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Article of the month: Long‐term oncological and functional follow‐up in low‐dose‐rate brachytherapy for PCa: results from the prospective nationwide Swiss registry

Every month, the Editor-in-Chief selects an Article of the Month from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to this post there is also an Editorial written by a prominent member of the urological community and a visual abstract created by Cora Griffin at King’s College London. We invite you to use the comment tools at the bottom of each post to join the conversation. 

If you only have time to read one article this month, we recommend this one. 

Long‐term oncological and functional follow‐up in low‐dose‐rate brachytherapy for prostate cancer: results from the prospective nationwide Swiss registry

Pascal Viktorin-Baier*, Paul M. Putora‡§, Hans-Peter Schmid*, Ludwig Plasswilm‡§, Christoph Schwab*, Armin Thoeni, Werner Hochreiter**, Ladislav Prikler††, Stefan Suter‡‡, Patrick Stucki, Michael Müntener§§, Nadja Blick§§, Hans Schiefer, Sabine Güsewell¶¶, Karin Zürn* and Daniel Engeler*

*Department of Urology, St. Gallen Cantonal Hospital, St. Gallen, Urology Clinic, Cantonal Hospital Lucerne, Lucerne, Department of Radiation Oncology, St. Gallen Cantonal Hospital, St. Gallen, §Department of Radiation Oncology, University of Berne, Clinic for Radiation-Oncology, Lindenhof Hospital Berne, Berne, **Urology Clinic, Hirslanden Clinic Aarau, Aarau, ††Urology Clinic, Uroviva Clinic Buelach, Buelach, ‡‡Urology Clinic Zug, Zug, §§Urology Clinic, Triemli Hospital, Zurich, and ¶¶Clinical Trial Unit, St. Gallen Cantonal Hospital, St. Gallen, Switzerland

Abstract

Objective

To evaluate the long‐term oncological, functional and toxicity outcomes of low‐dose‐rate brachytherapy (LDR‐BT) in relation to risk factors and radiation dose in a prospective multicentre cohort.

Patients and Methods

Data of patients from 12 Swiss centres undergoing LDR‐BT from September 2004 to March 2018 were prospectively collected. Patients with a follow‐up of ≥3 months were analysed. Functional and oncological outcomes were assessed at ~6 weeks, 6 and 12 months after implantation and annually thereafter. LDR‐BT was performed with 125I seeds. Dosimetry was done 6 weeks after implantation based on the European Society for Radiotherapy and Oncology recommendations. The Kaplan–Meier method was used for biochemical recurrence‐free survival (BRFS). A prostate‐specific antigen (PSA) rise above the PSA nadir + 2 was defined as biochemical failure. Functional outcomes were assessed by urodynamic measurement parameters and questionnaires.

Results

Of 1580 patients in the database, 1291 (81.7%) were evaluable for therapy outcome. The median (range) follow‐up was 37.1 (3.0–141.6) months. Better BRFS was found for Gleason score ≤3+4 ( = 0.03, log‐rank test) and initial PSA level of <10 ng/mL ( < 0.001). D’Amico Risk groups were significantly associated with BRFS ( < 0.001), with a hazard ratio of 2.38 for intermediate‐ and high‐risk patients vs low‐risk patients. The radiation dose covering 90% of the prostate volume (D90) after 6 weeks was significantly lower in patients with recurrence. Functional outcomes returned close to baseline levels after 2–3 years. A major limitation of these findings is a substantial loss to follow‐up.

Conclusion

Our results are in line with other studies showing that LDR‐BT is associated with good oncological outcomes together with good functional results.

Editorial: Low-dose-rate brachytherapy for prostate cancer stands the test of time – the Swiss experience

The clinical results from 12 Swiss centres reaffirm the benefits of Low Dose Rate Brachytherapy (LDR-BT) for the treatment of localised prostate cancer [1]. The authors are to be commended for collating and analysing prospective, countrywide, long-term data. This is an excellent example of Good Clinical Practice for the urology community, patients, commissioning groups and for governance purposes. Prostate brachytherapy offers suitable men with prostate cancer a high chance of long-term cure but with a low risk of urinary incontinence and most retaining erectile dysfunction [2].

Two thirds of the patients reported in the Swiss series had low-risk cancer who would now more commonly be offered active surveillance as an initial treatment option. However our own and other large mature series have shown similar treatment efficacy of LDR-BT, either as monotherapy as in the Swiss study, or as a boost to external-beam radiotherapy, for the treatment of patients with intermediate and high risk of disease relapse [3, 4]. Indeed the ASCENDE-RT trial recently showed that men with unfavourable intermediate or high-risk prostate cancer randomised to an LDR-BT boost arm, relative to a dose-escalated external-beam radiotherapy boost, were twice as likely to be free of biochemical failure at a median follow-up of 6.5 years. A slight increase in urinary toxicity was observed which may have been an issue related to implant technique [5].

The authors show LDR-BT affords excellent disease control that associates with post-implant dosimetry in keeping with current treatment guidelines. They also report an association between biochemical control and seed loss. It therefore becomes unclear the extent to which implant quality or implant technique, i.e. the use of loose or stranded seeds, influenced the oncological outcome, as it would appear that more than one brachytherapy technique has been used.

