the role of surgery in advanced prostate cancer · • understand prostate cancer metastases and...

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The role of surgery in advanced

prostate cancer

Brant A. Inman, MD, MS Cary N. Robertson Associate Professor of Urology

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All Rights Reserved, Duke Medicine 2011

Learning objectives

• Describe the lymphatic drainage of the prostate and

the role of lymphadenectomy

• Understand prostate cancer metastases and what

oligometastatic prostate cancer is

• Describe options for treating oligometastatic prostate

cancer

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Lymphatic drainage of the prostate

and lymphadenectomy

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Herman et al. Radiology 1963

Lymph vessels grow out

from the lymph sacs

along the major veins

The paired posterior lymph

sacs develop from the iliac

veins

Birth of Modern Day

Understanding

1904, Cuneo and Marcille

became the foundation for

future definitive works of the

prostate


Intra-Prostate Lymphatics

• First level lymphatics start near the fine capillaries

forming a network around each glandular acinus

• Extend to periphery forming a second network at the

capsule surface

• “Peri-prostatic network”

Delamere. General anatomy of the lymphatics. Chicago 1904


Prostate Lymphatics – 3 trunks

• Primary trunk

– Posterior prostate surface

– Ascends along bladder

– Crosses the internal iliac artery laterally

– Terminates on middle chain of external iliac node

packet



Prostate Lymphatics – 3 trunks

• Second trunk

– Posterior prostate

– Follows the prostatic artery

– Terminates in the middle of the internal iliac node

packet

– Additional collecting trunks run para-rectal

terminating on sacral promontory


Anterior-Posterior view of Pelvic Lympho-Vascular Anatomy


• 30 cadavers and 59 patients

• Mean number of nodes = 22

• Mostly obturator and external iliac

Weingartner et al. J Urol 1996


Why does the node count matter?

• Because if you don’t remove enough nodes, you will

be leaving cancer behind

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Node count Positive node rate

2-10 6%

10-14 9%

15-19 10%

20-40 18%

Briganti et al. Urology 2007

The 6 regions

Bern: Mattei et al. Eur Urol 2008

Primary lymphatic landing sites of the prostate transferred from 3D datasets and

superimposed into idealized anterior-posterior and medio-lateral projection of the pelvis

N=317

Primary lymphatic landing sites of the prostate transferred from 3D datasets and

superimposed into idealized anterior-posterior and medio-lateral projection of the pelvis

Bern: Mattei et al. Eur Urol 2008 N=317

Note Omni Retractor

Sentinel

Nodes

Positive

Node

Counts

Percent

positive

Bubble size proportional to node count

Leuven: Joniaui et al. Eur Urol 2013


Prostate cancer metastases

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Where does prostate cancer spread to?

• Simple answer

– anywhere and everywhere

• Erudite answer:

– That is true but, certain patterns are much more

common than others

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Japan: Saitoh et al. Cancer 1984 N=1885

(1958-1979)

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Japan: Saitoh et al. Cancer 1984

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Japan: Saitoh et al. Cancer 1984

~75% of

bone mets

were in the

spine

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Bern: Bubendorf et al. Human Pathol 2000 N=1589

(1967-1995)

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Bern: Bubendorf et al. Human Pathol 2000

28 Bern: Bubendorf et al. Human Pathol 2000

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Batson O. Annal Surg 1940

Batson’s vertebral

venous plexus

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Batson O. Annal Surg 1940


Oligometastatic prostate cancer

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So what is oligometastatic prostate cancer?

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Tosoaian et al. Nature Rev Urology 2017


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Despite the lack of a consensus definition,

does treating oligometastatic prostate cancer

with aggressive curative intent offer benefit?

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Maybe…

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JHU: Makarov et al. J Urol 2008

Recall that the untreated natural history of metastatic

prostate cancer can be very long


Different ways to get at this question

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Study design Problems

Population level data (e.g. SEER)

-Non-standardized imaging/staging

-Non-standardized treatment

-Selection bias

Case series and cohort studies

(single or multicenter) -Selection bias

Prospective trials

-Expensive

-Take long to get answer

-Many treatment options, which one to

choose?

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SEER (US): Culp et al. Eur Urol 2014

N = 8,185 M1 pts

RP 245, BT 129, NSR 7,811

2004-2010

This study was one of the first population studies to suggest

local therapy might have benefit

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NCDB (US): Loppenberg et al. Eur Urol 2016

N = 15,501 M1 pts

(1,470 got local therapy)

2004-2012

Low-risk patients seemed to benefit more from local therapy

(RP, brachy, EBRT)

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SEER-Medicare (US): Satkunasivam et al. J Urol 2015

N = 4,069 M1 pts

RP 47, IMRT 88, CRT 107, No local 3,827

2004-2009

SEER-Medicare data allow better

confounder adjustments for treatments

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Italy: Gandaglia et al. Eur Urol 2016

RP for prostate cancer with bone mets (MRI or bone scan)

N = 11

(2006-2011)

Median PSA = 11

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NCDB (US): Rustoven et al. J Clin Oncol 2016

Yet another population study

N=6,382

ADT 5844, EDT+RT 538, RP 69

2004-2012

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MSKCC: O’Shaughnessy et al. Urology 2016

09/29/16

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Figure 1. Percentage of patients that achieved undetectable PSA during the treatment phase increased with each component of multimodal

therapy. Response to treatment was assessed with serum PSA measurements and the frequency of patients who achieved undetectable PSA

after ADT alone, ADT + Surgery, and ADT + Surgery + Radiation is shown. M1a = extrapelvic nodal disease; M1b =bone metastasis

0%

80%

100%

33%

73%

93%

25%

75%

95%

0%

20%

40%

60%

80%

100%

ADT Alone ADT + Surgery ADT + Surgery + Radiation

M1a M1b Total

Page 19 of 29

Multimodality treatment to achieve undetectable PSA

N=20

43 Mayo: Karnes et al. J Urol 2015

11C-Choline PET-directed salvage lymphadenectomy

N = 52

Median PSA = 2.2

100% prior RP

80% post-RP therapy (EBRT, ADT, etc…)


What about targeting the mets with radiation?

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Summary of important points (1)

• LND quality = node count

– In high risk patients, aim for ≥ 20 nodes

• Prostate cancer metastases

– Nodes > Bone > Lung

• Oligometastatic prostate cancer probably has better

outcome than normal polymetastatic prostate cancer

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Summary of important points (2)

• Treatment of the prostate may provide some benefit

in oligometastatic patients

– All options seem reasonable

– Best data for RP, brachy and EBRT

• Treatment of the mets may also provide some benefit

– LND or EBRT for nodal mets

– EBRT for bony mets

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