Sexual dysfunction follows radical pelvic surgery in both sexes. Nerve sparing surgery is possible for both male and female pelvic cancers. Nature and pathophysiology of sexual dysfunction varies in men and women. Clinical evidence for rehabilitation is limited in men, and absent in women. However, every cancer survivor women deserves sex. It is our responsibility to help them

1. Penile Rehabilita,on a.er Prostate Cancer
Treatment: Is there an Analogy to Female
Pelvic Cancer?
Ege Can Serefoglu, MD, FECSM
UroKlinik, Istanbul, Turkey
1

2. Outline
• Cancer Treatment and Sexual Dysfunc=on
• Prostate Cancer and Sex
• Penile Rehabilita=on
• Relevance to Female Pelvic Cancer
2

3. Outline
• Cancer Treatment and Sexual Dysfunc:on
• Prostate Cancer and Sex
• Penile Rehabilita=on
• Relevance to Female Pelvic Cancer
3

4. Cancer Treatment and Sexual Dysfunc,on
• 40-100% of cancer survivors experience some form of sexual
dysfunc=on
• Almost all cancer treatments have the poten=al to alter
sexual func=on
• Surgery
• Chemotherapy
• Radia=on
• Hormones
• Sexual problems represent major quality QoL issue
• ORen associated with low treatment adherence
• With interven=on, up to 70% of pa=ents can have improved
sexual func=oning
4

5. How does cancer treatment affect sexuality?
SURGERY
- Resec=on of
sexual structures
- Damage to
surrounding =ssues
Sexual Dysfunc=on
5

6. Cancer Treatment and Sexual Dysfunc,on
SURGERY RADIATION
- Resec=on of
sexual structures
- Damage to
surrounding =ssues
Fibrosis
Sexual Dysfunc=on
6

7. Cancer Treatment and Sexual Dysfunc,on
SURGERY RADIATION
CHEMO-
THERAPY
- Resec=on of
sexual structures
- Damage to
surrounding =ssues
Fibrosis Gonadotoxicity
Sexual Dysfunc=on
7

8. Cancer Treatment and Sexual Dysfunc,on
SURGERY RADIATION
CHEMO-
THERAPY
ENDOCRINE
THERAPY
- Resec=on of
sexual structures
- Damage to
surrounding =ssues
Fibrosis Gonadotoxicity
Altera=ons in
hormonal
enviroment
Sexual Dysfunc=on
8

9. excitement
arousal
orgasm
desire
Four stages of the sexual response
Master & Johnson, Human Sexuality, 5th edi=on, 1995
9

10. excitement
arousal
orgasm
desire
Four stages of the sexual response
Master & Johnson, Human Sexuality, 5th edi=on, 1995
10

11. excitement
arousal
orgasm
desire
endocrine circula:on
Simplified basics of sexual func:on & its disturbances in cancer Tx
Surgery
Radio Tx
Chemo Tx
Hormonal Tx
Surgery (nerves)
Hormonal Tx
endocrine / nerves / neurotransmiGers
Radio Tx
Chemo Tx
Hormonal Tx
Master & Johnson, Human Sexuality, 5th edi=on, 1995
11

12. Outline
• Cancer Treatment and Sexual Dysfunc=on
• Prostate Cancer and Sex
• Penile Rehabilita=on
• Relevance to Female Pelvic Cancer
12

13. Prostate Cancer
• Cancer of the prostate (PCa)
is the most common solid
neoplasm of men
• incidence rate of 214 cases per
1000 men
• outnumbering lung and colorectal
cancer
• PCa is 2nd most common
cause of cancer death in
men
• Since 1985, there has been
a slight increase in the
number of deaths from PCa
Boyleand Ferlay. Ann Oncol 2005
Jemal et al. CA Cancer J Clin 2008
13

