Tag: PSMA-PET

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Editorial: Preoperative PSMA‐targeted PET imaging: more than just a tool for prostate cancer staging?

July 10, 2019/by Michael Gorin

The presence of lymph node metastases at the time of prostate cancer diagnosis has significant implications for treatment. According to current guidelines from the National Comprehensive Cancer Network, men with positive lymph nodes on initial staging imaging should be offered treatment with androgen deprivation (± abiraterone) along with consideration for external beam radiation therapy [1]. In contrast, men with clinically localised high‐ or very‐high‐risk prostate cancer have the option of undergoing radical prostatectomy. Unfortunately, currently available diagnostic imaging modalities (i.e. contrast‐enhanced CT and MRI) fall short in their ability to accurately identify lymph node metastases, which are often small and difficult to discern from other structures within the pelvis. Thus, there exists a conundrum: if we cannot accurately detect lymph node involvement, how can we appropriately manage it?

In this edition of the BJUI, Leeuwen et al. [2] report on the utility of molecular imaging with ⁶⁸Ga‐PSMA‐11 positron emission tomography (PET)/CT in the preoperative staging of men with prostate cancer. To date, the greatest clinical utility of PSMA‐targeted PET has been in the management of men with biochemically recurrent prostate cancer [3]. In the present study by Leeuwen et al. [2], 140 patients with newly diagnosed intermediate‐ or high‐ risk prostate cancer underwent ⁶⁸Ga‐PSMA‐11 PET/CT before radical prostatectomy with extended pelvic lymph node dissection. Surgical pathology served as the reference standard to which findings on ⁶⁸Ga‐PSMA‐11 PET/CT were compared. In total, 27.1% of men were found to have radiotracer uptake in their pelvic lymph nodes, resulting in a sensitivity of 53% and a specificity of 88%. In contrast, multiparametric MRI had a sensitivity of only 14%, albeit with a higher specificity of 99%. These findings are in line with prior studies evaluating the diagnostic performance of PSMA‐targeted PET imaging for preoperative prostate cancer staging [4]. Of greater interest, however, is the authors’ observation that positivity on ⁶⁸Ga‐PSMA‐11 PET/CT was strongly associated with postoperative PSA persistence (i.e. failure to cure). More specifically, after controlling for Gleason score, surgical margin status, and preoperative PSA level, positivity on PET/CT had an odds ratio of 5.87 (95% CI 1.30–26.59) for biochemical persistence. Furthermore, men with pN1 disease and a positive preoperative PET/CT (i.e. true positives) were over three times more likely to experience biochemical persistence than patients with pN1 disease and negative imaging (71.4% vs 21.4%). Thus, PSMA‐targeted PET not only stands to inform clinical staging, but also has the potential to offer independent prognostic information.

A future line of investigation is to explore the biological basis of the authors’ observation regarding PSMA as a prognostic marker. One explanation is that PET/CT identified men with higher volume lymph node metastases (a known prognostic factor), whilst patients with smaller more curable nodes were negative on imaging. After all, the authors state that the imaging test did not detect any pathologically positive lymph nodes <2 mm. Furthermore, only 27% of positive lymph nodes between 2 and 4 mm showed radiotracer uptake. Unfortunately, the authors did not account for differences in the volume of nodal metastases in their analysis. A second possible explanation for the authors’ observation is that PSMA is upregulated through the same signaling pathways that drive an aggressive prostate cancer phenotype, allowing for PSMA expression to provide prognostic information independent of tumour volume. Indeed, others have previously shown that PSMA expression, as measured by immunohistochemistry, corresponds with increasing tumour grade, stage and risk of biochemical failure [5]. Of course, these concepts are not mutually exclusive and further investigation is needed in order for PSMA‐targeted imaging to be rationally applied as a prognostic test.

