Adult Uro Oncology Flashcards
<p>ProtecT trial</p>
<p>Randomized 1,643 men with screen-detected PCa to active monitoring, radical prostatectomy, or radiation therapy with curative intent. At a median of 10 years, no differences in PCa mortality were observed across groups (PCa deaths per 1,000 person years: active monitoring 1.5, surgery 0.9, radiation 0.7, p = 0.48).</p>
<p>PIVOT trial</p>
<p>The Prostate Cancer Intervention Versus Observation Trial (PIVOT) found that radical prostatectomy did not improve overall or disease-specific mortality at a median follow-up of 12.7 years.1,3 However, surgery reduced the risk of progression (40.9% vs 68.4%; HR 0.39, 95% CI 0.32-0.48) and treatment for progression (33.5% vs 59.7%; HR 0.45, 95% CI 0.36-0.56) compared to watchful waiting.</p>
<p>SPCG 4</p>
<p>The Scandinavian Prostate Cancer Group Study No. 4 (SPCG 4) reported an improvement in overall and disease-specific mortality for men undergoing radical prostatectomy compared to watchful waiting. The absolute OS benefit favoring prostatectomy was 12%, which translated to a median 2.9 years of life gained at median 23 years of follow-up</p>
<p>Prostate cancer Active surveillance inclusion criteria</p>
<p>Men with very low risk and low risk PCa per AUA and NCCN guidelines (or clinically insignificant disease per Epstein criteria) are typically candidates for AS.
<br></br>
<br></br>These criteria include:
<br></br>1. Grade Group 1 (Gleason score ≤ 6)
<br></br>2. Clinical stage ≤ T2a
<br></br>3. PSA density < 0.15ng/mL/g
<br></br>4. < or ≤ 3 positive biopsy cores
<br></br>5. ≤ 50% cancer in each core</p>
<p>PUNCH trial</p>
<p>randomized patients with high-risk, clinically localized prostate cancer to neoadjuvant chemohormonal therapy with docetaxel and ADT plus radical prostatectomy or radical prostatectomy alone. Results indicated no difference in 3-year biochemical progression free rates, the primary endpoint. However, neoadjuvant chemohormonal therapy was associated with improved MFS and OS compared to surgery alone</p>
<p>RADICALS-RT trial</p>
<p>enrolled 1396 men with intermediate-to-high risk prostate cancer after radical prostatectomy, and randomized them to adjuvant vs. early salvage RT demonstrated no statistically significant difference with regards to biochemical progression-free survival and freedom from subsequent hormonal therapy between the treatment arms. Adjuvant radiotherapy was associated with an increased number of urinary and bowel adverse effects.</p>
<p>Recommended dose for conventonial fractionated EBRT in prostate cancer</p>
<p>Recommended doses for conventionally fractionated radiation are 75.6 to 79.2 Gy for low-risk cancers and up to 81 Gy for intermediate- and high-risk prostate cancers</p>
<p>What is EBRT</p>
<p>External Beam Radiation Therapy
<br></br>
<br></br>delivered using a linear accelerator (LINAC.) The LINAC generates a high energy electron beam that is passed through a tungsten target to generate a photon beam. These beams reach megavoltage energies (commonly 6-15 MV) capable of delivering ionizing radiation energies to targets deep in the body.</p>
<p>What is 3DCRT</p>
<p>Dimensional Conformal Radiation Therapy.
<br></br>
<br></br>The process of using CT images to generate a 3-dimensional radiation plan to maximize radiation dose to the target volume while minimizing dose to neighboring organs at risk (OAR’s)</p>
<p>What is IMRT</p>
<p>Intensity Modulated Radiation Therapy (IMRT) is a specialized form of EBRT. The process of generating an IMRT plan is similar to the generation of a 3DCRT plan. However, IMRT utilizes a process called inverse planning.</p>
<p>RT for low risk prostate cancer</p>
<p>Eligible patients: Men with NCCN low-risk prostate cancer (T1-2a and Gleason score 6 and PSA < 10 ng/ml).
<br></br>
<br></br>In addition to AS and RP, radiation treatment options for low-risk prostate cancer include EBRT or brachytherapy monotherapy.</p>
<p>RT for intermediate risk prostate cancer</p>
<p>Eligible Patients: T2b-T2c or T1-T2a with Gleason score 7 or PSA 10-20 ng/ml.
<br></br>Radiation Treatment
<br></br>
<br></br>Options: EBRT +/- short course androgen deprivation therapy, brachytherapy monotherapy, combination brachytherapy and EBRT +/- short course androgen deprivation therapy.</p>
<p>Ascende-RT trial</p>
<p>compared 46 Gy of pelvic EBRT with dose-escalation by 3DCRT (DE-EBRT) boost to 78 Gy or with an LDR boost.
<br></br>
<br></br>Men with both NCCN intermediate- (N==122, 30.7%) and high-risk disease (N=276, 69.3%) were eligible and received 1 year of ADT with 8 months delivered neoadjuvantly. With a median follow-up of 6.5 years there was a significantly greater risk of bPFS in men treated with DE-EBRT vs brachytherapy boost among the total population (HR=2.04, p=0.004) and among men with NCCN intermediate-risk disease (p=0.003). No benefit in prostate cancer specific or all-cause mortality could be observed.</p>
<p>RT for High/very HR prostate cancer</p>
<p>Eligible Patients: T3-T4 or Gleason score 8-10, or PSA > 20 ng/ml.
<br></br>
<br></br>Radiation Treatment options: EBRT + long course ADT or combination brachytherapy and EBRT + ADT.</p>
<p>Adjuvant RT post prostatectomy</p>
<p>Eligible Patients: pT3 disease, positive margins at prostatectmy.
<br></br>Radiation treatment options: EBRT to the prostatic fossa..
<br></br>
<br></br>Evidence shows improved Biochemical reurrence free survival and OS</p>
<p>Salvage RT post prostatectomy</p>
<p>Eligible Patients: detectable and rising PSA (≥ 0.1 ng/ml) without radiographic evidence of nodal or distant metastasis.
<br></br>Radiation treatment options: EBRT +/- ADT.
<br></br>
<br></br>those most likely to benefit include those with Gleason less than 7, with pre-RT PSA less than 2ng/mL, negative SVI, positive margins, and those with PSA doubling times greater than 10 months.
