ASCO GU 2019: Intensification Versus Deintensification in High-Risk Prostate Cancer

San Francisco, CA ( During the general session on optimizing diagnosis and treatment of clinically significant nonmetastatic prostate cancer at the Annual ASCO GU 2019 meeting in San Francisco, CA, Drs. Sridhar, Briganti, and Payne presented on the treatment of high-risk localized prostate cancer,   and issues related to intensification and deintensification of treatment from medical oncology, urology, and radiation oncology perspective.

Dr. Sridhar started her talk with a case summary of a high risk localized prostate cancer and requested an audience response on the treatment options. She then summarized the incidence and definition of high risk localized prostate cancer, which accounts for 15% of men presenting with local disease and predisposes the patient to a high risk of recurrence and cancer-related death.  Since biochemical recurrence is not a good surrogate for survival and there is significant heterogeneity in clinical behavior and outcomes, there is a need for novel molecular biomarkers or imaging approaches to improve risk stratification. This may also change the definition of high-risk disease in future which will better tailor a therapeutic approach and determine clinical trial eligibility.

She summarized the results of NCIC PR3 study which showed that ADT+RT is better than ADT alone. She also talked about the recently published SPCG4 study which showed that radical prostatectomy is beneficial in patients with long life expectancy. Therefore, there is a real need for a validated surrogate endpoint of survival and ICECAP initiative has reported that metastasis-free survival is a strong surrogate endpoint for overall survival in localized prostate cancer.

Despite local treatment of high-risk prostate cancer, biochemical failure, and cancer-specific mortality is high. Systemic therapies have shown a clear survival advantage in advanced cancer, and there may be a role for starting systemic treatment in early prostate cancer, as shown recently by STAMPEDE and CHAARTED trials. She summarized several studies which have shown that intensification of RT by adding ADT to RT significantly improves survival, and therefore ADT+RT is recommended by all guidelines. However, ADT is not without side effects. To minimize the side effects associated with ADT, studies have looked at a shorter duration of treatment, however the study comparing 18 vs 36 months of ADT was underpowered to show equivalence, and so should be viewed cautiously . Shorter duration of ADT has therefore not been widely adopted. There are also studies underway looking at intensification of RT with systemic chemotherapy, but longer follow-up is needed.

Similarly, adding ADT to radical prostatectomy has shown improvement with local control, but no improvement in DFS or OS. She also talked about the Prioriti and AFU-GETUG 20 studies that will offer a contemporary look at adding ADT to radical prostatectomy. Adding androgen receptor pathway inhibitors such as Abiraterone, Enzalutamide, have not shown improved outcomes in terms of complete pathologic response and there is an opportunity to test novel combinations. According to Dr. Sridhar, genomic profiling of patients such as the GUNS study may be the way of the future. Other studies such as PUNCH and ACDC studies are ongoing evaluating systemic chemotherapy in the neoadjuvant setting along with radical prostatectomy.

In summary, Dr. Sridhar mentioned that this is an exciting time in the field of high risk localized prostate cancer with many trials across many settings incorporating systemic treatment into their current treatment paradigm. The goal is to individualize and personalize therapy based on both biomarkers and a better understanding of the disease at the molecular level.

Dr. Briganti followed Dr. Sridhar’s excellent summary with intensification/deintensification options with surgery. He mentioned that SPCG 15 is an ongoing RCT looking at comparing primary radical prostatectomy and primary RT +ADT for locally advanced prostate cancer. Dr. Briganti highlighted the strength of surgery which is tailoring the surgical approach based on patient’s risk with potential decreased risk of over-treatment. He also pointed out that patients with multiple high-risk factors will benefit most from intensification. Before surgery, there is no role of ADT currently, but results of some trial as previously stated are awaited. During the surgery, extended lymph node dissection or wider surgical dissection may improve cancer control, based on results of MRI or frozen section. After the surgery, the use of RT and ADT can prevent local recurrence. Surgical approach can also be tailored to improve functional outcomes in patients to perform a nerve-sparing radical prostatectomy based on MRI results.

Dr. Briganti also mentioned that in some high-risk patients, performing extended and super extended lymph node dissection improves staging, but there is no randomized data available looking at cancer-specific outcomes. After surgery, due to the availability of a final pathology report, adjuvant RT can be tailored to avoid overtreatment. Postponing RT until early PSA progression or in patients with less pathologic risk factors also helps with deintensification. Some of the trial results are awaited in this arena. He also talked about patients with positive node disease and that the EAU guidelines support expectant management in carefully selected patients which is possible because of extended lymph node dissection.

Dr. Briganti summarized his outstanding talk by stressing that surgery allows for truly individualized approaches decreasing overtreatment in the management of high-risk disease in approximately a third of the high-risk patients, but multimodal treatment may be necessary for some patients.

