Complications of Prostate Cancer Treatment

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Complications of Prostate Cancer Treatment

• David D. Thiel MD
• Mayo Clinic Florida
• Department of Urology

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What about pain?

• Pain is not an element of prostate cancer unless
  there are bone metastasis
• Treated with androgen deprivation, steroids, etc

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Prostate Cancer Options

• Watchful waiting
• Active surveillance
• Surgery
• Retropubic
• Perineal
• Robotic
• Radiation Therapy
• External beam
• Brachytherapy
• Proton Beam

• Cryotherapy
• HIFU
• Cyber knife
• Androgen deprivation (ADT)

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Prostate Cancer Therapy Goals

• Eradicate Cancer
• Preserve Continence
• Prevent Regret
• Preserve Erections

Quality of Life
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Quality of life does Matter!!!

• HRQOL is 1 concern of men electing therapy for
  Pca (JUrol 2003)
• AUA survey (2000) of 1000 men
• 74 of men over 50 are afraid to have PSA
  checked due to possible side effects of Pca
  treatment.
• ITS NOT THE BIOPSY THEY ARE SCARED OF

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No free lunch

• There is no such thing as treatment for prostate
  cancer that doesnt have the risk of incontinence
  and erectile dysfunction

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The Trifecta

• The 3 Cs
• Cure Is psa unetectable
• Continence
• Coitus

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Continence

• What is continence?
• No pads ever
• Is insurance pad continence?
• Social continence
• Surgical intervention? If no surgery needed,
  incontinence isnt that bad
• Return to baseline urinary fx
• Some studies use AUA score!!!!

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Continence

• Everyones true fear
• Seldom marketed. Why?
• NOT COMMON

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3 Types of incontinence

• 1. Stress incontinence
• Cough and sneeze
• 2. Urge incontinence
• Cant get there in time
• 3. Mixed incontinence

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Stress Incontinence

• Is a sphincter problem
• See in all patients following RRP
• Occurs following XRT as well

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Incontinence

• All men are incontinent following surgery
• Continence must be regained
• Incontinence rates following RALP around 1-3
• 7 require an insurance pad

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Kegel excercises
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True Trifecta(RALP)

• Eliminate high grade disease (G8, 9, 10) and
  metastatic disease
• Eliminate obesity (BMI gt35)
• Eliminate SHIM score lt20
• Eliminate hormones
• Eliminate neurologic diagnosis
• TRUE TRIFECTA 50-55

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AUS Treatment Outcomes

• Published results on patients achieving and
  maintaining social continence (significantly
  improved) after AUS for post prostatectomy
  incontinence
• Gundian et al. 90 J. Urol. 142 1989
• Marks et al. 95 J. Urol. 142 1989
• Perez et al. 85 J. Urol. 148 1992
• Singh et al. 96 BJU 77 1992
• Litwiller et al. 90 J. Urol. 156 1996

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Urge Incontinence

• More common after radiation
• Is a sign of obstruction or bladder irritation
• Surgery removes obstruction

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Is Brachy a Kinder and Gentler Option?

• Brachytherapy is the most convenient treatment
  and has lowest rates of long-term complications
  compared to RRP or XRT
• - Grills, et al. (William Beaumont
  Hospital) J Urol 2003

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Table 6

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Grade 2 Toxicity Refresher

• Dysuria relieved with medication
• Incontinence some control
• Hesitancy requiring I/O cath or indwelling
  catheter
• Urgency Increased but not more than once an
  hour
• Hematuria not requiring tranfusion

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Table 7

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Grade 2 Toxicity Refresher

• Diarrhea 4- 6 stools per day. Not incontinent
  of stool
• Rectal Pain Pain requiring analgesics that does
  not interfere with quality of life
• Rectal Bleeding Requires medication but not
  transfusion

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Incontinence following radiation(Urge and/or
stress)

• Also operator dependent
• Seeds in wrong place (brachytherapy)
• Radiate wrong place (XRT)

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Urinary bother after radiation

• Alpha blocker therapy
• Flomax, Rapaflow, Uroxatrol, etc.
• Anticholenergic Therapy
• Detrol, Enabelex, Ditropan, etc
• O2 Chamber

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Worse-case scenario

• Urinary diversion
• Stool diversion
• Double bag

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RUG
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Devasting Comlications
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The best treatment for Radiation Induced voiding
dysfunction

• PREVENTION
• Avoid big prostates
• Avoid those with urinary bother
• Avoid those with inflammatory bowel disease
  (rectal bother)
• Avoid those with high residuals
• Avoid those with prostatitis

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ErectionsThe soul of man

• The biggest misconceptions
• The biggest marketing target
• The only reason men make bad choices
• In life
• AND in prostate cancer

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MarketingGuaranteed erections

• HIFU
• Selective cryotherapy
• Gamma knife
• All pray on the super-educated
• Too smart for their own good

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Defining ED in the Setting of Radical
Prostatectomy
Multivariate Analysis Clinical and Pathologic
Factors

• Significant Variables P value
• Age 0.0008
• Full potency preoperatively 0.0039
• Neurovascular bundle (NVB) status 0.0204
• Surgical technique (pre- and post-1993) 0.0001
• Not Statistically Significant Variables
• Pathological stage 0.1279
• Tumor volume 0.1483
• Preoperative prostate-specific antigen 0.3336
• UICC stage 0.5605
• Surgical margins 0.7534

