UNIVERSITATEA OVIDIUS DIN CONSTANA

FACULTATEA DE FARMACIE

Patologia tumoral
prostatei
COORDONATOR STIINIFIC
.L. UNIV. DR. DOICESCU DRAGO NICOLAE

ABSOLVENT
SABIUTA LARISA
CONSTANA
2015

Introducere
Cancerul de prostat este a doua cea mai frecvent
form de cancer n rndul brbailor la nivel mondial,
dar poate fi tratat n manier eficient atunci cnd este
detectat n stadiu iniial.
Scopul acestei lucrari este prezentarea generala a
formatiunilo tumorale ale prostatei punandu-se accent
pe adenomul de prostata si pe adenocarcinomul
prostatic. Partea personala consta in prezentarea
statistica a datelor culese de la Spitalul Clinic Judetean
de Urgenta Sf. Apostol Andrei Constanta, de pe
Sectia Clinic Urologie.
Motivatia alegerii acestei teme este convingerea
personala ca aceasta boala poate fi combatuta cu
succes si necesitatea de a aduce o contributie oricat de
mica la cresterea gradului de cunostinte despre
aceasta afectiune.

Anatomia prostatei

Vedere mediosagital a prostatei care arat raporturile

Anatomia prostatei

Uretera prostatic i membranoas

Clasificarea tumorilor maligne prostatice

A. Tumori
epiteliale

1.Adenocarcinoame (carcinoame primitive prostatice sau

adenocarcinoame convenionale)
2.Carcinoame cu celule tranziionale
Adenocarcinoame atipice
Ductale
Mucinoase (coloide)
Cu celule n inel cu pecete
Adenoscuamoase i scuamoase
Oncocitare
4.Carcinoame adenoid-chistice (bazaloide)
5.Carcinomul endometrial al utriculei prostatice
6.Tumori cu celule mici
Neuroendocrine
7.Tumori epiteliale rare
Carcinoame limfoepiteliom-like
Carcinoame sarcomatoide
Carcinoide

A. Carcinosarcoame
A. Tumori mezenchimatoase (sarcoame)
A. Tumori secundare
A. Tumori cu celule germinale
A. Tumori limfoide

Tumori benigne ale prostatei

BPH (Hiperplazia benign a prostatei) se dezvolt din
prostata tranziional, periuretral, ndeplinind
caracteristicile anatomice de formaiune periuretral,
supramontanal, prespermatic sau intrasfincterian
(n interiorul sfincterului neted).
Microscopic, nodulii sunt formai din hiperpiazie
stromal, fibro-adenomatoas, sau glandular, n toate
adenoamelede prostat existnd toate aceste
structuri,dar n proporii variabile

Adenom de prostat
evideniat microscopic

Manifestri clinice ale hiperplaziei

benigne a prostatei
Faza de prostatism:
Polakiurie nocturn moderat
Polakiurie nocturn moderat
Disurie marcat
Faza de retenie incomplet fr
distensie:
Apariia rezidiului vezical ce nu depete
capacitatea fiziologic a vezicii urinare
Faza de retenie incomplet cu
distensie:
Rezidiul depete capacitatea fiziologic

Manifestri clinice ale

adenocarcinomului prostatic

Manifestri locale:
Simptomatologie obstructiv
Simptomatologia iritativ
Hematuria
Hemospermia
Durerea loco-regional
Manifestri generale:
Osoase
Limfatice
Hepatice
Cerebrale

Diagnosticul cancerului de prostat

Tratamentul hiperplaziei benigne a

prostatei

Tratamentul chirurgical
Transuretrorezecia prostatei (TUR-P)
Transuretroincizia prostatei (TUI-P)
Adenomectomia deschis
Tratamentul medicamentos
Alfa-blocante Fenoxibenzamina, Prazosin, Alfuzosin,
Indoramin, Terazosin, Doxazosin, Tamsulosin.
Tratament hormonal Dihidrotestosteronul, Finasterida,
Mepartricina, Analogii GnRH, Antiandrogeni, Inhibitorii
de aromataze.
Fitoterapia - Pigenum africanum, Hypoxis rooperi,
Cucuibita pepo.