Professor Payne, a radiation oncologist, then started her talk by presenting the challenges faced by a high-risk prostate cancer patient such as local control and prevention of future distant micrometastatic diseases, which may be present at the time of initial diagnosis. These patients need multimodal treatment while balancing side effects.

Evolution of IMRT, brachytherapy, VMAT has allowed more focused treatment while avoiding side effects and several randomized studies have shown dose escalation results in improved biochemical free survival and delayed future systemic treatment. She pointed out the fascinating data presented from PACE-B trial this morning, showing no difference in acute G2+ toxicities in patients receiving  SBRT. Dose escalation showed improved survival for intermediate and high-risk prostate cancer patients only in a large non-randomized retrospective study from NCDB. This suggests intensification for high-risk patients and deintensification for low-risk patients receiving RT.

Professor Payne then summarized the ASCENDE-RT study, which showed that men treated with LDR-brachytherapy boost were twice as likely to be free of biochemical failure at a median follow-up of 6.5 years compared to the EBRT boost group; however, there was increased GU toxicity after LDR-brachytherapy boost. HDR brachytherapy in combination with EBRT is a well-established treatment option for intermediate and high-risk prostate cancer with randomized data showing a 31% risk reduction in biochemical and clinical relapse. Besides, there was no evidence that quality of life deteriorated with increased follow-up time. Long term follow-up data shows 83% cancer-specific survival at ten years and 75% survival at 15 years following EBRT and HDR brachytherapy. She also presented the recent data from the FLAME study which compared toxicity rates in patients with localized prostate cancer treated with standard fractionated EBRT with or without an additional integrated boost to the macroscopically visible tumor. In intermediate- and high-risk prostate cancer patients, focal dose escalation integrated with standard EBRT did not increase GU and GI toxicity when compared to the standard treatment up to two years after treatment. This suggests that the described focal dose escalation technique is safe and feasible. The CHHiP study showed that hypofractionated radiotherapy using 60 Gy in 20 fractions is non-inferior to conventional fractionation using 74 Gy in 37 fractions and is recommended as a new standard of care for external-beam radiotherapy of localized prostate cancer. Long term follow-up is awaited on these studies. There is no level 1 evidence comparing RT to radical prostatectomy in high-risk patients, but some retrospective studies favor RT.

She concluded her talk by mentioning that evolution of RT intensification has demonstrated benefits in treatment outcomes without increased toxicity. Future intensification should be aimed at men with higher risk disease determined by enhanced risk stratification with deintensification for lower risk patients. All treatment options must be discussed with the patient and patient’s comorbidities, choices and preferences must always be considered.

Presented by: 
Srikala S. Sridhar, MD, FRCPC, Princess Margaret Cancer Centre, University Health Network, Medical Oncologist
Alberto Briganti, MD, Ph.D., Vita-Salute San Raffaele University, Urologist
Heather Ann Payne, MBBS, FRCP, FRCR, University College London Hospitals NHS Foundation Trust, Radiation Oncologist

Written by: Abhishek Srivastava, MD, Society of Urologic Oncology Fellow, Fox Chase Cancer Center, Philadelphia, PA Twitter: @shekabhishek at the 2019 American Society of Clinical Oncology Genitourinary Cancers Symposium, (ASCO GU) #GU19, February 14-16, 2019 - San Francisco, CA
Everyday Urology - Oncology Insights
Publications focusing on urologic cancer treatments through original manuscripts
By Christopher Wallis


Prostate cancer, while commonly diagnosed in early forms, remains the second leading cause of cancer mortality in the United States and Europe.1 For patients who die of prostate cancer, some will be initially diagnosed and treated for metastatic castration-sensitive disease (mCSPC) while others will progress through non-metastatic castration-resistant disease (nmCPRC) following initial local therapy followed by androgen deprivation therapy (ADT) for biochemical recurrence. In either case, nearly all men who die of prostate cancer will have metastatic castration-resistant disease (mCRPC) prior to death.

By Thomas E. Keane, MBBCh, FRCSI, FACS
Published Date: December 2018

Prostate cancer is the leading incident cancer among men, and population growth and aging have fueled a 40% rise in global case burden since 2006.1,2 Despite recent improvements in treatment, patients with locally advanced and advanced prostate cancer experience significant emotional distress, diminished quality of life, and increased risk of cancer-specific mortality.1,2,3
By Neal Shore, MD, FACS
Published Date: September 2018

Radiation has been used to treat prostate cancer since the early 1900s.¹ In recent decades, advances in radiation delivery systems and the advent of computed tomography and magnetic resonance imaging have spurred the development of targeted, high-dose radiotherapy techniques such as intensity-modulated radiotherapy (IMRT), image-guided radiation therapy (IGRT), stereotactic radiation therapies, proton beam
By Matthew T. Roe, MD, MHS, MHS
Published Date: March 2017

