Essential Knowledge

STAMPEDE (Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy)

Overview: A multi-arm, multi-stage (MAMS) platform trial evaluating various treatments added to standard of care (SOC) in men with high-risk locally advanced or metastatic hormone-sensitive prostate cancer (mHSPC).

Key Arms & Findings:

• Docetaxel: Adding docetaxel to ADT improved overall survival (OS) in mHSPC (HR 0.78). Similar benefit seen in CHAARTED trial.
• Abiraterone: Adding abiraterone + prednisolone to ADT improved OS (HR 0.63) and failure-free survival (FFS) (HR 0.29) in both metastatic and non-metastatic high-risk disease.
• Radiotherapy (RT) to Primary: In men with low-volume metastatic burden (CHAARTED criteria), adding RT to the primary tumor improved OS (HR 0.68). No benefit in high-volume disease.

Clinical Implication:

• Standard of care for mHSPC is ADT + [Docetaxel OR Abiraterone/Enzalutamide/Apalutamide].
• Offer RT to primary for low-volume mHSPC.

EORTC Risk Tables for NMIBC

Purpose: Predict risk of recurrence and progression in Non-Muscle Invasive Bladder Cancer (NMIBC) at 1 and 5 years.

Key Factors (The 'Big 6'):

1. Number of tumors (Single vs. 2-7 vs. ≥8)
2. Tumor size (<3cm vs. ≥3cm)
3. Prior recurrence rate (Primary vs. ≤1/yr vs. >1/yr)
4. T stage (Ta vs. T1)
5. Carcinoma in situ (CIS) (No vs. Yes)
6. Grade (G1 vs. G2 vs. G3 - WHO 1973)

Scoring:

• Points assigned for each factor.
• Total score stratifies patients into Low, Intermediate, and High risk groups.

Update (EAU 2021): New risk stratification incorporates WHO 2004/2016 grading (Low/High Grade) and defines 'Very High Risk' (e.g., T1G3 + CIS, multiple/large T1G3).

CARMENA (Cancer of the Kidney and Treatment with Cytoreductive Nephrectomy and Sunitinib)

Question: Is cytoreductive nephrectomy (CN) necessary in the era of targeted therapy for metastatic RCC (mRCC)?

Design: Phase III non-inferiority trial. mRCC patients randomized to Sunitinib alone vs. CN followed by Sunitinib.

Findings:

• Overall Survival: Sunitinib alone was non-inferior to CN + Sunitinib (Median OS: 18.4 vs. 13.9 months).
• Benefit: CN group had higher morbidity and delayed systemic therapy.

Clinical Implication:

• CN should not be routinely performed in patients with intermediate/poor risk mRCC (IMDC criteria) who require systemic therapy.
• CN may still be considered for: Good performance status, low metastatic volume, symptom control (hematuria/pain), or complete metastasectomy candidates.

Acute Renal Colic Management

Diagnosis:

• Gold Standard: Non-contrast CT (NCCT) KUB.
• Ultrasound: First-line for pregnant women and children; adjunct for hydronephrosis assessment.

Medical Management:

• Analgesia: NSAIDs (Diclofenac, Indomethacin, Ibuprofen) are first-line (superior to opioids for colic pain). Opioids as second-line.
• MET (Medical Expulsive Therapy): Alpha-blockers (Tamsulosin) facilitate passage of distal ureteric stones >5mm. No benefit for <5mm stones.

Intervention Indications:

• Uncontrollable pain
• Sepsis/Infection (Obstructed infected kidney is a urological emergency -> Decompression via Stent or Nephrostomy)
• Anuria/Bilateral obstruction
• Renal failure
• Failure of conservative management (>4 weeks)

Prostate Cancer Screening & Early Detection

Recommendation: No population-based screening. Opportunistic screening after shared decision making.

Who to Screen (PSA + DRE):

• Men >50 years.
• Men >45 years with family history (brother/father with PCa).
• Men >45 years of African descent.
• Men with BRCA2 mutations (start from 40 years).

PSA Thresholds:

• No single cut-off. Use age-specific ranges.
• Risk Stratification:
  • PSA <1 ng/mL at 40y -> Low risk (screen every 2-4 yrs).
  • PSA >1 ng/mL at 40y or >2 ng/mL at 60y -> Increased risk (screen every 2 yrs).

Biopsy Indications:

• Elevated PSA (confirmed after few weeks, rule out UTI/ejaculation).
• Abnormal DRE.
• MRI First: mpMRI recommended before biopsy. PIRADS 3-5 warrants targeted biopsy.

Kidney Anatomy

Location: Retroperitoneal, T12-L3 vertebrae. Right kidney is slightly lower due to liver.

Fascial Layers (Inside to Outside):

1. Renal Capsule (True capsule)
2. Perirenal Fat
3. Renal Fascia (Gerota's fascia) - Anterior and Posterior layers fuse superiorly (adrenal) and laterally. Open inferiorly (allows nephroptosis).
4. Pararenal Fat

Anterior Relations:

• Right Kidney: Liver, Duodenum (2nd part), Ascending Colon, Small Bowel.
• Left Kidney: Stomach, Spleen, Pancreas (Tail), Descending Colon, Jejunum.

