A schematic of the rectal probe in contact with the prostate is show in this diagram.

Transcription

1 Hello. My name is William Osai. I am a nurse practitioner in the GU Medical Oncology Department at The University of Texas MD Anderson Cancer Center in Houston. Today s presentation is Part 2 of the Overview of Prostate Cancer. The objectives of this presentation are the following: upon completion of this lecture participants will be able to identify the symptoms of prostate cancer; discuss the initial examination of the patient suspected to have prostate cancer; describe the processes involved in the diagnosis of prostate cancer; discuss the prostate cancer staging process; and discuss treatments based on risk stratifications. Most patients diagnosed in the era of PSA do --- present without symptoms, in that they are diagnosed before they develop symptoms. Nonetheless, the common side --- symptoms of prostate cancer include erectile dysfunction, hematuria, bone pain in case of metastasis, incontinence of bowel or bladder, urinary retention or hydronephrosis in case of local spread of disease such as into the bladder, neuropathy from metastasis to the spinal cord and/or bone. If the patient presents with suspicion of prostate cancer, the initial step is to do a comprehensive physical --- history and physical exam. This includes laporatory --- laboratory tests, checking for PSA, PSA derivatives, and prostate cancer antigen 3. In addition, the patient will undergo a digital rectal exam during the physical exam. If there are suspicions that there is prostate cancer, a tissue dia --- diagnosis is obtained by a prostate biopsy. In addition, imaging studies are done including CT possibly of the chest, abdomen, and pelvis, whole body bone scan, and magnetic resonance imaging of the prostate and pelvis to determine the extent of disease locally. What are the indications for prostate biopsy? These include elevated PSA, rise in PSA, and symptoms. In addition, abnormal digital rectal exam by itself is sufficient to warrant a prostate biopsy. The National Comprehensive Cancer Network TM recommends a prostate biopsy for men with PSA over 2.6 that has a higher than normal PSA velocity. The American Urologic Association, on the other hand, has no single threshold for prostate biopsy. Rather, prostate biopsy is recommended based on digital rectal exam, PSA, PSA velocity, PSA density, family history of prostate cancer, ethnicity, prior prostate biopsy, or comorbidities. The prostate biopsy itself is an outpatient procedure, done under local anesthesia via periprostatic means. The procedure can be performed by a urologist, a physician s assistant, or a nurse practitioner. It is essential that patients undergo pre-procedure assessment in order to reduce the risk of complications. The patients are required to sign an informed consent prior to undergoing the procedure. And the risks assessments includes patients --- determining whether the patients are on anticoagulation therapy for pa --- such as patients with heart valve, rheumatic fever, or endocarditis. The patients should be prophylaxed for urinary tract

2 infection. And those that have a urinary tract infection adequately treated prior to the biopsy. This also applies to patients with immunodeficiency cons --- conditions that require antibiotic prophylaxis. Typical equipment for prostate cancer biopsy --- for prostate biopsy include the ultrasound as shown on the left panel and other equipment including the rectal probe and the spring-loaded biopsy needle. Each core biopsy is placed in a separate container and labed --- labeled with the anna --- anatomic site of the biopsy. During the procedure, the patient is positioned in either the right or left lateral decubitus position. And the clinician first performs a digital rectal exam to assess the anal sphincter for tonicity, look for anal pathology, and examine the prostate. An ultrasound image of the prostate is also obtained to assess gross anatomy of the prostate, zonal anatomy, and the size of the prostate. The ultrasound also aids in precision biopsies. A schematic of the rectal probe in contact with the prostate is show in this diagram. A typical prostate ultrasound image is shown above. There are variable biopsy schemes including sextant biopsies, five regional biopsies, eight core biopsies, or eleven core biopsies. The sextant biopsy involves sampling bilateral prostate from the apex, mid-gland, and base -- and base in the mid-sagittal plane. Ten core biopsies involve the sextant biopsy plus left and right anterior horns. Staging biopsies in --- involve targeting the neurovascular bundle, seminal vesicle, or extra -- extraprostatic space. The 12 core biopsy shown on the right hand panel is the preferred scheme and it is a sextant with lateral scheme. The --- There are 6 specimens obtained from the right and left libi --- labeled as shown above. The prostate biopsy procedure itself is a safe procedure, but there are potential complications. Minor complications include blood in the stool, dysuria, or hematuria, which can occur in about --- in up to 14.5% of patients that undergo a transrectal ultrasound guided biopsy of the prostate; bleeding up to 2.2%; hematospermia between 6.5% and 74.4%; and prostatitis, 1%. Major complications are few, but they do occur. These include infection up to 6.6%; urosepsis, 0.3%; urinary retention of blood clots 0.4% to 4.6%; hospitalization following biopsy up to 1.6%. Following the biopsy, the staging process then ensues. This includes --- The variables in the staging process include the histology and grade of the tumor, the findings from imaging studies that include the CT scans, bone scan, and MRI, which are used to determine the tumor, node, and metastatic stage of disease. In terms of histology, over 95% of prostate cancers are adenocarcinomas with the remainder divided amongst the adenosquamous and squamous cell carcinoma, basaloid or adenoid carcinoma, adenocystic carcinoma, lymphoepithelial-like