Tratamentul tumorilor maligne ale

prostatei

Boal localizat
Watchful waitng:
Prostatectomia radical:
Radioterapia curativ ( cu sau fr tratament hormonal
neoadjuvant)
Hormonal:
Terapii alternative: crioterapia.
Boala local avansat
Watchful waiting:
Prostatectomie radical:
Radioterapie:
Hormonal:
Boal recurent
Bola metastatic
Hormonal- terapie standard
Radioterapie n focar

Studiul Personal
Studiul personal a fost efectuat prin analizarea foilor
de observaie a pacienilor diagnosticai cu tumori ale
prostate din cadrul seciei Clinic Urologie a Spitalului
Clinic Judeean de Urgen Sntul Apostol Andrei
Constana, n colaborare cu Dr. Voinea Felix. Pacienii au
fost selectai din cei cei internai cu confirmarea
diagnosticului de adenom de prostat i cancer de
prostat n perioada 01 Septembrie 2014 01 Februarie
2015 pe secia Clinic Urologie. Datele au fost puse la
dispoziie sub acordul confidenialitii respectndu-se
normele etice i deontologice n vigoare.
Studiul personal are ca obictive:
Caracterizarea lotului de pacieni.
Distribuia pacienilor n funcie de stadiul bolii.
Evidenierea tratamentului aplicat.

Distrubuia pacienilor n funcie de diagnostic Distribuia pacienilor n funcie de vrst

20

20

24

18

25

15

16
20

16

Adeniom de prostat
Cancer de prostat

15

14
12

Total pacieni

Nur pacieni 10
8

10

6
5
0

4
2
Numr pacieni

Distribuia pacienilor cu adenom de prostat n funcie de vrst

12

10
9
8
7
6

10

Pacieni cu adenom
de prostat

6
4
2
0

70-80

Distribuia pacienilor cu cancer de prostat n funcie de vrst

10

Numr pacieni

60-69

10

13

14

50-59

1
50-59 60-69 70-80
Grupa de vrst

Numr pacieni

5
4
3
2
1
0

Pacieni cu cancer de
prostat

4
2

50-5960-6970-80

Grupa de vrst

Comparaia distribuiei n funcie de vrst a tuturor pacienilor

Pacieni cu adenom de prostat

Pacieni cu cancer de prostat

13

10

4
2
1

50-59

60-69

70-80

10

Distribuia pacienilor n funcie de mediul de via

Mediul Rural

Mediul Urban

35%
65%

Distribuia pacienilor n funcie de mediul de via

16

16
14

10

12
Numr pacieni

10

Mediul Rural
Mediul Urban

6
4
2
0

Sub-lotul A

Sub-lotul B

Cunotinele pacienilor cu privire la antecedente familiale legate de afeciunea lor

Numr total pacieni din sub-lot
Numa de pacieni cu cunotine despre antecedente familiale legate de afeciunea sa
24

16

11

Sub-lotul A (adenom de prostat)

Sub-lotul B (cancer de prostat)

Stadializarea clinic a adenomului de prostat

Stadiul I

Stadiul II

Stadiul III

4%
25%

71%

Stadializarea tumorilor maligne

T1c

T2

T3

6%

T3M1b

T4M1c

6%

19%
38%

31%

Tratamentul acordat pacienilor cu adenom de prostat

Tratamentu chirurgical

Tratament exclusiv farmacologic (Pazosin 4 mg/zi)

33%

67%

Repartizarea medicaiei la pacienii cu adenom de prostat tratai chirurgical

Finasterid 5 mg/zi Mepatricin 40 mg/zi

Numr pacieni

Abordul terapeutic la pacienii cu cancer de prostat

Prostectomie
laparoscopic radical +
flulamid 750 mg/zi
Estramustina+Vinblastin
+Paclitaxel
600mg+2mg+135mg
respectiv
Au refuzat terapia

