B2 Tumors Research Articles

Role of Nerve-Sparing Radical Prostatectomy for Clinical Stage B2 Prostate Cancer

To examine the role of nerve-sparing radical prostatectomy in patients with clinical stage B2 prostate cancer we reviewed the first 77 such patients in our series since we adopted the nervesparing technique. A total of 47 patients (61%) underwent bilateral and 26 (34%) underwent unilateral nerve-sparing prostatectomy, while in 4 (5%) both neurovascular bundles were resected. Among the patients followed for 12 months 27 of 41 (66%) treated with bilateral and 7 of 19 (37%) treated with unilateral nerve-sparing prostatectomy had potency preserved.With the strict clinicopathological criteria of organ-confined tumor, that is intracapsular tumor with negative surgical margins and undetectable postoperative prostate specific antigen levels, complete tumor excision was achieved in 17 patients (36%) treated with bilateral and 7 of 26 (27%) treated with unilateral nerve-sparing prostatectomy. All patients in whom both neurovascular bundles were resected had pathological stage C or D1 disease. Of the 24 patients who had complete tumor excision by the strict criteria only 15 (19.5% of the 77 preoperatively potent patients) had potency preserved.Of these patients 19 had microscopically positive margins without seminal vesicle invasion (pathological stage Cl) with undetectable postoperative prostate specific antigen levels. In addition, 4 patients had seminal vesicle involvement with negative surgical margins and undetectable postoperative prostate specific antigen levels. If these patients also are considered as having complete tumor excision, there was an over-all complete tumor excision rate of 61% (47 of 77), of whom 25 (32% of the 77 patients) had preservation of potency. Ten patients with clinical stage B2 tumor whose potency was preserved had histological and serological evidence of incomplete tumor excision. Of 53 patients with pathological stage Cl disease 9 (17%) had margins positive only in the regions of the neurovascular bundles.Preoperative prostate specific antigen and acid phosphatase levels, and findings on transrectal ultrasonography failed to predict accurately which patients had extracapsular tumor extension. Patients with poorly differentiated tumors and/or bulky disease on rectal examination had a higher incidence of extracapsular extension and positive margins.We conclude that in the majority of potent patients with clinical stage B2 prostate cancer not all of the goals of nerve-sparing radical prostatectomy are realized. Because of the high incidence of extracapsular tumor extension and positive surgical margins in patients with clinical stage B2 disease, and because some positive surgical margins may be owing to attempts to preserve potency we question whether nerve-sparing prostatectomy should be attempted in patients with bulky clinical stage B2 prostate cancer.

Patient Selection for, Results of, and Impact on Tumor Resection of Potency-sparing Radical Prostatectomy

Our results show that by using the nerve-sparing radical retropubic prostatectomy, potency can be preserved in the majority of appropriately selected patients without compromising the adequacy of tumor excision. However, proper patient selection is important. Patients with focal, well-differentiated tumors, especially young patients with stage A or B1 tumors, are ideal candidates. In patients with more extensive and less well-differentiated tumors, there is a higher risk of incomplete tumor excision. Although we suspect that the adequacy of tumor excision is determined more by the extent of the tumor than by the technique of radical prostatectomy used, we believe that nerve-sparing surgery should be used with great caution, if at all, in patients with extensive or high-grade tumors. In these patients, microscopic extracapsular tumor extension is extremely common, can be impossible to detect at the time of operation, and is less likely to be adequately encompassed by nerve-sparing techniques. On the other hand, our current data provide little evidence that excision of the neurovascular bundles is beneficial. It is possible that more extensive resections will not materially alter the incidence of positive margins or cure rates. Finally, it might be argued that all forms of radical prostatectomy are inappropriate for patients with poorly differentiated clinical stage B2 prostate cancer for whom there are no really effective treatment options. We continue to recommend radical prostatectomy for these patients based on the finding that patients with clinical stage B2 disease who have organ-confined tumors can be expected to have excellent long-term disease-free survival rates similar to those of clinical stage B1 patients. In the remaining patients who are clinically understaged, the prospects for the minimal microscopic tumor remaining being controlled with adjunctive radiation therapy may be better than those of controlling the bulky primary tumor with radiation therapy alone. This hypothesis will need to be tested in a randomized clinical trial.

