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| REVIEW ARTICLE |
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| Year : 2022 | Volume
: 8
| Issue : 2 | Page : 111-115 |
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Genitourinary cancer: A perspective review
Atul Khajuria1, Shilpa Sujit Kushte2
1 Department of Medical Laboratory Technology, NIMS College of Paramedical Technology, NIMS University, Jaipur, Rajasthan, India
2 NIMS College of Paramedical Technology, Jaipur, Rajasthan, India
| Date of Submission | 25-Nov-2022 |
| Date of Decision | 27-Nov-2022 |
| Date of Acceptance | 29-Nov-2022 |
| Date of Web Publication | 11-Jan-2023 |
Correspondence Address:
Atul Khajuria
Department of Medical Laboratory Technology, NIMS College of Paramedical Technology, NIMS University, Jaipur, Rajasthan
India
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/sujhs.sujhs_42_22
Genitourinary (GU) malignancy comprises nearly half of the cancers diagnosed in men, and the incidence of this group of cancers increases with age. The key to successful management is to define appropriate goals (cure vs. palliation) based on the history and extent of disease, physiology and life expectancy of the patients, and cost–benefit ratio of treatment options. Recently, a number of genomic and molecular studies have provided an insight into the oncogenesis and progression of GU cancers, particularly bladder, prostate, and kidney cancers. These comprehensive innovative analyses have led to new molecular classification based on the genomic expression profiles and the discovery of potential diagnostic and therapeutic molecular targets.
Keywords: Bladder cancer, penile cancer, prostate cancer, testicular cancer
How to cite this article:
Khajuria A, Kushte SS. Genitourinary cancer: A perspective review. Santosh Univ J Health Sci 2022;8:111-5 |
| Introduction | |  |
Genitourinary (GU) malignancies compass a heterogeneous group of cancers pertaining to a specific anatomical and physiological function. There is incredible biological diversity among primary GU malignancies.[1] It refers to cancers of the urinary system of men and women and the reproductive organs in men. Urinary cancers are diseases that form when abnormal cells grow in the prostate, bladder, kidney, adrenal gland, urethra, or other parts of the urinary tract system. Women also develop cancer in their reproductive organs and classified as gynecologic cancers.
Major parts of the urinary system include:
- Kidneys
- Bladder
- Urethra
- Ureters.
Major organs of the male reproductive system include:
- Prostate gland
- Testicles
- Penis.
Types of genitourinary cancers
- Adrenal cancer
- Adrenocortical carcinoma.
- Bladder cancer
- Urothelial carcinoma (UC)
- Urachal cancer.
- Kidney cancer
- Collecting duct carcinoma
- Renal cell carcinoma (RCC)
- Rhabdoid tumor of the kidney
- Renal pelvic cancer (ureteral cancer)
- Wilms' tumor (nephroblastoma).
- Penile cancer
- Prostate cancer
- Testicular cancer (germ cell tumor)
- Seminoma
- Nonseminoma
- Choriocarcinoma proud
- Teratoma.
| Adrenocortical Carcinoma | | |
It is a rare cancer that forms in the outer layer of tissue of the adrenal gland (a small organ on top of each kidney that makes steroid hormones, adrenaline, and noradrenaline to control heart rate, blood pressure, and other body functions). It is also known as adrenocortical cancer or cancer of the adrenal cortex.
Bladder cancer
It is the cancer that forms in tissues of the bladder (the organ that stores urine). Most bladder cancers are transitional cell carcinomas (cancer that begins in cells that normally make up the inner lining of the bladder). Other types include squamous cell carcinoma (cancer that begins in thin, flat cells) and adenocarcinoma (cancer that begins in cells that make and release mucus and other fluids). The cells that form squamous cell carcinoma and adenocarcinoma develop in the inner lining of the bladder as a result of chronic irritation and inflammation.
