introduction to radical prostatectomy: surgical …€¦ · introduction to radical prostatectomy:...

INTRODUCTION TO RADICAL PROSTATECTOMY:

Surgical Treatment for Prostate Cancer

Dr. Alan So

Associate Professor

Dept of Urologic Sciences

Vancouver Prostate Centre

University of British Columbia

Chair, GU Tumour Group at BC Cancer

Biography:

A graduate of the University of Alberta, Dr. So came to the Prostate Centre as a

Clinical Fellow in 2002, following completion of his residency at Dalhousie University.

His current research focuses on discovery and development of novel agents to treat

bladder cancer as well as development of the mechanisms of treatment resistance in

renal cell carcinoma. Currently, he is associate professor at the University of British

Columbia and Vancouver Prostate Centre. As well, leads the Clinical Trials Unit at

the Vancouver Prostate Cancer, is the Fellowship Director of the Uro-oncology

Program at UBC, and is the Chair of the GU Tumour Group at the BC Cancer.

OVERVIEW

This presentation will cover the following:

• Anatomy of the prostate

• Description of Radical Prostatectomy

• Open Radical Prostatectomy

• Laparoscopic Robotic Assisted Radical Prostatectomy

• Discussion of the Possible Side Effects of Radical Prostatectomy

• Follow-up after surgery

What is a Radical Prostatectomy

•“Radical” refers to surgery performed to remove cancer

•Radical prostatectomy is the removal of the prostate to treat prostate cancer and involves removal of:

•Prostate

•Seminal Vesicles

•Vas deferens

•Sometimes lymph nodes in the pelvis

ANATOMY OF THE PROSTATE

WHERE IS THE PROSTATE LOCATED?

The prostate gland is located deep

in the pelvis

• Below the bladder

• In front of the rectum

• Behind the pubic bone

• Surrounds the urethra

prostate

rectum

pubic bone

urethra

bladder

Who is best suited for a radical prostatectomy

•Men with disease that is confined to the prostate

•Medically fit for surgery

•> 10 year life expectancy

•Final decision: Informed Patient’s Choice

“LOCALIZED” PROSTATE CANCER

• When there is no evidence that the cancer has spread beyond

the prostate gland, it is considered “localized”. Localized

disease is:

• Treatable

• Slow growing in most men, which allows for time to choose a

treatment strategy

• We do not perform “radical prostatectomy” when prostate cancer has

spread, as this does not treat the cancer that has already spread

Tests Performed Prior to Surgery

•Sometimes, when there is suspected metastases (symptoms, high PSA or high Gleason Score) tests are performed before surgery:

•Bone Scan (to assess if cancer has spread to the bone)

•CT Scan (to assess if cancer has spread to the lymph nodes or other organs)

•MRI may also be ordered to help with surgical planning (nerve sparing)

SURGICAL OPTIONS FOR PROSTATECTOMY

• Open surgery (radical prostatectomy, RP)

• Laparoscopic Robotic assisted surgery (robotic RP)

• Laparoscopic RP

• Perineal

Advantages of surgery

•Overall well tolerated

•Excellent long term results

•Lymph nodes can be sampled

•Assessment of the prostate by the pathologist

•Avoidance of “aging” urinary problems

Other terminology:

•Nerve-sparing: the blood vessels and nerves that promote penile erections are left behind in the body and not taken out with the prostate

•Pelvic lymph node dissection: the lymph nodes surrounding and close to the prostate are taken out

The “Obturator” nodes are the ones usually taken out in

those at risk of having cancer spread to them

https://en.wikipedia.org/wiki/Nerves

https://en.wikipedia.org/wiki/Lymph_nodes

-Step 1: Removal of Prostate Gland, seminal vesicles, lymph nodes

-Step 2: Reconnection of the bladder to the urethra

Steps of surgery:

