Prostate Cancer - Oncology CE 2.0 3 PDF

Charlotte Eikaas 2023/24 PROSTATE CANCER EPIDEMIOLOGY: most common cancer in men; 95% AC DIAGNOSIS Occurs in 10-15% of men at some point, usually 50+ 1. PSA- prostate specific antigen (NOT CANCER SPECIFIC) Frequency increases...

Charlotte Eikaas 2023/24 PROSTATE CANCER EPIDEMIOLOGY: most common cancer in men; 95% AC DIAGNOSIS Occurs in 10-15% of men at some point, usually 50+ 1. PSA- prostate specific antigen (NOT CANCER SPECIFIC) Frequency increases with age: >50% of males have prostate Normal = 10 → 66% have cancer If 4-10 → 22% have cancer Age = #1 (male gender being a given…) Used in staging, prognosis and monitoring of treatment (+) family history with diagnosis 20) Bone scintigraphy: if PSA >10 + Gleason 9-10 + pain; check metastasis PRESENTATION Staging of PC (TMN)- combined with Gleason to give final verdict Peripheral location → asymptomatic Early transitional zone/ locally advanced peripheral T1 = barely visible, non-palpable disease: pain upon urination, increased urinary frequency, T2 = contained within capsule difficulty initiating urination, nycturia T3 = beyond capsule Progressive: hematospermia, impotence, impaired semen T4 = Infiltration beyond bladder/rectum production Advanced: bone pain- osteoblastic metastasis TREATMENT T1/T2 → either watchful waiting, prostatectomy or RT T3 → RT (NEVER operate- can’t be resected), watchful waiting SCREENING: not recommended, as many PCs are clinically T4/ N+/ M+ → hormonal therapy or watchful waiting insignificant; toxicity of treatment may worsen prognosis Watchful waiting: if expected lifespan F 2x 1. Urine sample- BLD+, LEU+, NIT – Older age groups affected (60+) 2. Renal USG- tumor is hyperechoic 3. CT with contrast- very important; 90% of RCCs can be RISK FACTORS & ETIOLOGY: most are uncertain diagnosed and staged by CT, eliminating need for biopsy 4. PET-CT: may be done to assess micrometastasis Smoking- MC Obesity & HTN +/- TMN- T = size, invasion, involvement of renal/ pelvic vessels Somatic/ hereditary mutations- VHL, tuberous Microscopic grading: Fuhrman score (I-IV) sclerosis SUBTYPES: may be determined by biopsy- done if tumor is TREATMENT: nephrectomy = only potentially curative treatment; unresectable, or if ablation is being considered should be aimed at preserving as many nephrons as possible. Renal tumors have their own capsules, easing surgical removal Clear cell carcinoma: 80-90% of RCC, tubular origin DD oncocytoma- may appear similar Main alternative to surgery = ablation Seen in VHL disease- most sporadic cancers RT- used in palliative treatment; chemo is ineffective also have loss of genes from VHL Targeted therapy: VEGFR TK + mTOR inhibitors- not much RCC most likely to invade renal vein used yet Papillary carcinoma Constant bleeding from unresectable tumor → renal a. Chromophobe carcinoma embolization PROGRESSION & PROGNOSIS PRESENTATION Invasion: may go through perinephric fat into renal vein, resulting in hematogenous metastasis Painless hematuria- MC symptom Metastatic sites: mainly lungs, bones, liver and adrenals; Abdominal mass + dull flank pain occurs in 30% Fever and weight loss- due to SAA amyloidosis Hypertension IVC syndrome Left-sided varicocele Paraneoplastic syndromes: polycythemia (EPO overproduction), hypercalcemia, fever, HTN, Cushing’s, femininization or masculinization, SAA amyloidosis 5  PRESENTATION NOT In Charlotte Eikaas 2023/24 PENILE CANCER EPIDEMIOLOGY: rare in Europe- MC in Brazil and central TREATMENT Africa Penile carcinoma in situ → circumcision (#1), topical imiquimod or 