Genitourinary Malignancies



Genitourinary Malignancies





LOCALIZED PROSTATE CANCER

Eric L. Smith


Epidemiology



  • Incidence: 240000, Most common non-skin CA in US men


  • Annual Mortality: 28000, 2nd most common cause of CA death in men


  • Elevated risk: Increasing age, AA, & +FHx


Screening



  • Mortality benefit from screening the general population has not been established


  • PLCO CA Screening Trial: Screening detected a higher incidence of CA, but no difference in OS after 13 y of follow-up, suggesting overtreatment of indolent CA (J Natl Cancer Inst 2012;104:125)


  • ERSPC: Screening detected a higher incidence of CA, a lower prostate CA specific mortality rate, no difference in overall mortality after 11 y of follow-up (NEJM 2012;366:981)


  • USPTF concluded that for every 1000 pts routinely screened w/PSA:



    • Prevent 0-1 D from prostate CA


    • Cause 100-120 men to undergo Bx for FP results, 1/3 of w/c would experience mod. sx from the Bx


    • Diagnose 110 men w/prostate CA


    • Cause ˜50 serious complications from tx, including ED (29 men), incontinence (18 men), CV events (2 men), VTE (1 man), & death due to the tx (<1 man)


    • Thus, they recommend against PSA based screening for prostate CA in any population (grade D recommendation) (Ann Intern Med 2012;157:120)


  • Other groups have concluded o/w, the ACS recommends annual-biannual PSA screening after a discussion of the risks/benefits to men ≥50 y if nl risk, ≥45 y if elevated risk (see above), ≥40 y w/multiple 1st-deg relatives w/prostate CA, in all cases only if pt has a predicted life expectancy of ≥10 y


Initial Workup



  • For PSA >4 or abnl DRE: Transrectal u/s guided bx, w/12 cores (J Urol 2006;175:1605)


  • Histology: Gleason Score is sum of the 1° + 2° histologic grade (range of each is grade 1-5, or well- to poorly differentiated), grade 1-2 is rarely if ever classified from a needle bx so effective scale is 3 + 3 to 5 + 5 = 6-10






















    Gleason Score Interpretation


    Gleason X

    Cannot be processed


    Gleason ≤6

    Well differentiated, good risk


    Gleason 7

    Moderately differentiated, intermediate risk


    Gleason 8-10

    Poorly differentiated, high risk



  • Clinical Grade



    • T1: Not palpable (T1c is diagnosed on PSA screening alone)


    • T2: W/n the prostate (T2c is involving both lobes)


    • T3: Extends through the prostatic capsule (T3b invades seminal vesicle)


    • T4: Invades adjacent structure other then seminal vesicle, ie, bladder, levator muscles, pelvic wall


Staging






















Simplified AJCC Anatomic Stage/Prognostic Groups


I

T1-T2a (Not palpable-≤1/2 of one lobe) + PSA <10 + Gleason ≤6


II

T1-T2a PSA ≥10 &/or Gleason ≥7, or


Any T2b (involving >1/2 of one lobe) or T2c (involving both lobes)


III

T3


IV

T4, N1, or M1




Prognosis



  • 5y Prostate Ca specific (relative to aged matched controls) Survival Rates at Time of Dx:



    • Local (stage I-II) nearly 100%


    • Regional (stage III, T4, N1) nearly 100%


    • Distant (M1) 29%


  • Prognosis for localized disease varies based on risk stratification w/validated nomograms to aid decision making


Initial Treatment (by Recurrence Risk) of Localized Disease

























  • Very Low (T1, Gleason ≤6, PSA <10, <3 + cores, <50% CA any core)

If life expectancy <20 y: Active surveillance w/PSA q6mos, DRE & repeat Bx q1y


If life expectancy ≥20 y: See low risk




  • Low (T1-2a, Gleason ≤6, PSA <10)

If life expectancy <10 y: Active surveillance


If life expectancy ≥10 y: Active surveillance, RT, or RP as all three are considered equivalent in terms of survival (NEJM 2012;367:203) although head to head trials of surgery vs. RT are lacking




  • Intermediate (T2b-c or Gleason 7 or PSA 10-20)

If life expectancy <10 y: Active surveillance or RT ± short-term ADT (as neoadj, concomitant, &/or adjuvant)


If life expectancy ≥10 y: RP or RT ± short-term ADT




  • High (T3a or Gleason 8-10, or PSA >20)

RT + long-term ADT (Lancet 2002;360:103) or radical prostatectomy (selected pts w/no fixation)




  • Very high (T3b-T4, locally adv)

RT + long-term ADT or radical prostatectomy (selected pts w/no fixation) or ADT alone if not candidate for definitive tx




  • Positive surgical margins after RP, consider adjuvant RT (NCCN guidelines version 1.2013)



Monitoring



  • After Definitive Rx: PSA q6-12 mos ×5 y then q12mos; DRE q12mos, may be omitted if PSA undetectable


Metastatic Work Up for Newly Diagnosed Disease



  • Determined by risk based on: DRE (clinical grade), PSA, & Gleason Score


  • If high-risk disease based on above, consider eval for:



    • Distant mets w/CT A/P


    • Bone mets w/bone scan if:



      • T1 + PSA >20


      • T2 + PSA >10


      • Gleason ≥8


      • T3-T4 or


      • Sx



RECURRENT/METASTATIC PROSTATE CANCER

Eric L. Smith


Biochemical Recurrence



  • By PSA After Definitive RT



    • Dfn: Post RT rising PSA by 2 ng/mL or more above the nadir PSA


    • W/U options include: Eval for local/distant disease: Bone scan, CT/MRI/US, prostate bx


