Download Current Opinion in Urological Cancer

Current Opinion in Urological
Cancer
Mr C Dawson MS FRCS
Consultant Urologist
Cromwell Clinic, Huntingdon
Edith Cavell Hospital, Peterborough
Urological Cancers
• Difficulties, and Recent Advances
- Prostate Cancer
- Bladder Cancer
- Renal Cancer
• Local Referral Protocols
• Case Discussions
• Q & A Session
Prostate Cancer - Dilemmas, and
Recent Advances
The scale of the problem
• Prostate Cancer is third commonest
cause of cancer death in men (after lung
and bowel) - mortality rate 34 per
100,000 men
• Incidence rises with age, only 12% of
clinically apparent cases arise before
the age of 65
• Men with a family history are at higher
risk, but the presence of lower urinary
tract symptoms is not a risk factor
The scale of the problem
• Rate of registration of prostate cancer is
rising
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Ageing of the population
Increased diagnostic accuracy and
recording of cases
Increased incidental detection after surgery
for BPH
? widespread use of PSA
The scale of the problem
• Natural History of Prostate cancer
uncertain
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30% of men over 50 (50% of men over 80)
have histological evidence of prostate
cancer at autopsy while showing no sign of
disease during life
Most men with prostate cancer die with CAP
rather than from it
• Many men (up to 40%) present with
locally advanced or metastatic disease
Difficulty 1 - The Diagnosis of Prostate
Cancer
• No symptoms specific for prostate
cancer
• Presenting symptoms therefore those of
BPH
• Full history and examination essential,
particularly digital rectal examination
(DRE)
• Biopsy of the prostate should be
performed in those with abnormal DRE
or raised PSA
The Role of PSA
• Single-chain glycoprotein of 240 amino acid
residues and 4 carbohydrate side chains
• Physiologic function is lysis of the seminal
coagulum
• Has a half-life of 2.2 days
• Prostate specific, but not-cancer specific
• Should not be used indiscriminately
Prostate Specific Antigen
• In addition to Prostate cancer, an
elevated level may be found with
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Increasing age
Acute urinary retention and Catheterisation
TURP
Prostatitis
Prostate biopsy
BPH
but NOT rectal examination
Difficulty 2 - The Problem with PSA
• Men with Prostate cancer may have a
normal PSA
• Men with BPH or other benign
conditions may have a raised PSA
• No longer thought to be prostatespecific
• What to do with men with PSA in the
range 4-10 ng/ml?
Refinements in the use of PSA
• Refinements theoretically most useful
when PSA between 4-10 ng/ml
• Below 4ng/ml prevalence of CAP ~
1.4%, above 10ng/ml prevalence rises
to 53.3%
• PSA Density
• PSA Velocity
• Age-Specific PSA
• Free vs. total PSA
Age Specific PSA Ranges
• Determined from evaluation of PSA
values and prostate volumes according
to age
• Age specific ranges make PSA a more
sensitive marker for men <60yrs, and
more specific in men > 60 yrs
Age Specific Reference Ranges
Age
40 - 49
50 - 59
60 - 69
70 - 79
PSA
<= 2.5
<= 3.5
<= 4.5
<= 6.5
Free versus Total PSA
• The majority of PSA in serum is bound to
alpha-1-antichymotrypsin (ACT)
• The proportion of free to total PSA is
significantly lower in CAP
• Not yet understood why this ratio changes in
CAP
• May be a way of discriminating patients with
BPH and those with CAP
Free versus Total PSA
• Choice of ratio cut-off remains to be decided
- balance between missing some cancers
and dramatically reducing the number of
biopsies
• The Free to Total (F/T) PSA Ratio is perhaps
best reserved for difficult diagnostic cases;
for example men with a PSA between 410ng/ml, or those who have previously had
a negative biopsy
Free versus Total PSA
• For men with PSA 4-10ng / ml and
% free PSA Probability of cancer %
0-10
56
10-15
15-20
20-25
>25
28
20
16
8
Difficulty 3 - Screening for Prostate
cancer
The Case For:
• In order to hope to cure a patient the
disease must be diagnosed when it is organ
confined
• The incidence of prostate cancer is rising by
3% per year
• Prostate cancer is now the second
commonest cause of death in men in
Northern Europe
Screening for Prostate cancer
The case against
• Transrectal ultrasound and biopsy has a
morbidity rate
• Negative biopsies lead to significant
patient anxiety
• Correct protocol has not yet been
defined
• May detect only incurable disease, or
small tumours that are clinically
unimportant (but…)
Cancers that are PSA detected
• have been shown to be clinically significant
• are frequently poorly differentiated or spread
widely throughout the prostate
• when removed by radical surgery will often
be upgraded or upstaged.
