Prostate Cancer Flashcards
Function and anatomy of prostate
-The prostate gland is a reproductive accessory organ in males which contributes to semen production, located beneath the bladder and surrounding the urethra.
-Consists of central, transition and peripheral zones, with 80% of tumours arising within peripheral zone.
Epidemiology of prostate cancer
-Prostate cancer is the commonest cancer affecting men in the UK, with 52,300new cases a year.
-After lung cancer, second most common cause of cancer death in men, accounting for 14% of cancer deaths in UK.
-Worldwide, 1.2 million new cases and 350,000 cancer-related deaths annually.
-Risk increases with age; most diagnoses occur in patients over 60.
-Highest incidences in high-income countries with longer life expectancies
-80% of men with prostate cancer are diagnosed with organ-confined disease. Their prognosis is excellent, with 5-year survival rates of 95 – 100%.
Presentation of prostate cancer
Lower urinary tract symptoms (LUTS) such as increased urinary frequency, decreased flow, nocturia, incomplete emptying, and haematospermia
Examination of prostate cancer
digital rectal examination (DRE) may reveal an enlarged, firm or craggy prostate
Blood tests for prostate cancer
-Prostate specific antigen (PSA). Abnormal if > 3.0 ng/ml in ages < 50 y/o, > 4.0ng/ml in 50 – 60 y/o and > 5.0 ng/ml in > 60 y/o. Note, PSA can be elevated in benign prostatic hypertrophy, following prostatitis/UTI and following instrumentation (such as urinary catheter) or examination. Not all prostate cancers produce PSA (such as poorly differentiated or neuroendocrine prostate cancer), though this is uncommon.
-If elevated PSA up or PR suspicious, refer to urology. Currently there is no PSA-based screening programme in the UK as studies evaluating screening programmes did not show a decrease in overall mortality and highlighted the risk of over-diagnosis of cancers that may never become clinically apparent. MRI-based screening may be introduced in the future
Prostate cancer radiology
Multi-parametric MRI prostate. Nuclear medicine (NM) bone scan (to exclude skeletal metastases) in higher-risk disease (high PSA or Gleason Score
Biopsy of prostate cancer
Normally done by TRUS (transrectal ultrasounds guided biopsy). Targeted biopsy carried out in more anterior lesions which are difficult to access via TRUS.
Pathology and risk stratification of prostate cancer
Prostate cancers are histologically graded using the Gleason score. Essentially the first and second most abundant cancer cell type are given a score between 3 and 5 based on histological features, creating a combined overall score (for
example 3 + 4 = 7, the lowest and highest possible overall grades are 3 + 3 = 6 and 5 +5 = 10). NB: Gleason scores of 1 -2 are benign.
-Risk stratification: The Cambridge Prognostic Group criteria are increasingly used to risk-stratify patients; this gives a score of 1 – 5 based on Gleason score, tumour T stage and PSA, with a higher score indicating disease at higher risk of relapse. Risk stratifying helps clinicians to decide on the most appropriate treatment for a patient
Management of low risk prostate cancer
-Treatment options depend on the risk of future biochemical relapse (i.e. a rising PSA following treatment). Patients with low-risk disease (PSA < 10 ng/ml, Gleason score < 6and early T-stage)
-Surgery in the form of radical prostatectomy (often robotically assisted)
-Radiotherapy
=External beam radiotherapy: four weeks of outpatient treatment
=Brachytherapy: single visit where radioactive seeds are inserted into the prostate under anaesthetic.
-Active surveillance – where patients do not immediately undergo treatment but enter a programme of PSA monitoring and repeat MRI and biopsy where indicated. Treatment can then be offered when higher-risk disease develops, as determined by biopsy
-Watchful waiting – where it is accepted that the patient will not benefit from radical treatment due to age or co-morbidities, and instead hormone treatment(see below) is started at the point of rising PSA or the development of symptoms (old frail comorbid patents)
*higher rates of sexual dysfunction and urinary incontinence following surgery, and higher rates of long-term bowel toxicity (diarrhoea, PR bleeding)following radiotherapy
Management of intermediate and high-risk prostate cancer
-Patients with intermediate or high-risk disease (PSA > 10 ng/ml, Gleason score > 6 or higher T stage), should be offered radical treatment in the form of radiotherapy or surgery.
