Oxford Textbook of Fundamentals of Surgery

William E. G. Thomas (ed.) et al.

https://doi.org/10.1093/med/9780199665549.001.0001
Published: 2016 Online ISBN: 9780191810817 Print ISBN: 9780199665549

CHAPTER

2.9.2 Genitourinary malignancies 

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Aidan Noon, James Catto

https://doi.org/10.1093/med/9780199665549.003.0048 Pages 373–377

Published: July 2016

Abstract
Genitourinary cancers include some of the most common (prostate adenocarcinoma is the most
common male cancer) and expensive (urothelial carcinoma is one of the most expensive human
cancers to manage) human malignancies. Changes in healthcare practice, such as screening for
prostate cancer and the use of abdominal imaging for the identi cation of incidental renal cancer, have
increased the detection of these cancers and produced a migration to low-stage disease at diagnosis.
Re nements in treatment, such as systemic chemotherapy for testis cancer, have improved the
prognosis for many genitourinary cancers, with the exception being bladder cancer. Surgery plays a
key role in the treatment of most genitourinary cancers and is often performed using traditional or
robot assisted laparoscopy (and increasingly through single incision surgery (LESS)). Molecular
biological research has led to targeted molecular therapies for patients with metastatic renal cell
carcinoma and urinary biomarkers for bladder cancer.

Keywords: renal cell carcinoma, urothelial cell carcinoma, prostate carcinoma, testicular carcinoma,
penile carcinoma
Subject: Urology, Surgery, Paediatric Surgery, Cardiothoracic Surgery, Peri-operative Care, Trauma and
Orthopaedic Surgery, Upper Gastrointestinal Surgery, Colorectal Surgery, Surgical Oncology, Neurosurgery,
Breast Surgery, Transplant Surgery, Vascular Surgery, Surgical Skills
Series: Oxford Textbooks in Surgery
Introduction

Genitourinary cancers include some of the most common and most expensive human malignancies to treat.
The outcomes from these cancers vary from excellent (low-risk prostate cancer) to poor (metastatic bladder
and renal cancer). Most of these cancers increase in incidence with ageing, and overall more men are
a ected by these cancers than women. This re ects the fact that prostate cancer is male speci c, and that
urothelial and renal cancers are linked to occupational exposure or cigarette smoking. Systematic screening
programmes (for prostate cancer) and opportunistic testing for haematuria (urinalysis) or abdominal pain
(widespread use of ultrasound scans) have increased the detection of most genitourinary cancers and

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induced a migration to lower-stage disease. Current challenges facing clinicians include the overtreatment
of indolent disease (Figure 2.9.2.1) and improving the treatment of advanced incurable cancers.

Fig. 2.9.2.1

Incidence of genitourinary cancers.

Source: data from Cancer Research UK, Latest cancer statistics publications, Copyright © Cancer Research UK 2013, available
from http://www.cancerresearchuk.org/cancer-info/cancerstats/incidence/

Kidney cancer

Incidence
In the UK, kidney cancer is the seventh and ninth most common malignancy in men and women,
respectively. It has a peak incidence in the sixth and seventh decade (Figure 2.9.2.1) and is more common in
1
men than women (2:1 ratio). Recognized risk factors include obesity and smoking. Approximately 4% of
2
cancers are hereditary.
Pathology
Kidney tumours include renal cell carcinoma (RCC) originating from the parenchyma (80% of all tumours),
urothelial carcinoma (arising from the renal pelvis: 18%), and rare tumours (such as lymphoma [1–2%] or
sarcoma [<1%]). There are histological variants of RCC, of which clear cell (ccRCC 75%), papillary (12%),
and chromophobe (4%) are the most common. Patients with Von Hippel–Lindau (VHL) syndrome inherit a
mutant VHL gene. Loss of this tumour suppressor predisposes patients to ccRCC (often bilateral).
Approximately 60% of ccRCCs harbour loss of VHL expression and this leads to overexpression of
3,4
angiogenic transcription factors (large ccRCC are often highly vascular).

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Renal tumours grow locally through the capsule and renal fat, and have the propensity to invade the renal
vein, inferior vena cava, and even reach the right atrium with tumour thrombus. The lungs are the most
common site for metastatic spread, followed by lymph nodes, the liver, and skeleton. RCC is staged
according to the TNM classi cation and graded by the Fuhrman system (I–IV). Survival decreases for
patients as stage or grade increases.