<br></br>
<br></br>-prostatic fossa/pelvic lymph node RT with short-term ADT confers better biochemical control.</p>
<p>List trials of adjuvant vs salvage radiation post prostatectomy</p>
<p>https://university.auanet.org/core/img/223_table7_2021.png</p>
<p>ProPSMA trial</p>
<p>prospective multi-institutional study in which patients with high risk prostate cancer (PSA>20, clinical stage T3-4, Grade Group 3-5) were randomized to gallium-68-PSMA-PSMA-11 PET/CT vs conventional imaging (bone scan and CT scan)
<br></br>
<br></br>PSMA PET-CT was more sensitive (85% [74-96] vs. 38% [24-52]) and specific (91% [85-97] vs 98% [95-100]) than convention first-line imaging for the detection of nodal or metastatic disease.</p>
<p>Guideline recommendation for prostate cN1 nodes on conventional imaging</p>
<p>systemic treatment with ADT +/- radiation therapy to the primary
<br></br>
<br></br>Currently, surgical management of cN1 patients should be restricted to patients enrolled in clinical trials</p>
<p>PROMIS trial</p>
<p>576 men underwent a 1.5 Tesla mpMRI followed by both TRUS biopsy and a template mapping prostate biopsy. For clinically significant cancer, mpMRI was more sensitive (93%; 95% CI 88-96%) and less specific (41%; 95% CI 36-46%). The authors concluded that using mpMRI to triage men might allow 27% of patients to avoid a primary biopsy and 5% fewer clinically insignificant cancers would be detected</p>
<p>PRECISION Study</p>
<p>500 men without a history of a prostate biopsy and a clinical suspicion for prostate cancer were randomized to undergo mpMRI with targeted biopsy versus standard TRUS prostate biopsy. Clinically significant prostate cancer was detected in 38% of the mpMRI targeted biopsy group as compared to 26% of the TRUS biopsy group (p=0.005) and fewer men in the mpMRI targeted biopsy group received a diagnosis of clinically insignificant cancer</p>
<p>ExoDx</p>
<p>a urine-based 3-gene exosome (ERG, PCA3, and SPDEF) expression assay validated for the risk of clinically significant PCa in men without a prior biopsy.</p>
<p>miR</p>
<p>a urine-based test interrogates small noncoding RNAs (sncRNA) isolated from urinary exosomes. This test was developed and validated to stratify patients with prostate cancer into risk categories</p>
<p>MPS</p>
<p>MPS (MyProstateScore, formerly Michigan Prostate Score (MiPS)): combination of serum PSA, urinary PCA3 and TMPRSS2:ERG validated to assess the risk of incident PCa and clinically significant PCa. In validation it was shown to improve upon the performance of PSA or PCA3 alone in detecting aggressive PCa</p>
<p>PCA3</p>
<p>a non-coding mRNA in urine, may help identify incident and clinically significant PCa</p>
<p>Select MDX</p>
<p>a urine-based risk assessment that measures DLX1 and HOXC6 against KLK3 mRNA levels in post-DRE urine validated for the risk of clinically significant PCa (≥3+4) in men without a prior biopsy</p>
<p>4K score</p>
<p>a blood-based validated risk assessment for clinically significant PCa in men at risk for PCa.</p>
<p>PHI</p>
<p>blood-based risk assessment using PSA, percent free PSA, and [-2]proPSA to estimate the risk of clinically significant PCa</p>
<p>Confirm MDX</p>
<p>is an epigenetic test of the PCa-associated genes GSTP1, APC, and RASSF1. It is assessed on non-cancerous biopsy tissue and is validated to predict the absence of PCa on subsequent biopsy (rules out need for further biopsy)</p>
<p>OncotypeDx</p>
<p>17-gene expression panel validated to predict the risk of adverse pathology at surgery and the risk of metastasis and death after treatment. It can be used to inform the decision between active surveillance and definitive therapy</p>
<p>Prolaris</p>
<p>a 31-gene expression panel validated to predict the risk of disease-specific mortality with conservative management and the risk of metastatic disease after treatment. It can be used following biopsy to better determine whether a patient should receive active surveillance or definitive therapy.</p>
<p>ProMark</p>
<p>an 8-protein proteomic assessment validated to assess the risk of adverse pathology. May be utilized for low or very low risk patients post biopsy to select active surveillance versus definitive therapy</p>
<p>Decipher</p>
<p>a 22-gene genomic classifier that is validated to predict the risk of metastasis to select patients who are better treated with definitive therapy</p>
<p>PCPT trial</p>
<p>Prostate cancer prevention trial
<br></br>
<br></br>Ca was detected by biopsy (which included end-of study biopsies) in a remarkable 24.4% of the study participants, and finasteride decreased the overall relative risk of PCa by 25%.</p>
<p>REDUCE trial</p>
<p>Reduction by dutasteride of Prostate cancer Events
<br></br>
<br></br>xamined the effects of dutasteride in a higher risk cohort (PSA 2.5-10 ng/ml and negative prior biopsy), with a similar relative risk reduction of 25% and an absolute reduction of 5.1%.73</p>
<p>SELECT Trial</p>
<p>randomized 35,533 men at low risk for PCa to regimens of either vitamin, or combinations of these agents.
<br></br>
<br></br>No significant differences were found in rates of PCa across the intervention groups. Therefore, Selenium or Vitamin E is not recommended for the prevention of PCa.</p>
<p>Most potent stimulator of the androgen receptor</p>
<p>dihydrotestosterone which is the principal androgen in the prostate cell</p>
<p>Mechanisms of castration resistant prostate cancer</p>
<p>1. Ability of CaP cells to use intracellular androgens via de novo synthesis or get it exogenously from the adrenal galnds and tumor microenvironment
<br></br>
<br></br>2. Increased AR expression
<br></br>
<br></br>3. AR gene mutation that allow the receptor to be activated by other ligands other than other androgens
<br></br>
<br></br>4. Alterations of AR signaling to promote tumor growth
<br></br>
<br></br>5. Synthesis of AR variants (AR-V7)</p>
<p>Treatment options for mCSPC (3)</p>
<p>1. ADT alone
<br></br>2. Docetaxel + ADT (CHAARTED, STAMPEDE)
<br></br>3. AA + ADT</p>
<p>CHAARTED TRIAL</p>
<p>790 men w/ newly dx mCSPC randomized to ADT vs. ADT+ 6 cycles of docetaxel. At median f/u of 53.7 mos, the median OS was 47.2 mos versus 57.6 mos in favor of the ADT + docetaxel arm (HR 0.72, (0.59-0.89), P=0.0018).
<br></br>
<br></br>There was a benefited seen in men withhigh vol dz but not in low vol dz</p>
<p>STAMPEDE Trial</p>
<p>Multi-arm, multi-stage of ~ 3000 men, wherein the addition of docetaxel to ADT improved OS. In the subset of 1086 men with metastatic disease, the median OS for men undergoing ADT alone was 45 mos compared to 60 mos in the ADT plus docetaxel arm (HR 0.76 (0.62-0.92), P=0.005).
<br></br>Also significant reduction of death in ADT + Doce arm long term
<br></br>
<br></br>ADT + Abiraterone: demonstrated that at a median follow-up of 40 months, abiraterone in addition to ADT led to an OS benefit in a group of 1,917 men. A 37% relative improvement in survival was noted with a HR of 0.63 (95% CI, 0.52-0.76, P < 0.0001).