3 carcinoma, small cell or neuroendocrine carcinoma, sarcomatoid carcinoma, or urothelial carcinoma. A detailed discussion of these hist --- histologic subtypes is done in a different lecture. The Gleason grade is arrived at by utilizing the Gleason Score System. The Gleason Scoring System was developed by Dr. Gleason based on his work in the VA Hos --- the VA Medical Center System. It describes the architectural appearance of prostate cancer cells under the microscope. And it is defined as the sum of the two most common grade patterns reported in the Gleason score. The patterns are divided from 1 to 5. One being the most well-differentiated and 5 being the least well-differentiated. When the pathologist ob --- observes more than 1 pattern, both are combined to establish a Gleason score. The predominant pattern is the first number and the second most predominant pattern is the second number. A combination of both gives the combined Gleason score. For example, if the first predominant pattern is 3 and the second most predominant is 4, the combined Gleason score is 3 plus 4 equal to 7. If there is one uniform pattern, the uniform pattern is used for both numbers. For example, if there is a uniform 3 pattern, the Gleason score will be 3 plus 3 equal to 6. The next step in the staging process is imaging. CT scans of the abdomen and pelvis, bone scan, and MRI are utilized to determine the local extent of disease as well as metastasis. Other reasons for imaging patients is to assess for the spread of disease locally or distant, like I said earlier. It is also used to assess the GU organs for pathology, determine the extent of disease in the prostate, and determine whether there has been an extracapsular extension beyond the prostate. It is also used to determine the progression of disease, recurrence of disease, or residual disease in patients after treatment. It is also used to monitor patients on active surveillance to assess for disease status. The final staging process is using the American Joint Committee on Cancer Staging System. This is a widely accepted system for staging most cancers, including prostate cancer. The cancer staging helps to determine the location of the primary cancer, size, and number of tumors, whether the tumor has spread to the local regional lymph nodes or to distant organs or nodes. The system utilizes the TNM scheme for staging. The T stands for the extent of primary tumor. The N stands for local regional node involvement. And the M stands for distant metastasis. The values assigned to the T range from 1 to 4 with subdivisions in each category, except for T4; and the N and M categories are divided into --- between 0 and 1 with subdivisions in the 1 category. Staging is either clinical or pathologic. Clinical stage refers to the findings of --- on physical exam, biopsy, and imaging that best describes the extent of disease without access to the surgically removed tumor. Pathologic stage is based on the findings after the prostate is surgically removed. I am going to spend some time on this staging system in order to because --- because an understanding of the staging system will help us in understanding the treatment recommendations provided in several slides beyond now. A TX stage means that the primary tumor cannot be accessed --- assessed; either because the patient has had treatment before a tissue diagnosis was obtained or for some other reason. A T0 indicates no evidence of primary tumor. T1 means clinically

4 inapparent tumor neither palpable nor visible by imaging. This is further subdivided into T1a, T1b, and T1c. T1a indicates an incidental histologic finding in 5% or less of tissue resected. T1b indicates tumor incidental -- incidentally found in more than 5% of tissue resected. T1c indicates tumor identified by needle biopsy, for example, because --- a biopsy that was done because a patient had an elevated PSA. T2 indicates tumor confined within the prostate. This is further subdivided into T2a, T2b, and T2c. In T2a stage, the tumor involves one-half of one lobe or less. T2b, the tumor involves more than one-half of one lobe, but not both lobes. T2c tumor involves both lobes. And then there is T3 where the tumor has extended beyond the prostate capsule. This is further subdivided into T3a and T3b. T3a means it s the extracapsular extension either unilateral or bilateral. T3b indicates the tumor had invaded the seminal vesicles. In T4 stage the tumor is fixed or invades adjacent structures other than the seminal vesicles such as the external sphincter of the bladder, the rectum, or the pelvic sidewall. Pathologic staging is also similar to the clinical staging, except that there is no stage --- pathologic stage T1. Pathologic stage T2 indicates that the disease is organ-confined. This is further divided into pt2a, pt2b, pt2c. In pt2a, there is uni --- unilateral disease involving one-half of one side or less. In pathologic stage pt2b the tumor is unilateral, involving more than one-half of one side, but not both sides of the prostate. And in pt2c stage, there s bilateral disease. In pt3, there s extracaps --- extraprostatic extension, meaning that the tumor has extended beyond the prostate capsule. This is further subdivided into pt3a, indicating there has been extraprostatic extension or microscopic invasion of the bladder neck; pt3b indicates seminal vesicle invasion. And pt4 indicates invasion of the rectum or pelvic sidewall. Clinical staging for the lymph nodes is done in the following manner. NX indicates regional lymph nodes were not accessed -- assessed for whatever reason. N0 indicates no regional lymph node metastasis and N1 indicates metastasis in the regional lymph nodes. The same applies to pathological staging where pnx indicates regional lymph nodes were not sampled. pn0 indicates lymph nodes were sampled, but no positive lymph nodes were found. And pn1 indicates metastasis in regional lymph nodes. In terms of the definition of distant metastasis, M0 indicates no distant metastasis. M1 indicates distant metastasis. M1 is further subdivided into M1a, M1b, and M1c. M1 --- M1a indicates non-regional lymph node metastasis. M1b indicates metastasis to bones. And M1c indicates other sites of metastasis with or without bone disease. Once the TNM stage has been established, this can --- these can be grouped into 4 stages: Group I, Group IIA, Group IIB, Group III, or Group IV, the higher the group the worse the prognosis and the higher the disease burden. Based on the findings on staging, treatment recommendations is --- Based on the findings on staging, patients are risk stratified and treatment recommended based on