In this series no prostate cancer-related deaths were reported. However the median follow-up length of 37 months is relatively short. Examples from more mature series show longer follow-up is needed to begin to document the low rates of prostate cancer-related deaths following LDR-BT. Lazarev et al [6] in a similar risk group distribution to the Swiss population, reported 97% prostate cancer-specific survival at 17-years with all deaths occurring more than 10 years after treatment. Morris et al [4] reported 99.1% cause-specific survival at 10 years with death events 9 years after treatment in low and intermediate-risk disease. Our own series showed 98% prostate-cancer-specific survival at 7 and 9 years post-implantation in high-risk (as defined by NICE) patients treated with monotherapy [3].

Treatment-related toxicity assessments in the Swiss series showed that baseline values are crucial to understand the impact of treatment on patient-reported outcomes. Higher post-implant scores were consistently observed in those patients with higher baseline scores. The patient-reported outcomes were similar to those from our series where sexual potency was preserved in 70-80% of men who were ≤60 years old at time of implant [7].

Salvage therapies are seldom given after LDR-BT as the local failure rate is low and the surgery complex. It was undertaken in only two patients in the Swiss series. In the era of mp-MRI and PSMA PET/CT scans and targeted biopsies, tumour recurrence can be better assessed.  Salvage surgery has been offered to approximately 0.5% (27/4200) of our patients, by either robotic-assisted radical prostatectomy or seminal vesiculectomy if the recurrence is localised to the seminal vesicle alone.

This nation-wide report from the 12 Swiss centres is a welcome addition to the extensive body of evidence that attests to the excellent results and generalisability of prostate LDR-BT. The treatment is efficacious and convenient for patients with a low toxicity profile. It is a cost effective option that should be offered to all suitable patients with localised prostate cancer.

by Stephen Langley

References

1. Viktorin-Baier P, Putora PM, Schmid HP, et al. Long-term oncological and functional follow-up in low-dose-rate brachytherapy for prostate cancer: results from the prospective nationwide Swiss registry. BJU Int 2020: 125(6).

2. Punnen S, Cowan JE, Chan JM, Carroll PR, Cooperberg MR. Long-term health-related quality of life after primary treatment for localized prostate cancer: results from the CaPSURE registry. European urology 2015; 68: 600-608.

3. Laing R, Uribe J, Uribe-Lewis S, et al. Low-dose-rate brachytherapy for the treatment of localised prostate cancer in men with a high risk of disease relapse. BJU Int 2018; 122: 610-617.

4. Morris WJ, Keyes M, Spadinger I, et al. Population-based 10-year oncologic outcomes after low-dose-rate brachytherapy for low-risk and intermediate-risk prostate cancer. Cancer 2013; 119: 1537-1546.

5. Morris WJ, Tyldesley S, Rodda S, et al. Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy (the ASCENDE-RT Trial): An Analysis of Survival Endpoints for a Randomized Trial Comparing a Low-Dose-Rate Brachytherapy Boost to a Dose-Escalated External Beam Boost for High- and Intermediate-risk Prostate Cancer. Int J Rad Onc Bio Phys 2017; 98: 275-285.

6. Lazarev S, Thompson MR, Stone NN, Stock RG. Low-dose-rate brachytherapy for prostate cancer: outcomes at >10 years of follow-up. BJU Int 2018; 121: 781-790.

7. Langley SEM, Soares R, Uribe J, et al. Long-term oncological outcomes and toxicity in 597 men aged ≤60 years at time of low-dose-rate brachytherapy for localised prostate cancer. BJU Int 2018; 121: 38-45.

Visual abstract: Long-term oncological and functional follow-up in low dose rate brachytherapy for PCa: results from the prospective nation-wide Swiss Registry

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COVID-19 and Prostate Cancer — Challenges and Solutions

The numbers are staggering. As of the date of this brief commentary, the World Health Organization has reported more than 4.6 million cases and upwards of 311,840 deaths worldwide from the COVID-19 pandemic. The virus responsible for the disease known as COVID-19, SARS-CoV-2, is highly infectious and the risks are clearly significant for nearly everyone. Nonetheless, the risk is much higher for some of us than for others. In particular, we have begun to understand the distinct risks faced by men with prostate cancer and the unique intersection of biological, health, and lifestyle factors in COVID-19 and prostate cancer. Although there is a great deal yet to be learned, there are indeed many aspects of the overlap between COVID-19 and prostate cancer that we have already been able to discern and which we have begun to address. Perhaps most striking, older men who are at greatest risk for prostate cancer may also be at greatest risk for COVID-19. 

New York City

Biology Makes a Difference – COVID-19 and prostate cancer share some common biological features. A gene responsible for male traits or characteristics, the androgen receptor, which is dysregulated or impaired in prostate cancer, is also important in COVID-19. Androgens can suppress the body’s immune response to infections and may explain the reason for higher rates of infection in men.  At the same time, a gene known as TMPRSS2 is also highly expressed in both COVID-19 and prostate cancer. In fact, these issues may be related—more androgens could signify greater expression of TMPRSS2 which could create greater susceptibility to the virus. These biological risks are compounded by a number of critical health conditions and lifestyle issues.