<br></br>
<br></br>The STAMPEDE randomized trial arm H included a comparison of ADT vs ADT plus external beam radiotherapy in 2061 men with newly diagnosed metastatic prostate cancer. Three-year survival was noted to be 81% with radiotherapy and 73% in the control group among men with low volume metastatic disease burden by CHAARTED criteria (HR 0.68, 95% CI 0.52-0.90, P=0.007).</p>
<p>GETUG-AFU 15 trial</p>
<p>Randomized, open-label phase 3 study of 385 patients that did not demonstrate statistically significant improvement in survival with the addition of docetaxel. Median survival was 58.9 mos in the ADT with docetaxel group, and 54.2 mos in the ADT alone group (HR 1.01, 95% CI 0.75-1.36).</p>
<p>LATTITUDE study</p>
<p>1,199 men with de novo mPC and with 2 of 3 high risk features (visceral disease, Gleason score of ≥ 8, presence of ≥ 3 lesions on bone scan) were randomized to ADT with abiraterone or placebo. Interim analysis showed a marked benefit in the abiraterone plus ADT group with a prolongation of radiographic progression-free survival and a 38% reduction in the risk of death compared to ADT and placebo.</p>
<p>Enzamet Trial</p>
<p>randomized 1125 mCSPC patients to receive ADT plus standard nonsteroidal anti-androgens or ADT plus enzalutamide. The three year OS was 80% in the enzalutamide group and 72% in the control group. At a median follow-up of 34 months, the HR for death was 0.67 (95% CI 0.52 -0.86, P=0.002) in favor of the enzalutamide group
<br></br>
<br></br>Caveat: good number experienced AE especially if they received Docetaxal.</p>
<p>MOA and dosing of Docetaxal</p>
<p>Microtubule inhibitor
<br></br>
<br></br>75 mg/m2/dose IV x 1 on day 1 of 21 day cycle; total 6 cycles</p>
<p>MOA and dosing of Abiraterone</p>
<p>Nonsteroidal inhibitor of CYP17A1
<br></br>
<br></br>1000 mg PO daily with prednisone 5 mg PO daily</p>
<p>MOA and dosing of Apalutamide</p>
<p>Nonsteriodal anti-androgen
<br></br>
<br></br>240 mg PO daily</p>
<p>MOA and dosing of Enzalutamide</p>
<p>Androgen receptor signaling inhibitor
<br></br>
<br></br>160 mg daily</p>
<p>MOA and Radiation dose for mCSPC</p>
<p>Causes DNA damage.
<br></br>
<br></br>2.75 gy x 20 Fractions</p>
<p>Titan Trial</p>
<p>phase 3 TITAN randomized trial of 1052 men compared ADT plus apalutamide to ADT plus placebo. An interim analysis showed OS at 24 mos was 82.4% in the apalutamide arm compared to 73.5% in the placebo arm. The HR for death was 0.67 (95% CI 0.51-0.89, P=0.005). The rate of AEs was similar in the apalutamide and placebo arms</p>
<p>HORRAD Trial</p>
<p>randomized 432 patients with PSA >20 ng/mL and primary bone metastases on bone scan between 2004 and 2014 to ADT with EBRT or ADT alone. The median PSA was 142 ng/mL with 67% of the patients having ≥ 5 bone metastases. With a median follow up of 47 months, no significant diff in overall survival (45 months in EBRT + ADT group and 43 months in the ADT group (p=0.4). There was an improvement in PSA progression in the radiotherapy group HR: 0.78; 95% CT: 0.63-0.97m p=0.02)</p>
<p>Treatment options for nmCRPC</p>
<p>Observation if PSADT > 10 mos and with hormone therapy when PSADT < 10 mos
<br></br>
<br></br>ADT + AA ( Enza, Apal, Daro)</p>
<p>Definition of nmCRPC</p>
<p>defined as the patient with a rising PSA despite castrate levels of testosterone following androgen deprivation therapy and no radiographic evidence of metastases on conventional imaging with CT or MRI abdomen/pelvis and bone scan</p>
<p>PROSPER Trial</p>
<p>1401 patients w/ nmCRPC and a PSA DT of 10 mos or less (mean PSA DT 3.7 mos) were randomized 2:1 to receive enza plus ADT or placebo plus ADT. The median MFS was 36.6 mos in the enza group vs 14.7 mos in the placebo group (HR 0.29, CI 0.24-0.35; p<0.001).
<br></br>
<br></br>Median OS was 67 months</p>
<p>SPARTAN TRIAL</p>
<p>1207 patients with nmCRPC and a PSA DT of 10 months or less were randomized 2:1 to receive apalutamide plus ADT or placebo plus ADT. Median MFS was 40.5 months in the apalutamide group as compared with 16.2 mos in the placebo group (HR for metastasis or death 0.28, 95% CI 0.23-0.35; p<0.001)
<br></br>
<br></br>Time to symptomatic progression was longer in the apa group.</p>
<p>ARAMIS</p>
<p>1509 patients w/ nmCRPC, PSA DT of 10 mos or less, baseline PSA level of 2 ng/mL and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 were randomized 2:1 to receive darolutamide 600 mg BID vs. placebo while continuing ADT. Median f/u was 17.9 mos. The median MFS was 40.4 mos with darolutamide compared to 18.4 mos w/ placebo (HR 0.41, 95% CI 0.34 to 0.50; p<0.001)
<br></br>
<br></br>Risk of death was lower and time to pain progression was longer.</p>
<p>Treatment strategies for mCRPC (8 categories)</p>
<p>Abiraterone, enazalutamide: mCRPC
<br></br>
<br></br>Sipuleucel: Asymptomatic/minimal symptoms, no live metastases
<br></br>
<br></br>Docetaxel, Cabazitazel: mCRPC
<br></br>
<br></br>Olaparib- DDR mutation following androgen receptor directed therapy
<br></br>
<br></br>Rucaparib- BCRA 1/1 mutation following AR directed therapy and taxane based chemo
<br></br>
<br></br>Radium- 223- Symptomatic bone mets
<br></br>
<br></br>Lu-PSMA-617- PSMA expressing mets. FDA breakthrough therapy designated
<br></br>
<br></br>Pembrolizumab: Unresectable or metastatic tumor with: 1. High Microsatellite instability or high tumor mutational burden (>/= 10)</p>
<p>Definition of castration resistance</p>
<p>serum testosterone level < 50 ng/dl or 1.7 nmol/L + 1 of the following:
<br></br>
<br></br>Biochemical progression: 3 consecutive rises in PSA at least one week apart, resulting in 25% increases over the nadir, and PSA greater than 2 ng/mL
<br></br>
<br></br>Radiographic progression: The appearance of new lesions: Either 2 or more new bone lesions on a bone scan and confirmed by other imaging modality (e.g., CT or MRI) if ambiguous or a soft tissue lesion measurable using RECIST criteria</p>
<p>Denosumab</p>
<p>human monoclonal antibody against RANK ligand (RANKL), acting to inhibit RANKL, the main driver of osteoclast formation, function and survival</p>
<p>What is PSMA</p>
<p>Prostate-specific transmembrane antigen, a transmembrane glutamate carboxypeptidase, is highly expressed on prostate cancer cells, with high expression being an independent biomarker of poor prognosis in both early- and late-stage disease</p>
<p>What is Radium-223</p>
<p>an isotope of radium that emits a low level of alpha particle radiation with an affinity for sites of bone metastases. It has a half-life of 11.4 days and works by causing double-stranded DNA breaks.</p>
<p>What is Sipuleucel</p>
<p>immunotherapy product that contains patient-specific autologous dendritic cells loaded ex vivo with a recombinant fusion protein consisting of prostatic acid phosphatase (PAP) linked to a granulocyte-macrophage colony stimulating factor (GM-CSF) designed to break immune tolerance to normal tissue antigen PAP.</p>
<p>What are PARPi's</p>
<p>Poly(adenosine diphosphate-ribose) polymerases (PARPs) are a large family of 18 proteins which are responsible for facilitating DNA repair caused by either single-strand break or base excision repair pathways. PARP inhibitors cause genomic instability and cell death due to the inability to repair damaged DNA.
