4The 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 menIncidence rises with age, only 12% of clinically apparent cases arise before the age of 65Men with a family history are at higher risk, but the presence of lower urinary tract symptoms is not a risk factor
5The scale of the problem Rate of registration of prostate cancer is risingAgeing of the populationIncreased diagnostic accuracy and recording of casesIncreased incidental detection after surgery for BPH? widespread use of PSA
6The scale of the problem Natural History of Prostate cancer uncertain30% of men over 50 (50% of men over 80) have histological evidence of prostate cancer at autopsy while showing no sign of disease during lifeMost men with prostate cancer die with CAP rather than from itMany men (up to 40%) present with locally advanced or metastatic disease
7Difficulty 1 - The Diagnosis of Prostate Cancer No symptoms specific for prostate cancerPresenting symptoms therefore those of BPHFull history and examination essential, particularly digital rectal examination (DRE)Biopsy of the prostate should be performed in those with abnormal DRE or raised PSA
8The Role of PSASingle-chain glycoprotein of 240 amino acid residues and 4 carbohydrate side chainsPhysiologic function is lysis of the seminal coagulumHas a half-life of 2.2 daysProstate specific, but not-cancer specificShould not be used indiscriminately
9Prostate Specific Antigen In addition to Prostate cancer, an elevated level may be found withIncreasing ageAcute urinary retention and CatheterisationTURPProstatitisProstate biopsyBPHbut NOT rectal examination
10Difficulty 2 - The Problem with PSA Men with Prostate cancer may have a normal PSAMen with BPH or other benign conditions may have a raised PSANo longer thought to be prostate-specificWhat to do with men with PSA in the range 4-10 ng/ml?
11Refinements in the use of PSA Refinements theoretically most useful when PSA between 4-10 ng/mlBelow 4ng/ml prevalence of CAP ~ 1.4%, above 10ng/ml prevalence rises to 53.3%PSA DensityPSA VelocityAge-Specific PSAFree vs. total PSA
12Age Specific PSA Ranges Determined from evaluation of PSA values and prostate volumes according to ageAge specific ranges make PSA a more sensitive marker for men <60yrs, and more specific in men > 60 yrs
14Free versus Total PSAThe majority of PSA in serum is bound to alpha-1-antichymotrypsin (ACT)The proportion of free to total PSA is significantly lower in CAPNot yet understood why this ratio changes in CAPMay be a way of discriminating patients with BPH and those with CAP
15Free versus Total PSAChoice of ratio cut-off remains to be decided - balance between missing some cancers and dramatically reducing the number of biopsiesThe Free to Total (F/T) PSA Ratio is perhaps best reserved for difficult diagnostic cases; for example men with a PSA between 4-10ng/ml, or those who have previously had a negative biopsy
16Free versus Total PSA 0-10 56 For men with PSA 4-10ng / ml and % free PSA Probability of cancer %>25 8
17Difficulty 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 confinedThe incidence of prostate cancer is rising by 3% per yearProstate cancer is now the second commonest cause of death in men in Northern Europe
18Screening for Prostate cancer The case againstTransrectal ultrasound and biopsy has a morbidity rateNegative biopsies lead to significant patient anxietyCorrect protocol has not yet been definedMay detect only incurable disease, or small tumours that are clinically unimportant (but…)
19Cancers that are PSA detected have been shown to be clinically significantare frequently poorly differentiated or spread widely throughout the prostatewhen removed by radical surgery will often be upgraded or upstaged.