Clinical presentation
Currently most tumours are detected incidentally through imaging for unrelated abdominal symptoms or
the investigation of haematuria. Patients with advanced disease present with a classic triad of loin pain,
haematuria, and a mass. For smaller lesions less than 3 cm, there can be diagnostic uncertainty (20–30% of
lesions are benign). Renal biopsy can help clarify the diagnosis. RCC is associated with a number of
paraneoplastic syndromes: hypercalcaemia, anaemia, hyponatraemia, elevated erythrocyte sedimentation
rate, polycythaemia, and Stau er’s syndrome (abnormal liver function tests, hepatic necrosis,
thrombocytopenia, fever, weight loss).

Management

Localized disease
5
Tumours con ned to the kidney (pT2) may be managed by surveillance, partial nephrectomy (termed
nephron sparing surgery) if anatomically possible, ablation (using energy to destroy the tissue) if small and
exophytic, or by radical nephrectomy (typically for larger tumours). The desire for long term nephron-
6
preservation has made partial nephrectomy the treatment of choice in suitable patients.

Locally advanced and metastatic disease

Locally advanced tumours, particularly with tumour thrombus involving the vena cava, are mostly removed
by open or robotic radical nephrectomy. RCC is resistant to chemotherapy. Patients with metastatic disease
are treated with targeted molecular therapy (sorafenib, sunitinib and temsirolimus) or immunotherapy
7,8,9
(PD-1 inhibitors).
Bladder cancer

Incidence
Bladder cancer (BC) is the fourth most common malignancy in men and seventh most common malignancy
in females. Risk factors include smoking (accounts for 50% of BC), occupational carcinogen exposure
(10%), cyclophosphamide, pioglitazone, and pelvic irradiation. Squamous carcinoma may arise following
chronic in ammation (e.g. long-term indwelling catheters, bladder stones, and schistosomiasis). BC is
10
more common in males than females.

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Pathology
Histologically most BC are urothelial cell carcinoma (UCC; 90%), followed by squamous cell carcinoma
(5%), adenocarcinoma (2%), and rare pathologies (sarcoma, lymphoma, etc.). BC is staged using the TNM
classi cation. Around 80% of tumours are non-muscle invasive at diagnosis (NMI = CIS, pTa and pT1).
Tumours are graded according the World Health Organization (WHO) 1977 (G1, G2, and G3) and the WHO
3
2004 (low or high grade) systems. BC commonly metastases to pelvic lymph nodes and the lungs.

Clinical presentation
Painless visible and non-visible haematuria are the most common presentations. Other presenting
symptoms include irritative urinary symptoms and recurrent or di cult to treat UTIs.

Management
Investigation of haematuria includes a exible cystoscopy and evaluation of the upper tracts (such as
computed tomography urogram). Patients with tumours then proceed to transurethral resection of tumour
(TURT). Subsequent management depends on the tumour stage, grade, multiplicity and the state of the at
urothelium.

Non-muscle-invasive disease
NMI tumours are treated by TURT and a single dose of intravesical mitomycin C (to reduce future
11
recurrences). Tumour excision should include underlying muscle (and sampling of the at urothelium in
high-grade cases). For high-grade NMI disease (any grade 3), patients may undergo re-resection within 6
12
to 10 weeks to ensure the tumour has been fully excised.
Muscle-invasive disease
Treatment options for muscle-invasive disease include radical cystectomy and radical radiotherapy. Cure
13
rates with cystectomy are improved with neo-adjuvant chemotherapy. Pelvic lymphadenectomy is
performed at the time of cystectomy to fully stage the disease and in an attempt to remove micrometastatic
disease. Excised nodes include the obturator and the external and internal iliac chains. Radical cystectomy
in the male involves removing the prostate (cystoprostatectomy) and in females involves removing the
uterus, cervix, and anterior vagina (anterior pelvic exenteration). Following cystectomy, urinary
reconstruction may be through formation of an ileal conduit (most common), construction of an orthotopic
14
neobladder (around 25%), catheterizable continent urinary pouch, or formation of a

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ureterosigmoidostomy (both rare). Less t patients or those seeking bladder preservation may be treated
with radical external beam radiotherapy.

Systemic treatments
Patients with symptomatic metastatic disease may be treated with palliative cisplatin-based chemotherapy,
although UCC is relatively drug resistant.

Upper tract disease

Urothelium lines the collecting system of the kidney and ureters, and these areas are also susceptible to
upper tract UCC in at-risk individuals. Patients commonly present with haematuria (occasionally clot colic)
or incidentally on cross-sectional imaging. Treatment is normally by radical nephroureterectomy
(laparoscopic or open). Patients with mid to lower ureteric lesions and single renal units may be amenable
to segmental ureteric excision and reimplantation/reconstruction. These patients require surveillance as
15
they are at high risk of recurrence within the bladder or the contralateral upper tract.