Kidney cancer
It is the cancer that forms in tissues of the kidneys. The most common type of kidney cancer in adults is RCC. It forms in the lining of very small tubes in the kidney that filter the blood and remove waste products. Transitional cell cancer of the renal pelvis is kidney cancer that forms in the center of the kidney where urine collects. Wilms' tumor is a type of kidney cancer that usually develops in children under the age of 5 years.
Penile cancer
It is a rare cancer that forms in the penis (an external male reproductive organ). Most penile cancers are squamous cell carcinomas (cancer that begins in flat cells lining the penis).
Prostate cancer
It is the cancer which forms in tissues of the prostate (a gland in the male reproductive system found below the bladder and in front of the rectum). Prostate cancer usually occurs in older men and may not require therapy based on the patient's age and the characteristics of the cancer.
Renal cell cancer
It is the most common type of kidney cancer. It begins in the lining of the renal tubules in the kidney. The renal tubules filter the blood and produce urine. It is also called as hypernephroma, renal cell adenocarcinoma, or RCC.
Renal pelvis cancer
The renal pelvis is the area at the center of the kidney. Urine collects here and is funneled into the ureter, the tube that connects the kidney to the bladder. Transitional cells line the renal pelvis and ureter. Transitional cells can change shape and stretch without breaking. Cancer in the transitional cells can start in your renal pelvis, ureter, or both.
Cancer that starts in the renal pelvis or ureter is rare, accounting for about 5% of cancers of the kidney and upper urinary tract.
Testicular cancer
Cancer that forms in tissues of one or both testicles is known as testicular cancer. It is most common in young or middle-aged men. Most testicular cancers begin in germ cells (cells that make sperm) and are called testicular germ cell tumors.
Urethral cancer
It is a rare cancer that forms in tissues of the urethra (the tube through which urine empties the bladder and leaves the body). Types of urethral cancer include transitional cell carcinoma (cancer that begins in cells that can change shape and stretch without breaking apart), squamous cell carcinoma (cancer that begins in flat cells lining the urethra), and adenocarcinoma (cancer that begins in cells that make and release mucus and other fluids).
| Epidemiology | | |
RCC, UC of the bladder, ureter, renal pelvis, and prostate adenocarcinoma (PC) are the most commonly encountered histological subtypes within GU cancer. Annual morbidity of 225,000 patients and a mortality of over 56,000 patients per year in the USA accounts for metastatic GU malignancies.
Bladder cancer (UC) is the ninth most frequently diagnosed cancer worldwide, ranks 13th in death ranks, and is the most common cancer of the GU system.[2],[3] The median age of diagnosis is 73 years making bladder cancer a disease of the elderly.[4] RCC is a heterogeneous disease with the majority of cases categorized into one of two major histological subtypes; 80% are clear cell RCC (ccRCC) and 20% are non-ccRCC.[5] RCC is a commonly encountered GU malignancy with over 320,000 patients diagnosed annually and an annual death toll of over 140,000 people worldwide. More alarming, the annual incidence has risen over the past 10 years and now accounts for nearly 4% of new cancer diagnoses in the USA.[6],[7] PC is the second most common cancer in men and the second leading cause of cancer death in the USA. A man's risk of developing PC is 1 out of 9.[8]
| Pathogenesis | | |
GU cancers are most common malignant diseases in men. In the United States, prostate, bladder, and kidney cancers are the first, fourth, and sixth most common cancers in men, respectively.[9]
Common clinical pathologies related to the GU tract:
- Benign prostate hyperplasia (BPH): It is a common condition with age in men. BPH is the enlargement of the prostate, especially the growth of smooth muscle and epithelial cells due to the hormone dihydrotestosterone, causing narrowing of the bladder outlet. BPH presented with symptoms such as urgency and nocturia. Treatment often includes 5-alpha-reductase inhibitors, which block the conversion of testosterone to dihydrotestosterone
- Cryptorchidism: The most common congenital defect where one or both testes fail to descend into the scrotum. However, the cause of cryptorchidism is unclear; the testicular descent fails during the two hormonally controlled stages of gestation at 8–15 weeks and 25–35 weeks. It increases the risk of testicular cancer by three to four-folds and causes subfertility due to increased testes temperature in the abdomen compared to the scrotum. The primary treatment for cryptorchidism is a surgical procedure called orchidopexy that is usually performed before one year of age to relocate the testes
- Hypospadias is a congenital defect results in a ventral urethral opening on the penis other than the tip. It might be the result of both environmental and genetic factors. The severity of hypospadias depends on the location of the urinary meatus. Anterior hypospadias (70% prevalence) is generally a minor condition where the urinary meatus exits from either glandular or sub-coronal portion of the penis. Posterior and penile hypospadias (30% prevalence) are far more problematic. Hypospadias usually needs to be corrected surgically as it can interfere with both urinary and sexual functions
- Urethritis: is the inflammation of the urethra due to bacterial infections such as Neisseria gonorrhoeae and Chlamydia trachomatis. It is the most common GU complaint in sexually active men under the age of 50 years, approximately 2.8 million cases reported annually in the United States. Discharge and dysuria are most commonly reported symptoms in urethritis at 61% and 50%, respectively. Antibiotic therapy usually resolves urethritis.
