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PRENATAL AND POST-PUBERTAL EPIDEMIOLOGY OF
ATROPHY IN GERM CELL CANCER JUSTIFY TESTIS
CONSERVATION STUDIES
Could endocrine preservation prevent excess
deaths from metabolic syndrome Tim Oliver and
Dan Berney
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Introduction
It is 10 years since the first reports testis
conservation with recovery of spermatogenesis
after chemotherapy cure of primary tumours. No
subsequent validation of the long term safety of
such a procedure as it requires follow up for at
least 20 years because of the persistence of
functional but in-utero sensitised spermatogonia
at heightened risk of redeveloping further
malignancy. This presentation summarises the
supportive landmarks that justify the
authors messianic view that testis conservation
should, like breast conservation, be offered as
an option to every man presenting with a
suspicious testis mass due to Role of atrophy
in developing premature andropause and so causing
late morbidity Short term safety of
chemo-conservation and activity of minimal chemo
against CIS. Long term function, low relapse rate
and increased frequency of patients who benefit
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SEMEN ANALYSIS ON NORMAL MALES AND GERM CELL
CANCER PATIENTS
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New primary testis cancer in MRC TE19
(Oliver et al 2005 Lancet 366293)
RT Radiotherapy PA Para-aortic
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Pattern of weight changes (/- 2kg) among
testicular cancer patients after orchidectomy
Surv Surveillance
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Impact of Stage and Histology of Outcome after
attempted testis conservation with Chemotherapy
Potentially Preservable Preserved testis
plus i) No evidence viable tumour at
orchidectomy ii)Less than 50 of testis involved
by tumour pre-chemotherapy
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Primary Tumour Size and Success of Testis
Conservation with Chemotherapy in Germ Cell Cancer
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Increasing proportion of patients with testis
tumours small enough for testis conservation
Powles et al, BJU international.
200595(9)1197-200.
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Endocrine Function and Sperm Counts after
Testis-Conserving Chemotherapy
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RELAPSE AFTER CHEMOTHERAPY INDUCED TESTIS
CONSERVATION
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CONCLUSIONS

• Patients with bilateral germ cell cancers have
  sperm precursors capable of being salvaged by
  chemotherapy and producing viable offspring
• Further tumours that develop after testis
  conservation by chemotherapy develop later than
  normal metastatic disease relapse and are usually
  stage 1 seminomas, so making it a safe procedure
• There is an urgent need to confirm the Danish
  groups observation that 10 of TT patients are
  rendered azo-spermic and 50 have reduction of
  their sperm count by orchidectomy of the tumour
  bearing testis, as if confirmed this increases
  the numbers of patients in whom testis
  conservation is justified

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Institute of Cancer
Summary of prenatal and post-pubertal
environmental and genetic factors in germ cell
cancer Epidemiology
Post Pubertal Factors Increasing FSH / Cyclin D2
Switch on drives CIS to Seminoma(S) to Non
Seminoma(NS) Orchitis / Testis Atrophy due to
viruses/chemicals/trauma/heat 4.0N 3.6N
2.7N. p53 bcl2 mdm2 DNA repair
activity. Trauma / surgery for crytorchidisim
NSgtS. Drug addict HIV NSgt S. Azothiaprine
immune-suppression NSgtS HIV(other) SgtNS
Cryptorchidism no op SgtNS Sedentary life early
puberty increases incidence Exercise late
puberty decrease incidence
Prenatal Factors Oestrogens / Xenoestrogens. Mater
nal Smoking (?diet). X linked gene (Xq27) and
Cryptorchdism (Oestrogen induced). C-kit gene
mutation (Induced by excessive in-utero
oestrogen). Twins MZgtDZ same pathology but less
testis cancer FH cancer NSgtS Diet High fat
increase Xenoestrogenic chemical exposure.
increases incidence Low fat decrease vitamin A
and D producing immunosuppression increases
incidence.
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Twins and Testis Cancer
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PRENATAL INFLUENCES AND RISK OF TESTIS CANCER
(Coupland et al Cancer causes and control 2002
15277)
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INCIDENCE OF MUTATED c-KIT GENE INUNILATERAL AND
BILATERAL GERM CELL TUMOURS
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Influence of Fluctuating Pain on Size of
Contralateral Testis in Patients Previously
Treated for GCC
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