UICCUnion Internationale Contre le Cancer.
Quinlan et al J Urol 1991 145(5)998. Rabbani,
Stapleton, Scardino. J Urol 1641929, 2000.
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Erectile DysfunctionOne Pitfall After Another

1. What is potency? (PDE5 use, etc.)
2. When is potency defined? (1 day vs 18 mos, etc.)
3. How is potency assesed?
4. Who is reporting the potency? (Marketing of
   technology)

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Sexual Dysfunctions Following Radical
Prostatectomy

• Changes in penile morphometry
• Penile length alterations
• Penile curvature
• Anejaculation
• Changes in Orgasmic function
• Anorgasmia
• Dysorgasmia (pain)
• Increased intensity
• Climacturia (sex specific urine leakage)
• Erectile Function
• Complete ED
• Partial erections
• Change in pharmacologic responsivity

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Quality of Life Depends on Prostate Cancer
Procedure
Brachytherapy
Prostatectomy
Radiotherapy
100
100
Radiotherapy alone
100
Nerve-sparing
Brachytherapy alone
Radiotherapy plus NHT
80
80
Brachytherapy plusradiotherapy, NHT, or both
Non-nerve-sparing
80




60
60


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Sexual Score
Sexual Score
Sexual Score
40
40

40



20
20

20









0
0
0
0
2
6
12
24
0
6
12
24
2
0
2
6
12
24
Follow-up(months)
Follow-up(months)
Follow-up (months)
N1201
Plt0.01 Significant, but below the threshold of
clinical relevance NHT neoadjuvant hormone
therapy Scores based on the Expanded Prostate
Cancer Index Composite (0-100)
Sanda MG, et al. N Engl J Med. 20083581250-1261.

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Percentage of Prostatectomy Patients Reporting
Specific Levels of Distress
Poor erections
Difficulty with orgasm

Erections not firm
Erections not reliable
Poor sexual function
Overall sexuality
problem
24 Months
Adapted from Sanda MG et al. N Engl J Med.
20083581250-1261.
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ED Before Prostatectomy
Association of age with probability of impotence
in MMAS

• Over 50 of men undergoing RP will already have
  ED
• Comorbidities
• 30-40 HBP
• 25-35 HL
• 5-10 DM
• 20-30 Smoking
• 30-40 Obesity

Probability
Feldman HA et al. J Urol. 199415154-61. Johannes
CB et al. J Urol. 2000163460-463.
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Recovery of Erections According to Preoperative
Sexual Functioning
Rabbani F, et al. J Urol. 20001641929-1934.
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My line

• Radiation is better up front for erections
• Surgery data catches up at 3 years
• At 3 years, there is not going to be a
  statistical difference

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Erectile Rehabilitation

• Use it or loose it
• Does surgery or radiation shrink the penis
• Knee replacement analogy

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What Choices Do We Have for Rehabilitation During
the Period of Profound Neurapraxia after NSRP?
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IU Alprostadil Summary

• Advantages
• easier to administer than ICI
• FDA approved therapy of ED
• Dosing 125, 250, 500, 1000 µg
• Efficacy
• Clinical experience suggests one in five patients
  respond at home.
• improved by band ( Actis? )
• Disadvantages
• significant penile pain ( 33 )
• dizziness / hypotension ( 2 - 6 )
• syncope ( 1 )
• office titration

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Intracavernosal Injection (ICI) Summary

• Advantages
• Efficacy in all etiologies of ED
• Initiates erection without stimulatiion
• Variety of vasoactive agents
• Only one FDA approved, Alprostadil PGE1
• Disadvantages
• Needle stick
• Office training Nurse specialist
• Office follow-up
• Refrigeration and shelf-life
• Lack of spontaneity
• Side effects priapism, pain, injection nodules,
  fibrosis

Dropouts,20 50 within first year
Lue. N Engl J Med. 20003421802-1813.
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PDE5 Inhibitors What Patients Need to
Understand Adverse Effects
ICSM Recommendations. Jackson G, et al. J Sex Med
201071608-26
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NSRP and Erectile Function My Observations

• The time required to regain EF following NSRP is
  unclear.
• Recovery has been documented in large clinic
  series up to 24 months.
• The resumption of spontaneous tumescence is a
  good indicator for the initiation of PDE5
  Inhibitor therapies.
• The focus of current interventions whether
  delivered in the operating room or afterward is
  on protection, preservation or rehabilitation of
  EF.
• The theory that neuropraxia may yield down
  regulation of cavernous tissue relaxors (NO,
  cGMP) and play a role in apoptosis / fibrosis has
  lead to various human clinical studies of
  vasoactive agents involving Intracorporal /
  Intraurethral PGE1 and PDE5-Inhibitors.
• To date (2008) the largest such trial of a
  PDE5-Inhibitor has confirmed that early dosing
  does improve erectile function, but has not shown
  any distinct benefit to daily dosing versus early
  on demand dosing for coital attempts.

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Complications of Prostate Cancer Treatment

• David D. Thiel MD
• Mayo Clinic Florida
• Department of Urology