CARCINOMA

PROSTAT
EPIDEMIOLOGI

 Kanker terbanyak kedua pada pria (15%).

 5% terjadi pada usia < 30 tahun, 59% pada usia > 79 tahun.
 Populasi terbanyak di Australia/New Zealand.
ETIOLOGI
 Riwayat keluarga
 Sindroma metabolik:
• Hipertensi dan lingkar pinggang ≥ 102 cm → ↑ risiko.
• Diabetes: metformin → ↓ risiko.
• Kolesterol tidak berkaitan dengan risiko PCa.
• Obesitas → ↓ risiko menderita low-grade PCa, tetapi ↑ risiko high-grade PCa.
 Diet
 Hormonal
 Kebotakan → higher risk of PCa death.
 Gonorrhoea → ↑ insidensi PCa.
 Kerja malam hari → ↑ risiko Pca (2.8%).
 Merokok → ↑ risk of PCa death.
 Pria dengan HPV-16 positif → ↑ risiko.
 Paparan ultraviolet → ↓ risiko PCa.
 Frekuensi ejakulasi ≥ 21x/ bulan menurunkan risiko Pca dibandingkan dengan frekuensi ejakulasi 4-7x/bulan
ETIOLOGI
DIETARY FACTORS
KLASIFIKASI
STAGING TNM (2017)
GLEASON SCORE

ISUP (2005) modified Gleason score (GS) of biopsy-detected  ISUP grades (2014)
PCa comprise of :
 Gleason grade of the most extensive (primary) pattern, plus
the second most common (secondary) pattern, if two are
present.
 If one pattern is present, it needs to be doubled to yield the
GS.
 For three grades, the biopsy GS comprises the most common
grade plus the highest grade, irrespective of its extent.
 When a carcinoma is largely grade 4/5, identification of <
5% of Gleason grade 2 or 3 glands should not be
incorporated in the GS.
 A GS < 5 should not be given based on prostate biopsies.
EAU risk groups for biochemical recurrence of localised and locally
advanced prostate cancer

High Low
CHAARTED ≥ 4 bone metastasis, including ≥ 1 outside vertebral column or spine Not high
(volume) OR
Visceral metastasis
LATITUDE ≥ 2 high-risk features of: Not high
(risk) • ≥ 3 bone metastasis
• Visceral metastasis
• ≥ ISUP grade 4
DIAGNOSTIC SCREENING

 Pria dengan risiko meningkat untuk menderita PCa:

• Usia > 50 tahun.
• Usia > 45 tahun dengan riwayat keluarga penderita Pca (paternal atau maternal).
• Ras African-Americans > 45 tahun.
• Pria dengan PSA > 1 ng/mL saat usia 40 tahun.
• Pria dengan PSA > 2 ng/mL saat usia 60 tahun.

 Interval untuk screening PSA dan DRE:

• Setiap 2 tahun pada pria dengan faktor risiko.
• Setiap 8-10 tahun pada pria tanpa faktor risiko.
DIAGNOSIS
PROSTATE SPECIFIC ANTIGEN (PSA)

 PSA is organ but not cancer specific → may be elevated in BPH, prostatitis and other non-malignant
conditions.
 PSA density:
• The level of serum PSA divided by the TRUS-determined prostate volume.
• The higher the PSA density → the more likely it is that the PCa is clinically significant.

 Measuring PSA kinetics:

• PSA velocity (PSAV): absolute annual increase in serum PSA (ng/mL/year).
• PSA doubling time (PSA-DT): measures the exponential increase in serum PSA over time.

 Free/total PSA ratio

• Prostate cancer was detected in men with a PSA 4-10 ng/mL by biopsy in 56% of men with f/t PSA < 0.10,
but in only 8% with f/t PSA > 0.25 ng/mL.
• No clinical use if the total serum PSA is > 10 ng/mL or during follow up of known PCa.
DIAGNOSIS
BIOPSI PROSTAT

Indikasi
 Pasien dengan harapan hidup > 10 tahun.
 Kadar PSA (> 10 ng/dl atau 4-10 ng/dl dengan kecurigaan lain).
 Kecurigaan pada colok dubur atau temuan metastasis yang diduga dari kanker prostat.

Indikasi biopsi ulang

 Peningkatan PSA dan atau PSA tetap tinggi.
 Suspicious DRE → 5-30% risiko PCa.
 Histopatologis: atypical small acinar proliferation (atypical glands suspicious for cancer) → 31-40% risiko PCa pada biopsi

ulang.
 Extensive (multiple biopsy sites, > 3) high-grade prostatic intraepithelial neoplasia (HGPIN) → 30% risiko PCa.
 A few atypical glands immediately adjacent to high-grade prostatic intraepithelial neoplasia (PINATYP) → 50% risiko PCa.
 Intraductal carcinoma as a solitary finding, > 90% risiko high-grade PCa.
 Positive multiparametric MRI (mpMRI) findings.
TATALAKSANA
DEFERRED TREATMENT
Active surveillance
 Menghindari terapi tidak perlu pada pasien
localised PCa yang tidak memerlukan terapi
segera, tetapi di saat yang bersamaan tahu kapan
waktu yang tepat untuk terapi curative.
 Closed surveillance dan regular follow up.
Watchful waiting
 Managemen konservatif untuk pasien yang tidak cocok
dilakukan terapi curative.
 Dilihat tanda-tanda local or systemic progression.
 Terapi paliatif sesuai gejala untuk memperbaiki QoL.
TATALAKSANA
RADICAL PROSTATECTOMY

 Goal: eradikasi cancer, preserving continence and potency.