Common Risk Factors – Studies from around the world have shown that several chronic health conditions or comorbidities create greater risk for contracting the virus, becoming more severely ill, or dying from COVID-19. It is indeed concerning that many of these are the same risks we see in prostate cancer: hypertension, diabetes, COPD, and obesity. Prostate cancer patients with multiple comorbid conditions may be at even greater risk. Cancer patients in general have weakened immune systems which makes them more vulnerable to infectious disease, further compounding the unique factors affecting men with prostate cancer. Some of the lifestyle factors that may contribute to chronic health conditions also appear to be risk factors for COVID-19 infection, most importantly smoking and high levels of alcohol consumption. We are especially concerned about men who are active smokers, as smoking has been clearly linked to worse outcomes in men who have become ill with COVID-19. We believe that the guidance we generally offer to prostate cancer patients is as, if not more, relevant now in this time of the COVID pandemic—adopt healthy habits, including smoking cessation, a nutritious diet, exercise, and proper management of chronic conditions most notably diabetes.

Looking Ahead – As the pandemic evolves and we look to the future, we are focused on ways to prevent the spread of infection and to create viable treatments for those who become ill. Worldwide, more than nine million men currently face decisions about biopsy, active surveillance, surgery, radiation, hormonal therapy, or chemotherapy related to prostate cancer in the context of COVID-19 and another 3 million more will find themselves facing these decisions by the end of this year. We are working intensely to address their needs. More than 1,460 clinical trials are underway to test therapeutic interventions to treat COVID-19. What we have come to understand about the shared biology between COVID-19 and prostate cancer and common risk factors will be invaluable. We must learn everything we can about the ways in which the virus impacts lung function as it relates to prostate cancer—the respiratory symptoms that result from infection have been especially lethal—and continue to explore the role of androgens in response to new drugs. Many drugs originally intended and approved for other uses are being tested for potential “repurposing” and new drugs and vaccines are under investigation. New clinical guidelines have been established for the treatment of prostate cancer patients at risk of or for those who have contracted the virus, and these guidelines will continue to evolve and be updated.

A Global Perspective – It is critical that we understand the COVID-19 pandemic both on the level of individual experience and global impact. For prostate cancer patients, this means recognizing the way that biology, related chronic health conditions, and lifestyle choices come together to impact the risk of disease, disease severity, and outcomes. Prostate cancer patients and their doctors must come together to find the way forward during this time of unprecedented crisis and opportunities for improving outcomes and quality of life for prostate cancer patients.

Ash Tewari, Zach Dovey and Dimple Chakravarty

Article of the week: Prostate cancer in kidney transplant recipients – a nationwide register study

Every week, the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to this post, there is an editorial written by a prominent member of the urological community and a video produced by the authors. Please use the comment buttons below to join the conversation.

If you only have time to read one article this week, we recommend this one. 

Prostate cancer in kidney transplant recipients – a nationwide register study

Ola Bratt*, Linda Drevin, Karl-Göran Prütz§, Stefan Carlsson, Lars Wennberg** and Pär Stattin††

*Department of Urology, Institute of Clinical Science, Sahlgrenska Academy, Gothenburg University, Department of Urology, Sahlgrenska University Hospital, Gothenburg, Regional Cancer Centre, Uppsala-Orebro, Uppsala, §Swedish Renal Registry, Ryhov Hospital, Jönköping, Section of Urology, Department of Molecular Medicine and Surgery, Karolinska Institute, **Department of Transplantation Surgery, Karolinska University Hospital, Stockholm, and ††Department of Surgical Sciences, Uppsala University, Uppsala, Sweden

Read the full article

Abstract

Objective

To investigate whether post‐transplantation immunosuppression negatively affects prostate cancer outcomes in male kidney transplant recipients.

Patients and Methods

We used the Swedish Renal Register and the National Prostate Cancer Register to identify all kidney transplantation recipients diagnosed with prostate cancer in Sweden 1998–2016. After linking these registers with Prostate Cancer Database Sweden (PCBaSe), a case‐control study was designed to compare time period and risk category‐specific probabilities of a prostate cancer diagnosis amongst kidney transplantation recipients versus the male general population. The registers did not include information about the specific immunosuppression agent used in all transplantation recipients. Data from PCBaSe were used to compare prostate cancer characteristics at diagnosis and survival for patients with prostate cancer with versus without a kidney transplant. Propensity score matching, Cox regression analysis and Fisher’s exact test were used and 95% confidence intervals (CIs) calculated.

 

Prostate cancer‐specific and overall survival for all 133 Swedish men who were diagnosed with prostate cancer after kidney transplantation between 1998 and 2016, and a control group of 665 men with prostate cancer without a kidney transplant, matched for age, year of prostate cancer diagnosis, educational duration, and county of residence. The curves were constructed with the Kaplan–Meier method. There was no evidence for a difference in cancer‐specific survival (log‐rank test: P = 0.37), but overall survival was shorter (log‐rank test: P = 0.003). KT, kidney transplantation; PC, prostate cancer.

