A N G E L A L A U ( P M H )

I H G M 2 2 / 2 / 2 0 1 4

Bone lesions: Malignant or Benign or Both?

Case Profile

M/71 (PK Ho) Good past health

Retired E&M supervisor

Father of 3 sons

Lives with elder son, GS & wife (recent #Patella with OT done) at public housing

Premorbid: main carer at home, ADL/iADL-I

Hospitalized PMH twice for 2 falls: 14/9/2012

4/11/2012

History

One minor fall in 7/2012 fell on bottom while attempting to sit on sofa, could get up by

himself, no severe pain, no medical consultation

1st presented to AED on 14/9/2012 12/9/12: fell from sofa backwards onto ground while standing

on sofa to clean a fan; severe pain and could not get up

R hip and L chest wall contusion

XR (CXR, L lower ribs, Pelvis & R hip) taken

Rx Voltaren & Triact prn

XRays

Called back AED

Called back & admitted EM ward 18/9/2012 Persistent R hip pain

XR R hip (14/9, 18/9): no fracture

Noted high BP 245/107

Cr 98, LFT normal, Hb 13.0; ECG normal

Rx Norvasc 7.5mg, Ibuprofen, Panadol, Pepcidine, Analgesic ointment

Refer GOPC

GOPD FU

FU GOPD for hypertension Persistent BP upon FU (21/9/12) Norvasc (28/9/12) Moduretic (3/10/12) Atenolol

Persistent mechanical R hip pain, able to walk unaided (3/10/12) Panadol (16/10/12) Voltaren SR

GOPC visit on 29/10/2012 not taking atenolol because feel dizziness with it still pain over R hip radiate to R LL, worst when weight bearing impression: HT , at least partially due to hip pain refer physiotherapy, NSAID, off atenolol , repeat other anti-HT

Admission

Admitted PMH on 4/11/12 Sliding down from sofa to floor due to L LL weakness

L sided weakness since last episode of fall 14/9/12

Leaned on L side while walking; with unsteadiness & recurrent falls (e.g. fell while attempting to hang up clothes)

Persistent R hip pain

Power

L side muscle tone

5 4

5 3

Investigations

CXR (4/11/12): RUZ fibrocaclifications show no interval change

XR pelvis (4/11/12): no fracture

CT brain (6/11/12): R frontal lobe infarct, Lacunar infarcts in genu of L internal capsule & R BG

TCD: Normal screening on IC & EC neck arteries

Dx: Stroke, delayed presentation

Progress during Rehabilitation

R hip pain and LBP XR LS spine (11/12/12)

Mild diffuse osteopenia

Degenerative changes with marginal

osteophytes noted in lumbar spine

Disc spaces and pedicles intact

XR R Hip & Pelvis

Normal alignment. No fracture seen

Phleboliths noted over both sides

XR Pelvis

Progress during Rehabilitation

R hip pain and LBP Failed to tolerate Tramadol due to GI upset

Analgesics

Voltaren SR (100mg) with PPI cover + Gabapentin (100mg bd & 300mg nocte) + Analgesic balm

Stroke prophylaxis

Aspirin (160mg) + Zocor (20mg) + Enalapril (5mg) + Norvasc (10mg)

Complication

Progressive Anaemia Hb 13 (18/9/12) 13.2(4/11/12) 10.1 (22/2/13) 8.4

(8/3/13)

OGD with Bx: mild chronic gastritis at antrum, HP –ve

FE/TIBC 8.6/48.8; FeSat 18%; Ferritin 843

FOB –ve X 3

VitB12 203 (28/11/12) ; 166 (13/3/13) pmol/L

RBC Folate 438 ; Serum Folate 6.8 (28/11/12) nmol/L

TSH 1.0 (normal)

Aspirin/Voltaren SR taken off

Rx: DF118

Colonoscopy booked

Progress during Rehabilitation

Team round (19/2/13): Patient is not participating in rehabilitation due to pain Pain score 5/10 (despite given analgesics)