14. Prostate Cancer
the most
important
medical problem
facing the male
popula=on.
14

15. 1. Radical Prostatectomy
15

16. 2. Radia,on Therapy
16

17. 3. An,-Androgen Therapy / Chemotherapy
17

18. Sexual Changes A.er PCa Treatment
• Loss of libido
• Erec=le dysfunc=on (30% aRer RP)
• Loss of ejacula=on
• Orgasmic changes
• Change in sensa=on (50-75%)
• Pain (10-20%)
• Orgasm associated incon=nence (at least 20%)
• Reduc=on in penile size (20% aRer RP)
18

19. Sexual Changes A.er PCa Treatment
• Loss of libido
• Erec=le dysfunc=on (30% aRer RP)
• Loss of ejacula=on
• Orgasmic changes
• Change in sensa=on (50-75%)
• Pain (10-20%)
• Orgasm associated incon=nence (at least 20%)
• Reduc=on in penile size (20% aRer RP)
19

20. Pathophysiology of ED aRer PCa Tx
Erec:le Dysfunc:on
Cavernosal failure
and venous leak
The longer these
persist, the more
likely ED occurs
Vascular risk factors Age
Vascular damage Neuropraxia or
Neurectomy
Structural changes
within the penis
(?? loss smooth muscle)
Psychological
impact
20

21. Pathophysiology of ED aRer PCa Tx
Erec:le Dysfunc:on
Cavernosal failure
and venous leak
Can we prevent
these structural
changes and
prevent ED?
Vascular damage Neuropraxia or
Neurectomy
Structural changes
within the penis
(?? loss smooth muscle)
Vascular risk factors Age
Psychological
impact
21

22. Outline
• Cancer Treatment and Sexual Dysfunc=on
• Nerve Sparing Radical Prostatectomy
• Penile Rehabilita:on
• Relevance to Female Pelvic Cancer
22

23. Penile Rehabilita,on
• Penile rehabilitation is defined as
• the use of any drug or device
• before, at or after radical prostatectomy
• to maximize erectile function recovery
• Purpose of penile rehabilitation includes:
• prevention of corpus cavernosal smooth muscle structural alterations,
• limit venous leak development
• maximize chances of a man returning to his preoperative EF
23

24. Nerve Injury (cavernous)
NEURAPRAXIA
Erec=le Silence
Cavernous Hypoxia
Smooth muscle cell apoptosis
Collagen Increase ⎡(TGF-β1)
Venous Leak (MCVO)
FIBROSIS
Structural Changes
Erectogenic
Interven=on
Penile Rehabilita,on
24

25. 1st STUDY: Intracavernosal Alprostadil (PGE)
• 30 pa=ents in an open, non-
randomised trial
• Tx started at 1st po month
• Con=nued for 3 months
• Assessment at 3rd po month
Montorsi et al, J Urol, 1997
25

26. Intracavernosal Alprostadil
Montorsi et al. J Urol 1997.
†
Recovery of spontaneous
erec:ons (%)
Alprostadil injec:on
n=12
No treatment
n=15
26

27. 1st STUDY: Intracavernosal Alprostadil (PGE)
• 30 pa=ents in an open, non-
randomised trial
• Tx started at 1st po month
• Con=nued for 3 months
• Assessment at 3rd po month
• Cri=que
• Small sample size (30 pts)
• Non-randomized trial design
• Preopera=ve erec=le status?
• No objec=ve measure of EF
Montorsi et al, J Urol, 1997
27

28. 1998 – “Viagra Year”
28

29. OTHER STUDIES: PDE5 inhibitors (Sildenafil,
Vardenafil, Tadalafil)
29

30. Sildenafil
Responders: Pa=ents with combined IIEF Q3/4 score of ≥8 and posi=ve
response to ques=on: “Over the past 4 weeks, have your erec=ons
been good enough for sa=sfactory sexual ac=vity?” at 8 weeks aRer
discon=nua=on of drug
McCullough et al. J Sex Med, 2008
30

