13- Basic principles in uro-oncology

Bladder and Upper Urinary Tract Cancers

• Bladder and upper urinary tract cancers are a significant urological concern.
• Learning outcomes include understanding risk factors, staging, treatment differences between bladder and upper urinary tract cancers, and treatment strategies.
• An overview of epidemiology, risk factors, evaluation, staging, grading, and current treatment strategies is provided.

Cancer Biology

• Cancer development proceeds through stages from normal tissue to hyperplasia to dysplasia to cancer.
• Cancer cells exhibit uncontrolled growth, lack programmed cell death response, invade tissues, and form new blood vessels (neovascularization).
• Cancer cells also can circumvent the immune system, and display genetic damage, and carcinogens can play a part as well.

DNA Structure

• DNA's structure is composed of nucleotides (guanine, cytosine, adenine, thymine).
• DNA is organized into chromosomes, histone, nucleosome, and genes.
• The cell cycle (G0, G1, S, G2, M) is highlighted.

How Does Cancer Form?

• Cancer cells form a mass distinct from normal cells.
• Cancer growth disrupts the normal tissue structure.

What Causes Cancer?

• DNA changes, specifically in genes, can cause cancer.

What Are Oncogenes?

• Oncogenes are genes that promote cell growth and division, and changes can cause cancer.

What Are Tumor Suppressor Genes?

• Tumor suppressor genes normally prevent excessive cell growth and division. Mutated tumor suppressor genes can cause cancer.

What Is the Tumor Microenvironment?

• The tumor microenvironment is the surrounding tissue that influences cancer development.
• Key components such as T cells, myeloid cells, macrophages, natural killer cells, and fibroblasts are part of the cellular composition of the tumor microenvironment.

How Does the Immune System Interact with Cancer?

• The immune system can attack cancer cells but can also be evaded by cancer cells.

What Causes Genetic Changes?

• Genetic changes in cancer can arise from heredity, viruses, UV radiation, smoking, chemicals, and cell division.

How Does Age Relate to Cancer?

• Age is a factor in cancer development.

What Is Metastasis?

• Metastasis involves the spread of cancer cells from the original tumor site to other parts of the body via the bloodstream.

Bladder Cancer

• Fourth most common cancer in men in 2014.
• 74,690 new cases and 15,580 deaths in 2014.
• Represents 7% of all cancers and 3% of all cancer deaths.
• Male to female ratio is 3:1.
• Peak incidence is between 60-70 years.
• Majority (~93%) are urothelial cancer (transitional cell carcinoma).

Bladder Cancer Risk Factors

• Exogenous factors include schistosomiasis, tobacco, cytostatics, sweeteners (saccharin, cyclamate), pelvic radiation, blackfoot disease, and chronic irritations.
• Endogenous factors include chronic inflammation with toxins (catheters) and conditions like
• Professions like dry cleaners, painters, autoworkers, truck drivers, paper manufacturers, metal workers, hairdressers, and tire, rubber, chemical and petroleum workers are at increased risk.

Symptoms and Signs

• Gross hematuria (visible blood in the urine) is the most common symptom (68-97%).
• Microhematuria (microscopic blood in the urine) occurs in 11% of cases.
• Hematuria timing can be initial, terminal, or continuous which can help identify its etiology.
• Irritative voiding symptoms (painful urination) and lumbar and suprapubic pain might also occur.

Diagnosis

• Cystoscopy is a common diagnostic procedure to examine the bladder.
• Urinary tumor markers (commonly cytology) can assist the diagnosis, and imaging techniques are employed extensively in diagnosis (Renal Ultrasound, IVP, CT Urogram, MR Urogram).

Staging

• 70% of bladder cancers are non-muscle invasive (superficial) and progress.
• 25% of cases are muscle-invasive.
• 5-year overall survival for muscle-invasive cancer is 78% (lower with node involvement).
• 5% are metastatic; chemotherapy can extend survival by 18 months;

Treatment and Prognosis

• Staging and grade factors influence treatment and prognosis.
• Factors including grade (low vs. high), tumor multiplicity, size of tumor, and whether invasive or not impacts prognosis.
• Up to 70% may recur in 5 years.

Surgical Therapies for Bladder Cancer

• Treatment strategies differ based on tumor stage and grade.
• Surgical therapies include transurethral resection of the bladder tumor (TURBT), intravesical therapy, radical cystectomy, and urinary diversion.
• Trimodal therapy combines radiation, chemotherapy, and surgery.
• Robotic approaches include partial and radical cystectomy.

Upper Urinary Tract Cancer

• Upper urinary tract cancers (UTUC) are less common than bladder cancer (5-10% of all cases).
• Patients are predominantly male (70.5%).
• Approximately 53.3% are ex-smokers or current smokers; about 58% present with symptoms, mostly hematuria.
• Cancer history in the bladder increases risk of developing UTUC.

Upper Urinary Tract Cancer Risk Factors

• Etiology of cancer can involve genetic predisposition, tobacco exposure, arsenic in drinking water, aristolochic acid from plants (and various others).

Upper Urinary Tract Cancer Histological Types

• Histologically, most UTUCs are urothelial cancers.
• In 15% of cases, UTUCs have a divergent squamous differentiation.
• Keratinizing squamous metaplasia can increase the risk of squamous cell cancers.
• Other rare subtypes include sarcomatoid and inverted growth.

Upper Urinary Tract Cancer Symptoms

• Visible or nonvisible hematuria is common in patients (70–80%).
• Flank pain (from clot or tumor) occurs in 20–32% of cases.
• Systemic symptoms (e.g., anorexia, weight loss) sometimes occur, and should signal evaluation for metastasis

Upper Urinary Tract Cancer Diagnosis

• CT urography is a primary diagnostic method owing to its high sensitivity and specificity (92% and 95% respectively).
• Other diagnostic tools include MR urography, 18F-FDG PET/CT.
• Urethrocystoscopy is an essential part of diagnosis to rule out complications and other possible issues.

Upper Urinary Tract Cancer Treatment/Management

• Patients with low-risk cancers often get kidney-sparing approaches for surgery, like flexible ureteroscopy or laparoscopic procedures.
• However, high-risk cancers necessitate radical nephroureterectomy and template lymphadenectomy.
• Staging of the cancer is essential prior to treatment.

Additional Information

• Prognostic factors exist, dividing into patient (age/ethnicity) and tumor characteristics (size, location) and can be utilized in evaluating and deciding treatment options to lower risk of recurrence or improve results.
• Molecular markers can be useful in diagnosis and treatment decisions, but retrospective and small sample size can affect use.
• Kidney-sparing surgery can help with low-risk UTUC.
• The use of a lymph node template during lymphadenectomy can enhance survival.
• Cisplatin-based neoadjuvant chemotherapy can be employed in UTUC patients.
• Immunotherapy options like nivolumab, avelumab, and durvalumab may be incorporated into treatment for specific cases of UTUC.

This quiz explores bladder and upper urinary tract cancers, focusing on risk factors, staging, and treatment strategies. Gain an understanding of cancer biology and DNA structure as they relate to these cancers. Test your knowledge on how these elements interact in the context of urological health.