PERSPECTIVE, PATTERNS OF SPREAD, AND PATHOLOGY
The grading system widely adopted for tumor histology is the Gleason system, which is based on the summation of the tumor grade in the largest area and in the next-largest area and has been incorporated into staging.
PERSPECTIVE AND PATTERNS OF SPREAD
The situation with regard to prostate cancer has undergone a complete metamorphosis since the introduction of the widespread testing of males with prostate-specific antigen (PSA) blood tests in the mid 1980s. The diagnosis of prostate cancer is often made on needle biopsy transrectally guided by ultrasound. Adenocarcinomas of the prostate arise in the true gland and rarely begin in benign hyperplastic enlargements that usually occur around the prostatic urethra. Pathologically, cancers tend to be multifocal, arising in the peripheral zone (90%), with only 1% from the central zone. The precursor lesion is often prostatic intraepithelial neoplasm. The Gleason grade ranges from 1 to 5, and sums range from 2 to 10; grades 7 to 10 are aggressive cancers.
The patterns of spread are limited by location and by the capsule surrounding the gland (Fig. 38.2; Table 38.2).
Most primary lesions invade the prostatic capsule first and then take the path of least resistance along the ejaculatory ducts into the space between the seminal vesicles and the bladder. The growth of the tumor outside the prostate is usually along the perivesical fascia rather than directly into the seminal vesicles. If the local lesion has extensively invaded the seminal vesical area, then there is a 75% probability that the regional nodes are involved. Clinically, however, palpable induration in the seminal vesicle region may prove histologically to be an inflammation and not tumor extension; however, any enlargement needs to be considered neoplastic until proven otherwise. Early invasion of cancers from the prostate directly into the bladder wall, distally into the membranous urethra, or along the vas deferens beyond the seminal vesicles are rare. As the prostate enlarges, it elevates the bladder and pushes into the rectum. It seldom produces an encircling lesion that can lead to constipation. Perineural invasion is common and can lead to severe perineal and sacral pain as the sacral plexus is involved.
Figure 38.1A–C | A. Gleason grade 1. B. Gleason grade 3. C. Gleason grade 5.
Figure 38.2 | Patterns of spread (cancer crab) of prostate cancer are color coded for stage: T0, yellow; T1, green; T2, blue; T3, purple; and T4, red; T1 is microscopic. The concept of visualizing patterns of spread to appreciate the surrounding anatomy is well demonstrated by the six-directional pattern (SIMLAP, Table 38.2). A. Coronal view. B. Sagittal.
PATHOLOGY
Pathologically, cancers tend to be multifocal arising in the peripheral zone (90%), with only 1% from the central zone. The precursor lesion is often prostatic intraepithelial neoplasm. (Table 38.1; Fig. 38.1A–C).
TNM STAGING CRITERIA
TNM STAGING CRITERIA
When introduced in the first edition of the American Joint Committee on Cancer AJCC Cancer Staging Manual (1978), the system was based largely on physical examination: T1 was intracapsular, with normal gland surrounding the tumor; in T2, the capsule was invaded and gland contour deformed; in T3, tumor extended beyond the capsule into lateral sulcus; and in T4, it was fixed to neighboring structures. By the fourth edition (1992), subcategories were introduced for each stage, and imaging techniques were allowed in the staging workup. In the fifth edition (1997), transrectal ultrasound (TRUS) allowed for more accurate tumor localization and guided needle biopsies. In the fifth and sixth editions, elevated PSA without identifiable or nonpalpable disease in normal glands but needle aspiration of microdeposits of cancer was staged as T1c. Incidental microfoci, found in >5% of biopsied tissue, is T1a; in T1b, ≤5%. T2 was subdivided by whether one or two lobes were involved. T3a was extracapsular spread, T3b was seminal vesicle involvement, and T4 was related to adjacent viscera being invaded, namely, bladder and more rarely the rectum. The anatomic reason for either of these organ invasions or lack thereof is due to the absence of capsule where the prostate meets the urinary bladder, but the rectum is protected by a rudimentary fused culde sac, Denonvilliers’ fascia, between prostate and rectum, a virtually impenetrable barrier (Fig. 38.3).
SUMMARY OF CHANGES SEVENTH EDITION AJCC
• Extraprostatic invasion with microscopic bladder neck invasion (T4) is included with T3a (Fig. 38.3).
• Gleason Score now recognized as the preferred grading system.
• Prognostic factors have been incorporated in the Anatomic Stage/Prognostic Groups
• Gleason Score
• Preoperative prostate-specific antigen (PSA).
The TNM Staging Matrix is color coded for identification of Stage Group once T and N stages are determined (Table 38.3). The T stage determines the stage group.
GENESIS AND EVOLUTION
Prostate cancer is the most common cancer, and its major stages (I to IV) have been consistently defined by the extent of the primary cancer T1 to T4. N1 and M1 are equated with T4 regionally advanced cancer (Table 38.6). The incorporation of the A, B, C, D stage groups of the American Urologic Association (AUA) occurred in the second edition (1982) of the AJCC Cancer Staging Manual. An increasing number of T category subgroups has occurred within each stage, particularly with acceptance of the PSA and needle biopsy for T1c. Most recently pathology grading has been added, with the shifting of early T1, T2 high-grade II, III, and IV cancers to stage II as a notable instance of stage category migration that will improve 5-year survival in both stages I and II. In addition, stage 0 has been eliminated and downstaged to stage I.