31. Vardenafil
15,8%
24,8%
28,9%
22,9%
32,0%
23,1%
38,2%
48,2%
29,1%
0%
25%
50%
75%
100%
6 months 9 months (End double
blind period)
11 months (End single
blind wash-out period)
Placebo Vardenafil nightly Vardenafil on-demand
Everyone is geong placebo
Montorsi et al, Eur Urol, 2008
31

32. Tadalafil
*
Montorsi et al, Eur Urol, 2014
32

33. Montorsi et al. Eur Urol 2014
Tadalafil
33

34. PDE5 Inhibitors and Rehabilita,on
• PDE5 inhibitors are effec=ve on drug-assisted EF in men
with ED following (nerve-sparing) RP
• Because PDE5 inhibitors need nitric oxide released from nerves
• Data failed to demonstrate a role for PDE5 inhibitors in
contribu=ng to the recovery of EF aRer RP
• Unassisted EF was not improved aRer cessa=on of ac=ve therapy for 9
mo.
• Pa=ents receiving PDE5 inhibitors achieve faster erec=le
func=on recovery
34

35. Outline
• Cancer Treatment and Sexual Dysfunc=on
• Nerve Sparing Radical Prostatectomy
• Penile Rehabilita=on
• Relevance to Female Pelvic Cancer
35

36. Gynecological Cancers
• Gynecologic cancers account for more than 90,000 of all new cancer
diagnoses in the US and approximately one million worldwide
annually
1. Siegel et al. CA Cancer J Clin 2013
2. Jemal et al. Global cancer sta=s=cs. 2014 36

37. Global
percentages
Western European
percentages
48
%
16
%
20
%
28
%
5%
11
%
26
%
45
%
Gynecological Cancers
37

38. Gynecological Cancers
• Gynecologic cancers account for more than 90,000 of all new cancer
diagnoses in the United States and approximately one million
worldwide annually
• Coping with cancer has physical and emo:onal consequences.
• Surgical tx oRen involves the removal of some (or all) of the
reproduc=ve organs (e.g. uterus, cervix, ovaries, and fallopian tubes)
• ≅90% of gynecological cancer pts have sexual dysfunc=on
• vaginal dryness, dyspareunia, and loss of desire
• ≅ 25% of pts with depression and anxiety disorder
• Emo:onal factors can nega=vely influence sexual response
• desire, arousal, and orgasm.
1. Carter et al. Gynecol Oncol 2005;97
2. Ganz et al. J Clin Oncol 1998
3. Matulonis et al. Int J Gynecol Cancer 2008
4. Schover. J Clin Oncol 2008
38

39. Relevance to Pelvic Cancer in Women
• What is the effect of radical surgery on female
sexual func=on?
• Is nerve sparing surgery possible?
• How does nerve sparing affect sexual func=on?
• Would addi=onal therapy be helpful?
39

40. Relevance to Pelvic Cancer in Women
• What is the effect of radical surgery on female
sexual func=on?
• Is nerve sparing surgery possible?
• How does nerve sparing affect sexual func=on?
• Would addi=onal therapy be helpful?
40

41. 4
3
2
1
0
nmol/L
Ovarian testosterone
Ovarian estrogens
Adrenal testosterone
puberty perimenopause
♣ Rhodes, JAMA
1999;282:1934-41 41

42. 4
3
2
1
0
nmol/L
Ovarian testosterone
Ovarian estrogens
Adrenal testosterone
puberty perimenopause
No estrogen
Acute menopausal
troubles
Potential signs of
androgen
deprivation
Less arousability
à diminished
orgasm capacity!
♣ Rhodes, JAMA
1999;282:1934-41
TAH+BSO
42

43. 4
3
2
1
0
nmol/L
Ovarian testosterone
Ovarian estrogens
Adrenal testosterone
puberty perimenopause
No estrogen
Acute menopausal
troubles
Potential signs of
androgen
deprivation
Less arousability
à diminished
orgasm capacity!
♣ Rhodes, JAMA
1999;282:1934-41
TAH+BSO
43