Results

Almost half of the 133 kidney transplantation recipients were transplanted before the mid‐1990s, when PSA testing became common in cancer centers. The transplant recipients were not more likely than age‐matched control men to be diagnosed with any (odds ratio [OR] 0.84, 95% CI 0.70–0.99) or high‐risk or metastatic prostate cancer (OR 0.84, 95% CI 0.62–1.13). None of the ORs for the different categories of prostate cancer increased with time since transplantation. Cancer characteristics at the time of diagnosis and cancer‐specific survival were similar amongst transplant recipients and the control group of 665 men diagnosed with prostate cancer without a kidney transplant.

Conclusions

This Swedish nationwide, register‐based study gave no indication that immunosuppression after kidney transplantation increases the risk of prostate cancer or adversely affects prostate cancer outcomes. The study suggests that men with untreated low‐grade prostate cancer can be accepted for transplantation.

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Video: Prostate cancer in kidney transplant recipients – a nationwide register study

:

Prostate cancer in kidney transplant recipients – a nationwide register study

Abstract

Objective

To investigate whether post‐transplantation immunosuppression negatively affects prostate cancer outcomes in male kidney transplant recipients.

Patients and Methods

We used the Swedish Renal Register and the National Prostate Cancer Register to identify all kidney transplantation recipients diagnosed with prostate cancer in Sweden 1998–2016. After linking these registers with Prostate Cancer Database Sweden (PCBaSe), a case‐control study was designed to compare time period and risk category‐specific probabilities of a prostate cancer diagnosis amongst kidney transplantation recipients versus the male general population. The registers did not include information about the specific immunosuppression agent used in all transplantation recipients. Data from PCBaSe were used to compare prostate cancer characteristics at diagnosis and survival for patients with prostate cancer with versus without a kidney transplant. Propensity score matching, Cox regression analysis and Fisher’s exact test were used and 95% confidence intervals (CIs) calculated.

Results

Almost half of the 133 kidney transplantation recipients were transplanted before the mid‐1990s, when PSA testing became common. The transplant recipients were not more likely than age‐matched control men to be diagnosed with any (odds ratio [OR] 0.84, 95% CI 0.70–0.99) or high‐risk or metastatic prostate cancer (OR 0.84, 95% CI 0.62–1.13). None of the ORs for the different categories of prostate cancer increased with time since transplantation. Cancer characteristics at the time of diagnosis and cancer‐specific survival were similar amongst transplant recipients and the control group of 665 men diagnosed with prostate cancer without a kidney transplant.

Conclusions

This Swedish nationwide, register‐based study gave no indication that immunosuppression after kidney transplantation increases the risk of prostate cancer or adversely affects prostate cancer outcomes. The study suggests that men with untreated low‐grade prostate cancer can be accepted for transplantation.

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Article of the week: Using data from an online health community to examine the impact of prostate cancer on sleep

Every week, the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to this post, there is an editorial written by a prominent member of the urological community. Please use the comment buttons below to join the conversation.

If you only have time to read one article this week, we recommend this one. 

Using data from an online health community to examine the impact of prostate cancer on sleep

Rebecca Robbins*, Girardin Jean‐Louis, Nicholas Chanko, Penelope Combs, Nataliya Byrne†‡, Stacy Loeb†‡

*Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA, Department of Population Health, New York University (NYU) School of Medicine, and Department of Urology, NYU School of Medicine and Manhattan Veterans Affairs, New York, NY, USA

Read the full article

Previous epidemiological studies have examined the relationship between sleep disturbances and prostate cancer risk and/or survival. However, less has been published about the impact of sleep disturbance on quality of life (QoL) for prostate cancer survivors and their in home caregiver. Although prostate cancer presents numerous potential barriers to sleep (e.g., hot flashes, nocturia), current survivorship guidelines do not address sleep. In addition to its impact on QoL, sleep disturbances also mediate the impact of cancer status on missed days from work and healthcare expenditures.

A broader examination of contributors to poor sleep in prostate cancer, and the impact on patients and caregivers would be an important contribution to raise awareness of these issues in the medical community, improve survivorship care, reduce healthcare costs, and stimulate future research. The objective of our letter is to analyse sleep barriers reported by patients with prostate cancer and caregivers posted to a large online health community. You can check lot of article on coolsculptny related to health.

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Editorial: The provision of comfort – addressing barriers to sleep in prostate cancer

“In whatever disease sleep is laborious, it is a deadly symptom,” is a famed aphorism by Hippocrates, because he deeply understood the role of sleep in the process of healing. One of the main goals of any comprehensive cancer management plan should be the provision of comfort. In academic literature, discussions of advances in prostate cancer treatment are often limited to novel therapeutics, such as immunotherapy. What gets often ignored in these discussions is the patient’s perspective—especially that of sleep disturbances. This is why an intriguing qualitative analysis in this BJUI issue by Robbins et al is a refreshing read [1]. The authors examined discussions on an online health community to elucidate the barriers to sleep among prostate cancer patients and caregivers.

Parsing through thousands of anonymized public comments, the authors report several interesting findings: one, majority of comments related to sleep (86%) are posted by patients—signifying high interest in this aspect of management; second, a plurality of comments discuss sleep medications (22%), with comments about advanced disease discussing these medications three times more than those discussing localized disease; third, associated side effects of fatigue and pain were largely observed in advanced disease comments, according to Discover Magazine many people is using this website https://observer.com/2020/05/best-cbd-hemp-flower/ to buy CBD and reduce the pain cause by the disease . Interestingly, the authors also used Linguistic Inquiry Word Count (LIWC) software—a reasonable tool to assess emotional states—and reported that advanced disease comments were significantly more negative in perspective than localized disease comments. This analysis is an especially useful contribution—and should enable contemporary Prostate Cancer Survivorship Care Guidelines to expand on the impact of sleep disturbances [1].