PROSTATE (CLINICAL)
Figure 38.3A | TNM prostate cancer diagram. Vertically arranged with T definitions on the left and stage groupings on the right. Color bars are coded for stage: stage I, green; II, blue; III, purple; IV, red; and metastatic, black.
Figure 38.1D | Prostate carcinoma. Gleason grading system. Grading: Prostatic adenocarcinoma is most commonly classified according to the Gleason grading system, which is based on five histologic patterns of tumor gland formation and infiltration. Recognizing the high frequency of mixed tumor patterns, the Gleason score is the sum of the grades (1 through 5) attributed to the most prominent pattern and that of the minority pattern. The best differentiated tumors have a Gleason score of 2 (1 + 1), while very poorly differentiated cancers have scores of 10 (5 + 5). Most tumors score 4 to 7 (2 + 2, to 3 + 4 or 4 + 3). When combined with the tumor stage, the Gleason grading system has prognostic valve: lower scores correlate with better prognoses.
PROSTATE (PATHOLOGIC)
Figure 38.3B | TNM prostate cancer diagram. Vertically arranged with T definitions on the left and stage groupings on the right. Color bars are coded for stage: stage I, green; II, blue; III, purple; IV, red; and metastatic, black.
T-ONCOANATOMY
ORIENTATION OF THREE-PLANAR ONCOANATOMY
The isocenter of the prostate is the central position in male pelvis oncoanatomy (Fig. 38.4). The prostate is positioned at the bladder neck. It is traversed by the proximal portion of the urethra, which is subject to compression and direct invasion. Once the cancer invades through the capsule, the common spread patterns are posterior, lateral, and/or superior. Lateral extension into the sulcus may lead to fixation of the gland to the lateral wall of the pelvis.
As the tumor extends superiorly, it invades into the seminal vesicle and it can block the ejaculatory ducts that traverses the substance of the gland. In its superior or anterior direction, a cancer can invade into the bladder because the capsular wall of the prostate thins and is in direct contact with its vesical muscular wall and lymphatics.
T-oncoanatomy
The prostate is both a glandular and a muscular organ that consists of four zones. It is firmly fixed in position by a dense capsule and ligamentous attachments. The zonal anatomy is defined in Fig. 38.5A legend. The urethra courses from the base of the bladder to the bulb of the penis. The cortical structure of the prostate's apex is directed below the perineum. Its flat base touches the base of the bladder. The lateral surfaces are convex, resting against the fascia of the levator ani muscles (Fig. 38.5).
• Coronal: The prostate sits at the pelvic inlet and is surrounded by a number of distinct ligamentous structures as it rests along the levator ani muscles and on the sphincter urethrae muscle and its superior fascia. The urogenital diaphragm along with the central tendon of the perineum (perineal body) and the deep perineal space act as a distinct floor.
• Sagittal: This diaphragm separates the prostate gland from the bulb of the penis. Posteriorly, Denonvilliers’ fascia separates the prostate gland from the rectum and acts as a major resistance to tumor invasion because it is composed of obliterated layers of the peritoneal cavity that extend downward.
• Transverse: The prostate gland lies anterior to the rectum and is readily palpable. Transrectal imaging with ultrasound and biopsy is possible because of this anatomy. Note that the prostatic venous plexus is rich anteriorly and communicates with the dorsal vein of the penis.
The ductus vas deferens and the seminal vesicles lie posterior to the bladder. They drain into the ejaculatory duct, which has the diameter of a lead pencil. The nerves of the prostate are derived from the pelvic sympathetic plexuses.
The color code for the anatomic sites correlates with the color code for the stage group (Fig. 38.3) and patterns of spread (Fig. 38.2) and the SIMLAP table (Table 38.2). Connecting the dots in similar colors provides an appreciation for the three-dimensional oncoanatomy.
Figure 38.4 | Orientation of T-oncoanatomy. The anatomic isocenter for three-planar anatomy of the prostate is at the coccyx level. Left. Coronal. Right. Sagittal.
Figure 38.5A | Zonal anatomy of the prostate. On the left, a young man with minimal transition zone (TZ) hypertrophy. Note that preprostatic sphincter (internal urethral sphincter) and periejaculatory duct zone (central zone of McLean) (CZ) are clearly defined. On the right, an older man with TZ hypertrophy, which effaces the preprostatic sphincter and compresses the periejaculatory duct zone. AFS, anterior fibro-muscular stroma; CZ, central zone; PZ, peripheral zone; SV, seminal vesicle.
Figure 38.5B–D | T-oncoanatomy. Connecting the dots. Structures are color coded for cancer stage progression.