Posterior Relations (Both):

• Diaphragm (Superiorly)
• Muscles: Psoas major (Medial), Quadratus lumborum (Middle), Transversus abdominis (Lateral).
• Nerves: Subcostal (T12), Iliohypogastric (L1), Ilioinguinal (L1).

Development of the Kidney

Three Stages:

1. Pronephros: Week 4. Non-functional, degenerates.
2. Mesonephros: Week 4-8. Temporary function. Wolffian duct develops from this.
3. Metanephros: Week 5 onwards. Permanent kidney.

Metanephros Formation:

• Ureteric Bud (from Wolffian Duct): Forms collecting system (Ureter, Pelvis, Calyces, Collecting Ducts).
• Metanephric Blastema (Mesoderm): Forms excretory units (Glomerulus, PCT, Loop of Henle, DCT).

Ascent of Kidney:

• Ascends from pelvis to abdomen (T12-L3) and rotates 90 degrees medially.
• Blood supply changes from iliac -> aorta (accessory arteries common if lower vessels persist).

Anomalies:

• Horseshoe Kidney: Fusion of lower poles. Gets stuck at IMA (Inferior Mesenteric Artery).
• Duplex System: Two ureteric buds or early splitting. Weigert-Meyer Rule applies.

Gleason Grading (ISUP Grade Groups)

Principle: Based on glandular architecture (differentiation), not cytology. Assessed at low power.

Patterns (1-5):

• Pattern 3: Discrete, well-formed glands. Varied sizes but separate.
• Pattern 4: Fused glands, cribriform (sieve-like), glomeruloid, or poorly formed glands.
• Pattern 5: Sheets of cells, necrosis (comedonecrosis), single cells, no gland formation.

Scoring:

• Biopsy: Most common + Highest grade (e.g., 3+4=7).
• Prostatectomy: Most common + Second most common.

ISUP Grade Groups (2014/2019):

• Group 1: Gleason 3+3=6 (Indolent, suitable for AS)
• Group 2: Gleason 3+4=7 (Favorable intermediate)
• Group 3: Gleason 4+3=7 (Unfavorable intermediate)
• Group 4: Gleason 4+4=8, 3+5=8, 5+3=8 (High risk)
• Group 5: Gleason 9-10 (Very high risk)

ProtecT (Prostate Testing for Cancer and Treatment)

Question: Compare Active Monitoring (AM), Radical Prostatectomy (RP), and Radiotherapy (RT) for localized prostate cancer.

Findings (10-year follow-up):

• Survival: No significant difference in prostate cancer-specific or overall survival between the three groups (very high survival >98% in all).
• Progression: RP and RT reduced the incidence of metastatic progression compared to AM.
• Side Effects: RP had more urinary incontinence and erectile dysfunction. RT had more bowel symptoms.

Clinical Implication:

• Men with localized PCa have excellent long-term survival regardless of treatment.
• Treatment choice involves trade-off between side effects (RP/RT) and risk of progression (AM).

POUT (Peri-Operative Chemotherapy versus Surveillance in Upper Tract Urothelial Cancer)

Question: Does adjuvant chemotherapy improve outcomes after nephroureterectomy (NU) for UTUC?

Design: Phase III RCT. Patients with pT2-T4 N0-3 M0 UTUC post-NU randomized to Surveillance vs. Adjuvant Chemotherapy (Gemcitabine-Cisplatin or Gem-Carbo).

Findings:

• Disease-Free Survival (DFS): Adjuvant chemotherapy significantly improved DFS (HR 0.45).
• Metastasis-Free Survival: Also improved with chemotherapy.

Clinical Implication:

• Adjuvant platinum-based chemotherapy should be considered the standard of care for patients with pT2+ UTUC after nephroureterectomy.

Testicular Cancer Management

Diagnosis:

• Markers: AFP, beta-hCG, LDH (must be taken BEFORE orchiectomy).
• Ultrasound: Mandatory.
• Staging: CT Chest/Abdomen/Pelvis.

Seminoma (Stage I):

• Surveillance: Preferred option (low recurrence rate).
• Adjuvant: Carboplatin AUC 7 (single dose) or Radiotherapy (para-aortic) for high-risk cases (tumor >4cm, rete testis invasion).

NSGCT (Stage I):

• Surveillance: Preferred for low risk.
• High Risk (LVI positive): Adjuvant BEP x 1 cycle recommended (reduces recurrence from 50% to <5%).

Metastatic Disease:

• Good Prognosis: BEP x 3 or EP x 4.
• Intermediate/Poor: BEP x 4.

TNM Staging for RCC (2017)

T Stage (Primary Tumor):

• T1: Tumor limited to kidney, ≤7 cm.
  • T1a: ≤4 cm.
  • T1b: >4 cm but ≤7 cm.
• T2: Tumor limited to kidney, >7 cm.
  • T2a: >7 cm but ≤10 cm.
  • T2b: >10 cm.
• T3: Tumor extends into major veins or perinephric tissues but not into ipsilateral adrenal gland and not beyond Gerota's fascia.
  • T3a: Renal vein or its segmental branches, or perirenal/sinus fat invasion.
  • T3b: Vena cava below diaphragm.
  • T3c: Vena cava above diaphragm or wall invasion.
• T4: Tumor invades beyond Gerota's fascia (including contiguous extension into ipsilateral adrenal gland).

N Stage (Nodes):

• N0: No regional lymph node metastasis.
• N1: Metastasis in regional lymph node(s).