<br></br>
<br></br>Olaparib
<br></br>Rucaparib</p>
<p>MOA and dosing of Cabazitaxel</p>
<p>Cabazitaxel is a second-generation taxane with a broader range of cytotoxicity, high potency that remains cytotoxic for docetaxel-resistant cell lines due to gp-1 overexpression with better blood-brain penetration than docetaxel.
<br></br>
<br></br>25mg/m2 q21 days + prednisone</p>
<p>MOA of Mitoxantrone</p>
<p>anthracycline chemotherapy that acts during multiple phases of the cell cycle to disrupt DNA synthesis and DNA repair.
<br></br>
<br></br>Currently no role for Mitotoxantrone in treating mCRPC</p>
<p>MOA and role of Docetaxel in mCRPC</p>
<p>second-generation taxane chemotherapy that inhibits microtubule assembly into the mitotic spindle, thus arresting the cell cycle during G2/M phase. Docetaxel may also increase apoptosis by downregulation of the BCL2 gene, which tends to be over-expressed in cancer cells.
<br></br>
<br></br>Tax trial: phase 3 doce plus prednisone vs mitotoxantrone + prednisone
<br></br>
<br></br>SWOG 9916: Phase 3 doce + estrasmustine vs mitotoxantrone + pred.
<br></br>
<br></br>Both trial Docetaxel group showed longer median survival compared to control.</p>
<p>Tests available to detect cortisol hypersecretion (Cushing Syndrome)</p>
<p>Overnight low-dose (1-mg) dexamethasone suppression test (OST): higher sensitivity for detecting subclinical
<br></br>
<br></br>Late-night salivary cortisol test (SCT): easiest
<br></br>
<br></br>24-hour urinary-free cortisol evaluation (UFC): standard test but more time intensive</p>
<p>How is a diagnosis of cushing syndrome made after OST</p>
<p>A putative diagnosis of Cushing Syndrome is made if the serum cortisol level is > 5 micrograms/dL following an OST</p>
<p>Conn Syndrome</p>
<p>hyperaldosteronism due to a single adrenal nodule
<br></br>
<br></br>classic syndrome includes hypertension, hypokalemia, and alkalosis, up to 40% of patients with this syndrome are normokalemic</p>
<p>How is primary hyperaldosteronism diagnosed</p>
<p>An ARR≥20 along with a concomitant aldosterone concentration above 15 ng/mL suggest the diagnosis of primary hyperaldosteronism</p>
<p>Screening Guidelines for hyperaldosternonism (8)</p>
<p>1. Any patient with sustained blood pressure above 150/100 on three separate measurements taken on different days
<br></br>
<br></br>2. Hypertension resistant to 3 antihypertensives
<br></br>
<br></br>3. Hypertension controlled with four or more medications
<br></br>
<br></br>4. Hypertension and low potassium
<br></br>
<br></br>5. Hypertension and a newly diagnosed adrenal incidentaloma
<br></br>
<br></br>6. Hypertension and concomitant sleep apnea
<br></br>
<br></br>7. Hypertension and a family history of early onset hypertension or stroke before age 40
<br></br>
<br></br>8. All first-degree relatives of patients with a diagnosis of primary aldosteronism</p>
<p>Medications that cause falsely elevated metanephrines</p>
<p>levodopa, monoamine oxidase inhibitors, benzodiazepines, tetracycline, and rapid withdrawal from clonidine</p>
<p>How is pheochromocytoma diagnosed</p>
<p>with plasma-free metanephrine and normetanephrine levels or 24-hour total urinary metanephrines and fractionated catecholamines
<br></br>
<br></br>Caveat: Metanephrines are more sensitive than catecholamines since metabolism is continuous, unlike catecholamine release which occurs episodically.2 The higher sensitivity of metanephrines also means they have a higher false positive rate. However, elevation above designated thresholds (>2x the upper limit of normal) in either study suggests the presence of pheochromocytoma</p>
<p>When should sex hormone testing be performed with adrenal masses?</p>
<p>not warranted unless the patient is suspected of having an adrenocortical carcinoma (mass > 4 cm) and/or obvious clinical stigmata of feminization or virilization.
<br></br>
<br></br>Measure DHEA with 17-Ketosteroids
<br></br>
<br></br>For women: Get serum testosterone
<br></br>
<br></br>For men get 17B-estradiol</p>
<p>When should sdrenalectomy be performed in nonfunctioning adrenal masses?</p>
<p>If the lesion size increases by ≥ 1 cm or develops functionality, surgery should be considered. However, 75-95% of incidentalomas remain stable in size while 2-8% of previously non-functioning lesions develop functionality, with hypersecretion of cortisol being the most common finding.</p>
<p>Associated syndromes with adrenocortical carcinoma</p>
<p>familial syndromes such as Li-Fraumeni, Beckwith-Wiedemann, MEN-1, McCune-Albright, and Carney complex.</p>
Main prognostic factors for adrenocortico carcinoma
tumor stage and completeness of surgical resection.
Most common sites of adrenal mets
Liver, (48%) lung (45%), LN (29%), bone (13%)
Standard treatment for adrenocortical carcinomas
Open adrenalectomy
Lymph drainage from the bladder
Level I: internal iliac, obturator, external iliac
Level II: comon iliac, presacral
Level III: paracaval, para-aortic, and interaortocaval
MCC of Granulomatous cystitis
Intravesical BCG
Treatment of BCG related granulomatous cystitis
treated with isoniazid (300 mg PO daily) and pyridoxine (vitamin B6, 25 mg PO daily) for 3 months.
Causes of bilharzial cystitis
parasitic infection caused by schistosomal species (s. haematobium and S. mansoni).
treatment of bladder malakoplakia
transurethral resection/biopsy followed by a prolonged course of antibiotics (1st line = quinolones, 2nd line = rifampin or trimethoprim). Drugs that activate cGMP (bethanechol and vitamin C) may be of benefit.
Treatment of Bladder amylodosis
Patients with a high volume of bladder amyloidosis or those recurring frequently with amyloid plaques in the bladder can be treated with intravesical DMSO (50 mL of 50% solution for 30 min every 2 weeks for 3-12 months) to dissolve the unwanted protein. Cystectomy is occasionally required.
Inflammatory Myofibroblastic Tumor
presents in patients with irritative LUTS or hematuria.
Post operative Spindle cell Nodule
Variant of IMT, occurs after previous surgery. indistinguishable from bladder cancer.
Genes associated with Lynch syndrome and Bladder cancer
MSH2, MSH 6, MLH 1, PMS2
seen in colon cancer, 80%) endometrial cancer (80%), gastric, ovrain, and urothelial cancer
Genes associated with Peutz Jeghers and Bladder cancer
STK 11
GI hamartomas, Mealonitc macules, intussusception, colon cance, Breast cancer, lung caner, Pancreatic/biliary cancer, sex cord stomal tumors
Genes associated with Cowden syndomr and Bladder cancer
PTEN, KLLN
Seen in mucocutaneous hamartomas (100%), Breast cancer (80%), Brain tumor, Thyroid cancer, Endometrial cancer, Kidney cancer, Colon cancer, Bladder cancer, melanoma, Macrocephaly
Genes associated with Li-Fraumeni and Bladder cancer
P53 & CHEK2
Involved soft tissue sarcoma, breast cancer, bladder cancer, adrenocorticcal carcioma, leujemia
Genes associated with neurofibromatosis and Bladder cancer
NF 1 (neurofibromin), NF2 (merlin)
Neurofibromas, lish nodules, scoliosis,s cafe au lait spots, acoustic neuromas, schwanomas, meningiomas
Recurrence rate of LgTa bladder tumor
15- 70% at one year but low rate of prgoression to higher stage disease with <5% progressing to MIBC
Recurrence rate of Hg Ta
13-40% progressing to lamina propria invasion, and 6-25% change of becoming muscle invasion
Risk of progression and rcurrence for T1 bladder tumor
50% within 3 years and 80%. cance of recurrence
Risk of recurrence of and progression of CIS
82% and 42-83% if not treated with adjuvant intravesical therapy
Adjuvant intravesical therapy of intermediate risk NMIBC
intermediate-risk patient a clinician should consider administration of a six-week course of induction intravesical chemotherapy or immunotherapy with BCG.