Current opinion?
• Remains divided
• Support for screening for prostate cancer is
growing among eminent urologists
(admittedly, those with an interest in prostate
cancer)
Advances in the management of
Prostate Cancer
Management of Prostate Cancer Hormonal
• The mainstay of treatment of metastatic
disease is Anti-androgens, LHRH agonist, or
Orchidectomy
• Maximal androgen blockade has not proved
of benefit for the majority of patients
• Intermittent androgen blockade may be of
benefit for selected patients, but the longterm durability and advantages are not clear
at present
Management of Prostate Cancer Surgery
• Radical Prostatectomy is available in
Peterborough
• Morbidity and mortality rates in published
series are low
• Long-term data on cure rates is still awaited
from clinical trials
Management of Prostate Cancer Radiotherapy
• Interstitial radiation therapy (brachytherapy)
appears to be making a comeback
• Used more widely in USA, results not
available to compare with external beam
radiotherapy, or surgery
• Early evidence that intermediate- or highrisk patients may do worse with
brachytherapy
Conclusions
• Incidence of CAP, and mortality from it, is
increasing
• Screening by currently available modalities
does not appear to reduce mortality, and
may be the cause of considerable morbidity
• PSA remains a useful tool if used judiciously,
particularly in the follow up of patients after
radiotherapy or radical prostatectomy
Conclusions
• No new medical treatments available, but
better understanding of currently available
ones
• Radical Prostatectomy offers the possibility
of cure, but may also cause significant
morbidity
• Future markers for biological activity
desperately required
Points to remember
• Always do a DRE in men presenting with
lower urinary tract symptoms
• Perform a PSA in these men, and refer if
PSA above age-specific reference range
• Always refer if DRE abnormal
• If you have uroflowmetry available it can
help decide on the management of the
patient’s lower urinary tract symptoms
Bladder Cancer
Bladder Cancers are...
• Predominantly Transitional cell
carcinoma (TCC) (>90%)
• Squamous (SCC)
– 75% of bladder cancers in Egypt
– only 1% of bladder cancers in England
• Adenocarcinoma - <2% of primary
bladder cancers
– Primary vesical (arise from urachal
remnant)
– Metastatic
Epidemiology - Incidence
• 54,000 new cases in U.S. in 1997 with
11,700 deaths
• 4th most common cancer in men (after
Prostate, lung, colorectal; 10% of all) - 5% of
all cancer deaths
• 8th most common cancer in women (4% of
all), 3% of all cancer deaths
Aetiology of Bladder Cancer
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Occupational Exposure to chemicals
Cigarette smoking
Analgesics
Bacterial / Parasitic infections
Bladder calculi
Pelvic irradiation
Cytotoxic chemotherapy
Presentation of Bladder Cancer
• 85% of patients present with Painless
haematuria
• “bladder irritation” (frequency, urgency,
dysuria) - often associated with diffuse CIS
or invasive cancer
• Flank pain (suggests ureteric obstruction)
• A pelvic mass
Management - depends on type
• The Good
• The Bad
• The Ugly
The Good
• Surveillance cystoscopy - about spotting change to
a worse stage or grade
• Small low-grade tumours  TUR followed by
surveillance
• Multiple / Large / Recurrent tumours, or CIS in
random biopsy  consider intravesical
chemotherapy (mitomycin c) or immunotherapy
(bcg)
• pT1 G3 tumours have a high rate of progression 
consider early cystectomy
The Bad
• Any TCC invading the muscle wall
• 25-30% 3 year survival
• No real advance in treatment over last 50
years
• Stage T2 or T3 - partial or radical
cystectomy, radiotherapy, or combination of
both
• Stage T4 - Chemotherapy, followed by
radiation or surgery
The Ugly
• Diffuse CIS is overtly Malignant
• 78% risk of invasion
• Intravesical chemotherapy preferred primary
treatment for CIS - treatment effective in
30% and produces complete regression in
50-65% of patients
• Radiotherapy and chemotherapy ineffective
• Early cystectomy required for recurrent CIS
Palliation of Symptoms
• Advanced local disease
– May lead to persistent bleeding, or pain
– bleeding  tranexamic acid or embolisation of
internal iliac arteries
– may sometimes require cystectomy
• Ureteric Obstruction
(hydronephrosis)
– usually signifies muscle invasive cancer
– Cystectomy if disease confined to bladder
– consider nephrostomy ??