These findings have considerable implications. To start with, these findings need to be contextualized within the larger body of evidence we have on impact of sleep disturbances on prostate cancer. In a recent study, Markt et al prospectively followed 32,141 men (with 4261 prostate cancer cases) using the Health Professionals Follow-Up Study (HPFS), and found no association between self-reported duration of sleep and prostate cancer outcomes [2]. However, the authors of the HPFS study did emphasize that sleep disruptions were associated with increased risk of developing lethal or aggressive prostate cancer. The finding by Robbins et al that a significant proportion of patients are discussing these issues through online communities suggests that the prevalence of sleep disturbance—and its impact on quality of life—among prostate cancer patients is poorly understood and inadequately measured.

Representative quotes highlighted by Robbins et al also reveal that prostate cancer patients often suffer from severe insomnia, indicating lack of sleep-related patient education initiatives. Additionally, quotes by caregivers also underscore that there is a general lack of information on how to address sleep disruptions for patients they attend to. This is a missed opportunity, as evidence suggests that nutritional therapy (soy supplementation, for example) and combination of resistance training with aerobic exercise may improve cancer related fatigue and quality of life among prostate cancer patients [3], although less is known about effective interventions that would improve sleep. Furthermore, disturbances in sleep have expensive implications for health care spending and workplace absenteeism—with prostate cancer survivorship phase accounting for 50% of total cancer care related costs [4]. Studies that have investigated this relationship report that sleep disturbances significantly increase the utilization of health care and workplace absenteeism, with the impact constituting 2% and 8%, respectively [4]. Given the exponential rise in overall health care spending in the United States, addressing costs stemming from preventable adverse events is urgent—this present study demonstrates that more creative interventions are wanting.  

Beyond economic and survivorship care concerns, this qualitative study paints a grim picture of the conversations happening in these online patient communities, with comments revealing a negative emotional state for many. While sleep disturbances are an important contributor for this development, lack of patient education can also engender greater confusion and distress. Findings from this study should spur greater interest and support for devising and implementing patient-centered initiatives that improve sleep quality. This is required not only because these will likely improve the quality of life for prostate cancer patients, but also because we have a moral responsibility to provide comfort for these patients.

by Junaid Nabi

References

1.         Robbins R, Girardin JL, Chanko N, Combs, P, Byrne N, Loeb S Using data from an online health community to examine the impact of prostate cancer on sleep. BJU Int. 2020; 125(5).

2.         Markt SC, Flynn-Evans EE, Valdimarsdottir UA, Sigurdardottir LG, Tamimi RM, Batista JL, et al. Sleep Duration and Disruption and Prostate Cancer Risk: a 23-Year Prospective Study. Cancer Epidemiol Biomarkers Prev. 2016;25(2):302-8.

3.         Baguley BJ, Bolam KA, Wright ORL, Skinner TL. The Effect of Nutrition Therapy and Exercise on Cancer-Related Fatigue and Quality of Life in Men with Prostate Cancer: A Systematic Review. Nutrients. 2017;9(9):1003.

4.         Gonzalez BD, Grandner MA, Caminiti CB, Hui S-KA. Cancer survivors in the workplace: sleep disturbance mediates the impact of cancer on healthcare expenditures and work absenteeism. Support Care Cancer. 2018;26(12):4049-55.

Cowbells and conundrums – the 3rd Advanced Prostate Cancer Consensus Conference

by Professor Declan G Murphy

Urologist & Director of Genitourinary Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia

Twitter: @declangmurphy

The 3rd Advanced Prostate Cancer Consensus Conference (APCCC) took place in Basel in late August 2019, and the subsequent manuscript was published in European Urology just recently. We delayed posting this blog until now as the recommendations were under embargo until the manuscript went online. As with the previous two APCCC events (which took place in St Gallen; the so-called “St Gallen meetings”), this “Basel meeting” and its resultant recommendations are certain to provoke discussion due to the contentious nature of the topics which feature. Indeed, much of the raison d’etre of the meeting is to create recommendations from key opinion leaders to help guide decision-making in prostate cancer, particularly in areas where confusion exists, and where traditional guidelines are not clear.

The format is as follows:

  • The meeting takes place every two years and includes two full days of plenary sessions from world leaders, and one half-day of voting to try and achieve consensus on hot topics
  • 72 of the world’s leading experts in prostate cancer are invited to deliver plenary addresses, and more than 750 delegates from 65 different countries
  • Ten areas of controversy are featured in the plenary sessions, and invited experts participate in a live vote on the final day to see if consensus can be reached. More than 120 questions are selected by the panel over the previous few months.
  • The level of consensus was defined as follows: answer options with 75% agreement were considered consensus, and answer options with 90% agreement were considered strong consensus.
  • The results are published in a detailed manuscript (40 pages!) in European Urology

The meeting is convened by Dr Silke Gillessen and Dr Aurelius Omlin who are world-renowned experts in prostate cancer. One of the unique and most enjoyable aspects of the APCCC is the unashamed Swiss-ness which Silke and Aurelius bring to the meeting. The meeting is conducted in a very relaxed manner with excellent interaction between the Faculty which is part of the high value of the meeting. Of course, one would expect a meeting in Switzerland to run efficiently, and Silke and Aurelius wield a goat’s bell for the one minute warning; if you hear the cow bell, then the time is up!