Numr pacieni

11

10

12

Concluzii
Tumorile prostatei se pot prezenta n forme clinice variate, fiind at maligne ct i
benigne, fiecare necesitnd individualizarea terapiei.
Cea mai uzual metoda de diagnostic a afeciunilor prostatei este tueul rectal,
reprezentnd o tehnic sigur i ieftin de diagnostic.
Din punct de vedere farmacologic, terapia tumorilor prostatei se poate face cu
antagoniti alfa-1 n cazul tumorilor benigne si a hormonoterapiei testosteronice, sau
cu chimioterapia antineoplazic i teraie antiandrogenic n cazul tumorilor maligne.
Din punct de vedere chirurgical, prostectomia laparoscopic este modalitatea cea mai
utilizat de tratament pentru tumorile maligne ale prostatei.
Majoritatea pacienilor luai n studiu provin din mediu rural, fapt confirmat de
literatura de specialitate i explicat prin dieta mai bogat n grasimi a acestora ce are
o influen semnificativ asupra dezvoltrii afeciunilor prostatei.
Vrsta pacienilor are o inluen mare asupra dezvoltrii tumorilor prostatei, incidena
cea mai mare pentru tumorile benigne fiind ntre 60 si 69 de ani n timp ce incidena
cea mai crescut pentru tumorile maligne fiind ntre 70 i 80 de ani.
S-a putut constata o incliden mare a cazurilor de tumori maligne n stadiul T2 i T3la
pacienii luai n studiu.
Terapia farrmacologic a tumorilor maligne a inclus att tratament hormonal ct si
terapie chimioterapic anti-neoplazic.
Din nefericire, nu exist nc un tratament curativ complet pentru cancerul de
prostat sau pentru adenomul de prostat care sa nu implice riscurile prostectomiei si
reactiile sale adverse, dar prin cercetare este posibil descoperirea unor ageni
terapeutici noi ce vor conduce n timp la vindecarea lipsit de riscuri a acestei
afeciuni.