5-FU, laser ablation RISK FACTORS & ETIOLOGY T1/T2 → wide local excision, partial or total glansectomy; possibly RT Caused by HPV 16, 18, 31 and 33 (HPV 6 +11 = warts) T3/T4 → partial penectomy + radical inguinal Risk factors: poor hygiene, not being circumcised, lymphadenectomy phimosis, lichen sclerosis, smoking (verrucous PC), UVA exposure PROGRESSION & PROGNOSIS: Sentinel nodes = inguinal nodes SUBTYPES Risk of perineural invasion Very poor prognosis- a very aggressive type of cancer Penile carcinoma in situ Bowen disease: single lesion, old males, becomes invasive in 10% Bowenoid papulosis: multiple lesions, sexually active adults, virtually never becomes invasive Invasive SCC: MC subtype of penile cancer PRESENTATION: mass on penis; very variable morphology- may be lump, ulcer, sore, crust, wart, etc; may also produce inguinal lymphadenopathy DIAGNOSIS: biopsy confirms cancerous state; other modalities may be used to determine stage Pelvic USG/MRI- to examine penis and nearby structures Lymph nodes If palpable → biopsy of affected node If non-palpable → sentinel node biopsy TNM T1= only glans T2 = invading spongiosum T3 = invading corpus cavernosum T4 = anything beyond 6  Charlotte Eikaas 2023/24 TESTICULAR CANCER EPIDEMIOLOGY DIAGNOSIS: mainly based on enzymes and USG; note that the enzymes are not diagnostic, and cannot be used for screening MC malignant cancer in young males- AA 20-35 y/old Adult males → usually seminoma USG = gold standard for diagnosis Children → usually yolk sac tumors Biopsy CANNOT be done; biopsy = orchidectomy LDH = serum marker for all GCT, but also many other cancers RISK FACTORS & ETIOLOGY AFP = marker for yolk sac tumors Cryptorchidism- only known etiology; other are RF B-HCG = marker for seminoma + choriocarcinoma Testicular dysgenesis syndrome Abdominal CT + chest RTG/CT Klinefelter syndrome Staging using Royal Marsden Hospital classification; limited to… Neoplasia in contralateral testis 7 a) < 2 ou 1. Testes only Genetic- mutations of KIT (CD117) or BAK ↳ 2. 3) 25 am a ( > 5 Sub - diaphragmatic lymph nodes ↳ 3. Supra - diaphragmatic lymph nodes (e.g., mediastinal) SUBTYPES: 95% are germ cell tumors, listed below. The remaining are sex-chord/stromal tumors or mixed ↳ 4. Hematogenous metastasis Seminoma: MC testicular cancer in adults; average age 40-50 TREATMENT: mainly based on orchidectomy + chemo y/old, best prognosis. May grow very big. Extremely Seminoma stage I: radical orchidectomy + surveillance radiosensitive and chemosensitive Seminoma stage II: surgery + RT (non-bulky) or chemo Non-seminomas: metastasize earlier- both via lymph and (bulky tumor) blood to liver and lungs. 90% achieve full remission with Non-seminoma stage II: surgery + chemo aggressive chemo Seminoma/non-seminoma stage III+IV: surgery + chemo +/- resection OR RT of residual mass Embryonal carcinoma: 2nd MC in adults, 20-30 y/old, aggressive High chemosensitivity AND radiosensitivity Yolk sac tumor: MC in children, AFP+, good prognosis Complications of treatment: infertility, secondary tumors- Teratoma stomach, bladder, colon Choriocarcinoma: rare, but highly malignant, extensive hematogenous metastasis in most cases- very poor No hormonal therapy! prognosis PROGRESSION & PROGNOSIS: strongly depends on subtype; very good in most cases, since its usually seminoma PRESENTATION Spread (seminoma) Visible/palpable tumor in scrotum- testicular cancer is 1. Lymphatic- paraaortic nodes- comes first the most common cause of PAINLESS testicular 2. Hematogenous- germ cell tumor most likely to give bone swelling metastasis; occurs