 

As before, the invited panel is a truly global gathering of world experts in prostate cancer:


A truly global gathering of world leaders in prostate cancer

The ten areas of controversy for #APCCC19 are as listed below, followed by a summary of some of the notable areas of consensus, along with some areas of non-consensus.

  1. Locally advanced prostate cancer
  2. Biochemical recurrence of prostate cancer after local therapy
  3. Management of the primary tumour in the metastatic setting
  4. Management of newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC), including oligometastatic prostate cancer
  5. Management of nonmetastatic (M0) castration-resistant prostate cancer (CRPC)
  6. Management of metastatic CRPC (mCRPC)
  7. Bone health and bone metastases
  8. Molecular characterisation of tissue and blood
  9. Interpatient heterogeneity
  10. Side effects of hormonal treatments and their management

It was interesting to note the proportion of voting panellists by discipline as listed below, in particular the healthy proportion of urologists in a meeting focussed on advanced prostate cancer:

And also by region as listed below.

Obviously a massive amount of territory gets covered during this meeting, but I have highlighted some of the key recommendations within each of the ten areas of controversy below:

Locally advanced prostate cancer:

This section featured plenary addresses on node-positive prostate cancer from myself and radiation oncologist Dr Mack Roach. There was strong consensus that some sort of loco-regional treatment with surgery or radiation (RT) should be offered to men with node-positive prostate cancer, combined with androgen deprivation therapy (ADT) for men undergoing RT. The impact of PSMA PET/CT in defining N1 disease was considered and was recommended for accurate staging (pending the read out of the proPSMA trial which had not yet been published). Regarding duration of ADT, there was no consensus with answers ranging from six months to three years.

Biochemical recurrence (BCR) of prostate cancer after local therapy:

One of the stand-out themes of this year’s APCCC was the impact of PSMA PET/CT for imaging prostate cancer, and Lu-PSMA theranostics as a treatment for mCRPC. I am pleased to say that much of the focus of this was on data from here in Australia, and there was much favourable comment on how Australia has led in this area. It is fair to say there was a reasonable amount of envy also for how much access we have to PSMA PET/CT compared to many other parts of the world. In one of the opening plenaries, Professor Ian Davis did a terrific job overviewing this, and did introduce some cautionary tones about the management impact of novel imaging.

There was consensus that PSMA PET/CT should be used for the assessment of BCR following radiation or surgery. This is a new recommendation compared with the previous meeting, and is in line with the most recent EAU Prostate Cancer Guidelines. What PSA level should we image at? Most discussion centred around a PSA of 0.2ng/mL or greater following surgery.

For patients undergoing salvage RT, there was consensus that this should be accompanied by a short period (4-12 months) of ADT. 83% of panellists voted in favour of offering salvage RT before PSA reaches 0.5ng/mL, with 37% offering RT before PSA reaches 0.2ng/mL. There was consensus that ADT alone should not be used for the majority of patients with rising PSA and no evidence of metastases following prior local therapy.

Management of the primary tumour in the metastatic setting

This was certainly a hot topic. There was much discussion around the role of RT to the primary in men presenting with metastatic prostate cancer (in addition to lifelong ADT), and the most recent data from STAMPEDE led to a strong (98%) consensus for the use of RT in men presenting with low-volume metastatic prostate cancer. Volume was defined based on conventional imaging using classic CHAARTED criteria. The recommended dose was 55Gy over four weeks as per STAMPEDE.

Should we extrapolate from this data and offer surgery as local therapy in the same group of patients? There was 88% consensus that we SHOULD NOT offer surgery, other than within a clinical trial. There was also consensus that patients with N1 disease should be offered RT to the nodes in addition to the primary.

Management of newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC), including oligometastatic prostate cancer

This is clearly one of the fastest moving areas in advanced prostate cancer and there was much new data to consider. The panellists reached consensus on 12 areas of mHSPC including:

  • Nomenclature – there was 77% consensus that we should avoid the term “castration”, although there was not consensus on what other term we should use! In describing treatment-naïve men, it is easy as we can use the term mHSPC. However, when treatment resistance emerges, we are still left with mCRPC (87% consensus).
  • I must say there was an outstanding intervention from patient advocate, Mr Millman, after the initial round of voting on this topic, saying how much patients detest the use of the term “castration”. I could not have agreed more. This led to the convenors calling for a repeat vote with subsequent vote in favour of avoiding the use of the term.
  • 95% consensus for obtaining histological evidence of prostate cancer in men suspected of having M1 disease; 96% consensus that ADT could be initiated prior to biopsy.
  • Most striking – 100% of panellists voted for ADT combined with something else (docetaxel or an androgen receptor (AR) pathway inhibitor) in patients with de novo high-volume mHSPC. There was much discussion about which combination should be offered, but there was no consensus. The decision can be individualised based on patient factors and local registration and reimbursement status. In Australia that means docetaxel for most patients while we awai tregistration/reimbursement for agents such as abiraterone, enzalutamide and apalutamide.
  • There was also consensus for combination approaches in men with de novo low-volume mHSPC, with 85% voting in favour of some additional systemic therapy in addition to ADT, and 80% supporting RT to the primary.
  • Similarly, in men with relapsing high-volume or low-volume mHSPC, there was consensus to offer combination systemic approaches, with no consensus on which therapy to offer in addition to ADT.
  • There was consensus (78%) that in men with mHSPC diagnosed with conventional imaging, that no additional imaging (ie PSMA PET/CT) should be utilised. That horse has already bolted in Australia where it is not unusual for men to be diagnosed with M1 disease using PSMA PET/CT in the first instance.