20Current opinion? Remains divided Support for screening for prostate cancer is growing among eminent urologists (admittedly, those with an interest in prostate cancer)
22Management of Prostate Cancer - Hormonal The mainstay of treatment of metastatic disease is Anti-androgens, LHRH agonist, or OrchidectomyMaximal androgen blockade has not proved of benefit for the majority of patientsIntermittent androgen blockade may be of benefit for selected patients, but the long-term durability and advantages are not clear at present
23Management of Prostate Cancer - Surgery Radical Prostatectomy is available in PeterboroughMorbidity and mortality rates in published series are lowLong-term data on cure rates is still awaited from clinical trials
24Management of Prostate Cancer - Radiotherapy Interstitial radiation therapy (brachytherapy) appears to be making a comebackUsed more widely in USA, results not available to compare with external beam radiotherapy, or surgeryEarly evidence that intermediate- or high-risk patients may do worse with brachytherapy
25Conclusions 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 morbidityPSA remains a useful tool if used judiciously, particularly in the follow up of patients after radiotherapy or radical prostatectomy
26ConclusionsNo new medical treatments available, but better understanding of currently available onesRadical Prostatectomy offers the possibility of cure, but may also cause significant morbidityFuture markers for biological activity desperately required
27Points to rememberAlways do a DRE in men presenting with lower urinary tract symptomsPerform a PSA in these men, and refer if PSA above age-specific reference rangeAlways refer if DRE abnormalIf you have uroflowmetry available it can help decide on the management of the patient’s lower urinary tract symptoms
30Bladder Cancers are...Predominantly Transitional cell carcinoma (TCC) (>90%)Squamous (SCC)75% of bladder cancers in Egyptonly 1% of bladder cancers in EnglandAdenocarcinoma - <2% of primary bladder cancersPrimary vesical (arise from urachal remnant)Metastatic
31Epidemiology - Incidence 54,000 new cases in U.S. in 1997 with 11,700 deaths4th most common cancer in men (after Prostate, lung, colorectal; 10% of all) - 5% of all cancer deaths8th most common cancer in women (4% of all), 3% of all cancer deaths
32Aetiology of Bladder Cancer Occupational Exposure to chemicalsCigarette smokingAnalgesicsBacterial / Parasitic infectionsBladder calculiPelvic irradiationCytotoxic chemotherapy
33Presentation of Bladder Cancer 85% of patients present with Painless haematuria“bladder irritation” (frequency, urgency, dysuria) - often associated with diffuse CIS or invasive cancerFlank pain (suggests ureteric obstruction)A pelvic mass
34Management - depends on type The GoodThe BadThe Ugly
35The GoodSurveillance cystoscopy - about spotting change to a worse stage or gradeSmall low-grade tumours TUR followed by surveillanceMultiple / 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
36The Bad Any TCC invading the muscle wall 25-30% 3 year survival No real advance in treatment over last 50 yearsStage T2 or T3 - partial or radical cystectomy, radiotherapy, or combination of bothStage T4 - Chemotherapy, followed by radiation or surgery
37The 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 patientsRadiotherapy and chemotherapy ineffectiveEarly cystectomy required for recurrent CIS
38Palliation of Symptoms Advanced local diseaseMay lead to persistent bleeding, or painbleeding tranexamic acid or embolisation of internal iliac arteriesmay sometimes require cystectomyUreteric Obstruction (hydronephrosis)usually signifies muscle invasive cancerCystectomy if disease confined to bladderconsider nephrostomy ??
