Case Presentation

Dr. Muhammad Humayun KabirMBBS, FCPS, MRCS(Edin)

BSMMU, Dhaka, Bangladesh

Particulars of patient

●Name: Mohiuddin Ahmed●Age: 67 years●Sex: Male●Occupation: Retired service holder●Address: Dhaka●Date of admission: 09.15.15●Date of discharge:

Presentation

Urinary frequency, urgency, occasional dribbling of urine and nocturia 06 months back.

HISTORY OF PRESENT ILLNESSAccording to the statement of the patient, he was reasonably alright about 06 months back. Then he developed lower urinary symptoms in the form of urinary frequency, poor urine flow, occasional dribbling of urine and nocturia. He also complained of difficulty in initiating voiding and a sense of incomplete evacuation. He had a feeling of epigastric and lower abdominal discomfort. His symptoms were worsening rapidly.

With this complaints, he consulted a private hospital in Dhaka where he was investigated and was advised to admit in BSMMU. On 04.02.15, pt got admitted in the department of Hepatology, BSMMU. On the next day (05.02.15), he was catheterized, was further evaluated and treated conservatively. On 14.02.15 a referral was sent to department of Urology, BSMMU.

He does not give any history of:

• Bleeding during micturition

• Passage of any stone during micturition

• Cough, haemoptysis, chest pain, bone pain or dyspnoea.

• fever with chills and rigor

• Traumatic injury to the spine

He is normotensive, non diabetic and non asthmatic.

Family history: Married, having 3 children, all are in good health.

Personal history: Non-smoker

History of allergy: No known history of allergy to any drug or food.

Systemic enquiry reveals no other abnormality.

General Physical Examination

● Appearance: normal looking● Behaviour: Co-operative● Anaemia: absent● Jaundice: absent● Pulse:80 bpm● BP:120/70 mm of Hg● Respiration: 18 breaths/min● Oedema: absent● Dehydration: absent● JVP: not raised● Lymph nodes: not enlarged● Heart: S1S2 normal, no added sound

Abdominal and genitourinary examination

Inspection:● Patient is catheterized using a 16 Fr bichannel Foley catheter

connected with a closed collecting bag containing about 200 ml straw coloured urine.

● Abdomen is normal in shape with centrally placed inverted umbilicus

● No visible lump, engorged vein or any scar mark

Palpation: ● No palpable lump, no tenderness. ● Liver, spleen and kidneys are not palpable● Renal angle: non-tender● Urinary bladder: not palpable● Testes and both epididimis: normal

Percussion:● No ascites

Auscultation:● Bowel sound present

DRE: ●Perianal sensation- intact, anal tone – normal●Prostate is moderately enlarged, hard in

consistency, irregular surface with few hard nodules involving both the lobes, overlying mucosa is free, median sulcus is obliterated.

Lower limb neurological and other systemic examination revealed no abnormality.

Investigations available at the time of referral were:

Date

28.01.15 05.02.15 ( After catheterization) 07.02.15 14.02.15

S. Creatinine (mg/dl)

6.33 5.3 2.6 1.0

07.02.15●S. PSA: 43.2 ng/ml

●CA 19-9: 11.6 U/ml ( normal upto 35 U/ml)

●CEA : 2.93 ng/ml (Normal upto 5.0- non smoker, 10 - smoker)

●Patient underwent TRUS guided prostate biopsy in the department of urology, BSMMU (after antibiotic prophylaxis and bowel preparation ) on 28.02.15 as OPD basis and tissue sent for histopathology.

●His postoperative period was uneventful. He was catheterized again and advised to consult with HPR report.

●Patient was counseled regarding the disease process and treatment options. He chose bilateral

orchidectomy rather than Injecting gosereline monthly/ 3 monthly.

●On 09.03.15: Tab Flutamide 250 mg tds started.

●Bilateral orchidectomy was done under LA at Minor Operation theatre. Antibiotics and appropriate

analgesics were prescribed.

●Serum PSA and S. testosterone were advised after the operation.

Investigations

Date

28.01.15 05.02.185 07.02.75 14.02.1514.03.15

(Bil. orchidectomy

done)09.05.15

S. Creatinine (mg/dl)

6.33 5.3 2.6 1.0 0.83

S. PSA (ng/ml)

43.2 55.12 0.09

S. Testosterone (ng/dl)

92.60 <0.20

●Patients catheter was removed one week after three orchidectomy after 2 days of intermittent clamping of catheter but patient failed to void. Pt was again catheterized.