Regarding oligometastatic disease, there was consensus that if metastasis-directed therapy (MDT) is to be considered, that the extent and location of disease should not be defined using conventional imaging (79%), but should be defined using more sensitive imaging such as PSMA PET/CT (75%). There was also strong consensus that a distinction should be made between lymph node-only disease, and M1 disease involving other sites. Systemic therapy should be used in addition to local therapy to all local sites of disease (75%). I must say that I was pretty surprised that consensus was reached on this point, as guidelines still suggest that MDT approaches should still only be offered within clinical trials.

Management of nonmetastatic (M0) castration-resistant prostate cancer (CRPC)

What even is M0 CRPC? Once again, PSMA PET/CT dominated the conversation. Although there is a relatively recently accepted definition of high-risk M0 CRPC (castrate levels of testosterone; PSA doubling time of </= 10 months; M0 based on conventional imaging), it is fair to say that there was much interest in the role of PSMA PET/CT in this population of patients. Data about to be published at the time of the meeting reported that 98% of patients in this setting will have identifiable disease on PSMA PET/CT despite being M0/N0 on conventional imaging. There these patients are actually mCRPC, rather than M0 CRPC, albeit based on novel imaging with a lead-time bias. Nonetheless, following various overviews of the recent pivotal data showing improvements in metastasis-free survival (MFS, conventional imaging) in patients with M0 CRPC receiving enzalutamide, apalutamide or darolutamide, the panel voted 86% in favour of using one of these agents in this population of high-risk M0 CRPC. We also voted 86% in favour of NOT extrapolating this data to M0 CROC patients with PSA doubling time of greater than 10 months.

Management of metastatic CRPC (mCRPC)

Another huge area with much data to consider. Although much of this had been considered at the previous APCCC and indeed, there were many areas where consensus was not reached eg which agent to use for first-line mCRPC (docetaxel vs AR pathway inhibitor). Despite general enthusiasm for molecular profiling/precision medicine approaches (and some outstanding talks on these areas), there was 85% consensus that we should not use AR-V7 status when considering mCRPC patients for abiraterone or enzalutamide. There was consensus that a steroid dose of prednisone 5mg bd should be used when starting mCRPC patients on abiraterone, and an 86% consensus that a tapering course of steroids should be used when discontinuing abiraterone or docetaxel.

There was considerable interest in the role of reduced dose abiraterone (250mg with food, instead of 1000mg without food), based on a phase II study, and the panel voted 86% in favour of a reduced dose regimen when there are resource or patient constraints on receiving the full dose.

One of the standout talks of the meeting was delivered by Prof Michael Hofman on the role of Lu-PSMA in progressive mCRPC as he presented data from the phase II trial at Peter Mac published in Lancet Oncology (to date, the only prospective data on Lu-PSMA), and on the TheraP randomised controlled trial from Australia which will read out at ASCO in June this year. For patients with PSMA imaging-positive mCRPC who have exhausted approved treatments and cannot enrol in clinical trials, 43% of panellists voted for Lu-PSMA therapy in the majority of patients, and 46% voted for it in a minority of selected patients. For selecting patients for 177Lu-PSMA therapy, 64% of panellists voted for PSMA PET/CT plus FDG PET/CT with or without standard imaging, 21% voted for PSMA PET/CT plus standard imaging, and 15% voted for PSMA PET/CT alone. Although consensus was not reached on this issue, it was clear that the panel were very influenced by Michael’s excellent presentation on this topic, highlighting observations in the Peter Mac phase II trial that the use of FDG PET/CT in addition to PSMA PET/CT led to enhanced patient selection for Lu-PSMA therapy.

Bone health and bone metastases

There was 77% consensus in favour of routine screening for osteoporosis risk factors (e.g. current/history of smoking, corticosteroids, family history of hip fracture, personal history of fractures, rheumatoid arthritis, 3 alcohol units/day, and BMI), in patients with prostate cancer starting on long-term ADT. There was 86% consensus that mCRPC patients with predominantly bone disease and without visceral metastases, should be considered for radium-223 therapy, although this hardly applies to Australia where radium-223 is difficult to access and not reimbursed (plus Lu-PSMA available).