Prostate cancer

Incidence
Prostate cancer is the most common male malignancy and the second leading malignant cause of death in
men in the UK. The incidence of the disease is increasing re ecting opportunistic screening using prostate-
speci c antigen testing (PSA) and the ageing population (<0.1% of cases occur in men < 50 years of age).
Post-mortem studies reveal many men have small well-di erentiated prostate cancers (termed latent or
insigni cant; found in half of 50 year olds and the majority of 70 year olds) and so the key clinical challenge
is to discriminate between indolent and aggressive tumours. Approximately 10% of cancers have an
16,17
inherited genetic component.

Pathology
Most prostate cancers are adenocarcinoma and are staged according to TNM: T1 disease is non-palpable
(diagnosed from TURP or needle biopsy); T2 is palpable disease con ned to the prostate; T3 is extracapsular
extension beyond the prostate; and T4 is invasion into adjacent organs. Gleason grading evaluates the
architectural disruption of the cancer and assigns two scores between 1 (best di erentiated) to 5 (worst) for
the two most common disease patterns (e.g. 3 + 4 = 7). Prostate cancer metastasizes to pelvic lymph nodes
18
and the axial skeleton. Visceral metastases are uncommon and usual herald a poor prognosis.
Clinical presentation

Localized disease
Most localized tumours are detected through PSA testing. Otherwise, localized cancers rarely cause lower
urinary tract symptoms (mostly due to benign prostatic enlargement) but can be found in the tissue
removed during TURP, or during investigation of haematuria, or other symptoms. PSA is a serine protease
important for liquefying the ejaculate. PSA is produced by prostate tissue and in cancer there is architectural
disruption of the glands that allows PSA to reach the circulation. Screening using PSA testing has been

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shown in randomized controlled trials to decrease prostate cancer mortality, but at the expense of over
19
detection and over treatment. As such, screening has not yet been introduced in the UK. Glandular
architectural disruption (leading to an elevated serum PSA) is also found with infection, instrumentation of
the lower urine tract, and ejaculation. Thus, PSA has a low speci city (25% of men with elevated PSA have
cancer) and low sensitivity (25% of cancers have a PSA < 4.0 ng/µL) for the disease.

In patients thought likely to bene t from treatment, histological con rmation is provided by needle biopsy
of the prostate using a transrectal or transperineal approach guided by a rectal ultrasound probe. Not all
patients are diagnosed by their rst set of biopsies. If clinical suspicion remains, patients may be subjected
to multiple biopsy procedures with the chance of detecting clinically important disease falling after each
biopsy. Di usion-weighted MRI and template biopsy protocols can be used amongst other techniques to try
to detect lesions that might be missed using a standard prostatic biopsy protocol. It is important to note that
prostatic biopsy carries a risk of severe sepsis (<1%) and for this reason the decision to pursue a
18
histologically diagnosis of prostate cancer must be balanced against this risk.

Locally advanced and metastatic disease

Patients with more advanced disease may present in a number of ways depending on the e ect of the
tumour. An enlarging prostatic cancer can cause hydronephrosis and obstructive nephropathy resulting in
overt renal failure. Patients with skeletal metastases may present with bone pain, acute spinal cord
compression, symptoms of bone marrow failure, or hypercalcaemia.

Management
The management of prostate cancer depends on the patient (performance status, age, symptoms) and the
tumour (extent judged by PSA, clinical stage, and Gleason grade).

Treatments with curative intent

In low-risk cases, patients should consider a period of active surveillance (close observation using protocols
with serial PSA measurement, interval re-biopsy, and MRIs) rather than risking the side e ects of radical
treatment. Triggers for radical intervention are a rapidly rising PSA or a 10 ng/uL threshold, or an increase in
grade/stage. Patients with locally con ned (≤pT2) and locally advanced (pT3) tumours are suitable for
radical treatment. These include radical prostatectomy (the gold standard treatment) that may be
performed via an open, laparoscopic, or robotically assisted technique, and radical radiotherapy in the form
of external beam or brachytherapy (for certain tumours). Side e ects of surgery include stress urinary
incontinence (1–5% at 1 year) and erectile dysfunction (common). Both can be reduced by nerve-sparing
procedures in suitable tumours. Focal ablative techniques exist in the form of cryotherapy, high intensity
20
focused ultrasound, or photodynamic treatments.
Systemic and palliative treatments
Patients with incurable disease (metastatic or not suitable for curative treatments) may be managed
expectantly (watchful waiting). In this setting palliative treatments are initiated when a patient becomes
symptomatic. Systemic treatments normally start with androgen deprivation by surgical castration or
hormone manipulation. Testosterone release may be stopped by supraphysiological non-cyclical
administration of luteinizing hormone-releasing hormone (LHRH) agonists (note: these cause an initial
testosterone surge) or an LHRH antagonist. Patients presenting with spinal cord compression due to a
hormone naïve prostate cancer should have urgent castration (emergency orchidectomy) and if performed
21
early enough, this o ers a rapid and dramatic improvement to the patients’ symptoms. Patients that

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develop symptoms during hormone treatment or display a biochemical relapse (successively rising PSAs)
may be o ered second-line hormone manipulation (anti-androgens). Other options include taxane
20
chemotherapy, abiterone. Radiotherapy or Zoledronic acid can be used for bone pain.