OPEN RP VS ROBOTIC RP

Incision for open

prostatectomy

Incisions for Laparoscopic

Prostatectomy

ROBOTIC PROSTATECTOMY

da Vinci® Surgical System

• 3-D visualization

• Surgeon direct instruments’ movements using

console controls

Compared to open surgery:

• Less bleeding

• Potential for earlier recovery of urinary control

• Reduced “scarring” of bladder / urethra

connection (called bladder neck contracture)

WHAT TO EXPECT AFTER SURGERY

• Hospital stay is usually 1 night

• Minimal to moderate discomfort

• Catheter in the penis to drain urine: 1-

2 weeks

• 3-6 weeks off work (depending on

type of work, more for manual or

physically active jobs)

ADVANTAGES of SURGERY

• Generally well tolerated, recovery within 4-8 weeks in most

• Lymph nodes can be sampled to check for spread of cancer

• Assessment by a pathologist of the entire prostate

• Removal of cancer in the prostate may have long term benefit as well

as short term psychological advantages

• Sometimes other additional treatments, such as radiation with or

without hormone therapy, are also required

• Removal of the prostate prevents benign prostatic hypertrophy (BPH)

related urinary problems

SIDE EFFECTS RELATED TO SURGERY

• Erectile dysfunction (ED):

- Depends on age and functional level before surgery

- Younger men with full function have the best chance at

recovery

- May also experience penile shortening

Erectile Dysfunction is due to damage to the erectile nerves

Cross-Section of Prostate

Rectum

Neurovascular Bundles of

Walsh

Prostate

Surgical Approach

•Sparing of nerves maximizes return of normal erections

•This approach may not be possible is there is :•Significant volume of tumor in the area of the nerves

•High grade tumor (aggressive disease) in the area of the nerves

•Climax and penile sensation not affected- just penile rigidity

MANAGING ERECTILE DYSFUNCTION

• Sometimes called sexual or penile rehabilitation

• Treatments may include:

• Medications

• Intraurethral suppositories

• Penile injections

• Vacuum devices

• Penile implants

SIDE EFFECTS RELATED TO SURGERY

• Incontinence:

• most experience incontinence during the first 3 months

• 1 in 10 men continue to have some level of stress

incontinence past a year but total loss of control is rare

MANAGING URINARY INCONTINENCE

• Although long-term incontinence may be rare, a majority of men

post-operatively will have some leakage of urine with straining /

coughing etc. (Stress incontinence)

• Management is initially conservative with Kegel Exercises to

strengthen the pelvic floor muscles

• Pelvic floor physiotherapy and biofeedback can be helpful to

maximize recovery

• If incontinence persists, surgical option may be helpful

Other potential rare side effects

• Blood transfusion: < 5 %

• Bladder neck scarring: rare

• Rectal injury: rare

HOW DO WE KNOW WHETHER TREATMENT IS WORKING?

Follow up visits

• PSA

• Expect it to be very low, if not

undetectable, 3 months after surgical

treatment

• After surgery, PSA should be undetectable

WHAT IF MY CANCER REOCCURS?

• Some of these treatment options can be explored, depending upon the

initial treatment and the nature of the recurrence, e.g.:

• Radiation to the pelvis

• Androgen deprivation

Conclusion

•Prostate cancer surgery for cure is called radical prostatectomy

•Surgery can be performed in those with localized disease

•There are different ways to perform radical prostatectomy

•There are some side effects that may be associated with surgery which can be treated with by your Urologist

Knight Cancer Instituteat Oregon Health & Science University

Advances In Radiation Therapy for Prostate Cancer

Arthur Y. Hung, M.D.

Associate Professor

Dept of Radiation Medicine

Knight Cancer Institute

Oregon Health & Science University

Biography:

Arthur Hung, M.D. is an associate professor of radiation

medicine and a associate professor of ophthalmology as well

as serves as medical director of the Radiation Therapy

Training Program. He received his medical degree at The

Ohio State University. Dr. Hung joined the faculty in 2002

after finishing his residency at the University of Texas – MD

Anderson Cancer Center.