39Palliation of Symptoms Painful bony metastases radiotherapyPalliative radiotherapy may also control local symptomsBlocked Catheter - may be difficult to manage
40SummaryNo new treatments available for the treatment of bladder cancerEarly diagnosis remains importantSurveillance essential to spot the change to more aggressive forms
41Points 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
43Renal cell carcinoma 3% adult cancers, M:F ratio 2:1 Majority of patients diagnosed in 6th to 7th decadeSporadic and hereditary forms existNo specific causative agent detected - smoking suggested as a significant risk factor
44Presentation of renal cell carcinoma “Classic triad” of pain, haematuria, and flank mass (rare)More commonly just pain and haematuriaSymptoms of metastatic diseaseParaneoplastic syndromesINCIDENTAL - discovered while investigating another problem - now accounts for 50%
45Investigation Ultrasound - to distinguish solid from cystic mass CT - Staging, prior to surgeryMRI - less sensitive than CT for lesions less than 3cmAngiography - tumour in solitary kidney, or if partial nephrectomy considered
47Treatment of Renal Cancer Radical nephrectomy (remains the only effective method of treating primary renal carcinoma)Embolisation
48Treatment of metastatic disease Generally poor prognosisRenal cancer remains refractory to treatment with ChemotherapyHormonal therapyImmunotherapyPalliative nephrectomyChemotherapy - Most drugs lack any therapeutic efficacy.Hormonal therapy - Basis for hormone therapy of advanced renal cancer was the demonstration of its efficacy against and oestrogen-induced clear cell tumour in the adult Syrian hamster.Progesterone therapy (Medroxyprogesterone acetate [Provera]) ) given twice weekly continues to be a method of management in the absence of more effective agents.However, no proper study has proved the efficacy of these agents in the management of advanced renal carcinoma.Immunotherapy - theory is that host immune functions play a role in tumour control and that these immune functions can be stimulated.Several reports of small numbers of patients treated with BCG have shown some benefit. INTERFERON - Type 1 (alpha) interferon has been used in metastatic renal cancer and responses of 16.5% (complete), and 26% (partial) have been noted. Responses appear independent of preparation used, and correlate with those patients who have undergone previous nephrectomy, and who have a good performance status, a long disease-free interval, and lung-predominant disease. TCGF (IL-2) is a 15k dalton glycoprotein produced by Th cells. In vivo it generates LAK cells, and enhances NK cell function, augments alloantigen responses, and stimulates production of T cells with antitumour function. Variable responses have been produced, but id does seem that in some patients IL-2 can alter the natural history of the disease - probably 5% complete, and further 10-15% partially. NB side effects are awful! - fever, chills, malaise, nausea, vomiting, diarrhoea, Renal and cardiopulmonary“Adjunctive” nephrectomy - Anecdotal evidence that removal of primary tumour may lead to regression of metastases. However regression occurs in <1% after adjunctive nephrectomy, and such regressions are often short lived. One study of 73% patients followed for 5 years reported a spontaneous regression rate of 6%, so it is difficult to support a routine practice of adjunctive nephrectomy. Nephrectomy prior to trial of interferon therapy has been suggested to improve outcome, but this has not been conclusively shown.Campbells p
49Palliation of advanced symptoms Persistent bleeding / pain - treatable by embolisationPain from locally advanced disease - only effective remedy is radical surgery
50Points to rememberRefer ALL cases of frank (visible) haematuria urgently – do not delay because of assumption of a benign causeBe aware of the manifold ways that bladder and renal cancer can present
52Local Referral Protocols Very Urgent Cases – contact duty team at Edith Cavell Hospital who will admit cases if necessaryUrgent “GPM” referrals – Outpatient Slots available with all consultants within 2 weeksRefer GPM cases by fax –No specific investigations required in advance (except PSA if appropriate)
53Microscopic haematuria Investigate all dipstick proven microscopic haematuria (i.e. anything more than “trace” haematuria)All patients require renal ultrasoundIf patient < 45 years old, AND normal renal ultrasound refer for Nephrological opinionPatients > 45 years old, and ALL those with abnormal renal ultrasound refer to Urology
55Case Discussion 1 65 year old lady Previously well apart from mild hypertensionNo medications6/12 history of frequency and urgencyHas had one proven UTI but other 3 MSUs negative
56Case Discussion 1 What investigations would be appropriate? What would you do next?What might be the diagnosis?
57Case Discussion 256 year old man with 9 month history of nocturia and frequencyOtherwise wellPSA 3.7Rectal examination normalHe is not worriedWhat would you do?
58Case Discussion 3 47 year old man comes to surgery Has read about prostate cancer in newspaperIs concerned because his father (aged 74) has been diagnosed with prostate cancer recentlyWhat would you do?
59Case Discussion 4 53 year old woman with right sided abdominal pain You send her for an USS scanShe has gallstones but the scan shows a lesion in the lower pole of the right kidneyWhat would you do next?
60Case Discussion 5 24 year old man with swollen testis Has been uncomfortable for some timeReferred for USS 3 weeks ago – “signs consistent with infection”No improvement despite antibioticsWhat would you do next?