44. 4
3
2
1
0
nmol/L puberty perimenopause
Ovarian estrogens
Ovarian testosterone
Adrenal testosterone
No estrogen
Acute menopausal
troubles
Androgen
Insufficiency
• Sexual desire ê
• Arousability ê
• Genital sensitivity ê
• Pubic hair ê
• Fatigue é
• Bone density ê
• Muscle mass ê
• Diminished mood
(depression)
Additional
chemotherapy
TAH+BSO
44

45. Relevance to Pelvic Cancer in Women
• What is the effect of radical surgery on sexual
func=on? DETRIMENTAL
• Is nerve sparing surgery possible?
• How does nerve sparing affect sexual func=on?
• Would addi=onal therapy be helpful?
45

46. Relevance to Pelvic Cancer in Women
• What is the effect of radical surgery on sexual
func=on?
• Is nerve sparing surgery possible?
• How does nerve sparing affect sexual func=on?
• Would addi=onal therapy be helpful?
46

47. Relevance to Pelvic Cancer in Women
• What is the effect of radical surgery on sexual
func=on?
• Is nerve sparing surgery possible? YES
• How does nerve sparing affect sexual func=on?
• Would addi=onal therapy be helpful?
47

48. Is Nerve Sparing Surgery Possible?
• Nerve-sparing radical
hysterectomy (NSRH)
• Preserva=on of
hypogastric nerve
• Preserva=on of the
inferior hypogastric plexus
48

49. Is Nerve Sparing Surgery Possible?
Bladder dysfunc=on
Time of catheterisa=on
Xue et al. Cell Physiol Biochem. 2016
49

50. Relevance to Pelvic Cancer in Women
• What is the effect of radical surgery on sexual
func=on?
• Is nerve sparing surgery possible?
• How does nerve sparing affect sexual func=on?
• Would addi=onal therapy be helpful?
50

51. How does nerve sparing affect sexual
func,on?
• Pelvic nerve injury nega=vely impacts female (rat) genital blood flow
and induces vaginal fibrosis
• Increased Collogen I, Collogen III,
• Decreased Alpha ac=n (SM), nNOS (eNOS unchanged)
Cas=glione et al. BJOG. 2015
51

52. How does nerve sparing affect sexual func,on?
• Vaginal blood flow is measured
with photo-plethysmography
• Conven=onal RH (n=13)
• Nerve sparing RH (n=10)
• Control (n=14)
• Results
• Conven=onal RH reduced the
vaginal blood flow compared to
controls (p=0.016)
• Blood flow in nerve sparing RH was
slightly bever than conven=onal
(p=0.097)
52 Pieterse et al. Int J Gynecol Cancer, 2008

53. How does nerve sparing affect sexual
func,on?
• Sexually ac=ve cervical cancer
pa=ents undergoing RH
• 20 conven=onal RH
• 20 NS-RH
• Both RH and NS-RH worsened
postopera=ve FSFI scores (P <
0.001)
• Pa=ents undergoing NS-RH had
higher postopera=ve FSFI scores
53 Bogani et al. J Sex Med 2014

54. How does nerve sparing affect sexual
func,on?
Bogani et al. J Sex Med 2014
54

55. How does nerve sparing affect sexual
func,on?
Anorectal func=on
Sexual func=on
Xue et al. Cell Physiol Biochem. 2016
55

56. Relevance to Pelvic Cancer in Women
• What is the effect of radical surgery on sexual
func=on?
• Is nerve sparing surgery possible?
• How does nerve sparing affect sexual func=on?
• Would addi=onal therapy be helpful?
56