late Gynecomastia Highly curable malignancy, even in advanced stage! Epididymitis Recurrence is not uncommon; usually within 2 years 7  Charlotte Eikaas 2023/24 BREAST CANCER spicular microcalcifications lesson or EPIDEMIOLOGY DIAGNOSIS: mandatory steps = PE + history, mammography, USG of breast + axilla and biopsy; other tests depend on stage + clinical MC non-skin malignancy in women 2nd most deadly cancer after lung cancer MRI with BIRADS: 1-2 = nothing; 3-4 = benign; 4-5 => biopsy; Rare in women - HER2+ → Trastuzumab- receptor antagonist + CHEMO histochemistry confirm by central scar (2+) FSH Chemo: in triple neg, metastasis, or if unresponsive to High breast density (more glands) on mammography hormonal therapy Contralateral breast cancer, endometrial cancer Bisphosphonates: taken for 5y if N+, or after chemo Preventative: Oophorectomy (↓75%), Tamoxifen therapy, Aromatase inhibitors, exercise, pregnancy, breastfeeding- accumulative effect PROGRESSION & PROGNOSIS Originate from DCIS (higher risk, MC precursor) or LCIS Strongly depends on subtype; Luminal A has great prognosis, Triple neg very poor SUBTYPES Most important prognostic factors: tumor size, lymph node Luminal A: MC; highly + for ER and PR- responsive to status, ER-status and HER2 status hormonal therapy- best prognosis Mortality: has decreased in the last decades in Western Luminal B: ER+, PR +/-, may respond to hormonal therapy Europe + USA - due to adjuvant therapy and use of HER2+: ER and PR-, worse prognosis, but we may use mammography targeted therapy; negative prognostic, positive predictive F Metastatic BC is uncurable- goal is prolonging life; MC sites Triple negative: worst prognosis; ER-, PR- HER2- are bone, lung, liver and brain CNs pleura umph nodes , , Prognosis of metastatic BC: good = skin, soft tissue, bone, and Each molecular subtype can be of different histological subtypes; single lung lesions; bad = viscera I liver brain peritonium SC) , , , , Luminal A = usually invasive ductal carcinoma NST; HER2 = apocrine or micropapillary; TN = medullary, metaplastic or secretory carcinoma OTHERWISE NOTEWORTHY > - kist-proliferation HER2 positivity: checked by immunohistochemistry (+1) = PRESENTATION negative; (+2) → do FISH to confirm; (+3) = positive Painless palpable mass = MC Prevention- screening: mammography every 3y from 50-70 Skin changes: retraction, Peau d’orange (dimpling), nipple y/old- ↓mortality in women >50 y/old; self-examination is inversion, satellite nodules NOT recommended Lymphadenopathy- usually axillary nodes > - may edema cause ar m Spiculated mass on MG = highly suggestive of cancer Inflammation- must be diff. from mastitis Breast cancer = #1 origin of metastatic bone cancer- most. common cause of pathologic fractures 22  Charlotte Eikaas 2023/24 ENDOMETRIAL CANCER EPIDEMIOLOGY DIAGNOSIS MC gynecological malignancy; 6% of cancers, 2% of Based on PE, biopsy and dilatation + curettage- 90% cancer deaths sensitivity; may do hysteroscopy- 100% sensitivity Growing incidence- due to ↑obesity + aging Assessment of spread: USG, CT, MRI, chest RTG, bone Mainly affects postmenopausal women- AA 63 scintigraphy Staged on MRI/CT with FIGO system- based on location SUBTYPES: divided into 2 main groups and spread, not size 1. Endometrioid- 90%, nice type Onset 55-65 y/old TREATMENT Originates from atypical complex hyperplasia RF: age, obesity, diabetes, HTN, infertility, Total hysterectomy = main treatment- also includes Caucasian origins, unopposed estrogen removal of ovaries, fallopian tubes +/- LN stimulation (HRT, Tamoxifen), early menarche