PE showed marked tenderness over Rt pelvis and sacrum

Previous X-rays of Ribs, Hips, LS spine & pelvis revealed osteopenia and #Rib

?Sacral insufficiency fracture complicating fall & osteoporosis

Check VitD level

Rx Calcitonin & anti-osteoporosis Rx

Book CT sacrum

Vitamin D Deficient

Serum vitamin D level (20/2/13) 25OH D2 <10 nmol/L

25OH D3 18 nmol/L

Total 25OH VitD 18 nmol/L

<12.5 nmol/l Severe deficiency

12.5-29 nmol/l Moderate deficiency

30-49 nmol/l Mild deficiency

Ca/PO4: 2.31/1.25, iCa 1.19

Albumin: 36 (4/11/12)

ALP: 105 (4/11/12) 898 (15/5/13)

CT sacrum (11/3/2013)

Mixed sclerotic & lytic areas in L5, S2 to S4 sacrum and L iliac bone; small lytic area in R iliac bone.

Findings are suggestive of multiple bone metastasis, with pathological fractures in L5 vertebra and R iliac bone.

Prostate enlarged

Prominent right groin lymph node (1.5cm)

Approach to CT bone lesion

Morphology & Age Well-defined osteolytic

<40 years old Giant cell tumor / Osteblastoma / Enchondroma

Chondrosarcoma / HyperPTH with Brown tumor >40 years old

Metastases / Myeloma

Ill-defined osteolytic <40 years old

Giant cell tumor >40 years old

Metastases / Myeloma / Chondrosarcoma

Sclerotic <40 years old

Bone island / Healed lesions / Enchondroma / Osteoma >40 years old

Metastases Bone island

Infection

Images from www.radiologyassistant.nl

What is in our mind?

Differential Diagnoses

Malignant: Metastases

Prostate / Breast / Lung / Lymphoma / Carcinoid

Benign: Severe Vitamin D deficiency

Paget’s disease

ALP with normal Ca & PO4

Tuberculosis infection

Sacral insufficiency fractures

Post-traumatic osteomyelitis of Rt iliac bone & L5 vertebra

Bone island

Sacral Insufficiency Fracture

Stress fracture: normal stress applied to abnormal bone that lost elastic resistance

Causes: Osteoporosis / metabolic bone disease

Imaging CT / MRI

Therapy Conservative – strict bed rest & pain control

Rehabilitation – after 6-15months

Sacroplasty

Complications Immobilization

Work Up

PE DRE – Anal tone intact, Hard Prostate 3FB

Shotty R groin LN ~0.5cm

Inflammatory markers CRP 7.7 (3/4/13) / ESR 41 (22/2/13)

Spt AFB smear C/ST –ve

EMU AFB C/ST -ve

Tumor markers (13/3/13) PSA: 355

CEA: 2.2 / AFP: 8.2 / CA 19.9: 13

IgA 2.29 / IgG 13.1 / IgM 1.08 / SPE – no abnormal band

Spt Cytology -ve

XRays

Private CT thorax & Abdomen (13/3/2013)

Primary site at R prostate gland Evidence of R extra-capsular spread and neurovascular bundle

encasement.

Multiple bone metastases Sclerotic metastases with compression # over C7, T4, T9 and L5 Sclerotic-lytic metastases of L 1st 3rd & 7th ribs Mixed sclerotic-lytic metastases at sacrum and bilateral ilium

Lymphadenopathy: Extensive pelvic & intra-abdominal nodal metastases Thorax: pre-vascular and right axillary region

Lungs: A large area of fibrocalcific scarring with concave borders seen at R lung

apex, measuring 2 X 5.8cm Cluster of small centrilobular nodules over RLL, more likely infection

than malignancy

Bone scan (20/3/2013)

US Urinary

Prominent irregular prostatic mass protruding into bladder

R kidney 8.2cm & L kidney 9.6cm, no focal lesion or hydronephrosis

Disease Progress

Disseminated Ca prostate Oncology (5/4/2013)