References

NCCN Clinical Practice Guidelines in Oncology: Prostate Cancer (Version 4.2018). 2018. Accessed November 2018. Available at: https://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf.
Leeuwen, PJ, Donswijk, M, Nandurkar, R et al. Gallium‐68‐prostate‐specific membrane antigen (⁶⁸Ga‐PSMA) positron emission tomography (PET)/computed tomography (CT) predicts complete biochemical response from radical prostatectomy and lymph node dissection in intermediate‐ and high‐risk prostate cancer. BJU Int 2019; 124: 62– 8
Han, S, Woo, S, Kim, YJ, Suh, CH. Impact of ⁶⁸Ga‐PSMA PET on the management of patients with prostate cancer: a systematic review and meta‐analysis. Eur Urol 2018; 74: 179– 90
Gorin, MA, Rowe, SP, Patel, HD et al. Prostate specific membrane antigen targeted ¹⁸F‐DCFPyL positron emission tomography/computerized tomography for the preoperative staging of high risk prostate cancer: results of a prospective, phase II, single center study. J Urol 2018; 199: 126– 32
Minner, S, Wittmer, C, Graefen, M et al. High level PSMA expression is associated with early PSA recurrence in surgically treated prostate cancer. Prostate 2011; 71: 281– 8

Capitalising On Our Strengths: The 70th USANZ ASM

March 14, 2017/by admin Z.9

Canberra, our nation’s capital and the host city for the 2017 USANZ ASM, is a gem in its own right, but one which was created to satiate two feuding states locked in a bitter rivalry. In 1908, Canberra embodied the very meaning of compromise and collaboration, a technique which has garnered much success for our Country over the ensuing 100 odd years. Arguably the first official Australian collaborative effort, this way of thinking has become an almost uniquely Australian attribute and a strength imbued in our national pride.

Canberra from up high, a breathtaking backdrop for a fantastic USANZ ASM.

Given this year’s mantra of: “Capitalising on our strengths” It is perhaps fitting then, that the 70^th anniversary of the Urological Society of Australia and New Zealand (USANZ) Annual Scientific Meeting (ASM) including the Australia and New Zealand Urological Nurses Society (ANZUNS) 22^nd ASM, should be held in such a location. In addition to providing some wonderful tourist opportunities for guests including the War Memorial, the National Gallery and Parliament House.

Convenors A/Prof Nathan Lawrentschuk and Kath Schubach went to great efforts to successfully welcome both national and international guests and Scientific Program Directors A/Prof Shomik Sengupta and Carla D’Amico ensured a star-studded academic program addressing contemporary updates in Urological evidence based practice, which were aptly discussed both inside and outside the confines of the National Convention Centre.

Senior YURO members standing outside Parliament House (from left to right): Dr. Daniel Christidis, Dr. Tatenda Nzenza, Dr. Todd Manning, Dr. Shannon McGrath

The representation by International faculty was exceptional, with countless urological household names from world leading centres across the globe both involved in the academic program and socially. Urological goliaths including Prof. Christopher Chapple, Prof. Prokar Dasgupta and Prof. Laurence Klotz weighed in on various topical issues providing an intercontinental perspective that complimented the equally impressive national line-up of speakers.

As with previous years, use of social media was rife, with those not able to attend kept in the loop via #Usanz17 and a steady stream from the ever focused twitterati. The ASM provided more than 5 million impressions and over 2800 individual tweets from more than 400 participants. The usual suspects were eminent as always, along with a few newcomers who provided impact in their own right. The official USANZ 2017 App also kept participants up to date via timely notifications and was user friendly.

Guests were spoilt for choice in the convention centre during well timed breaks, which was perpetually abuzz with attendees networking. In the background the ‘Talking Urology’ team headed by Mr Joseph Ischia and A/Prof Nathan Lawrentschuk provided a steady stream of captivating interviews with guests, regarding a myriad of urological topics. Simultaneously, numerous academics gave brief summaries of research posters during allocated presentation sessions. Exhibitors provided a captivating backdrop for these activities including many hands-on simulators and challenges for those keen to test their dextrous mettle. All the while guests relished a variety of delectable culinary options.

Guests networking at the Gala Dinner, whilst being entertained by opera classics in the Great Hall foyer of Parliament House

The meeting’s common themes were strong and pertinent to contemporary urology. They centred around collaborative research efforts such as the ANZUP trials group and the Young Urology Researchers Organisation (YURO), technology especially PSMA PET and social media and social justice including women in urology and operating with respect. Discussions were directed by chairpersons during purposefully allocated Q&A times at the conclusion of each session, a new and well received addition to this years meeting. This was generously embraced by both senior and junior academics and led to intriguing symposiums and at times heated debate.