Adjuvant intravesical therapy of intermediate risk NMIBC
high-risk patient with newly diagnosed CIS, high-grade T1, or high-risk Ta urothelial carcinoma, a clinician should administer a six-week induction course of BCG
Induction course. of BCG
The standard induction course is the same for immunotherapy and chemotherapy: the agent is instilled intravesically weekly for a total of 6 doses and then cystoscopy is performed 6 weeks later to assess for response.
BCG maintenance schedule
The most common maintenance schedule for BCG is the Lamm/SWOG regimen (triplets of BCG given at 3, 6, 12, 18, 24, 30 and 36 months) which was associated with a 19% improvement in the 5-year recurrence-free survival (41% vs. 60%) and 6%_ improvement in the 5-year worsening-free survival [no progression including pT2 or greater, use of cystectomy, systemic chemotherapy, or radiation therapy; 70% vs. 76%, p=0.04)
BCG refractory and next steps
persistent disease after 6 months of BCG therapy or who have progression of disease at 3 months (such as Ta/CIS to T1). Most guidelines recommend assessment at 6 months since
BCG relapsing
Describes patients who recur after BCG treatment. This can be early (within 12 months), intermediate (12-24 months), or late (>24 months).
BCG intolerance
describes disease persistence secondary to inability to receive adequate BCG due to toxicity/side effects
BCG unresponsive and next steps
BCG refractory or those who relapse within 6 months of treatment. There is no additional benefit to more BCG treatment in BCG-unresponsive patients and these are the patients for whom cystectomy is indication or enrollment onto trials of novel therapeutics.
Nadoferagene firadenovec
replication incompetent type 5 adenovirus designed to infect the bladder and produce the anticancer cytokine interferon α2b
T4 Bladder cancer
Tumor invades any of the following: prostatic stroma, seminal vesicles, uterus, vagina, pelvic wall, abdominal wall
T4a Bladder cancer
Tumor invades prostatic stroma, uterus, vagina
T4b Bladder cancer
Tumor invades pelvic wall, abdominal wall
Distal boundary for LND for MIBC
node of cloquet
Proximal boundary for LND for MIBC
Standard: bifurcation of the common iliac
Extended: bifurcation of the inferior abdominal Aorta
Super extended: Aorta at the origin of the IMA
lateral boundary for LND for MIBC
Genitofemoral nerve
Inferior boundary for LND for MIBC
Internal iliac LN floor pelvis
Posterior boundary for LND for MIBC
Sacrum
Overall disease specific survival for organ confined, node negative, UC
60-85% over 5-10 years
5 year disease specific survival in patients with extravesical UC disease
50%
Absolute contraindication of continent/orthotopic neobladder
A positive invasive urethral margin on frozen section during cystectomy.
Relative contraindications for orthotopic urinary diversion (10)
- Positive intra urethral margin
- Gross positive margin
- Pubic bone involvement
- Neurological dz impairing patients dexterity or continence
- Severe urethral stricture disease in male pts
- Chronic renal failure (cr>1.8, GFR <40)
- Hepatic insufficiency
- Chronic enteric inflammatory disease
- Malignant bowel disease
- Unwillingness/inability to perform self cath.
MOA Cisplatin
binds deoxyribonucleic acid (DNA) and produces intra-strand crosslinks and DNA adducts, thus inhibiting DNA replication
SE of Cisplatin (3). Which is the dose limiting SE
The dose-limiting toxicity of cisplatin is nephrotoxicity, which peaks at 2 weeks following treatment and is generally reversible. Other potential adverse effects include neurotoxicity (peripheral neuropathy) and ototoxicity (hearing loss)
SE of Carboplatin. Which is the dose limiting SE
The principal dose-limiting toxicity of carboplatin is bone marrow suppression, particularly thrombocytopenia. However, carboplatin has not been demonstrated to have equivalent efficacy to cisplatin
MOA Paclitaxel
Paclitaxel blocks cell cycle in mitosis by binding to tubulin and interfering with assembly of microtubules
Dose limiting SE of Paclitaxel
Its principle dose-limiting toxicity is hypersensitivity, peripheral neuropathy, and myelosuppression.
Drugs approved for the primary treatment of metastatic bladder cancer patients who are cisplatin-ineligible and have high PD-L1 expression
Pembro and Atezo
Drugs approved for second-line use after progression on platinum-containing chemotherapy metastatic BCa
Pembro, Avelumab, nivolumab
FDA approved drug used as maintenance therapy after first line platninum based chemotherapy
Avelumab
avelumab maintenance following chemotherapy represents the new standard of care for patients with metastatic or unresectable locally advanced disease
Common toxicities observed in patients with immune checkpoint inhibitors
fatigue, pruritis, nausea, diarrhea, asthenia, anemia
Rare toxicities observed in patients taking immune checkpoint inhibitors
Endocrinopathies, pneumonitis, colitis, myositis, severe skin rx
Erdafitinib
fibroblast growth factor receptor tyrosine kinase inhibitor. It has been granted accelerated FDA-approval for patients with metastatic urothelial carcinoma with FGFR2 or FGFR3 genetic alterations that progressed on platinum-based chemotherap
Systemic option for BCG unrepsonsive NMIBC
Pembrolizumab: Blocks the PD-1 receptor and prevents it from interacting with PD-L1 and PD-L2 ligands
Dose
200 mg q 3 weeks
400 mg q 6 weeks
immuno reactions big concern
Indications for radical cystectomy in NMIBC
Small Capacity contract4d bladder or NGB
BCG unresponsive HR bladder cancer
Very large >10cm bladder tumor
Variant histology ( micropapillary, nested, plasmacytoid, neuroendocrine, sarcomatoid), extensive squamous, or glandular differentiation, or presence/absence of LVI.
Surveillance of HR NMIBC
cystoscopically at 3 month intervals for the first two years, and then at 6 month intervals for the next 2-3 years, and then annually thereafter
Surveillance of LR NMIBC
Low-risk patient whose first surveillance cystoscopy is negative for tumor, a clinician should perform subsequent surveillance cystoscopy six to nine months later, and then annually thereafter
management of nested variant UC
radical cystectomy, limited reports of efficacy of NAC
management of micropapillary UC
histo is similar to ovarian papillary serous carcinoma. No clear evidence for NAC although there is some pathological downstaging at time of RC
management of Plasmacytoid UC
A/w higher rates of positive surgical margins and has propensity to develop peritoneal carcinomatosis.
A/w worse CSS outcomes. No consensus of efficacy of NAC, Cystectomy alone or AC.