Bilbiografie

Lytton B, Prostate cancer: a brief history and the discovery of hormonal ablation treatment, The journal of urology, 2001.
Huggins CB, Hodges CV, Studies on prostate cancer: The effects of castration, of estrogen and androgen injection on serum phospathases in metastatic carcinoma of
the prostate, Cancer Research, 1941.
Schally AV, Kastin AJ, Arimura A, Hypothalamic fillicle-stimulating hormone (FSH) and luteinizing hormone (LH)-regulation hormone: structure, physiology and clinical
studies. Fertility and sterility, 1971.
Tolis G, Ackman d, Stellos A, Mehta A, Labtie F, Fazekas AT, Comaru-Schally AM, Schally AV, Tumor growth inhibition in patients with prostatic carcinoma treated with
luteinizing hormone-releasing hormone agonists, Proc Natl, Acad. Sci. U.S.A., 1982.
Sinescu I, Gluck G., Tratat de Urologie Editia I-a, Editura Medicala, Bucuresti, 2008.
Myers Rober, Structure of the adult prostate for ma clinicians standpoint, Clinical Anatomy, 2000.
Cockett , Koshiba K, Color Atlas of Urologic Surgery, Wilkins 1996.
Sinescu I, Gluck G, Harza M, Tumorile prostatice. Urologie oncologica, Bucuresti, Editura Universitara Carol Davila, 2006.
Walsh P, Retik A, Vaughan D, Anatomy in Campbells Urology Eighth Edition, WB Saunders Company, 2002.
Andriole GL, Grupp RL III, Buys SS , Mortality results from a randomized prostate-cancer screening trial, N Engl J Med, 2009.
Schro der FH, Hugosson J, Roobol MJ, Screening and prostate-cancer mortality in a randomized European study, N Engl J Med, 2009.
https://upload.wikimedia.org/wikipedia/commons/1/19/Prostate_histology.jpg.
Angelescu N, Tratat de Patologie Chirurgicala, Editura Medicala, Bucuresti, 2003.
https://commons.wikimedia.org/wiki/File:Prostate_adenocarcinoma_(6).jpg
Epstein Jonathan, The prostate and Seminal Vesicles, Sernbergs Diagnostic Surgical Pathology, WB Saunders Company, 1997.
http://www.webpathology.com/image.asp?case=25&n=16.
Adolfsson J, Steinck G, Hedlung PO, Deffered treatment of locally advanced nonmetastatic prostate cancer: a long term follow-up, J. Urol., 1999.
http://najms.net/v05i04p208f01h/.
http://img.medscape.com/pi/emed/ckb/pathology/1603817-1607642-1612111-1711047.jpg.
http://www.webpathology.com/image.asp?case=58&n=29.
Whitmore WF, Jr, Natural history and staging of prostate cancer, Urol Clin. North Am., 1984.
Sinescu I, Urologie CLinica, Editura Medicala Amaltea, Bucuresti, 1998.
Gerber GS, Chadwich D, Feneley RCL, Routine screening for cancer of the prostate, J,. Natl. Cancer Inst., 1991.
Brawer MK, Beatue J, Wener MH, Vessella RL, Preston SD, Lange PH, Screening for prostatic carcinoma with prostate specific antigen. Results of the second year,
J.Urol., 1993.
Eastham JA, May R, Robertson JL, Thibeault MM, Tremblay M, Labrie F, Development of a nomogram that predicts the probability of a prositive prostate biopsy in men
with an abdormal digital rectal examination and a prostate-specific antigen between 0 and 4 ng/ml, Urology, 1999.
Lodding P, AUsi G, Bergdahl S, Frosing R, Lilja H, Pihl CG, Hugosson J, Characteristics of screening detected prostate cancer in men 50 to 66 years old with 3 to 4
ng/ml prostate specific antigen, J. Urol, 1998.
Mettlin C, Relative sensitivit and specificity of serum prostate specific antigen (PSA) level compared with age-referenced PSA, PSA density and PSA change , Cancer
1994.
Oesterling JE, Free, complexed and total serum prostate specific antigen in a comunity-based population of healthy men. Establishment of age-specific reference
ranges, SAMA, 1993.
https://static1.squarespace.com/static/53222c80e4b054545c86bec9/53225e87e4b09e8c9a11a277/532f809de4b0eaed9ab884a7/1429651786573/?format=1000w
Urmeaza
EAU Guidelines 2003.
Steineck G, Helgesen F, Adolfsson J et al. Quality of life after radical prostatectomy or watchful waiting. N Engl J Med 2002.
Johansson E, Bill-Axelson A, Holmberg L et al. Time, symptom burden, androgen deprivation, and self-assessed quality of life after radical prostatectomy or watchful
waiting: the randomized Scandinavian prostate cancer group study number 4 (SPCG-4) clinical trial, Eur Urol, 2009.
Bolla M, Van Tienhoven G, Warde P et al. External irradiation with or without longterm androgen suppression for prostate cancer with high metastatic risk: 10-year
results of an EORTC randomised study, Lancet Oncol, 2010.