USANZ 2017 Friday Highlights

The first official day of proceedings provided a smorgasbord of morning and afternoon workshops ranging from technical skills courses to the medico-legal implications of E-Health and technology. This was followed by an allocated networking session for Urology trainees with International faculty.

Officially opening the conference in the Royal Theatre of the convention centre, A/Prof Lawrentschuk introduced this year’s Harry Harris orator; Elizabeth Cosson, AM CSC. Her speech entitled “leading with grit and grace” eloquently detailed her journey in the armed forces and highlighted the difficulties of the unmistakably imbalanced workplace for women in the military. Her talk clearly underlined her role in not only forging a highly successful career for herself but also for those women following in her footsteps. Her inspiring dialogue was synchronous with contemporary issues surrounding Urological practice, especially concerning equality for women but more resolutely, appropriate equity both in training and established practice.

With the tone well established for an exceptional meeting, guests enjoyed a variety of canapés and drinks in the exhibition hall, unwinding with social discussion.

YURO President, Dr Todd Manning talks to young researchers with help from Prof. Henry Woo and A/Prof. Lawrentschuk during the YURO annual meeting

Saturday Highlights

Plenary sessions aplenty began the second day of proceedings with International academic giants including Prof. Klotz, Prof. Chapple, Prof. Traxer and Prof Nitti mixed in with National heavy hitters such as Prof Frank Gardiner, Mr Daniel Moon and outgoing USANZ president Prof. Mark Frydenberg.

Afternoon sessions included subspecialty discussions and some stellar Podium Poster presentations, with an especially impressive mix of senior and junior researchers regarding countless and diverse urological topics.

Sunday Highlights

Heralding the beginning of another exceptional day, the ‘Women in Urology’ breakfast symposium chaired by Dr Anita Clark along side distinguished panellists including Dr Caroline Dowling and Dr Eva Fong was a conference stand out for many.

Following this, more plenary sessions filled the remainder of the pre-lunch program, leading into the highly anticipated Keith Kirkland and Villis Marshall presentations by Urology SET trainees. The presentations did not disappoint. As in previous years, research of unyielding professional and academic quality was offered by the group of future urologists, who as is tradition weathered the gauntlet of probing and tough questions from the floor. All presentations were captivating in their own right. 2017 Villis Marshall winner Dr Marlon Perera presented ground-breaking research regarding the reno-protective role of zinc in contrast nephropathy. Dr Amila Siriwardana was deservedly awarded the Keith Kirkland award for his multicentre retrospective review on Robot assisted salvage node dissection to treat recurrences detected by PSMA PET.

Following these presentations, the YURO annual meeting once again heralded a complement of enthusiastic, innovative and clever minds from all Australian states, eager to pursue research opportunities through collaborative means. Joined this year by Prof. Henry Woo, the group was fortunate to receive his valuable insight and feedback regarding past success and future direction. The group solidified upcoming positions of leadership and highlighted new directions in educational, research and mentorship avenues for younger members.

The Gala Dinner is a stand out affair during each ASM and this year was no exception. Guests were provided with the unique opportunity to see Australia’s Parliament House from the inside. The night began with surprise operatic renditions of many well known classics in the spacious foyer of the Great Hall and culminated with a climactic performance of Nesson Dorma. Guests then enjoyed a delectable 3 course meal in identical fashion to a rare collection of political royalty including; Barack Obama, Prince William and the Duke and Duchess of Cambridge.

Twitter metrics tabulated from the conference via the #Usanz17 (courtesy of Symplur LLC)

Monday Highlights

The final day of proceedings saw once again provided an array of interesting and thought provoking topics. The clear highlight of the morning was the metaphorical prize fight between Mr Joseph Ischia and Dr Shankar Siva debating the roles of surgery and radiotherapy in Oligometastatic disease. Although these two went toe to toe over many rounds, the inevitable conclusion was understandably a draw. Although on PowerPoint slide pictures alone, Dr Siva’s extensive use of Star Wars based analogies won my vote.

Insight and introduction to the 71^st USANZ ASM was then delivered and as a Melbournian my bias was admittedly hard to hide. Attendees received a taste of the excitement to come, with what is assured to be another blockbuster cast of national and international urologists led boldly by Convenor Mr Daniel Moon and Scientific Program Director Prof. Declan Murphy. I for one, eagerly anticipate the return of the ASM to out Nation’s culinary and cultural capitol and I’m sure guests in 2018 will be captivated by the world most liveable city!