Multimodal approach is common
Management of squamous cell carcinoma
radical cystectomy. NAC inconsistent benefit.
Management of Adenocarcinoma of the bladder
typically at the dome of the bladder.
Mx involves partial cystectomy, or radical cystectomy with PLND
NAC not recommended, but AC may have a role similar to UC
Management of Neuroendocrine carcinoma of the bladder
includes small cell, large cell, and mixed patterns.
Mx includes multimodal therapy starting with upfront Chemo
cisplatin/etoposide, etoposide alone, or ifosfamide/doxorubicin.
Common sites of bladder metastasis
Obturator nodes (74%)
External iliac (65%)
Presacral and internal iliac nodes (25%)
Perivesical nodes (16%)
minimal recommendation for lymph node removal at time of cystectomy
external, internal, obturator lymph nodes (standard)
Extended lymph node dissection
external, internal, obturator, aortic bifurcation, or IMA, with pre-sacral nodes.
5 year OS for pT2 UC
65%
5 year OS for pT3 UC
50%
5 year OS for pT4 UC
47%
5 year OS for node positive UC
31%
Percent improvement in OS and CSS with NAC
5-7% and 9%
ddMVAC NAC regimen for bladder cancer
MTX day one
Vinblastine day two
Doxorubicin day 2
Cisplatin Day two
GCSF day 3
Cycle repeats every 14 days.
Relative contraindications to performing an orthotopic or continent urinary diversion
- positive intraop urethral margin
- gross positive margins
- pubic bone involvement
- neurologic disease impairing dexterity or continence
- Severe urethral stricture dz in men
Chronic renal failure (Cr >1.8, GFR <40)
Hepatic insufficiency
Chronic enteric inflammatory dz
Malignant bowel disease
Unwillingness/inability to perform self catheterization
Metabolic abnormalities with colon or ileum used for urinary diversion
hyperchloremic, hypokalemic, metabolic acidosis
Radiosensitizing chemotherapy agents used for trimodal therapy
5-FU, and mitomycin
or
single agent cisplatin and gemcitabine
Dose limiting toxicity of cisplatin
nephrotoxicity (peaks at 2 weeks following tx and is reversible).
others: ototoxicity, neurotoxicity (peripheral neuropathy)
Dose limiting toxicity of carboplatin
bone marrow suppression.
not equivalent in efficacy to cisplatin
Dose limiting toxicity of paclitaxel
hypersensitivity, peripheral neuropathy, myelosupression
Dose limiting toxicity of gemcitabine
myelosuppression.
role of Avelumab maintenance in metastatic bladder cancer
Avelumab maintenance following chemotherapy is the new standard of care for patients with metastatic or unresectable locally advanced disease. FDA approved.
FDA approved FGFRi for metastatic UC
erdaftinib
in patients with FGFR2 and FGFR3 alterations that progressed on platinum based chemotherapy
Clinical manifestations of CHL
retinal angiomas, endolymphatic sac tumors, benign CNS hemangioblastomas, pancreatic cysts, islet tumors, epidiymal cystadenomas, pheochromocytomas
Location of mutated VHL tumor suppressor gene
chromosome 3p25-26.
codes for E3 ubiquitin ligase complex which regulates degradation of regulatory proteins including hypoxia inducible factor (HIF-1 and HIF-2).
Overaccumulation of intracellular HIF –> upregulation of VEGF
Characterization of papillary RCC
bilateral and mutifocal Type 1 pap RCC
Genetic alteration a/w hereditary papillary RCC
c-met proto oncogene at 7q31
Characterization of hereditary leiomyoma RCC
papillary type II RCC with agressive clinical behavior needing early surgical intervention.
Clinical manifestation of hereditary leiomyoma RCC
painful cutaneous and uterine leiomyomas
Genetic alteration a/w HLRCC
1q42-44, the site of the fumarate hydratase tumor suppressor gene
Characterization of birt-hogg-dube syndrome
bilateral multifocal, chromophobe RCC, oncocytomas, hybrid renal tumors
Clinical manifestations of birt-hogg-dube syndrome
fibrofoliculomas of the head and neck, pulmonary cysts, spontaneous pneumothorax
Genetic alteration a/w BHD
17p11.2 encoding tumor suppressor gene Folliculin
Characterization of BAP1 Tumor predisposition syndrome
unifocal ccRCC
Clinical manifestations of BAP1 tumor predisposition syndrome
uveal and cutaneous melanomas and mesotheliomas
Genetic alteration a/w BAP1
BAP1 gene mapped to 3p2.
Characterization of hereditary paraganglimoa-pheochromocytoma syndrome
Unifocal tumor with neoplastic cells
Clinical manifestations of Hereditary paraganglioma pheochromocytoma
paragangliomas, pheochromocytomas, GI stromal tumors
Genetic alteration a/w HPPS
Succinate dehydrogenase which is a mitochondrial enzyme complex made up of four protein subunits
Indications for renal mass biopsy
- When mass is suspected to be hematologic, metastatic, inflammatory, or infectious
When RMB will directly influence treatment -election
When is RMB not indicated
RMB is not required for young/healthy patients who are not willing to accept the uncertainties associated with RMB or for older/frail patients who will be managed conservatively independent of RMB.
Renal mass occuring from PCT
ccRCC - a/w loss of 3p
Papillary RCC
Renal mass a/w polysomy 7& 17, loss of Y, and MET mutations
Type I papillary RCC
Renal mas a/w mutation in fumarate hydratase gene
Type II papillary RCC
HLRCC
Renal mass arising from the collecting duct
Chromophobe and is histologically similar to oncocytoma
Collecting duct carcinoma: rare and aggressive with poor prognosis
Rare and most aggressive form of RCC
renal medullary carcinoma. Occurs in young AA adults with sickle cell trait.
Neves Zincke Classification of Renal mass tumor thrombus
More useful for surgical approach
Level 0: tumor thrombus limited to renal vein
Level 1: Extending ,/= above the renal vein
Level 2: Extending >2 cm above the renal vein but below the hepatic veins
Level 3: At or above the hepatic veins but below the diaphragm
Level 4: Extending above the diaphragm
Vascular occlusion prior to IVC thrombectomy
Renal artery supplying the affected kidney
Infrarenal IVC below thrombus
Lumbar veins feeding into the IVC
Contralateral renal vein
Hepatic blood supply that extends about the hepatic veins. A pringle maneuver performed to decrease the hepatic blood flow by placing a clamp across the hepatic artery and portal vein within the hepatuduodenal ligament. Mainly done for level 3 or higher tumor thrombus
Suprarenal IVC above the thrombus.
one potentially fatal complication of thrombectomy that should be discussed prior to surgery
1-2% risk for intraoperative embolization of thrombus causing obstruction of pulmonary arteries
Keynote-564 adjuvant monotherapy post nephrectomy
KEYNOTE-564:154 Safety and Efficacy Study of Pembrolizumab (MK-3475) as Monotherapy in the Adjuvant Treatment of Renal Cell Carcinoma Post Nephrectomy.
Phase III randomization of 950 patients
Eligibility criteria: clear cell carcinoma pT2G4; pT3; pT4; pTxN+; M1 resected to NED
Pembrolizumab 200mg IV q3 week for 12 months versus placebo
pembrolizumab was associated with significantly longer disease-free survival than placebo (DFS at 24 months, 77.3% vs. 68.1%; hazard ratio for recurrence or death, 0.68)
when in local treatment of metastatic sites appropriate in patients with metastatic RCC
solitary or oligometastatic RCC that is resectable.