 Widmark A, Klepp O, Solberg A et al. Endocrine treatment, with or without radiotherapy, in locally advanced prostate cancer: an open randomised phase III trial,
Lancet, 2009.
Warde P, Mason M, Ding K et al. Combined androgen deprivation therapy and radiation therapy for locally advanced prostate cancer: a randomised, phase 3
trial Lancet, 2011
Joseph C, Presti Jr, Neoplasms of the prostate gland , Smiths General Urology, 15 th Edition, Mc Graw-Hill, 2000.
Huggins C, Hodges CV, Studies on prostatic cancer. The effect of castration, of estrogen and androgen injection on serum phosphatase in metastatic carcinoma
of the prostate, Cancer Res, 1941.
Melton LJ, Alothman KI, Achenbach SJ, Decline in bilateral orchiectomy for prostate cancer in Olmsted county, Mynesota, 1956-2000, Mayo Clin. Proc, 2001.
Byar DP, Corle DK, Hormone therapy for prostate cancer; results of the Veterans Administration Cooperative urological Research Group Studies, NCI Monogr.,
1988.
De Boogt HJ, Smith PH, Pavone-Macaluso M, Suciu S, Cardiovascular side effects of diethylstibestrol, cyproterone acetate, medroxyprogesterone acetate and
estramustine phosphate used for the treatment of advanced prostatic cancer: results for European Organization of Research on Treatment of Cancer Trials
30761 and 30762, J. Urol, 1986.
Kaisary AV, Antiandrogen monotherapy in the management of advanced prostatic cancer. Eur. Urol, 1997.
Chang A, Yeap B, Davis T, Blum R, Hahn R, Khanna O, Double-blind, randomized study of primary hormonal treatment of stage D2 prostate carcinoma: flutamide
bersus dyethylstilbestrol, J Clin Oncol, 1996.
Denham JW, Steigler A, Lamb DS et al. Short-term neoadjuvant androgen deprivation and radiotherapy for locally advanced prostate cancer: 10-year data from
the TROG 96.01 randomised controlled trial, Lancet Oncol, 2011;
DAmico AV, Manola J, Loffredo M et al. 6-month androgen suppression plus radiation therapy vs radiation therapy alone for patients with clinically localized
prostate cancer: a randomized controlled trial, JAMA, 2004;
Hanks GE, Pajak TF, Porter A et al. Phase III trial of long-term adjuvant androgen deprivation after neoadjuvant hormonal cytoreduction and radiotherapy in
locally advanced carcinoma of the prostate: the Radiation Therapy Oncology Group Protocol 9202, J Clin Oncol, 2003.
Bolla M, de Reijke TM, Van Tienhoven G et al. Duration of androgen suppression in the treatment of prostate cancer, N Engl J Med, 2009.
Galvao DA, Taaffe DR, Spry N et al. Combined resistance and aerobic exercise program reverses muscle loss in men undergoing androgen suppression therapy
for prostate cancer without bone metastases: a randomized controlled trial, J Clin Oncol, 2010.
McLeod DG, Iversen P, See WA et al. Bicalutamide 150 mg plus standard care vs standard care alone for early prostate cancer, BJU Int, 2006;
Kunath F, Keck B, Antes G et al. Tamoxifen for the management of breast events induced by non-steroidal antiandrogens in patients with prostate cancer: a
systematic review, BMC Med, 2012.
Thompson IM, Tangen CM, Paradelo J et al. Adjuvant radiotherapy for pathological T3N0M0 prostate cancer significantly reduces risk of metastases and
improves survival: long-term follow up of a randomized clinical trial, J Urol, 2009.
Trock BJ, Han M, Freedland SJ et al. Prostate cancer-specific survival following salvage radiotherapy vs observation in men with biochemical recurrence after
radical prostatectomy, JAMA, 2008.
Moul JW, Wu H, Sun L et al. Early versus delayed hormonal therapy for prostate antigen only recurrence of prostate cancer after radical prostatectomy, J Urol,
2004.
Hussain M, Tangen CM, Berry DL et al. Intermittent versus continuous androgendeprivation in prostate cancer. NEJM 2013.
Prostate Cancer Trialists Collaborative Group. Maximum androgen blockade in advanced prostate cancer: an overview of the randomised trials, Lancet, 2000;
Ryan CJ, Smith MR, de Bono JS et al. Abiraterone in metastatic prostate cancer without previous chemotherapy, N Engl J Med, 2013.
Tannock IF, de Wit R, Berry WR et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med, 2004.
Berthold DR, Pond GR, Soban F et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer: updated survival in the TAX 327
study, J Clin Oncol 2008.
Price P, Hoskin PJ, Easton D et al. Prospective randomised trial of single and multifraction radiotherapy schedules in the treatment of painful bony metastases,
Radiother Oncol 1986.
Chow E, Harris K, Fan G et al. Palliative radiotherapy trials for bone metastases: a systematic review, J Clin Oncol 2007.
Fizazi K, Carducci M, Smith M et al. Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a
randomised, double-blind study, Lancet 2011.

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PENTRU ATENIE