 Prosedur: mengangkat seluruh prostat dengan kapsulnya (tetap intact) seminal vesicles, diikuti
vesico-urethral anastomosis.
 Teknik operasi: open, laparoscopic or robot-assisted (RARP).
 Extended pelvic LN dissection (eLND): informasi staging dan prognosis.
 Nerve-sparing surgery: pada localised Pca, kontraindikasi pada cT2c atau cT3 atau ISUP grade >
3. Guide: intra-operative frozen-section, pre-operative mpMRI.
 Neoadjuvant ADT pra-RP (3 bulan): ↓ pT3 (downstaging), ↓ positive margins, ↓ insidensi LN
positif.
 TATALAKSANA
RADIOTHERAPY

 Intensity-modulated radiotherapy (IMRT),  Low-dose rate brachytherapy

dengan/tanpa image-guided radiotherapy (IGRT) menggunakan radioactive seeds yang
→ gold standard untuk EBRT. ditanam dalam prostat secara permanen.
 Dose escalation: 74-80 Gy.
 Kombinasi RT + LHRH ADT lebih baik
dibandingkan RT saja atau RT diikuti deferred
ADT.
 Durasi:
• Intermediate risk → 6 bulan.
• High risk → 3 tahun.
TATALAKSANA
HORMONAL THERAPY

Testosterone-lowering therapy (castration)

 Surgical castration (primary treatment modality for ADT) → castration level (testosterone < 50

ng/dL).
 Bilateral orchiectomy/subcapsular pulpectomy → castration level < 12 jam.
TATALAKSANA
HORMONAL THERAPY

Estrogen
 Estrogens → testosterone suppression.
 Not associated with bone loss.
 Oral diethylstilboestrol (DES) → thromboembolic complications, (not considered as standard first-

line treatment)
TATALAKSANA
HORMONAL THERAPY

Luteinising-hormone-releasing hormone agonists

 Long-acting LHRH agonists → main forms of ADT.
 Delivered as depot injections on a 1-, 2-, 3-, 6-monthly, or yearly, basis.
 Injeksi pertama → ↑ transient LH dan FSH → testosterone surge atau flare-up phenomenon (onset

2-3 hari setelah injeksi, bertahan 1 minggu).

 The clinical flare effects: ↑ nyeri tulang, BOO akut, obstructive renal failure, kompresi spinal cord,

dan cardiovascular death akibat hypercoagulation.

 Anti-androgen → ↓ insidensi clinical flare.
 Anti-androgen therapy 4 minggu.
 Castration level dicapai dalam 2-4 minggu.
 Comparable to orchiectomy.
TATALAKSANA
HORMONAL THERAPY

Luteinising-hormone-releasing hormone antagonists

 Berikatan dengan reseptoptor LHRH → ↓ LH, FSH dan kadar testosterone tanpa menimbulkan

flare.
 Degarelix: dosis standard 240 mg pada bulan pertama, diikuti injeksi 80 mg per bulan.
 Kebanyakan pasien mencapai level kastrasi pada hari ke-3.
TATALAKSANA
HORMONAL THERAPY

Anti-androgens
 Steroid: cyproterone acetate (CPA), megestrol acetate dan medroxyprogesterone acetate.
 Non-steroid: nilutamide, flutamide dan bicalutamide.
 Anti androgen berikatan dengan reseptor androgen → unchanged/ sedikit ↑ level testosterone.
 Anti-androgen steroid memiliki properti progestational → inhibisi di system saraf pusat (crossing the

blood-brain barrier).
TATALAKSANA
LOW-RISK DISEASE

Active surveillance
 Kriteria:
• ISUP grade 1.
• < 2-3 positive cores with < 50% cancer involvement in every positive core.
• Clinical T1c or T2a.
• PSA < 10 ng/mL.
• PSA density < 0.15 ng/mL/cc.

 Kontraindikasi (pathology):
• Predominant ductal carcinoma (including pure intraductal carcinoma).
• Sarcomatoid carcinoma.
• Small cell carcinoma.
• EPE or LVI in needle biopsy.
• Perineal invasion.