His research is focused on developing and refining the latest

technology to deliver radiation with more effectiveness and

less toxicity than ever before possible and clinical interests

are in cancers of the genitourinary tract, gastrointestinal tract,

hepatobiliary system, soft tissue sarcomas, and melanomas.


Advances in Radiation Therapy

• What is radiation?

• How does it work?

• How is the radiation delivered?

– External beam radiation

– Brachytherapy

– Intraoperative radiation

• Stereotactic Body Radiation Therapy

– as primary treatment for prostate cancer

– as treatment for metastatic prostate cancer


Concepts of Radiation


The Biological Effect of Radiation

• Radiation therapy uses high-energy electro-magnetic

energy, like radiowaves, microwaves, & visible light

• Ionizing Radiation damages DNA in rapidly dividing cells


Radiation Damages DNA


Normal Tissue repairs DNA Damage


Advances in Radiation Therapy

Goal of treatment is to deliver radiation to just the prostate

• focusing the radiation on only the tumor eliminating collateral damage

to normal tissue

– External beam radiation

• Linear Accelerator

• Proton Therapy

• Stereotactic Body Radiation

– Internal Radiation

• Prostate Brachytherapy

• HDR Brachytherapy

– Intraoperative Radiation


External Beam Radiation


Modern Linear Accelerator


Traditional Radiation Therapy


Targeting Prostate Cancer with Radiation


Focusing the Radiation

CT-Guided Targeting


Intensity Modulated Radiation Therapy

IMRT


Elekta Versa HD Accelerator


Radiation Beam Shaping


Cyberknife


Brachytherapy


Prostate Brachytherapy


Brachytherapy


Intraoperative Radiation


Intrabeam – Intraoperative Radiotherapy


Complete Treatment

System

No room shielding

Mobile--use in multiple

operating rooms

6 MeV - 12 MeV

3 – 10 cm Field Size

10 Gy/min dose rate

Mobile IOERT Solution


Stereotactic Body Radiation Therapy

SBRT

• What is it?

– a radiation technique where advanced treatment delivery and

radiation planning technology are used to deliver HIGH doses per

day in a safe and effective manner

– also known as Stereotactic Ablative Body Radiation therapy

(SABR)

– we use our technical capabilities to deliver radiation at the highest

level of accuracy and reproducibility

– 5 or less treatments


Stereotactic Body Radiation Therapy

• SBRT can be used as primary radiation therapy for prostate cancer

– instead of a prostatectomy

– instead of daily treatments for 5-9 weeks

• SBRT can be used to target metastases from various cancers

– delay progression of disease

– delay starting more aggressive systemic therapies


SBRT as primary treatment for prostate cancer

• 5 fractions

– conventional fractionation (39 – 45 treatments)

– moderate hypofractionation (20 – 28 treatments)

• First U.S. trial reported in 2007 with acceptable toxicity

– initial results: 4 year biochemical freedom from relapse 90%

– 33.5 Gy / 5 fractions

– GI toxicity (37.5%)

• bleeding, discomfort, mucous discharge

• no Grade 3 or higher


SBRT as primary radiation treatment for prostate cancerHow does it compare in a randomized trial?

• PACE-B

– international phase 3 randomized non-inferiority trial

– between 2012 – 2018, 874 men randomly allocated to:

• standard treatments: 78 Gy over 39 fx / 62 Gy over 20 fx

• versus SBRT: 36.25 Gy over 5 fractions


SBRT as primary radiation treatment for prostate cancerPACE-B

• Standard Fractionation (20 – 39) • SBRT (5 fractions)


SBRT as primary radiation treatment for prostate cancerPACE-B


SBRT as primary radiation treatment for prostate cancer

Scandinavian HYPO-RT-PC

• 1200 patients from 2005 – 2015 randomly assigned

– conventional fractionation (78 Gy / 39 fractions)