Preoperative staging of rectal carcinoma with MR imaging: surgical and histopathologic correlation.

Twenty-nine patients with rectal carcinoma were examined with magnetic resonance (MR) imaging at 1.0 T. In most patients a Helmholtz coil was used and a bowel distention obtained with a barium enema balloon tip. The MR findings were graded according to the modified Astler-Coller staging classification and correlated with the surgical or histopathologic results. Correct diagnosis was made in nine of the 12 patients with stage A and B1 tumors. Overestimation occurred in the other three patients, who had previously undergone radiation therapy or surgery. Local stage was correctly assessed in 11 patients with stage B2 carcinoma and in six patients with stage B3 tumors. Enlarged lymph nodes were detected in four of seven patients with nodes containing carcinoma. In two other patients with enlarged nodes, no carcinoma was identified at histologic examination. MR imaging may enable correct staging of local extent of rectal carcinoma, particularly in patients who have not previously undergone radiation therapy or surgery. However, evaluation of lymph nodes is less accurate.

Nerve-Preserving Bilateral Retroperitoneal Lymphadenectomy: Anatomical Study and Operative Approach

In a study of the sympathetic trunk in 18 cadavers a new anatomical approach for modified bilateral retroperitoneal lymphadenectomy was developed, which is characterized by unilateral preservation of the L3 ganglion and the fibers arising from this ganglion. Furthermore, the sympathetic trunk and its lumbar branches were dissected, including the connections between the right and left sympathetic trunks arising from the L3 and L4 ganglia. On the right side the fibers were found dorsal to the inferior vena cava from where they pass into the aortocaval zone. Caudal to the inferior mesenteric artery these fibers communicate with the left para-aortic fibers. The precise topographic inter-relationship between the L2 and L3 ganglia was studied; the lower margin of the L3 ganglion was located 1cm. cranial to the origin of the inferior mesenteric artery.Based on these findings a modified operative technique was developed for stages B1 and B2 testicular tumors. With the help of this modification it should be possible to preserve ejaculatory function in 50% of the patients who undergo an operation for small retroperitoneal tumors. However, this modification can be justified only if the recurrence rate is not higher than that with radical bilateral lymphadenectomy.

Results of treatment of uterine cervix cancer by radiotherapy

The results of treatment of uterine cervix cancer by radiotherapy alone in 259 patients in the period January 1973 to December 1984 are reported. They are analyzed according to patients age, stage, tumor volume, extent of parametrial infiltration, hydronephrosis and nodal status. It is shown that age, tumor volume, extent of parametrial invasion and nodal metastases are the main prognostic factors. Analysis of pelvic failures shows that external radiotherapy followed by curietherapy seems to be the best method for patients with T 2b and T 3b tumors of small volume (less than 60 mm in diameter), particularly when parametrial infiltration is limited. Patients with T 2b tumors of large volume (barrel shaped) seem to need a more aggressive approach, and a higher number of complications are therefore expected. Patients with T 3b and massive parametrial infiltration, with T 4 and nodal metastases need new and different approaches, possibly including adjuvant chemotherapy.

A 5- to 21-year follow-up and analysis of 250 patients with rectal adenocarcinoma.