Metastatic CA prostate for androgen ablation with medical or surgical castration

Refer Urology x TRUS Bx Orchidectomy

Urology (22/4/2013)

Patient opted for bil Orchidectomy without TRUS Bx

Bil Orchidectomy done 24/4/13

Patho: No evidence of malignancy

PSA 355 10.7 (9/13) 28 (12/13)

ALP 898 (15/5/13) 590 (17/6/13) 108 (31/12/13)

Problem lists

Pathological # L5 vertebra and R iliac bone Morphine SR 90mg bd & Panadol 500mg q4h prn

Attempted palliative RT to L spine but patient cannot tolerate set up position, RT cancelled

Moderate VitD deficiency CaCO3 & Alfacalcidol (switched to cholecalciferol later)

Total 25OH VitD 90 (7/8/2013)

NcNc anaemia On B12 & Folate & Fe supplement

Hb 8.4 (8/3/13) 10.2 (15/5/13) 11 (31/12/13)

Problem lists

HT BP 88/45 – 115/65 mmHg

Atenolol, Enalapril, Norvasc taken off

Hyperlipidaemia TC 5.8/LDL 3.9 (6/11/2012), Rx: Zocor

Taken off with CK 488

Recheck TC 2.7/LDL 1.3 (8/3/2013)

Constipation Senokot 15mg bd & Fleet enema alternate daily

Depression GDS (18/7/13) 10/15 (very depressed), Rx Zoloft

Rehabilitation Progress

Upon discharge to OAH (31/7/2013) Tolerate 10 min of sit out

BI 56/100

ADL-I up to feeding and grooming, dressing with assistance, transfer with 2 assistance

Discussion

Prostate cancer

Incidence 3rd most common cancer in men

10.7% of new cancer cases in male in 2010

45.3 per 100,000 male

~1000 newly dx case/year

Mortality 5th leading cause of male cancer deaths in HK

3.8% of male cancer deaths

~300 deaths/year

Risk factors

Age, Median age of dx 72

Family hx BRCA2 & BRCA1 mutations

Ethnic African-Americans

Smoking

Obesity

Others Prostatitis (RR=1.6)

Hx of Syphilis / gonorrhea (RR=1.4)

Decision for PSA screening

Information

Support for decision-making

Decision for Prostate Bx

PSA level

DRE findings

Risk factors

Risk & benefit of Bx Having to live with the dx of clinically insignificant prostate

cancer

When clinical suspicion of prostate cancer is high (high PSA /evidence of bone met identified by positive isotope bone scan or sclerotic metastases on plain radiographs) No prostate bx for histological confirmation needed

TNM Staging

Extend of tumor

Evaluation of LN

Distant metastasis

Risk Stratification

National Comprehensive Cancer Network (NCCN)

Low-risk

Localized to 1 lobe of prostate, PSA <10 ng/ml, GS 6

Intermediate-risk

Intracapsular extension, PSA 10-20 ng/ml, GS 7

High-risk

Extracapsular extension, PSA >20 ng/ml, GS 8-10

Prostatectomy / ADT / RT

Watchful wait / Active surveillance

Low-risk

1st visit Multiparametric MRI

Year 1-4 PSA every 3-4 months

DRE every 6-12 months

Prostate Re-Bx

Year 5 onwards PSA every 6 months

DRE every 12months

Radical Tx for disease progression

*NICE guideline 2014

Intermediate/High-risk

Radical Prostatectomy Intermediate / high-risk patient * High-risk : Post-op RT

ADT plus RT (2-3 years) High-risk patient ADT & RT 10-year overall survival then ADT alone ** ADT & RT 15-year cancer specific mortality rate #

Androgen Deprivation Therapy (ADT) Bilateral Orchiectomy Gonadotropin releasing hormone (GnRH) agonist Antiandrogen