57. Pharmacological “rehabilita,on” DOES NOT
seem to be possible (for now)
Radical prostatectomy Radical Hysterectomy
Innerva=on Cavernous nerve Inferior hypogastric pelxus
Neurotransmiver NO NO and VIP
Consequence of injury Erec=le Dysfunc=on Impaired vaginal (??
clitoral) blood flow
Type of injury in radical
surgery
Nerve excision Nerve excision
Type of injury in nerve
sparing surgery
Neuropraxia ??
Pathophysiology of sexual
dysfunc=on
Probably hypoxic injury
with loss of smooth
muscle
??
Ra=onale for rehabilita=on Preserva=on of smooth
muscle via
pharmacological
oxygena=on or neural
protec=on
??
Evidence for rehabilita=on Conflic=ng Absent
57

58. What shall we do then?
SURGEONS - Get rid of false beliefs about sexuality..!
• Another doctor will take care of it
• Pa=ents never ask about it, so they must not care
• I don’t know how to help
• I don’t have =me
• I don’t agree with their lifestyle
• They should be happy to be alive
• They are too old, sick, young, etc.
• I will offend them by asking
• Nothing can be done so it’s cruel to bring it up
58

59. What shall we do then?
• 5As model have been offered to facilitate communica=on between
cancer pa=ents and the healthcare team.
1. Ask—raise the topic throughout the con=nuum of care;
2. Advise—normalize any difficul=es/concerns; and reassure that help is
available;
3. Assess—brief assessment to iden=fy symptoms in order to ini=ate further
discussion and provide treatment recommenda=ons;
4. Assist—provide resources such as pa=ent educa=onal materials,
informa=on sheets, or booklets; and referral for specialists (counselor,
gynecologist urologist); and
5. Arrange follow-up—pa=ents should receive follow-up on the topic or
referral at subsequent visits.
Park et al. Cancer J 2009
59

60. Types of Sexual Difficul,es in Cancer Survivors
• Sexual Desire
• Fewer thoughts or fantasies
• Less responsive to partner’s touch/
ini=a=on
• Sexual Arousal
• Difficulty with lubrica=on or erec=on
• Change in physical sensa=ons
• Orgasm
• Longer =me to climax
• Unable to climax
• Less intense climax
• Pain
• Decreased lubrica=on
• Vaginal =ssue atrophy
• Infec=on or
• Nerve increased sensi=vity to touch
• Vaginismus – muscle spasms
• Vulvodynia – neuropathic sharp
intense pain
• Body Image
• Surgical scars, loss of body parts
• Changes in body, muscle tone, skin
• Weight gain or loss or shiR
• Recep=veness to Sexuality
• Mood changes: irritability, depression,
worry
• ‘Protec=ng partner’ reduces in=macy
60

61. Treatment Op,ons for Female Cancer
Survivors
• Listen to the sexual complaints of the pa=ents
• Don’t forget the partner
• Cogni=ve behavioral therapy combined with sexual health
educa=on
• Teach to control pelvic muscles: tense & relax
• Suggest coital posi=ons that minimize deep penetra=on
• Menopausal symptom management
• Hot flashes, vaginal dryness, dyspareunia, chronic UTIs, and incon=nence
• Consider a set of graduated vaginal dilators (with pelvic floor ex.)
• Pain medica=ons
• Use non-hormonal lubricants and moisturizers
• If lubricants don’t help, consider vaginal estrogen (if possible)
• Counseling for rela=onship conflict or depression
61

62. Conclusion
• Sexual dysfunc=on follows radical pelvic surgery in
both sexes
• Nerve sparing surgery is possible for both male and
female pelvic cancers
• Nature and pathophysiology of sexual dysfunc=on
varies in men and women
• Clinical evidence for rehabilita=on is limited in men,
and absent in women
• However, every cancer survivor women deserves
sex
• It is our responsibility to help them
62

63. Next Exam of MJCSM : 28 February
2018, Lisbon, Portugal
63

64. 64

65. THANK YOU…
65