Heart disease and cancer are the leading causes of death in the United States.1 Prostate cancer (PC) is the most common cancer in American men, and PC is most frequently diagnosed among men aged 65 to 74 years.2 The American Cancer Society’s estimates for PC in the United States for 2017 are about 161,360 new cases. Of these, about 26,730 are expected to die of the disease.1 
Library Resources
The State-of-the-Evidence in Brief Reviews by Experts
Written by Christopher J.D. Wallis, MD, PhD and Zachary Klaassen, MD, MSc
August 31, 2020
The rapid spread of Coronavirus Disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) has dramatically reshaped the structure of Western society, including on health care delivery.
Written by Christopher J.D. Wallis, MD, PhD and Zachary Klaassen, MD, MSc
July 2, 2020
Prostate cancer is a clinically heterogeneous disease with many patients having an indolent course requiring no interventions and others who either present with or progress to metastasis. While underlying dominant driving mutations are not widespread, there have been a number of key genomic mutations that have been consistently identified in prostate cancer patients,
Written by Zachary Klaassen, MD, MSc and Christopher J.D. Wallis, MD, PhD
May 14, 2020
The coronavirus has the potential to impact the integrity and patient safety of ongoing trials as well as increase the operational burden on trial programs, therefore potentially limiting access to trials and new therapies for oncology patients. Opportunities for clinical trial enrollment may still be provided to patients during the COVID-19 outbreak, but likely require thorough evaluation on a case-by-case basis.
Written by Zachary Klaassen, MD, MSc and Christopher J.D. Wallis, MD, PhD
December 10, 2019

Despite prostate cancer (PCa) being the second most common cause of cancer mortality among American men,1 there are 2.9 million men in the United States living with PCa. As such, there are many “PCa survivors” that are either on active surveillance (AS)/watchful waiting (WW) or have undergone treatment for localized (ie. radiation therapy (RT), radical prostatectomy (RP), focal therapy, etc) or advanced disease. 

Written by Zachary Klaassen, MD, MSc
December 18, 2019

Understanding and elucidating the underlying genetic basis of carcinogenesis has been the holy grail for cancer researchers, for both the scientific understanding of disease pathophysiology and potential therapeutic implications. Perhaps the best example of the therapeutic implications of understanding carcinogenesis come from chronic myeloid leukemia where the identification of the “Philadelphia chromosome”;