– ultra-hypofractionation (42.7 Gy / 7 fractions)

• median f/u 5 years, freedom from biochemical failure 84% both arms



Scandinavian HYPO-RT-PC Figure 3: Urinary toxicity and patient-reported problems



Scandinavian HYPO-RT-PC Figure 4: Bowel toxicity and patient-reported problems



bowel protection – SpaceOAR hydrogel


SBRT for Oligometastases

Oligo- From the Greek ‘oligos’, few, scanty

• Traditional treatment of patients with metastatic disease has been

based on systemic therapies that aim to delay progression and extend

life, but not to eradicate the disease completely.

• The oligometastatic paradigm suggests that in some patients,

metastatic disease is not widespread and may be constrained to

develop in only a small number of sites.

• This paradigm suggests that patients with oligometastases might be

amenable to a curative treatment approach.


SBRT for OligometastasesSABR-COMETStereotactic ablative radiotherapy versus standard of care palliative treatment in patients with oligometastatic cancers: a

randomised phase 2, open-label trial

• 99 patients randomized to control (standard treatment) vs. radiation

– 1 – 5 metastatic lesions

– original tumor: breast, colorectal, lung, prostate, other




• median overall survival

– 25 months for control (standard treatment)

– 41 months for SABR

• Adverse events of Grade 2 or worse

– 9% control

– 29% SABR

• 4.5% treatment-related deaths

– radiation pneumonitis, pulmonary abscess, gastric ulcer


SBRT for OligometastasesSTOMP Surveillance or Metastasis-Directed Therapy for Oligometastatic Prostate Cancer Recurrence

• 62 patients randomly assigned to standard treatment or

metastasis-directed therapy

– 3 or fewer lesions on PET

– metastasis-directed therapy

• surgery to remove disease

• or SBRT (30 Gy over 3 fractions)

– primary endpoint: Can metastasis-directed therapy delay the

need to start ADT

– ADT start: symptomatic progression, > 3 metastases, or local

progression of baseline-detected metastases



• @ 3 years of f/u

– 30% Metastasis-Directed Therapy

had not started ADT

– no grade 2 to 5 toxicity

– QOL similar at baseline and 3-

month and 1-year



• @ 3 years of f/u

– 25% with biochemical recurrence-

free survival in the metastasis-

directed group

• median ADT-free survival

– 13 months in surveillance group

vs.

– 21 months for the metastasis-

directed therapy group


SBRT for OligometastasesORIOLE Outcomes of Observation vs. Stereotactic Ablative Radiation for Oligometastatic Prostate Cancer

• Phase 2 study (1 - 3 metastases)

• 64 men randomized 2:1 to

receive SABR or observation

• primary outcome was

progression @ 6 months

• Progression-Free Survival

– observation 5.8 months

– SABR not yet reached (p=0.005)


Advances in Radiation Technology

• Radiation technology has enabled better targeting

–IMRT

–SBRT

• Targeted Therapy with Radiation = – Reduced Toxicity

– Better Tumor Control

Preserving Quality of Life while eradicating cancer.


Advances In Radiation Therapy

for Prostate Cancer

Arthur Hung, M.D.

Julie N. Graff, MD

Section Chief of Hematology/Oncology

VA Portland Health Care System

Associate Professor of Medicine

Knight Cancer Institute

Oregon Health & Science University

Biography:

Dr. Graff went to medical school at George Washington University where she received her MD with distinction in 2003. She moved to Portland, OR,

and completed residency and fellowship at the Oregon Health & Science University in 2009. Since that time, she has been on the faculty at the Knight

Cancer Institute OHSU and on the staff at VA Portland Health Care System, where she has been the chief of hematology/oncology since 2018.