Testicular carcinoma

Incidence
Testicular cancer is responsible for 1% of male tumours in the UK. The lifetime male risk is 1:500 for a
normally descended testicle. The major risk factors for this disease are testicular maldescent, rst-degree
22
relative with the disease, subfertility, Kleinfelter’s syndrome, and Kallman’s disease.

Pathology
Ninety- ve per cent of tumours derive from germ cells and the remainder are non-germ cell tumours (3%
Leydig cell and 1% Sertoli cell). Germ cell tumours are divided into seminomatous (70%: classic,
spermatocytic, or anaplastic) and non-seminomatous germ cell tumours (NSGCTs: 30%). NSGCTs are
subdivided according the WHO classi cation (mature teratoma, immature teratoma, embryonal carcinoma,
choriocarcinoma, yolk-sac tumour, or mixed). Elevated serum testicular tumour markers (alpha-
fetoprotein produced by yolk-sac elements, beta subunit of human chorionic gonadotrophin produced by
syncytiotrophoblasts, and lactate dehydrogenase) are seen in 50% of tumours. Testicular tumours
22
metastasize rst to the para-aortic lymph node chain.

Clinical presentation
Testicular carcinoma most commonly presents as a hard mass arising within the body of testicle. Patients
with advanced disease may manifest abdominal swelling (enlarged lymph nodes), breathlessness (lung
23
metastases), or weight loss.

Management
Testicular carcinoma is diagnosed clinically and con rmed ultrasonically. Patients with obvious signs of
metastatic disease should be referred to oncologists for consideration of immediate chemotherapy. Radical
23,24
inguinal orchidectomy is the gold standard treatment.
Post-orchidectomy management
Patients undergo cross-sectional imaging with a computed tomogram scan. The stage of their disease,
including tumour marker status, is combined with histological information to risk stratify the patients.
Motivated patients with low-risk disease are suitable for regular clinic surveillance. Patients at high risk of
recurrence may be o ered radiotherapy (not NSGCTs, which are radio-insensitive), chemotherapy, or
prophylactic lymph node dissection. Patients with metastatic disease may be o ered radiotherapy or
23,24
chemotherapy with surgical lymph node excision being reserved for residual disease.

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Penile cancer

Penile carcinoma is a rare condition with an incidence of 1/100 000 population (approximately 350 men/year
in the UK). Risk factors include human papilloma virus 16, 18, 31, and 33. Patients present with a lesion or
thickening of the glans or prepuce. There are a number of recognized premalignant lesions, for example
25
erythroplasia of Queryat, Bowen’s disease, and leukoplakia. Penile carcinoma progresses in a step-wise
manner with metastases to the inguinal and then pelvic lymph nodes. Patients may present (30–60%) with
enlarged inguinal lymph nodes and assessment of these will reveal malignancy in approximately 50% of
cases. The majority of tumours are squamous cell cancers (95%) and there are a number of recognized
subtypes. Three growth patterns are commonly observed: super cial spreading, nodular, and verrucous
(exophytic). Initial management requires biopsy of the penile lesion and assessment of the lymph nodes.

Treatment of the lesion depends on the grade and stage of the tumour. Carcinoma in situ can be treated by
topical ointments (imiquimod or 5- uorouracil cream), laser ablation, cryotherapy, phytotherapy, or
surgical resurfacing. Ta/T1 lesions can be treated by glandular resurfacing, wide local excision, or
glansectomy. For T2 lesions a ecting the corpus spongiosum, glansectomy is the treatment of the choice
and partial penectomy is employed for lesions a ecting the corpus cavernosum. T3 lesions are treated by
radical penectomy, and T4 lesions can be treated with neo-adjuvant chemotherapy with salvage surgery if
su cient down staging is achieved.

Management of the lymph nodes depends on their size (i.e. palpable or not palpable). Impalpable nodes can
be sampled using sentinel lymph node biopsy (injecting a blue dye/radiolabelled nanocolloid around the
tumour to locate the rst lymph node draining the lesion). Patients with positive lymph nodes undergo
26
lymph node dissection.
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