5 the following variables: life expectancy, total serum PSA, Gleason score, clinical stage, and number of positive core biopsies. The risk categories are very low-risk, low-risk, intermediate-risk, high-risk, locally advanced, and metastatic disease. I will discuss each of these risk categories in detail as we go forward. The available treatment options depending on the risk category include active surveillance where treatment is postponed but the patient is actively watched and treatment offered if there s progression of disease. Definitive therapy, including radical prostatectomy, radiation therapy, external beam --- which includes external beam radiation, brachytherapy, or proton beam radiation. Other treatment options include hormone therapy and radiation therapy in combination or alone, and hormone therapy by itself in cases of metastatic disease. Chemotherapy is used in prostate cancer in the late --- later stages where the disease is become androgen-insensitive. In the very low-risk category, the characteristics are patients with clinical T1c. If you refer back to our AJ --- American Joint Committee on Cancer Staging System, it ll help to understand the disease burden in these cases. Clinical T1c is the stage, in this case, Gleason score 6 or less, a PSA of 10 ng. per ml. or less, and fewer than 3 prostate biopsy core positive with each core less than or equal to 40% positive. The PSA density, when available, shou --- should be less than 0.5 ng. per ml. And the life expectancy should be --- the life expectancy of less than 20 years or greater than or equal to 20 years or less than 10 years. For patients with life expectancy less than 20 years, active surveillance is a preferred option because the thinking is that the disease does not pose a risk to life expectancy. The protocol for active surveillance is PSA every 6 months, digital rectal exam every year, repeat biopsy at least every 12 months. For patients with life exp --- expectancy greater than 20 years, indicating that the tumor --- the cancer may pose a risk to life expectancy, active surveillance is an option. However, definitive therapy including radiation therapy and radical prostatectomy is also offered. For patients with low-risk of recurrent disease, the clinical stage is clinical stage T1 to clinical stage T2a. The Gleason score would be less than 6 or equal to 6. The PSA of less than 10 ng. per ml., a life expectancy of greater than 10 or equal to 10 years, or a life expectancy of less than 10 years. If the life expectancy is less than 10 years, the rec --- the recommendation is active surveillance. Again, in this case the thinking is that the disease does not pose a sufficient threat to life expectancy. And the protocol is essentially the same as the vely --- very low-risk for recurrence category, which is a PSA every 6 months, digital rectal exam every year, repeat biopsy at least every 12 months. In cases where patients have a life expectancy greater than 10 years and this - -- the thinking that the disease may pose a risk to life expectancy, definitive therapy is recommended, including radiation therapy, radical prostatectomy with or without pelvic lymph node dissection.

6 For patients in the intermediate-risk category, the characteristics include a clinical stage T2b to clinical stage T2c, or Gleason Score 7, or PSA between 10 to 20. If the life expectancy of the patient is less than 10 years, active surveillance is also an option with the same protocol, PSA every 6 months, digital rectal exam every year, or definitive therapy of radiation therapy with or without short-term neoadjuvant, concomitant adjuvant hormone therapy with or without brachytherapy. For patients with life expectancy greater than 10 years, the option of active surveillance is not offered. And definitive radiation therapy is offered because of the risk to life expectancy. Radical prostatectomy with or without pelvic lymph node dissection is also an option for these patients. In patients with high or very high-risk of recurrence, meaning they have clinical T3a, or Gleason score 8 to 10, or PSA greater than 20, definitive therapy is offered, active surveillance is not an option. The radiation therapy could --- radiation therapy offered could be plus long-term neoadjuvant, concomitant, or adjuvant hormone therapy or radiation therapy plus brachytherapy with or without short-term neoadjuvant, concomitant, or adjuvant therapy, or radical prostatectomy plus pelvic lymph node dissection. For patients with metastatic disease which means any T stage and nodal involvement, hormone therapy plus radiation therapy plus long-term neoadjuvant, concomitant, adjuvant hormone therapy is recommended. And for patients with distant metastasis, which means any T grade --- any T stage, any N stage, an M1 or above, the recommended treatment is hormone therapy only. In summary, prostate cancer patients generally do not present with symptoms since the introduction of PSA prostate cancer screening. Prostate biopsy provides tissue diagnosis for prostate cancer. Prostate cancer treatment is individualized according to the specific patient and tumor-related factors. Active surveillance is appropriate for select group of patients. And that is the conclusion of my presentation. Thank you for your attention and we welcome your feedback.