●Two attempts of TWC were failed within last one month.

USG of KUB region (09.05.15)

USG of KUB region (09.05.15)

USG of KUB region (09.05.15)

Comment:

●Bilateral HDUN

●Cystitis

●Intravesical protrusion of median lobe of the prostate.

●Prostate volume 20 cc

Operation note

●Date: 11.05.15

●Name of operation: TURP

●Indication: Metastatic carcinoma of the prostate (post orchidectomy status) with refractory urinary retention.

●Anesthesia: SAB

● Findings:

●Postoperative period:

Follow up and future management:

Hormone Therapy for Prostate Cancer

●It had been known for at least a century that prostatic epithelium undergoes atrophy after castration

Figure: Hormonal interventions and endocrine axis in prostate cancer.

●Figure 109–1. Hormonal interventions and endocrine axis in prostate cancer.

MECHANISMS OF ANDROGEN AXIS BLOCKADE

Four therapeutic approaches for androgen axis blockade in current clinical use:

1) ablation of androgen sources,

2) inhibiting androgen synthesis,

3) antiandrogens, and

4) inhibition of LH-RH and/or LH release.

Ablation of Androgen Sources

Bilateral orchiectomy quickly reduces circulating testosterone levels to less than 50 ng/dL. Within 24 hours of surgical castration, testosterone levels are reduced by greater than 90%.

Inhibition of LH-RH: LH-RH Agonists

●The LH-RH agonists exploit the desensitization of LH-RH receptors in the anterior pituitary after chronic exposure to LH-RH, thereby shutting down the production of LH and, ultimately, testosterone.

●The initial exposure to more potent agonists of LH-RH results in a flare of LH and testosterone levels. This ‘flare up phenomenon’ can result in a severe, life threatening exacerbation of symptoms.

●The flare, associated with up to a 10-fold increase in LH, may last for 10 to 20days.

●Coadministration of an antiandrogen functionally blocks the increased levels of testosterone.

●Although it had been argued that the administration of the antiandrogen should precede the administration of the LH-RH agonist by a week, others have found no differences in PSA levels with the simultaneous administration of both agents.

RESPONSE TO ANDROGEN BLOCKADE

●After the initiation of ADT the vast majority of prostate cancer patients will show some evidence of clinical response: the magnitude and rapidity of that response remain the best predictors of its durability.

●An incomplete or sluggish response is evidence of a significant androgen-refractory population.

●Patients who had more than an 80% drop of PSA within 1 month of initiating ADT had a significantly longer disease-free progression rate.

●A rise in PSA level, which is evidence of the emergence of castration resistant disease, preceded bone metastatic progression by several months, with a mean lead time of 7.3 months.

GENERAL COMPLICATIONS OF ANDROGEN ABLATION

1. Osteoporosis

●The longer a man remains on ADT, the greater the risk of fracture.

Treatment of osteoporosis:

●Smoking cessation, weight-bearing exercise, and vitamin D and calcium supplementation (1200 to 1500 mg/day and 400 IU/day, respectively)

●Oral alendronate

●bisphosphonate zoledronic acid

2. Hot Flashes

●Not life threatening but are most common side effects of androgen ablation, affecting between 50% and 80% of patients.

●Described as a subjective feeling of warmth in the upper torso and head followed by objective perspiration.

●Treatment of hot flashes should be reserved for those who find them bothersome

●progestational agent megestrol acetate (20 mg, twice per day)

3. Erectile Dysfunction and Loss of Libido

●Loss of sexual functioning is not inevitable, up to 20% of men on ADT able to maintain some sexual activity.

●Treatment for loss of libido is extremely.

●Medical treatments, such as oral phosphodiesterase type 5 inhibitors, or local treatments, such as intracavernosal injections of alprostadil, can be effective in selected patients but may not be used over the long term.

4. Changes in Body Habitus

●A loss of muscle mass and increase in percent fat body mass are common in men undergoing ADT

5. Diabetes and Metabolic Syndrome

6. Gynecomastia

7. Anemia:

●Normochromic, normocytic, and very common:

●Treatment: recombinant human erythropoietin.

Combined Androgen Blockade