HIV related testis cancerfact or fiction

1
HIV related testis cancer-fact or fiction?

• Thomas Powles
• St Bartholomews Hospital London
• Chelsea and Westminster Hospital
• Orchid Cancer Appeal

2
Introduction

• In the 1980s and 90s HIV affected mainly young
  men so we were not surprised when we saw 1 or 2
  GCTs in the clinics.

3
Introduction

• In the 1980s and 90s HIV affected mainly young
  men so we were not surprised when we saw 1 or 2
  GCTs in the clinics.
• Unlike Kaposis sarcoma and NHL, GCT is not
  associated with a viral onocogene and had not
  been extensively reported in the organ transplant
  population. So why should it occur more
  frequently in HIV?

4
All of the early age matched data in the pre
HAART era showed and increased relative risk of
GCT (RR2-7)
5
Seminoma vs NSGCT
Pgt0.05
HIV negative
seminoma
HIV positive
JCO 2003
6
Is it just immune suppression or is it something
else causing this?
7
Recent meta-analyis of 400,000 HIV/AIDS patients
and 40,000 organ transplant patients.
Lancet 2007
8
Why are patients with HIV predisposed to seminoma?
9
Which factors predispose to HIV related seminoma.
Univariate analysis (n70,000)
10
What about chronic moderate immune suppression
All HIV positives (n-11,000)
20 yrs post HIV
CD4
All HIV positive non AIDS defining cancer
patients n-174
11
What are the causes of HIV related seminoma?

• There is reduced lymphocyte infiltration in HIV
  related seminomas (Parker et al EJC 2002).
• This also suggests immune surveillance plays a
  role.

12
Why is seminoma more common?

• The lack of immune surveillance in HIV
  accelerates the development of these disease,
  which is why patients are presenting 10 yrs
  earlier.
• Therefore is the incidence truly raised or are
  predisposed patients just presenting more
  quickly resulting in a temporary increase in the
  incidence?

13
The incidence of GCT of the testis in the
1980-2003 in AIDS only patients
Goedert et al 2005
270,000 patients.
14
Other possible causes

• Advanced AIDS is associated with testicular
  atrophy, and spermatogenic arrest.
• These in turn may predispose to GCT resulting in
  an increased incidence in HIV.
• As the incidence of advanced AIDS falls so does
  the incidence of the disease .

15
Myths about HIV related testis cancer

• HIV related GCT is a more aggressive and
  chemo-resistant disease.
• Patients should receive modified treatment
  because the dont tolerate treatment.
• HIV positives dont turn up for surveillance.
• Chemotherapy and HAART cant be given together

16
Facts about HIV related testis cancer

• Patients are younger than HIV negatives
• They have relatively well preserved immune
  function
• Less aggressive seminoma is most common
• More patients present with metastatic disease
  compared to their HIV negative counterparts.
• Some of the population is very motivated

JCO 2003, BJC 2004 J Clin Epi 2007
17
What is the outcome if patients are given
standard treatment?

• Case control study
• 35 patients (diagnosed 1985-2002).
• Treatmed with standard care.
• HAART was given or continued with the advice of
  the HIV doctors

18
Overall survival
No treatment related deaths
19
What about the disease free survival?
20
Relapse free survival for patients with
metastatic disease treated with standard care
21
What are the problems with chemotherapy and
radiotherapy in HIV positives in the HAART era
CD4 counts recover within 3 month of
chemotherapy If given with HAART.
22
Disease free survival for patients with stage I
disease treated with orchidectomy and surveillance
23
Treatment options for stage I disease

• Surveillance is safe in good complaint patients.
• It avoids potentially harmful therapy.
• What do we do if compliance is an issue?

24
Conclusions

• The incidence was increased in the pre HAART era
  but it looks like it has normalised now.
• Patients should be treated in an identical manner
  to the HIV negatives and this results in
  excellent outcome.
• In stage I disease avoiding adjuvant
  myelo-suppressive therapy looks attractive
• In the long term HIV is likely to be a bigger
  problem for most of these patients therefore
  close collaboration with the HIV physicians is
  important

25
Conclusions

• The incidence was increased in the pre HAART era
  but it looks like it has normalised now.
• Patients should be treated in an identical manner
  to the HIV negatives and this results in
  excellent outcome.
• In stage I disease avoiding adjuvant
  myelo-suppressive therapy looks attractive
• In the long term HIV is likely to be a bigger
  problem for most of these patients therefore
  close collaboration with the HIV physicians is
  important

26
Conclusions

• The incidence was increased in the pre HAART era
  but it looks like it has normalised now.
• Patients should be treated in an identical manner
  to the HIV negatives and this results in
  excellent outcome.
• In stage I disease avoiding adjuvant
  myelo-suppressive therapy looks attractive
• In the long term HIV is likely to be a bigger
  problem for most of these patients therefore
  close collaboration with the HIV physicians is
  important

27
Conclusions

• The incidence was increased in the pre HAART era
  but it looks like it has normalised now.
• Patients should be treated in an identical manner
  to the HIV negatives and this results in
  excellent outcome.
• In stage I disease avoiding adjuvant
  myelo-suppressive therapy looks attractive
• In the long term HIV is likely to be a bigger
  problem for most of these patients therefore
  dont stop HAART and work with HIV doctors