High risk cancers: consider RT/chemo in addition to (52), personal history surgery of breast, ovarian cancer, family history of Inoperable →RT endometrial cancer Metastatic → chemo or hormonal therapy- Genetic RF: Cowden syndrome (PTEN), MSI progesterone, tamoxifen (HNPCC), TP53 if high grade PROGRESSION & PROGNOSIS 2. Non-endometrioid-10%, bad type; either serous (MC), clear cell, carcinosarcoma; Prognostic factors: grade, lymph node status, myometrial invasion Onset 65-75 y/old Good prognosis: endometrioid AC, adenosquamous, mucinous AC Sporadic origins Associated with endometrial atrophy Bad prognosis: serous AC (worst), clear cell, sarcoma Genetic RF: 90% of serous EC have TP53 Risk of metastasis by direct spread to peritoneum mutation- usually sporadic High risk of metastasis- cells exfoliate and reach peritoneal cavity through fallopian OTHERWISE NOTEWORTHY tubes NOT associated with HPV PRESENTATION - abnormal bleeding ow periods May have asymptomatic period - long periods extra Uterine sarcomas: 2-4% of uterine cancers; either carcinosarcoma Abnormal bleeding- in 90%, early symptoma (MC), leiomyosarcoma or endometrial stromal sarcoma. MC in African Americans, AA 50-60 y/old. RF include obesity, HRT/ Vaginal discharge- bloody, purulent Tamoxifen, infertility, diabetes, early menarche and late Pain- pelvic, abdominal, vertebral menopause. Diagnosed like endometrial AC. Treated by surgery Systemic- weight loss, anemia, constipation, lower +chemo/RT, unless metastatic- chemo/hormonal therapy extremity edema 23  Charlotte Eikaas 2023/24 CERVICAL CANCER EPIDEMIOLOGY DIAGNOSIS 4th MC cancer in women worldwide; 85% in Screening: PAP smear starting between 18-25, done every 1-3 developing countries; MC cancer in women in some years until 60-65 y/old + HPV test every 5 years after 30 y/old; parts of Africa allows detection long before symptoms Now rare in western world, but will ↑ in incidence Diagnosis: speculum exam with biopsy + MRI (gold standard) + with migration from non-vaccinated countries CT scan for nodal status + PET/CT - distant metastasis + planning Mean age 50 y/old RT RISK FACTORS & ETIOLOGY Staging- FIGO: 0= CIS; I = confined to cervix; II= slightly beyond cervix; III= reached pelvic wall or lower 1/3rd of vagina; IV = Mainly HPV exposure (16, 18, 31, 33); risk of this ↑ invading bladder, rectum, or metastatic with poverty, early sexual debut, promiscuous lifestyle, STDs Multiple pregnancies Secondary RF: smoking, immunodeficiency (AIDS) TREATMENT: mainly based on surgery and radiotherapy; chemo Long-term use of hormonal contraception has benefit in later stages (photo below) DES- diethylbestrol exposure in utero- clear cell Stage 1A: hysterectomy; or conization, if young and carcinoma (vaginal/cervical) planning to have children IB-IIA: radical hysterectomy + lymphadenectomy- SUBTYPES Wertheim-Meigs surgery with isplatin > - SCC- 80-90% IIB-IVB: RT with concomitant chemo; teletherapy and/or AC- 15% brachytherapy- prolongs survival; NO SURGERY Pembrolizumab-PD-1 Newest-immuno- - targeted therapy-Bevacizumab Be Platimum based chemo , moleullar PRESENTATION PROGRESSION & PROGNOSIS Often completely asymptomatic for many years- Slow process over 10-20 years; HPV → CIN → CIS → usually detected by screening invasive carcinoma Negative prognostic factors: positive pelvic nodes, Advanced cancer positive surgical margin, deep stromal infiltration, May present with bleeds- postmenopausal, after sex, vascular- lymphatic permeation irregular menstruation 5YS: 0= 100%; I = 85%; II = 65%; III = 35%, IV= 7% Vaginal