-These patients also benefit from receiving androgen deprivation therapy (ADT), where LHRH agonists or antagonists (see below) are used to suppress testosterone production (which stimulates prostate cancer growth). Depending on risk-factors, this is given for between 4 and 24 months.
-Patients where prostate cancer had spread to nearby lymph nodes or who have locally advanced disease (i.e., the primary tumour is invading nearby structures) can also benefit from receiving chemotherapy (e.g., docetaxel) before undergoing radiotherapy. Recently, oral anti-cancer drugs known as androgen receptor inhibitors (ARSI, e.g., abiraterone) have been approved for this use.
-In cases where prostate cancer has spread to lymph nodes, the radiotherapy field is extended to include the entire pelvis. If a surgical approach is taken, then a lymph node dissection should be carried out, however the risk of residual disease is high and for that reason radiotherapy is often favoured over surgery in these cases
Management of metastatic prostate cancer
5% of patients present with metastatic disease, where the cancer has spread to distant lymph nodes, visceral organs or bones. This is incurable, but relative to other advanced cancers, the prognosis of metastatic prostate cancer is reasonably good, with 5-yearsurvival rates of 50%. Some patients can be managed with relatively little treatment toxicity for several years.
-The most common sites of metastases are bone or lymph nodes. Patients may present symptomatically with bone pain (often with raised alkaline phosphatase in blood tests),incidentally on imaging for other causes, a raised PSA, or by developing biochemical relapse following radical treatment.
Systemic anti-cancer therapy in prostate cancer
The mainstay of treatment is androgen deprivation therapy (often known as hormone treatment) and normally a high response rate (>90%) is seen for a number of years. The treatment of choice is usually an LHRH agonist. In response to starting LHRH agonists, there is an initial rise in testosterone (before negative feedback kicks is) so patients should receive a short course of androgen-receptor blockers (bicalutmide/casodex) at the time of the first injection. LHRH antagonists (degarelix/firmagon) work quicker and do not cause an initial rise in testosterone
=Patients stay on androgen deprivation for the rest of their lives. In addition to this, other systemic anti-cancer agents in the form of chemotherapy, androgen receptor signal inhibitors (ARSI’s) and radionucleotide treatment can be given.
=For fit patients, it has been shown in a number of studies that survival can be improved by giving other systemic anti-cancer treatments around the time of starting androgen deprivation therapy. Giving “up-front” chemotherapy in the form of six months of docetaxel was found to improve survival. More recently, it was found giving ARSI’s
(such as abiraterone or enzalutamide) resulted in similar improvements in survival, but with much less toxicity – and so is becoming increasingly favoured.
=ARSI’s can be continued until the point of disease progression (usually determined by arising PSA or cancer growth on CT or bone scan). At this point patients can receive chemotherapy (docetaxel), with second lines of chemotherapy (cabazitaxel) available if there is further progression following this.
=Patients with bone-only metastases who have progressed following several lines of treatment can be offered radionucleotide treatment in the form of Radium 223, which has been shown to modestly improve survival.
=In unfit patients, treatment takes the form of hormone therapy alone, with the options of palliative radiotherapy for painful metastases. Patients should also be managed supportively with good pain control and the involvement of the palliative care team for difficult to control symptoms or end-of-life care
Palliative radiotherapy
Bone metastases are common in advanced prostate cancer. Radiotherapy can be very effective at managing pain related to metastases and can also be used to improve symptoms from locally advanced primary disease that may be causing pain or bleeding(haematuria). Palliative radiotherapy involves giving a short course of treatment (usually between one, five or occasionally ten days of treatment), specifically targeted to the symptomatic area. Treatment is generally well tolerated but can result in fatigue, pain flare and sometimes bladder or bowel disturbance if treating the pelvis