Dr. Graff focuses on helping patients with cancer live well. She sees patients with genitourinary cancers, such as prostate, kidney, bladder and

testicular cancers, but her research is on prostate cancer. She has designed and implemented many clinical trials that have resulted in some dramatic

results. She became internationally recognized for her work in immunotherapy in prostate cancer. This work has spun off into multiple trials. In 2018,

she earned a prestigious $1M Movember Challenge Award from the Prostate Cancer Foundation to study the effect of manipulation of the gut

microbiota on responses to immunotherapy in Veterans with advanced prostate cancer. The correlative work for this first-in-field research is led by co-

principal investigators Dr. Amy Moran (immunologist) and Dr. Karen Sfanos (molecular pathologist). The critical work of understanding the genetic

underpinnings of the biopsied tumors is led by Reid Thompson, MD, PhD. Together they hope to enhance prostate cancer responses to

immunotherapy.

Dr. Graff is passionate about education and mentors multiple learners, ranging from pre-medical students to assistant professors. She is the recipient

of resident and fellowship teaching awards. She is also very interested in diversity of leadership and is heading an effort to help female junior faculty in

hematology/oncology. Also, she is incredibly passionate about giving Veterans the best cancer care in Oregon and beyond.

No evidence of disease:Nothing on imagingPSA undetectable

PSA Recurrence:Nothing on imagingPSA detectable

Metastatic Cancer:Spread on imagingPSA detectable

Adapted from Saylor. Journal of Clinical Oncology 2011; 29(27): 3705.

*Some disagreement

This study included 1997 men who had a radical prostatectomy at Johns Hopkins between 1982 and 1997. They were followed for a mean of 5.3 years (range of 0.5-15 years).

Of the 1997 men, 315 (15%) had a biochemical recurrence, defined as a PSA ≥ 0.2 mg/ml. Eleven of them received early hormonal therapy and were not included in this analysis.

Pound. JAMA 1999; 28 (17): 1591.

Pound. JAMA 1999; 281 (17): 1591.

Those you can

see

Those you can

feel

Other

Weight gain Hot flashes Bone density

loss

Muscle loss Fatigue Lipid changes

Hair pattern

changes

Depression Decreased

insulin

sensitivity

Fat

redistribution

Mental slowing Heart

disease(?)

Testicle/penis

size decrease

Anemia

• Statistics

• Some may not do well

• Gleason 8, 9, 10

• Pre-treatment PSA >

2.0 ng/ml

• Negative margins

• PSA doubling time ≤ 10

months

• Seminal vesicle

invasion

Bicalutamide plus radiation versus radiation alone

Active Surveillance

Albertsen, P. C. et al. JAMA 2005;293:2095-2101.

*Until 1999, PSA ≤15 and Gleason ≤3+4 were used.

Romero-Otero J, et al. Int J Urol 2015; Epub Nov 2015

Laurence Klotz et al. JCO 2015;33:272-277

Mark Garzotto, MDProfessor of Urology and Radiation Medicine, OHSU Knight Cancer InstituteUrology Section Chief, VA Portland HCS

Multidisciplinary Care of High-Risk Localized Prostate Cancer

Biography:Dr. Garzotto has a long standing interest in trying to refine the diagnostic approaches to the detection of prostate cancerincluding incorporation of MRI and novel statistical methods such as machine learning. His research group identified theViet Nam war-era defoliant, Agent Orange as a risk factor for aggressive prostate cancer. He is considered an expert inthe design of novel treatment regimens for locally advanced prostate cancer including combination therapy such aschemoradiation and immuno-hormonal regimens. He is the Chief of the Urology at the Portland VA Medical Centerwhere he also serves as the Lead Investigator for the VA NAVIGATE Program that conducts NCI-sponsored trials formultiple cancer types. Understanding the molecular drivers of cancer is a prime interest of his, as he feels thisknowledge is essential to the pursuit of improved outcomes for patients. He has a strong interest in teaching as he feelsthe future of medicine is dependent on the continued growth in knowledge. He has been awarded the DepartmentFaculty Teacher of the Year Award several times.