Molecular characterisation of tissue and blood

The plenaries on this topic were some of the most stimulating of the whole meeting. Truly outstanding talks from the pre-eminent leaders in the world. Among the consensus areas were:

  • 90% support for the assessment of germline BRCA1/2 status in M1 prostate cancer patients at some stage of the disease
  • 94% consensus that mismatch repair status (MSI high) should be assessed at some stage in M1 disease, most likely in mCRPC.
  • 96% consensus that PD-1 inhibition should be considered for MSI high patients at some stage in the disease course
  • Strong consensus (93%) for PARP inhibitor or platinum therapy at some point during the disease course in patients with a deleterious germline BRCA1/2 mutation
  • Genetic counselling and/or germline DNA testing for patients with newly diagnosed metastatic (M1) castration-sensitive/naïve prostate cancer: consensus (84%) for genetic counselling and/or germline DNA testing for the majority of patients with newly diagnosed metastatic prostate cancer.

Interpatient heterogeneity

There were some terrific talks on heterogeneity in prostate cancer, including ethnic and regional diversity, and the assessment and management of older patients. This year’s meeting expanded on this section compared to previously to acknowledge the diversity of prostate cancer around the world, and the fact that much of the data used to make recommendations is based on particular patient cohorts. The panel did reach consensus (76%) for the extrapolation of efficacy data to patients older than the majority of patients enrolled in a trial.

Side effects of hormonal treatments and their management

Professor Mark Frydenberg was one of the invited plenary speakers in this session and did a terrific job overviewing the management of hot flushes. I have not seen this topic discussed better anywhere in the world. There were also terrific talks on strategies to mitigate other side-effects. The panel reached strong consensus (94%) for the use of resistance and aerobic exercise to reduce fatigue in patients receiving systemic therapy for prostate cancer (apart from therapy dose reduction if possible).

Need more detail?

If you are interested in more detail, please download the manuscript from European Urology (open access), or visit Urotoday where the plenary lectures are available, along with exclusive interviews with many of the invited experts.

Finally, the 4th APCCC will take place from 7-9th October 2021. It will take place in the beautiful city of Lugano towards the Italian side of Switzerland. I encourage anyone with a strong interest in prostate cancer to consider attending. It will be a most stimulating and enjoyable few days immersed in the world of prostate cancer, and conducted with wonderful Swiss hospitality once again by the fabulous Silke Gillessen and Aurelius Omlin.

Article of the week: Salvage radical prostatectomy following focal therapy: functional and oncological outcomes

Every week, the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to this post, there is an editorial written by prominent members of the urological community. Please use the comment buttons below to join the conversation.

If you only have time to read one article this week, we recommend this one. 

Salvage radical prostatectomy following focal therapy: functional and oncological outcomes

Jaime O. Herrera-Caceres*, Gregory J. Nason*, Noelia Salgado-Sanmamed, Hanan Goldberg*, Dixon T.S. Woon*, Thenappen Chandrasekar*, Khaled Ajib*, Guan Hee Tan*, Omar Alhunaidi*, Theodorus van der Kwast, Antonio Finelli*, Alexandre R. Zlotta*, Robert J. Hamilton*, Alejandro Berlin, Nathan Perlis* and Neil E. Fleshner*

*Division of Urology, Department of Surgical Oncology, Department of Radiation Oncology, and Department of Pathology and Laboratory Medicine, University Health Network, University of Toronto, Toronto, ON, Canada

Read the full article

Abstract

Objectives

To report the oncological and functional outcomes of salvage radical prostatectomy (sRP) after focal therapy (FT).

Patients and Methods

A retrospective review of all patients who underwent sRP after FT was performed. Clinical and pathological outcomes focussed on surgical complications, oncological, and functional outcomes.

Fig. 1. Impact of PSM on the absence of detectable disease after sRP (including PSA persistence and/or BCR).

Results

In all, 34 patients were identified. The median (interquartile range [IQR]) age was 61 (8.25) years. FT modalities included high‐intensity focussed ultrasound (19 patients), laser ablation (13), focal brachytherapy (one) and cryotherapy (one). The median (IQR) time from FT to recurrence was 10.9 (17.6) months. There were no rectal or ureteric injuries. Two (5.9%) patients had iatrogenic cystotomies and four (11.8%) developed bladder neck contractures. The mean (sd) hospital stay was 2.5 (2.1) days. The T‐stage was pT2 in 14 (41.2%) patients, pT3a in 16 (47.1%), and pT3b in four (11.8%). In all, 13 (38%) patients had positive surgical margins (PSMs). Six (17.6%) patients received adjuvant radiotherapy (RT). At a mean follow‐up of 4.3 years, seven (20.6%) patients developed biochemical recurrence (BCR), and of these, six (17.6%) patients required salvage RT. PSMs were associated with worse BCR‐free survival (hazard ratio 6.624, 95% confidence interval 2.243–19.563; P < 0.001). The median (IQR) preoperative International Prostate Symptom Score and International Index of Erectile Function score was 7 (4.5–9.5) and 23.5 (15.75–25) respectively, while in the final follow‐up the median (IQR) values were 7 (3.5–11) and 6 (5–12.25), respectively (P = 0.088 and P < 0.001). At last follow‐up, 31 (91.2%) patients were continent, two (5.9%) had moderate (>1 pad/day) incontinence, and one (2.9%) required an artificial urinary sphincter.

Conclusions

sRP should be considered as an option for patients who have persistent clinically significant prostate cancer or recurrence after FT. PSMs should be recognised as a risk for recurrent disease after sRP.

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