 Follow up: serial DRE (1x/tahun), PSA (1x/6 bulan), biopsi ulang (interval minimal 3-5 tahun).
TATALAKSANA
INTERMEDIATE-RISK DISEASE

Active Surveillance
 Kriteria: ISUP grade > 1 dan PSA > 10 ng/mL.
 Lakukan mpMRI dan systematic re-biopsy (eventually targeted) might improve the accuracy of
staging.
TATALAKSANA
INTERMEDIATE-RISK DISEASE

Surgery
 RP → ↓ all-cause mortality. But not death from PCa at 10 years.
 The risk of having positive LNs: 3.7-20.1%.
 eLND should be performed if the estimated risk for pN+ > 5%.

Radiation therapy
 External beam radiation therapy
• Patients suitable for ADT can be given combined IMRT with short-term ADT (4-6 months).
• For patients unsuitable for ADT or unwilling to accept ADT the recommended treatment is IMRT or VMAT at an escalated
dose (76-80 Gy) or a combination of IMRT or VMAT and brachytherapy.
 Brachytherapy monotherapy
• Low-dose rate brachytherapy can be offered to highly selected patients (ISUP grade 2 with < 33% of biopsy cores involved
with cancer).
• Fractionated HDR brachytherapy as monotherapy can be offered.
TATALAKSANA
HIGH-RISK LOCALISED DISEASE

Radical prostatectomy External beam radiation therapy

 Kriteria:
• Tumor tidak terfiksir ke dinding pelvik.
• Tumor tidak menginvasi ke sfingter uretra.
• Low tumour volume.
 Extended PLND harus dikerjakan pada semua
kasus high-risk PCa.
 Gunakan combined modality approach: dose-
escalated IMRT/VMAT + long-term ADT (min 2-3
tahun).
 LDR brachytherapy boost dengan supplemental
EBRT dan hormonal treatment bisa dipertimbangkan.
 Dose-escalated EBRT (dosis total 78 Gy) atau EBRT
(dosis total 46 Gy) diikuti LDR brachytherapy boost
(prescribed dose 115 Gy).
 Toksisitas terjadi akibat striktur uretra dan
inkontinensia.
TATALAKSANA
LOCALLY ADVANCED PROSTATE CANCER
TATALAKSANA
ADJUVANT POST RADICAL PROSTATECTOMY
CASTRATION-RESISTANT PCa
(CRPC)
NON-METASTATIC CRPC
 Consensus statement by the PCa Radiographic Assessments for Detection of Advanced Recurrence
(RADAR) group:
• Suggested bone scan and CT scan when the PSA reached 2 ng/mL and if this was negative it
should be repeated when the PSA reached 5 ng/mL, and again after every doubling of the PSA
based on PSA testing every 3 months for asymptomatic men.
• Symptomatic patients should undergo relevant investigation regardless of PSA level.

 Terapi: enzalutamide atau apalutamide.

CASTRATION-RESISTANT PCa
(CRPC)
METASTATIC CRPC
1st line treatment 2nd line treatment
 docetaxel/estramustine (EMP), every 3 weeks, 60  abiraterone + prednisone, or
mg/m2, EMP 3x280 mg/day, or  radium-223
 docetaxel, every 3 weeks, 75 mg/m2 + prednisone  cabazitaxel + prednisone
2x5 mg, or
 enzalutamide
 docetaxel, weekly, 30 mg/m + prednisone 2x5
2

mg, or
 abiraterone + prednisone, or
 enzalutamide, or
 sipuleucel-T
TERIMA KASIH
 NAC sebelum radicalnprostatectomy

▪ neoadjuvant ADT has significant impacts on surgical outcomes of locally advanced disease
▫ decreasing PSA and prostate volume
▫ lower rates of positive surgical margin and lymph node positivity
▫ down-staging pathological T stage, there is no clear improvement in the biochemical recurrence and
survival
▪ As ADT can only suppress cancer cells depending on androgen and may induce the epithelial–mesenchymal
transition, it is possible a portion of androgen-independent cancer cells have been mobilized during the
perioperative period and invisible to PSA and imaging detection, which leads to recurrence and metastasis.
▪ In that regards, NAC have been considered to optimize the management of high-risk and locally prostate
cancer. Although conflicts still exist on the survival benefit of NAC, as well as the dosage of taxanes and the
combination regimens, NAC will improve the outcome of a subset of patients with locally advanced
prostate cancer.

▪ Sumbert: Neoadjuvant chemotherapy before radical prostatectomy for locally advanced prostate cancer Protocol for a systematic review and meta-analysis Tianhai
Lin, MD, PhDa,b, Xiong Yang, MDa , Lina Gong, MDa , Hang Xu, MDa , Shi Qiu, MD, PhDa , Ruichao Yu, MD, PhDc , Sheng Sun, PhDd , Liangren Liu, MD,
PhDa , Peng Zhang, MD, PhDa , Ping Han, MD, PhDa , Jingqiu Cheng, PhDb , Lu Yang, MD, PhDa, ∗ , Qiang Wei, MDa, ∗
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Indikasi radikal prostatektomi

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EAU Guideline