It can be said with certainty that this years USANZ 70^th ASM presented a scientific program as strong as ever within a fascinating and historical backdrop and complimented by a lively social atmosphere. This consensus of a highly successful meeting, I’m sure was shared by all.

I look forward to seeing you all next year and hope you are eagerly anticipating the ‘flat whites’.

Dr. Todd G Manning, Department of Surgery, Austin Health, Melbourne, and Young Urology Researchers Organisation (YURO), Australia. Twitter: @DocToddManning

EAU 2016 Congress Day 3

March 18, 2016/1 Comment/by Kari Tikkinen

Das bringt mich weiter! While the sun was shining in Munich, the 3^rd day of the 31^st EAU Annual Congress continued with very well attended plenary and poster sessions. And that is no wonder because the EAU Scientific Committee had created such an attractive program, including amazing plenary sessions during the morning and a plethora of informative poster sessions in the afternoon.

Professor Hendrik Borgmann (@HendrikBorgmann) has already covered highlights of the opening days 1 and 2 of this year’s Congress in his BJUI blog. We will give you some highlights of Day 3 and highly recommend you to take a look on EAU congress website, Day 3, which has archived a huge amount of material to allow you to catch up on sessions you may have missed. Indeed, lots of webcasts are available!

We focused on non-oncology plenary morning sessions and oncology poster sessions afternoon. Here are some of our highlights:

SURGERY IN THE ELDERLY – As our urological patients become older and older, surgery for octogenarians, or even nonagenarians, is increasingly common. The morning session covered various aspects on diagnosis and treatment of benign prostatic hyperplasia and other urological conditions in the ageing patient.

Professor Cosimo De Nunzio began the morning with “Highlights” on lower urinary tract symptoms and prostatic disease presented during this year’s EAU congress. Also this year, as many as every third abstract was on either prostate cancer or prostatic hyperplasia.

Indeed, the plenary session on Day 3 also covered prostatic disease.

Professor Alexander Bachmann talked about surgery for BPO in the elderly. He pointed out that in elderly (high-risk) patients we do not need a complete anatomical tissue removal, we do not need a (very) long-term follow-up and that we do not need tissue for prostate cancer diagnosis. Instead, we need a safe and efficient operation with individual adaptation of the technique and preferably feasibility in an ambulatory setting or local anaesthesia.

Professor Bachmann further emphasized that it would be preferable if surgery for the elderly would be performed by experienced surgeons, and that age per se is not a reason to not operate. There are several new minimally invasive operations available, and especially for elderly less is often more.

HOW AND WHEN TO STOP ANTICOAGULATION – Managing perioperative thromboprophylaxis for patients who already receive anticoagulants remains a challenge. Associate professor Daniel Eberli and Professor Per Morten Sandset covered many of these aspects in their helpful presentations.

Dr. Eberli told us that bridging therapy (options for stopping or not stopping anticoagulation in the above figure) is eminence-based, as no papers exist showing benefits. He also presented data from the recent NEJM trial (BRIDGE study; see Table below), which showed that stopping anticoagulation without bridging was non-inferior to perioperative bridging for the prevention of arterial thromboembolism and decreased the risk of major bleeding.

Dr. Eberli gave us all a take home message to discuss and question our local bridging guidelines as new evidence is very likely not supporting them (concluding slide below).

Professor Sandset recommended that during the perioperative period only use aspirin in high-risk patients, that is, those with recent thrombotic event or extensive coronary heart disease. He also informed us that stopping antiplatelet therapy 5 days before surgery (figure below) is often the way to go, and agreed with Dr. Eberli regarding bridging therapy statements.

Professor Sandset also gave helpful information regarding use of direct oral anticoagulants (DOACs) in urological surgery:

There were numerous poster sessions available on Day 3, as usual, many of them on prostate cancer. We have selected some of the highlight abstracts presented.

PROSTATE CANCER – On Day 3, prostate cancer presentations dominated once again in a number of poster, abstract and thematic sessions but also kidney, bladder, testicular and penile cancer sessions, which provided new interesting data.