Cancer Statistics, 2020:

Trends in Male Cancer Mortality, US 1930-2017

CA: A Cancer Journal for Clinicians, Volume: 70, Issue: 1, Pages: 7-30, First published: 08 January 2020,

DOI: (10.3322/caac.21590)

PSA introduced

Prostate Cancer Heterogeneity: Not One Disease

http://prostate-cancer.org/the-gleason-score-a-significant-biologic-manifestation-of-prostate-cancer-aggressiveness-on-biopsy/Modern Pathology (2004) 17, 292–306, advance online publication, 13 February 2004; doi:10.1038/modpathol.3800054

http://prostate-cancer.org/the-gleason-score-a-significant-biologic-manifestation-of-prostate-cancer-aggressiveness-on-biopsy/

Prostate Cancer Disease State at Initial Diagnosis(SEER Incidence Cases, 2008-2017)

https://seer.cancer.gov/ SEER*ExplorerCooperberg et al. JCO 2010Tilki et al. J Urol 193:1970, 2016

Low

Intermediate

High/Very High

0

10

20

30

40

50

60

70

80

Localized Regional Distant

Perc

ent

https://seer.cancer.gov/

High-risk Localized Prostate CancerNCCN Guidelines 2020

Feature NCCN High-RiskNo more than 1 feature

NCCN Very High-Risk2 or 3 High risk features, OR

Stage T3a (extracapsular) T3b (Seminal Vesicle)T4 (adjacent structures)

PSA > 20 ng/mL N/A

Gleason 8 - 10 Primary 5 (ie 5+3, 5+4, 5+5)

# Cores N/A > 4 cores Gleason 8-10

https://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf

How is High-risk Localized Prostate Cancer Treated?

T1-2 WHO 3 orT3-4,N0-1

Randomized (n=415)

Radiotherapy +adjuvant goserelin

3.6 mg (n=207)

Radiotherapy Alone(n=208)

Hormonal Therapyat progression

EORTC 22863 Radiotherapy + Adjuvant ADT vs Radiotherapy Alone

Study Design

EORTC = European Organization for Research and Treatment of Cancer

Radiation: 50 Gy over 5 weeks + 20 Gy over 2 weeks

ZOLADEX 3.6 mg sc every 4 weeks starting day 1 of radiation and continuing for 3 years

Cyproterone acetate: 150 mg po qd for 1 month starting 1 week prior to ZOLADEX

Median follow-up at 45 months

and 66 months

Bolla M et al. NEJM 1997; 337(5)295-300; Bolla M et al. Lancet. 2002;360:103-108.

EORTC 22863: Radiation ± ADT for 3 yrs. Overall Survival 66-Month Follow-up

Bolla M et al. Lancet. 2002;360:103-108.

Overa

ll S

urv

ival

(%)

Combined Treatment

Radiotherapy Alone

0 1 2 3 4 5 6 7 8

Log-rank test p < .0001

Hazard ratio 0.51

(95% Cl: 0.36-0.73)

100

90

80

70

60

50

40

30

20

10

0

O N

81 208 199 177 146 106 70 46 30 16

50 207 197 183 166 142 93 71 43 24

Number

at Risk

Time Since Randomization (Years)

RTOG 0521: Docetaxel Chemotherapy After Radiation Treatment

StageGleasonscore PSA

Any T stage

≥9 <150

7-8 ≥20-150

≥T2 8 <20

Arm 1

AndrogenSuppression (24 mos)

+External RT (8 wks)

HighRisk

Randomize

Arm 2

AndrogenSuppression (24 mos)

+External RT (8 wks)

+Docetaxel beginning 4 wks after RT

(6 cycles)

RTOG 0521: Overall Survival

4 yr OS 93% vs. 89%

HR 0.70 (90%CI: 0.51-0.98)

Rosenthal et al JCO, 2019

SPCG-4: Surgery Results in Improved Cancer Survival and Reduction in Metastatic Spread