N-ONCOANATOMY AND M-ONCOANATOMY
N-ONCOANATOMY
A rich lymphatic network exists with lateral drainage and posterior sacral trunk. In addition to the internal and external iliac lymph nodes, it is possible, because of the latter trunk, for prostate cancers to bypass pelvic lymph nodes and spread directly to retroperitoneal lymph nodes in the para-aortic region first. The most commonly involved lymph node is the obturator node. In addition, there is a rich network of lymphatics that drain into internal and external iliac nodes and along the superior hemorrhoidal veins and a posterior sacral trunk directly into para-aortic nodes (Fig. 38.6A; Table 38.4A). The incidence for lymph node involvement is based on the part in nomogram for prediction of final pathologic stage based on the PSA, the Gleason score, and clinical stage of the primary cancer (Table 38.4B).
M-ONCOANATOMY
The arteries are branches of the rectal (hemorrhoidal) and inferior vesical arteries. The thin-walled veins are set inside and outside the prostatic capsule, forming a plexus of prostatic-vesical veins. This rich plexus of veins surrounds the prostate and interconnects with the blood in the dorsal vein of the penis. These veins drain into another rich plexus of veins in addition to the internal iliac vein. A rich anastomosis of inter-vertebral veins ascends from the internal iliac veins. This is referred to as the Batson's circulation. This venous pathway accounts for the distribution and frequency of osseous metastases; it also connects with ventral venous plexus (Fig. 38.6B).
Figure 38.6 | A. N-oncoanatomy. Obturator nodes of hypogastric or internal iliac chain. B. M-oncoanatomy. Batson's vertebral venous plexus.
STAGING WORKUP
RULES OF CLASSIFICATION AND STAGING
Clinical Staging and Imaging
Clinical assessment before treatment includes a digital rectal examination and needle biopsy guided by TRUS. For nonpalpable disease, imaging with endorectal magnetic resonance imaging (MRI) is superior to computed tomography (CT). Enhanced CT is valuable for assessing lymph nodes, but if PSA is low (20 mg/mL) and the Gleason grade is favorable (7), sophisticated imaging is discouraged because of a high false-positive rate with imaging. Stages T2A, 2B, and 2C of the fourth edition have returned because the recurrence-free survival rate was significantly different for definitions in the fifth edition (Table 38.5; Fig. 38.7).
Pathologic Staging
With a total prostatectomy seminal vesiculectomy, regional nodes are carefully examined for surgical margins by descriptors: R1, microscopic; R2, macroscopic. A positive rectal biopsy permits pT4 and a positive biopsy of extraprostatic soft tissue justifies pT3, as does a positive biopsy of seminal vesicles.
PROGNOSIS AND CANCER SURVIVAL
Oncoimaging Annotations
• TRUS is recommended if either digital rectal exam or PSA is abnormal.
• The main role of TRUS is in ultrasound-guided biopsy.
• The role of CT is detection of lymph node or other distant metastases.
• Endorectal MRI (eMRI) is superior to the use of body coil.
• eMRI renders the highest detection of extracapsular extension or seminal vesicle invasion, but variations in image quality and interpretation are among the main reasons for the slow dissemination of this technique.
• Early results on the use of spectroscopic MRI are promising, but the modality is still considered a research tool.
• Treatment follow-up is limited by imaging; either TRUS (with biopsy) or eMRI is most commonly used.
PROGNOSIS
The limited number of prognostic factors are listed in Table 38.6.
CANCER STATISTICS AND SURVIVAL
When considered together, the male genital and urinary systems are the major sites of malignancy. Prostate cancer alone accounts for 200,000 new patients annually. There are 100,000 new urinary tract cancers and 2.5-more male genital cancers, or 250,000 cases annually.
Between 1988 and 1992, the incidence rate of prostate cancers tripled from 75,000 new cases annually to 225,000. Prostate cancer in men is similar to breast cancer in women, accounting for 33% of all cancers and outdistancing lung cancer (13%) and colon and rectum cancers (11%) combined. The 5-year survival is best of all cancers at 98.5%, but this cancer still causes 30,000 deaths yearly and is the second-leading cause of cancer death among men in the United States. Despite declining death rates in whites, African American men are dying of prostate cancer at twice the rate. Significant geographic variation has been observed; it is highest among blacks in the United States, followed by whites in Scandinavia and the United States. The lowest rates are in Asia.
Figure 38.7 | A. 1. Prostate. 2. Rectum. 3. Obturator internus muscle. 4. Spermatic cords. B. 1. Prostate. 2. Rectum. 3. Levator ani muscle. 4. Pectineus muscle. 5. Obturator externus muscle. 6. Obturator internus muscle. Correlates with Fig. 38.5D.
The dramatic gains in survival are due to multidisciplinary achievements in screening, early detection, precise diagnoses, and effective multimodal therapies. The cancer statistics reveal perhaps the greatest gains in survival in oncology over the last five decades. For local stage I, male genitourinary tumors are all 90% to 100% curable according to the latest Surveillance Epidemiology and End Results data: kidney, 90%; bladder, 94%; testes, 99%; and prostate, 100%. Mortality rates are declining. The pediatric Wilms’ tumor was the first malignancy in childhood to be cured, achieving >90% long-term survival, heralding the success of multimodal treatment that would be achieved in adult tumors in urology (see Table 38.7).