Molecular markers, genomic profiling and individualized risk and treatment assessments were presented and discussed in poster session 58, and summarized by Stacy Loeb (@LoebStacy). Further advances in prostate cancer biomarkers in prostate cancer were presented in poster session 84. These new tools are moving from bench to bedside and urologists can hopefully incorporate these new tools to cancer care sooner rather than later.

In sessions on prostate cancer diagnostics, more advanced risk profiling tools were highlighted. For instance, STHLM3 test combines history of the patient, clinical parameters, biochemical markers and genetic markers. It was presented earlier in the congress and on Day 3 further health, economic and clinical evaluations were presented in Thematic session 12. It is one example of the tests showing promising results to potentially decrease the number of prostate biopsies needed. Other similar risk profiling tools were also presented during the congress. In addition to PSA only, evaluation of the smart use of already available clinical and biochemical parameters and the combination of genetic markers may bring individualized risk assessment of prostate cancer to the next level.

In poster session 62 on Day 3, diagnostic proceedings in prostate cancer with co-morbidity evaluation, biopsy strategies and MRI imaging were presented. A combination of molecular markers and imaging may be the way to proceed in future. These aspects were covered nicely in Thematic session 12.

MRIs have been heavily integrated in prostate cancer diagnostics during recent years. Image guidance in prostate biopsies seem to be making a breakthrough in prostate cancer diagnostics. Targeted biopsies with cognitive or MRI-TRUS fusion imaging were shown to be the way to enhance the results and reliability of biopsies and cut down the number of biopsies. However, as biopsies are still needed in prostate cancer diagnostics, use of the pre-biopsy MRI protocols were suggested to be done only in clinical trial setting. Many aspects of MRI diagnostics of prostate cancer were elegantly summarized in Thematic session 11.

New sophisticated imaging technologies in addition to MRI were present in several sessions during the meeting. Diagnostic enhancement has been seen also in metastatic prostate cancer. PSMA-PET seems to be replacing choline-PET-TT in evaluation of relapsing and metastatic prostate cancer (e.g. Thematic session 10). More reliable diagnostics and imaging of prostate cancer are also enhancing the treatment decision and treatment choice of patients with local prostate cancer. Finding the right patients for the active surveillance protocols is also being helped with advanced diagnostics. Indeed, finding only patients who need treatment for prostate cancer should be the ultimate goal for enhanced diagnostics as discussed in poster sessions 66 and 75 on Day 3. There are also high expectations on focal therapy (e.g. poster session 66), which at the moment is still experimental but will likely be a real option for patients with low volume prostate cancer verified by imaging.

The role of quality of life evaluations and patient reported outcomes measured were heavily discussed during the congress in all treatment modalities of both local and advanced prostate cancer. Survivorship issues are an increasingly important issue when more effective treatments both in local and advanced prostate cancer are available.

In metastatic disease, the use of early chemotherapy in combination with hormonal treatment has been implemented very rapidly to clinical use after the results of the CHAARTED and STAMPEED studies. Further evaluation of early chemo in metastatic disease is still needed and the patient selection needs still clarification. Hormonal therapy still has a very marked role in metastatic prostate cancer and new advances can also be found in new strategies of using castration therapy as presented in poster session 67. Urologists should actively follow the changing landscape of the medical treatment of metastatic prostate cancer and be active in treatment planning and treatment of these patients. At the same time with poster session 62 novel drugs and new forms of isotope radiation therapy in castration resistant prostate cancer were discussed in poster session 61. These open new possibilities for potential treatments.

The clinical and scientific content of the program of the Day 3 was of a very high standard, and reflective of the breadth of contemporary research in many areas within urology. Besides this session, it was our pleasure to meet old and new urological friends worldwide. The annual EAU meeting remains a highly effective method of knowledge translation and provides the opportunity for collaboration between surgeon scientists and other researchers in the field. As always in big congresses, there are so many interesting sessions going on at the same time, that it is hard to pick up and follow everything you would like to. We hope that this report provides some memories and take home messages of the Day 3 to the readers of the BJUI and BJUI blogs.

We look forward to future BJUI and EAU happenings!

Kari Tikkinen

Urology resident, adjunct professor of clinical epidemiology

Helsinki University Hospital, Helsinki, Finland

@KariTikkinen

Mika Matikainen

Chief of urology, adjunct professor of urology