Palliation of Symptoms
• Painful bony metastases  radiotherapy
• Palliative radiotherapy may also control local
symptoms
• Blocked Catheter - may be difficult to
manage
Summary
• No new treatments available for the
treatment of bladder cancer
• Early diagnosis remains important
• Surveillance essential to spot the change to
more aggressive forms
Points to remember
• Refer ALL cases of visible haematuria
• Never assume that visible haematuria is
solely due to “infection”
• Remember that bladder cancer can present
with “malignant cystitis” – symptoms of
pain/urgency/frequency
Renal cell carcinoma
• 3% adult cancers, M:F ratio 2:1
• Majority of patients diagnosed in 6th to 7th
decade
• Sporadic and hereditary forms exist
• No specific causative agent detected smoking suggested as a significant risk
factor
Presentation of renal cell carcinoma
• “Classic triad” of pain, haematuria, and flank
mass (rare)
• More commonly just pain and haematuria
• Symptoms of metastatic disease
• Paraneoplastic syndromes
• INCIDENTAL - discovered while
investigating another problem - now
accounts for 50%
Investigation
• Ultrasound - to distinguish solid from cystic
mass
• CT - Staging, prior to surgery
• MRI - less sensitive than CT for lesions less
than 3cm
• Angiography - tumour in solitary kidney, or if
partial nephrectomy considered
CT Scan of Renal tumour
Treatment of Renal Cancer
• Radical nephrectomy
(remains the only
effective method of
treating primary renal
carcinoma)
• Embolisation
Treatment of metastatic disease
• Generally poor prognosis
• Renal cancer remains refractory to
treatment with Chemotherapy
• Hormonal therapy
• Immunotherapy
• Palliative nephrectomy
Palliation of advanced symptoms
• Persistent bleeding / pain - treatable by
embolisation
• Pain from locally advanced disease - only
effective remedy is radical surgery
Points to remember
• Refer ALL cases of frank (visible)
haematuria urgently – do not delay because
of assumption of a benign cause
• Be aware of the manifold ways that bladder
and renal cancer can present
End of part 1
Local Referral Protocols
• Very Urgent Cases – contact duty team at
Edith Cavell Hospital who will admit cases if
necessary
• Urgent “GPM” referrals – Outpatient Slots
available with all consultants within 2 weeks
• Refer GPM cases by fax – 01733 875726
• No specific investigations required in
advance (except PSA if appropriate)
Microscopic haematuria
• Investigate all dipstick proven microscopic
haematuria (i.e. anything more than “trace”
haematuria)
• All patients require renal ultrasound
• If patient < 45 years old, AND normal renal
ultrasound  refer for Nephrological
opinion
• Patients > 45 years old, and ALL those with
abnormal renal ultrasound  refer to
Urology
End of Part 2
Case Discussion 1
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65 year old lady
Previously well apart from mild hypertension
No medications
6/12 history of frequency and urgency
Has had one proven UTI but other 3 MSUs
negative
Case Discussion 1
• What investigations would be appropriate?
• What would you do next?
• What might be the diagnosis?
Case Discussion 2
• 56 year old man with 9 month history of
nocturia and frequency
• Otherwise well
• PSA 3.7
• Rectal examination normal
• He is not worried
• What would you do?
Case Discussion 3
• 47 year old man comes to surgery
• Has read about prostate cancer in
newspaper
• Is concerned because his father (aged 74)
has been diagnosed with prostate cancer
recently
• What would you do?
Case Discussion 4
• 53 year old woman with right sided
abdominal pain
• You send her for an USS scan
• She has gallstones but the scan shows a
lesion in the lower pole of the right kidney
• What would you do next?
Case Discussion 5
• 24 year old man with swollen testis
• Has been uncomfortable for some time
• Referred for USS 3 weeks ago – “signs
consistent with infection”
• No improvement despite antibiotics
• What would you do next?
End of Part 3
Questions and Answers