Written by Zachary Klaassen, MD, MSc
November 15, 2019
Despite the exciting advances in treatment over the last decade for metastatic castration-resistant prostate cancer (mCRPC), the disease remains incurable with a median overall survival of 12-35 months.1-4 Targeting the immune system to expand treatment options in the advanced disease state has resulted in significant improvements
Written by Hanan Goldberg, MD
December 10, 2019
In 2018 1.3 million prostate cancer (PCa) cases were diagnosed worldwide, with approximately 20% having metastatic disease.1 Oligometastatic PCa is defined as a state of low-volume metastatic disease that appears to be prognostically different and likely amenable to different treatment options, which could potentially change the disease trajectory when compared with high-volume metastatic disease.2
Written by Zachary Klaassen, MD, MSc
April 16, 2019
In 2018 in the United States, there will be an estimated 164,690 new cases of prostate cancer (19% of all male cancer incident cases, 1st) and an estimated 29,430 prostate cancer mortalities (9% of all male cancer deaths, 2nd only to lung/bronchus cancer).1 Over the last four decades, there was a spike
Written by Zachary Klaassen, MD, MSc
April 16, 2019
The discovery of prostate-specific antigen (PSA) in the late 1970s and its widespread application and adoption in the 1980s and 1990s ushered in the prostate cancer screening and disease monitoring era. As the first tumor marker for prostate cancer, it is organ specific but not cancer specific.1
Written by Zachary Klaassen, MD, MSc
April 16, 2019
Secondary to the introduction of prostate specific antigen (PSA) screening in the 1980’s/1990’s, symptomatic presentation of prostate cancer has become less frequent. Symptoms of locally advanced prostate cancer may include obstructive urinary symptoms, gross hematuria, and/or upper tract urinary obstruction leading to renal failure.
Written by Zachary Klaassen, MD, MSc
April 16, 2019
Over the last decade, imaging for prostate cancer has improved immensely. Specifically, prostate multiparametric MRI (mpMRI) has improved primarily as a result of an increase in magnet strength from 1 to 3-tesla. mpMRI consists of anatomic and functional imaging techniques:
Conference Coverage
Conference Highlights from Recent Conference Coverage
Presented by Michael Cookson, MD, MMHC
As the therapeutic landscape evolves to include increasingly complex combinations of systemic therapies with or without local therapies, advances in imaging, and germline and somatic testing, treating men with advanced prostate cancer is increasingly one that must embrace multidisciplinary management approaches.
Presented by Neal D. Shore, MD, FACS, and Ashley Evan Ross MD, PhD
During the second prostate cancer session at the 2020 Annual Meeting of the Society of Urologic Oncology (SUO), Drs. Neal Shore and Ashley Evan Ross debated the use of relugolix as a new standard of care for androgen deprivation therapy (ADT) for the treatment of prostate cancer.
Presented by Reham Alghandour, PhD
Metformin is a biguanide agent which is commonly used in the first-line treatment of patients with type 2 diabetes. For many years, there has been an interest in its potential anti-cancer properties, particularly in prostate cancer.
Presented by William T. Lowrance, MD, MPH
The AUA 2020 virtual annual meeting was highlighted by an update on the AUA guidelines for advanced prostate cancer, presented by Dr. William Lowrance and Dr. Michael Cookson. Dr. Lowrance notes that this guideline was produced by a multidisciplinary panel with representation from the AUA, ASCO, ASTRO, and SUO was well as a patient advocate.
Presented by Elena Castro, MD, PhD
San Francisco, CA ( In this talk, Dr. Elena Castro gave an overview of the genomic landscape of advanced prostate cancer. It has been shown that in over 70%
Presented by Samuel Denmeade
Washington, DC ( As part of the SUO 2019 advanced prostate cancer session, Dr. Samuel Denmeade discussed his work with bipolar androgen therapy (BAT)
Presented by Samuel Denmeade, MD
Washington, DC (  Since Huggins’ noble prize-winning work on the role of androgens in prostate cancer progression in 1940, hormonal suppression has been the mainstay
Presented by Kelly Stratton, MD
Athens, Greece ( Dr. Kelly Stratton gave an overview of the role of surgery in advanced prostate cancer. Advanced prostate cancer 
Presented by Derya Tilki, MD
Athens, Greece ( Dr. Derya Tilki was the first to present at the Educating Masterclass on Biochemical Recurrence after Radical Prostatectomy.
Presented by Karim Fizazi, MD, PhD
Barcelona, Spain ( At the Friday session at the 2019 European Society for Medical Oncology annual meeting (ESMO) meeting on prostate cancer, Karim Fizazi
Presented by Maria J. Ribal, MD
Barcelona, Spain ( Dr. Maria Ribal from Barcelona started the urogenital cancer treatment at a glance session by giving an overview of challenging paradigms in advanced prostate cancer. Dr. Ribal notes that not only is the incidence of prostate cancer the highest among male malignancies,
Presented by Himisha Beltran, MD
San Francisco, CA ( Dr. Misha Beltran presented a summary of the biologic basis for sequencing novel treatments for metastatic prostate cancer.  There is an increasing need for biomarkers in advanced prostate cancer management
Presented by Srikala S. Sridhar, MD, FRCPC, Alberto Briganti, MD, PhD, and Heather Ann Payne, MBBS, FRCP, FRCR
San Francisco, CA ( During the general session on optimizing diagnosis and treatment of clinically significant nonmetastatic prostate cancer at the Annual ASCO GU 2019 meeting
Presented by Kim Chi, MD
Phoenix, Arizona ( The LATITUDE study, published in July 2017, was a phase III randomized, clinical trial that evaluated the efficacy of abiraterone 
Presented by Laurence Klotz, MD
Tel-Aviv, Israel ( Laurence Klotz, MD gave a presentation on intermittent androgen deprivation therapy (IADT) and its association with cardiovascular disease (CVD). He began stating the many advantages of intermittent androgen deprivation therapy.
Presented by Jehonathan Pinthus, MD
Tel-Aviv, Israel ( Jehonathan Pinthus, MD presented the RADICAL PC trial and elaborated on the correlation of prostate cancer (PC) to cardiovascular disease (CVD). It is known that PC patients are at risk for CVD. Patients are deemed to be high-risk if they have a global risk estimate for severe CVD events with a rate of more than 2% per year.
Presented by Silke Gillessen, MD
Copenhagen, Denmark (  Dr. Sommer gave an overview of the complications associated with the treatment for advanced prostate cancer. The first topic discussed was the acute side effects of androgen deprivation therapy (ADT). These include decreased libido, erectile dysfunction, hot flashes, and fatigue.
Presented by Karim Fizazi, MD, PhD
Chicago, IL ( Dr. Karim Fizazi and colleagues presented their much-anticipated results from the LATITUDE trial at the 2017 ASCO annual meeting’s plenary session. In a phase III, double-blind, randomized setting, LATITUDE tested androgen deprivation therapy