True or False:
Cytoreductive nephrectomy should be considered as first line therapy universally in mRCC
False. Especially in intermediate and poor risk dz.
two phase III RCT (Surtime and CARMENA) demonstrated CN did not improve 28 week PF recurrence (surtime), and CN w/ post sutent vs sutent alone demonstrated benefit.
1st line Agents used for treatment naive Good risk mCCRCC
Sunitinib
Pazopanib
Pembrolizumab + Axitinib
Avelumab + Axitinib
Nivolumab + Cabozantinib
Pembrolizumab + Lenvatinib
Bevacizumab + IFN
1st line Agents used for treatment naive intermediate risk mCCRCC
Nivolumab+Ipilimumab
Pembrolizumab+Axitinib
Avelumab + Axitinib
Nivolumab + Cabozantinib
Pembrolizumab + Lenvatinib
Temsirolimus (poor risk patients)
1st line Agents used for previously treated mCCRCC
Preferred: Nivolumab, Cabo
Other reqs: Axitinib, lenvatinib +everolimus, Tivozanib
Characteristics of NSGCT
Most common GCT
Peak incidence 35-40
5% contain syncytiotrophoblasts (resulting in bHCG production)
Arise from ITGCN
Characteristics of Embryonal Ca
Poorly differentiated, able to differentiate into other NSGCT
Peak incidence 25-35y
Aggressive tumor with high rate of metastasis
Characteristics of Yolk Sac (endodermal sinus tumor)
Pure tumors are rare
Most common GCT in children/infants
Present in 40% of mixed GCTs
Generally produce AFP (never produce bHCG)
Schiller-Duval bodies are classic pathologic finding
Characteristics of Choriocarcinoma
Less common,
very aggressive type of GCT (1% pure, 10% mixed tumors)
Peak incidence 20-30
Early hematogenous spread (including brain)
High bHCG common,
no AFP production
Characteristics of Teratoma
Contain well or incompletely differentiated cell layers of endoderm, mesoderm, and/or ectoderm
Pure teratomas do not produce AFP or bHCG.
Pure teratomas rarely seen in adults (more common in pediatric population)
Approximately half of mixed GCT contain teratomatous elements
Chemoresistant, radiation-resistant
Morbidity related to local growth (“Growing Teratoma Syndrome”) and potential for malignant transformation
Only role for testis sparing surgery
should only be considered in a small tumor in a solitary testis, when small bilateral tumors exist, or increased suspicion of a benign tumor.
primary drainage of left testicle
para-aortic lymph node
primary drainage for right testicle
infrarenal inter-aortocaval lymph nodes, followed by paracaval and para-aortic regions.
pT1 testicular tumor
Tumor limited to the testis and epididymis without lymphovascular invasion, may invade tunica albuginea but not tunica vaginalis
pT2 testicular tumor
Tumor limited to the testis and epididymis with lymphovascular invasion or tumor involving the tunica vaginalis
pT3 testicular tumor
Tumor invades the spermatic cord with or without lymphovascular invasion
pT4 Testicular tumor
Tumor invades the scrotum with or without lymphovascular invasion
Stage 1 testicular tumor
pT1-4, N0, M0, SX
Stage II testicular tumor
Any pT, N0, M0, S1-3
Stage III testicular tumor
Any pT, Any N, M1, SX
Testicularu serum tumor marker staging
Sx: Tumor markers not available or performed
S0: Tumor markers within normal limits
S1: LDH <1.5 x normal, hCG<5000 IU/L, AFP <1000 ng/ml
S2: LDH 1.5-10 x normal, hCG 5000-50000 IU/L, AFP 1000-10000 ng/ml
S3: LDH >10 x normal, hCG>50000 IU/L, AFP >10000 ng/ml
Good Prognosis Non-Seminoma
- Testicular/retroperitoneal primary and
- No nonpulmonary visceral metastases and
- Post-orchiectomy STM (all of):
— AFP <1000 ng/ml and
— hCG <5000 IU/L and
— LDH <1.5 x normal
Intermediate Prognosis Non-seminoma
- Testicular/retroperitoneal primary and
- No non-pulmonary visceral metastases and
- Post-orchiectomy STM (any of):
— AFP 1000-10000 ng/ml and/or
— hCG 5000-50000 IU/L and/or
— LDH 1.5-10 x normal
Poor prognosis Non-seminoma
- Mediastinal primary
- Non-pulmonary visceral metastases
- Post-orchiectomy STM (any of):
— AFP >10000 ng/ml and/or
— hCG >50000 IU/L and/or
— LDH >10 x normal
Good Prognosis seminoma
- Mediastinal primary
- Non-pulmonary visceral metastases
- Post-orchiectomy STM (any of):
— AFP >10000 ng/ml and/or
— hCG >50000 IU/L and/or
— LDH >10 x normal
Intermediate prognosis seminoma
- Any primary site and
- Non-pulmonary visceral metastases and
- Post-orchiectomy STM:
— Normal AFP and
— Any hCG and
— Any LDH
Poor prognosis seminoma
No seminoma patients are poor prognosis
Preferred management of Stage 1 seminoma
Surveillance
More than 80% of patients with stage I seminoma are cured with orchiectomy alone, therefore surveillance is the preferred approach, and the disease specific survival for stage I disease is 99% irrespective of the management strategy used
Adjuvant option for stage 1 seminoma
1 or 2 cycles of carboplatin (AUC=7 x 1 or 2 cycles)
Options for Stage 1 NSGCT
(i) Surveillance, which is the preferred option
(ii) RPLND
(iii) cisplatin-based chemotherapy.
Option for patients with stage 1 NSGCT who do not accept surveillance or primary RPLND
1 cycle
Bleomycin, Etoposide, Cisplatin
Stage 1 NSGCT N1 treatment recommendation
surveillance based on low risk of recurrence (~10 - 20%)
Stage 1 NSGCT N2-3 treatment recommendation
Chemotherapy preferred based on higher recurrence rate (~50-70).
Following grossly complete resection, with normal post-RPLND STM, recommended regimens include either EP or BEP for 2 cycles for pN1 or pN2 disease; or 4 cycles of EP or 3 cycles of BEP for pN3 disease.
Mainstay treatment for Stage IIA pure seminoma
RT
Mainstay treatment for stage IIB pure seminoma
Chemotherapy
Preferred treatment for management of Stage II seminoma with bulky lymphadenopathy
bulky lymphadenopathy (> 3 cm), chemotherapy is preferred to RT, with both the NCCN and EAU guidelines recommending 4 courses of EP or 3 cycles of BEP
Standard treat,emt pf Stage IIC seminoma
The standard treatment for IIC seminoma patients is chemotherapy with 3 cycles of BEP or 4 cycles of EP
management of advanced seminoma after 1st line therapy with persistent mass
The NCCN guidelines recommend surveillance of masses ≤ 3 cm, while masses > 3 cm can either be observed or be further evaluated with a 2-18fluoro-deoxy-2-D-glucose positron emission tomography (PET) scan performed at least 6 weeks after completion of chemotherapy. For FDG-avid masses, resection or biopsy is recommended.
If the final pathology demonstrates viable tumor, patients should receive 2 additional cycles of chemotherapy. In the case of incomplete resection of viable tumor, then 4 cycles of second-line chemotherapy is recommended.
