to confer not just an increased risk of prostate cancer, but an increased risk of developing aggressive or a lethal prostate cancer, which has provoked some concern.

This topic is not new and other studies have shown that this risk does not exist or at best, the risk is minimal and the quality of evidence not good enough to change practice. Does this current paper change all that? It will certainly change the nature of counselling for men considering vasectomy as there may well be a case to consider. As the population of men presenting for vasectomy are not a typical population who would be counselled about the early detection of prostate cancer, perhaps this other difficult counselling area also needs to be broached.

HELP!!!!

 

Declan Murphy is a urologist at Peter MacCallum Cancer Centre in Melbourne, Australia, and Associate Editor at BJUI. Twitter @declangmurphy

 

 

© 2024 BJU International. All Rights Reserved.