| Diagnosis | | |
The tools and tests used to diagnose GU cancer depend on the type and location of the cancer suspected, as well as factors such as the patient's medical history and overall health status.
Imaging studies such as:
- Computed tomography
- Magnetic resonance imaging
- Ultrasound
- Positron emission tomography
- Intravenous pyelogram
- Angiography
Additional Diagnostic Tests such as:
- Endoscopy: The use of a thin, flexible tube (endoscope) to visualize parts of the urinary tract
- Tissue (biopsies) and body-fluid samples: Pathologists evaluate such specimens for the presence of cancer
- Molecular tissue testing: DNA analysis of a tissue sample, used to determine tumor-specific genes, proteins, and other characteristics
| Molecular Classification and Diagnosis of Genitourinary Tumors are as Follows | | |
Molecular characterization is currently mandatory in most human malignancies for precise diagnosis and to predict response to targeted biological drugs. Molecular classification and diagnosis of GU tumor in the landscape of solid tumors is possible since few molecular prognostic and predictive biomarkers have been identified so far in these tumor types [Table 1]. | Table 1: Novel biomarkers of possible future implementation in genitourinary cancer
Click here to view |
Next generation sequencing (NGS) approaches now provide mind-changing information in the fields of kidney cancer diagnosis, predictive oncology of urothelial cancer, understanding the causes of testicular and penile cancer, and the comprehension of the drivers of prostate cancer progression beyond androgen regulation. The classification of kidney cancer will be based soon on molecular changes.
The causes of non-HPV-related penile cancer are largely unknown. The emerging high incidence of testicular cancer could be explained only on the basis of molecular changes.
The response to novel therapeutic agents in prostatic and urothelial cancer will require thorough molecular tumor characterization. The hereditary risk of patients with early onset prostate cancer and their potential treatment with targeted therapy requires germline and somatic genetic assays.
The implementation of effective biomarkers for the response to immune checkpoint inhibitors in GU cancer is based on the assessment of inflammatory expression profiles and the tumor mutational burden.
| Treatment | | |
The treatment of GU malignancies has dramatically evolved over recent year. The advance that has gained the most recent traction has been the advent of immunotherapies, particularly immune checkpoint inhibitors. Immunotherapy has increased overall survival and even provided durable responses in the metastatic setting in some patients. The early success of immune checkpoint inhibitors has led to further drug development with the emergence of novel agents which modulate the immune system within the tumor microenvironment.
Treatment of newly diagnosed PC depends on anatomic extent of disease, histologic grade, and serum prostatespecific antigen level. Localized PC is often initially treated with either radical prostatectomy or radiation therapy. However, statistics show 27%–53% of patients will develop biochemical recurrence.[10] Androgen receptors play a crucial role in the pathogenesis of PC and remain the key therapeutic target.[11]
For some patients with GU cancers, chemotherapy or other drug therapies are the best course of treatment. Many factors, such as tumor location and stage, as well as the patient's overall health, preferences, goals, and ability to tolerate different drugs, help doctors determine the most appropriate drugs or other treatment strategy.
| Chemotherapy | | |
The goal of chemotherapy is to kill the cancer cells that make up the GU tumor. Chemotherapy can be used alone, before or after surgery, or in addition to radiation therapy to destroy remaining tumor cells and far-flung cancer cells that could cause the disease to recur.