Radiation Therapy (RT) External beam RT External beam & brachytherapy

*PIVOT trial. N Engl J Med.2012;367(3):203 **NCIC Intergroup phase III trial. Lancet.2011;378(9809):2104 #Scandinavian Prostate Cancer Gp Study, open randomised phase III trial.2014 ASCO

Disseminated Tx

Medical (ADT) / Surgical Orchiectomy

Chemotherapy

Table from 2014UpToDate

Monitor Adverse effects

Radical Prostatectomy Sexual dysfunction Urinary incontinence

ADT Hot flushes Sexual dysfunction Osteoporosis

Zoledronic acid/Denosumab* (for castration-resistant CA prostate with bone met, failed analgesics & palliative RT)

Gynaecomastia Fatigue Anaemia

RT Radiation-induced enteropathy

* Efficacy and safety of zoledronic acid in men with castration-sensitive prostate cancer and bone metastases: Results of CALGB 90202 (Alliance). J Clin Oncol 2013; 31

Same in Elderly?

Prostate Cancer in Elderly

Effect of Age, Tumor Risk, and Comorbidity on Competing Risks for Survival in a U.S Population-Based Cohort of Men with Prostate Cancer Annals of Internal Medicine Sept2013 Population-based cohort 3183 men with non-metastatic prostate cancer at diagnosis Baseline comorbidity

DM / HT CHF / IHD / MI / Angina / CVA GIB / Cirrhosis or liver disease / IBD Chronic lung disease Arthritis Depression

Tumor characteristics Initial treatment Overall & Disease-specific mortality through 14years FU

Mortality Curve

Assess Comorbidities

Cumulative Illness Score Rating-Geriatrics (CISR-G) Grade 0: no problem

Grade 1: current mild problem or past significant problem

Grade 2: moderate disability or morbidity, requires first-line therapy

Grade 3: severe/constant significant disability/uncontrollable chronic problem

Grade 4: extremely severe/immediate treatment required/end-organ failure/severe Impairment in function

ADL & iADL

Nutritional status

Health Status of Elderly

Society of Geriatric Oncology (SIOG) Healthy

No serious comorbidities, ADL/iADL-I, no malnutrition Same as young

Vulnerable with reversible problem 1 uncontrolled comorbidity, iADL-d but functionally-I, at risk of

malnutrition Same as young exclude radical prostatectomy

Frail with non-reversible problem ADL-pd, malnutrition Symptomatic mx without definitive Tx (e.g androgen deprivation)

Terminal Bedridden, major comorbidities, cognitive impairment Palliative

Discussion

2008 US Preventive Services Task Force >75 cessation of screening and treatment *

Life expectancy <10 years

50% other-cause mortality

Against PSA screening in healthy men

Effect of Age, Tumor Risk, and Comorbidity on Competing Risks for Survival in a U.S Population-Based Cohort of Men with Prostate Cancer Age 60 with 3 comorbidities

10 years mortality ~50%

All cause mortality >potential survival benefit from aggressive therapy

*Screening for prostate cancer: U.S.Preventive Services Task Force recommendation statement. Ann Intern Med.2008;149:185-91. [PMID: 18678845]

Progress of Mr Ho

Progress of Mr Ho

Upon FU (18/12/2013) Kyphotic

Bedchair bound

Complicated with UTI with AROU (31/12/2013) with foley inserted, Rx Augmentin

Foley weaned 15/1/2014

Xrays (22/7 & 21/8/13)

Take Home Message

Sacral / Pelvic fractures may be subtle on XR

Sclerotic bone lesions take time to develop on XR

Devastating pain warrant further imaging

Screening & Mx of prostate cancer is subjected to individual’s health & risk of disease progression Healthy / Vulnerable elderly with 1 comorbidity &

functionally-I

Radical prostatectomy / ADT / RT / Watchful wait / Active surviellance

Frail elderly ADL-pd, malnutritioned / Bedridden

Symptomatic Tx / Palliative

~Thank you~