    • Candidate for salvage surgery if original T1-T2, NX or N0, life expectancy >10 y, current PSA <10


    • No distant mets identified, prostate bx pos, candidate for salvage as above


    • Local tx options: RP, cryosurgery, brachytherapy ± ADT


    • No distant mets identified, prostate bx neg, or not candidate for salvage


    • Observation vs. ADT (see below) Consider intermittent ADT


  • By PSA After Definitive RP



    • Dfn: Undetectable PSA after RP w/subsequent detectable PSA >0.2 ng/ml that is confirmed on subsequent determination


    • W/U options include: bone scan, CT/MRI/US, bx prostate bed if suggested by imaging


    • No distant mets identified



      • Observation vs. Salvage RT ± ADT vs. ADT alone, consider intermittent ADT


  • Distant mets identified See below


Initial Treatment for Metastatic Castration Sensitive Disease



  • Dfn: Prostate Ca that responds to lowering testosterone to castrate levels (conventionally defined as <50 ng/dl)


  • N1 RT + long-term neoadj/concurrent/adj ADT (2-3 y) or ADT alone


  • M1 ADT or dual ADT + anti-androgen


Androgen Deprivation Therapy



  • GnRH agonists such as leuprolide as daily or depot inj ± anti-androgen such as bicalutamide for at least 7 d to prevent flare


  • GnRH agonist + anti-androgen (eg, bicalutamide, nilandron)


  • Degarelix (pure GnRH antagonist, thus avoiding initial disease flare)


  • Rarely/historically: Orchiectomy


  • S/e: Hot flashes, vasomotor instability, osteoporosis, fractures, obesity, diabetes, HLD, CAD, decreased libido, mood lability S/e increase w/duration of tx


Treatment for Castration Resistant Disease



  • Dfn Progressive disease despite castrate levels of testosterone


  • Maintain castrate levels of testosterone w/GnRH agonist


  • 2nd hormone Rx: Anti-androgens as above, anti-androgen withdrawal, abiraterone, ketoconazole


Treatment for Castration Resistant Disease Continued



  • Docetaxel Taxane (NEJM 2004;351:1502; JCO 2008;26:242)


  • Sipuleucel-T DC leukapheresed & exposed to prostatic acid phosphatase Ag fused to GM-CSF ex vivo, & re-introduced; OS benefit but no change in PSA or tumor burden, appropriate only if asx, ECOG 0-1, no visceral mets, not on: Steroids, RT, chemo, or immunotx, & life expectancy >6 mos (NEJM 2010;363:411)


  • Cabazitaxel Taxane derivative, only used post docetaxel (Lancet 2010;376:1147)


  • Abiraterone Acetate Inhibits cytochrome P450 c17 (lyase, hydroxylase) reduces testosterone/dihydrotestosterone from adrenal, testis, & tumor sources, approved for pts both pre & post docetaxel (NEJM 2010;364:1995; NEJM 2013; 368:138)


  • Enzalutamide Inhibits nuclear translocation, DNA binding, & coactivator recruitment of/by androgen receptor, post docetaxel (NEJM 2012;367:1187)



    • Notes: Above are the only 5 systemic agents that have shown increased OS in this setting.


  • Mitoxantrone for Pts who are not candidates for docetaxel

All agents above except enzalutamide & sipuleucel are given in combination w/prednisone.



Mechanism of Action of Anti-Androgen Therapies






Figure 13-1


Clinical Use Algorithm



  • Castration-resistant mets before docetaxel



    • Maintain castrate levels of testosterone w/LHRH agonist


    • Further options include:



      • Abiraterone


      • Sipuleucel-T (if meets requirements above)


      • Docetaxel


      • Palliative RT


      • Bone-seeking radiopharmaceuticals


  • POD Post-Docetaxel Rx



    • Maintain castrate levels of testosterone w/LHRH agonist


    • Further options include:



      • Abiraterone


      • Enzalutamide


      • Cabazitaxel


      • Docetaxel rechallenge if previously sensitive


      • Mitoxantrone


      • Sipuleucel-T (if meets requirements above)


  • Special Consideration for Bone Mets



    • In addition to above:



      • Denosumab or Zoledronic acid to lower risk of SREs in castration-resistant disease


      • If symptomatic: Palliative RT or radionuclide (β emitters)


Small Cell



  • Distant mets identified on imaging



    • Consider bx if suspect small cell


  • Small cell pos on bx treat similar to SCLC



    • Cis/Etoposide


    • Carbo/Etoposide


    • Docetaxel-based regimens



Monitoring



  • After N1 or M1 Physical exam & PSA q3mos,



BLADDER CANCER

Helena A. Yu

Dean Bajorin


Epidemiology



  • Most common malignancy of the urinary system, ˜74000 Pts will be diagnosed in the US in 2012, ˜15000 will die of their disease.


























Pathologic Subtypes


Urothelial (Transitional Cell) Carcinoma (UC)

Most common subtype in the US, Western Europe (90%), men > women, median age at dx 73


SCC

Schistosomal: Most common subtype where infxn w/Schistosoma haematobium are prevalent (up to 75%), men >> women, median age at dx ˜40


Non-schistosomal: RFs include chronic UTIs, bladder stones, pelvic RT, chronic indwelling foley, men = women, median age at dx ˜60s


Adenocarcinoma

Urachal: Arises from urachal remnant at the bladder dome (presents earlier, better outcomes, women > men)


Non-urachal: Typically advanced at dx, poor outcome


Other

Sarcoma, paraganglioma, melanoma, neuroendocrine, lymphoma


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Aug 17, 2016 | Posted by in ONCOLOGY | Comments Off on Genitourinary Malignancies

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