Chemotherapy sometimes is combined with radiation therapy (chemoradiation) to treat GU cancer, such as in cases when tumors don't respond to chemotherapy alone or cannot be removed entirely with surgery. Chemoradiation is also an option for some patients who wish to avoid surgery altogether or are not good candidates for it.
| Personalized Drug Therapies | | |
Several targeted drugs kill certain types of GU cancer cells based on a tumor's unique molecular makeup. The cellular characteristics of some tumors can help physicians predict whether the disease will respond well to the treatment in specific patients.
Tumor analysis at the cellular level is another way UT Southwestern specialists can personalize medical therapies. Our researchers are making important strides in understanding how kidney cancer develops, for example, and we are working to translate our research findings into new therapies that target the disease's molecular pathways.
| Radiation Therapy | | |
Worldwide, there are five treatment stereotactic radiation regimens for early- and intermediate-risk prostate cancer being adopted at many progressive centers. The stereotactic radiation approach is also being applied effectively to treat small kidney cancers and a deadly complication of kidney cancers in which the tumor extends into the veins (inferior vena cava tumor thrombus). Additionally now, a new effort has been to combine stereotactic radiation therapy along with immunotherapy which directly stimulates the body's own immune system to react against metastatic prostate and kidney cancers.
Some offer brachytherapy treatments, which involve implanting tiny radiotherapy seeds about the size of a grain of rice that are able to destroy cancer cells when leaving the rest of the body unharmed.
| Surgical Treatment | | |
Procedures such as laparoscopic surgery and robotic surgery are effective alternatives to traditional open surgery techniques.
- Laparoscopic surgery (keyhole surgery): Uses several half-inch incisions instead of one long incision to remove tumors and other cancerous tissues.
- Robotic surgery: Enhances precision by offering three-dimensional imaging, reducing surgeon tremor, and eliminating the inverted manipulation of instruments usually required in laparoscopic procedures.
Smaller incisions mean fewer risks and quicker recovery, allowing patients who need further treatment, such as chemotherapy, to get it done sooner that impact significantly on the overall success rate of treatment for GU cancer.
| Disease-Specific Surgery Techniques | | |
Robotic surgery is used widely for prostate cancer, as well as for many cancers of the kidney and bladder and early cases of testicular cancer. Even partial kidney removal, a highly complex procedure, can now be done robotically in the hands of an experienced surgeon.
| Conclusion | | |
GU malignancies encompass a heterogeneous group of cancers pertaining to a specific anatomical and physiological function. Molecular characterization is currently mandatory in most human malignancies for precise diagnosis and to predict response to targeted biological drugs.
NGS technologies nowadays represent a simple and quite inexpensive tool to dissect the molecular alterations of single cancers. GU tumors represent the new frontier of the molecularly driven therapies and immunotherapies.
We hope this will provide a new perspective which will lead to an improved understanding of the complex molecular and genomic mechanisms underlying the oncogenesis and progression of GU cancers.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
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| 10. | Mottet N, Bellmunt J, Bolla M, Briers E, Cumberbatch MG, De Santis M, et al. EAU-ESTRO-SIOG guidelines on prostate cancer. Part 1: Screening, diagnosis, and local treatment with curative intent. Eur Urol 2017;71:618-29. |
| 11. | Hu R, Dunn TA, Wei S, Isharwal S, Veltri RW, Humphreys E, et al. Ligand-independent androgen receptor variants derived from splicing of cryptic exons signify hormone-refractory prostate cancer. Cancer Res 2009;69:16-22. |
[Table 1]
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