discharge- yellowish, bloody, foul-smelling Pain in pelvis, back and/or leg Dysuria Hydronephrosis- when cancer invades wall of bladder and blocks ureters; renal failure = MC cause of death 24 conization (remove come shaped part of cerrix)  Charlotte Eikaas 2023/24 OVARIAN CANCER EPIDEMIOLOGY DIAGNOSIS - No early symptoms. No screening Increasing incidence due to aging population First step = transvaginal USG abdomen + pelvis; followed Most lethal gynecologic cancer- 70% detected at by CT to determine extent and plan treatment advanced stage Chest CT/RTG: check for pleural effusion + spread above 3% of cancers, 5% of cancer deaths diaphragm Biopsy- definitive diagnosis RISK FACTORS & ETIOLOGY predisposing factors. ↳ usually not due to Hereditary: BRCA1/2, HNPCC, Gorlin syndrome, Peutz- TREATMENT required ↑ surgical staging is Jegher syndrome- 5-10% of cases Surgical: oophorectomy, often with salpingectomy and Other risk factors are not well proven: nulliparity, hysterectomy also appendectory omextectory pllviccymp tomy) , , endometriosis, prolonged estrogen exposure, Chemo: as adjuvant therapy (with platin analogues taxanes) + infertility, personal/family history of various cancers Advanced stage: cytoreductive surgery + chemo Protective: tubal ligation, contraceptives GCT/stromal tumors- very chemosensitive Staging- FIGO- most important for prognosis SUBTYPES Surface epithelial cell tumors: MC group (70%); accounts for PROGRESSION & PROGNOSIS 90% of malignant tumors; occur in women 20+ Most lethal gynecological cancer; usually discovered late- Serous SECT: MC subtype; either low or high grade; no screening, often no symptoms most are low grade; high grade is associated with TP53 No great treatment exists and BRCA mutations, and grow rapidly High risk of peritoneal dissemination- omental caking- Other: mucinous, endometrioid, Brenner, Clear cell MC route of metastasis Germ cell tumors: 15-20%, occur in 0-30 y/olds; all are malignant; teratomas, dysgerminoma, yolk sac tumor, ↳ maybe benign choriocarcinoma; chemosensitive OTHERWISE NOTEWORTHY Sex chord stromal tumors: 2-3%, occur in all ages, but usually Marker: Ca-125; not very specific; used to check for in reproductive age; very rarely malignant; Granulosa cell, recurrence and monitoring treatment. Normal level = Sertoli-Leydig tumor, fibromas, thecomas, fibrothecomas 35U/mL, ovarian cancer → 2000-3000 PRESENTATION- occurs at advanced stage Lower abdomen discomfort- bloating, fullness, loss of appetite, nausea, flatulence Vaginal bleeding Constipation/ diarrhea Frequent urination- tumor pressing on bladder 25  Charlotte Eikaas 2023/24 VAGINAL CANCER EPIDEMIOLOGY DIAGNOSIS Rare Pelvic exam + colposcopy + biopsy MC in older adults and elderly Cervical cancer must be excluded- similar presentation- PAP smear RISK FACTORS & ETIOLOGY: Age- 50-70 y/old TREATMENT: HPV+ Early → surgery Fetal DES exposure, vaginal adenosis Late → RT History of cervical cancer Vaginal irritation Uterine prolapse PROGRESSION & PROGNOSIS Smoking SUBTYPES: SCC = 85%: AA 60-80 y/old Adenocarcinoma = 7%: AA 12-30 y/old Clear cell AC: very rare, linked to DES exposure in utero- was given from 1945-1970 to prevent miscarriages Other subtypes: malignant melanoma, leiomyosarcoma, rhabdomyosarcoma PRESENTATION Bleeding/discharge not related to menstruation- esp. postmenopausal bleeding Difficult/painful urination Pain during intercourse Pelvic pain ↳ Constipation vulvar cancer Palpable mass · disease of old age · possibly associated with HpV ① Trophoblastic disease-rare disease curable nighly - extremely chemosensitive - 26