Management of Stage IIA NSGCT pN1
if an adequate complete RPLND was performed and no concerns of surgical compromise exist, surveillance is preferred for pN1.
Management of Stage IIA NSGCT pN2
chemotherapy is preferred with EP or BEP for 2 cycles due to the ~50% risk of relapse
Management of Stage IIA NSGCT pN3
Chemotherapy with 4 cycles of EP or 3 cycles of BEP is recommended for pN3 disease given the nearly 100% relapse rate
Management of Stage IIB NSGCT
Primary chemotherapy with 4 cycles of EP or 3 cycles of BEP may be used for IIB disease. Following chemotherapy, post-chemotherapy RPLND (PC-RPLND) is recommended for any residual masses > 1cm on subsequent imaging in the setting of negative STM
Low risk UTUC
Unifocal disease
Tumor size <2cm
Low-grade cytology
Low-grade URS biopsy
No invasive aspect on CTU
High-risk UTUC
Hydronephrosis
Tumor size >2cm
High-grade cytology
High-grade URS biopsy
Multifocal disease
Previous radical cystectomy for bladder cancer
Variant histology
T/F: Intraluminal BCG is not recommended for the management of UTUC
True
UTUC POUT Trial
demonstrated that adjuvant chemotherapy consisting of 4 cycles of gemcitabine-cisplatin (gemcitabine-carboplatin if GFR 30–49 ml/min) resulted in improved progression-free survival compared with surveillance
UTUC CheckMate 274
evaluated adjuvant nivolumab in a similar setting. This study, which was double-blinded and placebo-controlled, demonstrated that nivolumab improved the proportion of patients disease-free at 6 months from 60.3% to 74.9%, improving median disease-free survival from 10.8 to 20.8 months
Indication for Radical nephroureterectomy in UTUC
High-grade UTUC and low-grade UTUC, where nephron-sparing options are not feasible or oncologically appropriate
Indication for Radical nephroureterectomy in UTUC
High-grade UTUC and low-grade UTUC, where nephron-sparing options are not feasible or oncologically appropriate
Cellular lining of the male anterior penile urethra
SSE-Stratified Squamous Epithelium –> SCU-Stratified Columnar Epithelium, –> PSCU-Pseudostratified Columnar Urothelium
Blood supply to anterior male urethra
internal iliac–> internal pudendal–> common penile artery–> 3 branches: (1) bulbuourethral artery, (2) Cavernosal Artery, (3) dorsal artery
Blood supply to posterior male urethra
inferior vesical and middle rectal
Lymphatic drainage of the anterior male urethra
superficial and deep inguinal lymph nodes
Lymphatic drainage of posterior male urethra
pelvic lymph nodes
Cellular lining of the distal female urethra
Non-keratinized stratified squamous cells
Blood supply of the female distal urethra
Vaginal artery
Blood Supply of the female proximal urethra
Internal pudendal artery
Lymphatic drainage of the female distal urethra
Superficial and deep inguinal nodes
Lymphatic drainage of the proximal female urethra
External iliac, internal iliac and obturator nodes
Most common location of urethral carcinoma in men
proximal urethra (urothelial)
Tis Urethral carcinoma
-Carcinoma in situ
-Prostatic urethra or periurethral or prostatic ducts without stromal invasion
pTa urethral carcinoma
Non Invasive papillary carcinoma or verrucous carcinoma
pT1 urethral carcinoma
Invades lamina propria
pT2 urethral carcinoma
Invades corpus spongiosum or periurethral muscle.
- Invades prostatic stroma (either by ducts or direct extension)
PT3 Urethral carcinoma
invades corpus cavernosum or anterior vagina
invades peri-prostatic fat
pT4 urethral carcinoma
invades adjacent organs (bladder, rectum, uterus)
Recommended image modality for staging urethral carcinoma
MRI
Treatment of choice for small non invasvie tumors of the distal urethra
TUR, consider prostatic biopsioes prostatic biopsies since tumor recurrences can involve the prostatic urethra in up to 40% of cases
Surgical management of pT3 urethral carcinoma
Tumors invading the corpora cavernosa (T3) require penectomy. For tumors of the distal penile urethra, partial penectomy may be possible
T/F men s/p radical cystectomy require urethrectomy if evidence of prostatic urethral recurrence is present
False
25% of radical cystectomy specimens performed for urothelial carcinoma will have some degree of prostatic involvement. However, most patients do not require urethrectomy (distal to the prostate) and only those with clear clinical evidence of urethral cancer distal to the prostatic urethra should undergo urethrectomy at the time of cystectomy.
pTa penile cancer
Noninvasive localized squamous cell carcinoma
pT1 penile cancer
Glans: Tumor invades lamina propria
Foreskin: Tumor invades dermis, lamina propria, or dartos fascia
Shaft: Tumor invades connective tissue between epidermis and corpora regardless of location
All sites with or without lymphovascular invasion or perineural invasion and is or is not high grade
pT1a penile cancer
Tumor is without lymphovascular invasion or perineural invasion and is not high grade (i.e., grade 3 or sarcomatoid)
pT1b penile cancer
Tumor exhibits lymphovascular invasion and/or perineural invasion or is high grade (i.e., grade 3 or sarcomatoid)
pT2 penile cancer
Tumor invades into corpus spongiosum (either glans or ventral shaft) with or without urethral invasion
pT3 penile cancer
Tumor invades into corpora cavemosum (including tunica albuginea) with or without urethral invasion
pT4 penile cancer
Tumor invades into adjacent structures (i.e., scrotum, prostate, pubic bone)
cN1 penile cancer
Palpable mobile unilateral inguinal lymph node
cN2 penile cancer
Palpable mobile ≥ 2 unilateral inguinal nodes or bilateral inguinal lymph nodes
cN3 penile cancer
Palpable fixed inguinal nodal mass or pelvic lymphadenopathy unilateral or bilatera
pN1 penile cancer
≤2 unilateral inguinal metastasis without extranodal extension
pN2 penile cancer
≥3 unilateral inguinal metastases or bilateral metastases
pN3 penile cancer
extranodal extension of lymph node metastases or pelvic lymph node metastases
Management of Tis and Ta penile tumors
topical therapy using 5% imiquimod or 5-fluorouracil as well as wide local excision encompassing circumcision for penile tumors situated on the penile foreskin are the preferred primary treatment approaches
Management of low grade cT1 penile cancer
preferably offered penile preserving surgery consisting of a wide local excision +/- thick split thickness (STSG) or full thickness (FTSG) skin graft, with alternative options being laser ablative therapy or radiotherapy.
Management of nonpalpable lymph nodes in penile cancer
T1 or higher high grade
proceed with bilateral superficial ILND with deep ILND if any positive LN. Have to get at least 15 nodes
Management of palpable (non-bulky) nodes
LN divided into NB ILN (<4 cm) and those with Bulky ILN
Patients should undergo dx FNA or go straight to ILND if clinical suspcious for mets
If FNA is negative or non -dx then proceed wto wife erxcisional LN biopsy
If negative–surveillance
IF positive- ILND
Management of palpable (bulky lymph nodes) in penile cancer
first step is get tissue diagnosis
upfront ILND for highly symptomatic patients
ipsilateral PLND in pts with 2+ positive ILN on superficial or deep