45% decrease in cancer death

46% reduction in metastatic disease

Bill-Axelson et al. NEJM 364:18, 2011Bill-Axelson et al. NEJM 379:2319, 2018

PIVOT: Surgery vs. ObservationProstate CA Deaths:high-risk disease

NEJM 367: 203-213, 2012

Rationale for Upfront Therapy Prior to Surgery

• Early treatment of metastatic disease

• Improved local control

• Rapid assessment of tumor response

Pre-operative Use of Novel Anti-Androgens in Intermediate and High-risk PCA

Treatment Duration Endpoint

TAPS (N=35)(NCT00298155)

LHRH+dutasteride ±bicalutamide ±ketoconazole

3 mo. Tissue Androgens

NeoAbi (N=58)(NCT00924469)

Abiraterone (3 vs. 6 mo) + LHRH

3 vs 6 mo. Tissue androgens

Neo-Enza (N=52)(NCT01547299)

Enzalutamide ± LHRH + Dutasteride

6 mo. Path CR

NeoAbiEnza (N=75)(NCT02268175)

Enzalutmide + LHRH ±Abiraterone

6 mo. Path CR or Minimal Residual disease

Path Outcomes from Neoadjuvant ADT with Enza/Leuprolide (EL) ± Abi/Pred (ELAP)

Parameter ELAP (n=50) EL (N=25)

Stage

P0 10% 8%

Min. Residual Dz. 20% 8%

T2 40% 36%

T3a/b 50% 56%

Node + 10% 12%

SM+ 18% 12%

ECE 46% 52%

SV+ 18% 28%

Upstaging 42% 60%

McKay et al JCO, 2019

Further Advances Will Require Multidisciplinary Approach

• Advanced Imaging

• Incorporation of Genomics

• Novel Therapeutics

– Anti-androgens

– Small Molecule Inhibitors

– Immunotherapy

OHSU Advanced Imaging Research Center

• Director: Charles Springer, PhD

• Bruker 12T MRI

• Siemens 7T MRI

• Siemens 3T

Li et al. J Magn Reson. 2016

PCA is heterogeneous but has a low mutational burden

Rubin et al. Cold Spring Harb Perspect Med, 2018Lawrence et al Nature 2013

Harnessing the Immune System:The Case for Checkpoint Inhibitors

http://www.onclive.com/publications/contemporary-oncology/2014/February-2014/Immune-Checkpoint-Blockade-in-Cancer-Inhibiting-CTLA-4-and-PD-1PD-L1-With-Monoclonal-Antibodies

Stress-induced Immunogenic Cell DeathConverting a Tumor from “Cold” to “Hot”

Radogna et al Biochem Pharm 2018Mercader et al PNAS, 2001Ochoa de Olza Lancet Oncology, 2020

Drug Treatment

• Pembrolizumab 200 mg IV Q/3 weeks

• Enzalutamide 160 mg po QD x 16 weeks

• GNRH agonist x 4 months

Radical Prostatectomy + node dissection at 16 weeks• pathologic CR

• pathologic Staging

• correlative studies

Pre-operative pembrolizumab plus intensive androgen axis blockade prior to

prostatectomy for high risk localized prostate cancer

High/Very-high-risk Prostate Cancer (N=32)• Gleason grade > 8-10

• PSA > 20 ng/ml

• Clinical stage T3a (resectable) Objectives:

Primary: pCR, safety/tolerability

Secondary:

pCR by PD-1 status,

clinical and biochemical recurrence

HRQOL

fecal microbiome correlates

Funding: Merck, AstellasNCT03753243

Conclusions: High-Risk Prostate CA

• Early Detection is key to attaining dz. control

• Effective therapies are available, but are not yet optimal

• Treatment combinations administered by a Multidisciplinary team holds great promise

introduction to radical prostatectomy: surgical …€¦ · introduction to radical prostatectomy:...

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