A total of 250 patients with rectal adenocarcinoma were operated on at the University of Chicago Medical Center between 1965 and 1981. The operation performed was curative resection in 154 patients, palliative resection in 16 patients, diverting colostomy in 21 patients, exploratory laparotomy in 11 patients, and transanal removal in 48 patients. Of the 154 curative resections, 115 were abdomino-perineal (APR), three were total proctocolectomies, and 36 were low anterior resections (LAR). No anastomotic complications were observed in this latter group. Operative mortality was 3%. Complete follow-up was obtained in 152 patients (98.7%). Five- and 10-year actuarial survival rates were 68.8 and 59.4%, respectively, for patients with Dukes' B1 adenocarcinoma (n = 32), 55.8 and 44.2% for Dukes' B2 tumors (n = 52), and 42.9% and 25.4% for Dukes' C tumors (n = 63). Distant metastases developed in 59 patients (39.6%), and pelvic recurrence developed in another 18 patients (12%); 5-year survival rates were 23.6% and 22.2%, respectively. Multivariate analysis with Cox regression showed that stage (p = 0.0001), race (p = 0.03), tumor morphology (p = 0.02), and vascular and/or lymphatic microinvasion (p = 0.001) were statistically significant in their association with survival. Logistic regression analysis confirmed these results and allowed for the estimation of 5-year survival probabilities in 16 groups of patients defined by various associations of these four factors. These estimates ranged from a high of 92% in Caucasian patients with Stage B, exophytic tumors with no vascular or lymphatic microinvasion, to a low of 14% in black patients with Stage C, nonexophytic tumors and with the presence of vascular and/or lymphatic microinvasion. Univariate analysis showed that histologic type (p = 0.0006), stage (p = 0.05) and vascular and/or lymphatic microinvasion (p less than 0.001) were significantly associated with the incidence of pelvic recurrence. Analysis of the extent of the operation revealed that the incidence of pelvic recurrence was reduced by the performance of a wide pelvic lymphadenectomy (9.4% vs. 16.4%), but the result did not reach statistical significance (p = 0.16). In conclusion, this study confirms the well-established prognostic value of the Dukes' staging classification of rectal carcinoma. Further, the analysis reveals that race, tumor morphology, and the presence or absence of lymphatic and/or vascular microinvasion significantly influence outcome. By associating these four statistically significant and independent variables, the prognosis for any individual patient can be estimated more precisely than by using Dukes' staging alone.(ABSTRACT TRUNCATED AT 400 WORDS)

Adjuvant postoperative radiation therapy for colonic carcinoma.

One hundred thirty-three patients with Stage B2, B3, and C colonic carcinoma had resection for curative intent followed by adjuvant postoperative radiotherapy to the tumor bed. The 5-year actuarial local control and disease-free survival rates for these 133 patients were 82% and 61%, respectively. Stage for stage, the development of local regional failure was reduced for patients receiving postoperative radiotherapy compared with a historic control series. Local recurrence occurred in 8%, 21%, and 31% of patients with Stage B3, C2, and C3 tumors who had radiation therapy, respectively, whereas the local failure rates were 31%, 36%, and 53% in patients treated with surgery alone. There was a 13% and 12% improvement in the 5-year disease-free survival rate in the patients with Stage B3 and C3 lesions who had radiotherapy compared with the historic controls. For patients with Stage C disease, local control and disease-free survival rates decreased progressively with increasing nodal involvement; however, local control and disease-free survival rates were higher in the patients who had radiotherapy than in those who had surgery alone. Failure patterns in the patients who had radiotherapy did not show any notable changes compared with those for patients who had surgery alone. Postoperative radiation therapy for Stage B3, C2, and C3 colonic carcinoma is a promising treatment approach that deserves further investigation.

Pelvic and sacropelvic exenteration for locally advanced or recurrent anorectal cancer.

Postirradiation "fixed" anorectal tumors are often considered incurable. Since 1980, we have carried out 12 pelvic and seven sacropelvic exenterations for this problem (adenocarcinoma, 18; squamous cancer, one). Nine tumors were primary; ten were recurrent (five after an anterior resection and five after an abdominoperineal resection). Prior irradiation ranged from 3000 to 12,000 rad (30 to 120 Gy). Four patients had synchronous distant metastases; three died of disease (one with local recurrence), and the fourth patient has been living with disease (distant metastasis). Fifteen patients (four with B2 tumors and 11 with Astler-Coller C2 disease) had no extrapelvic disease. One patient died of postoperative complications; two others died free of disease. Three of the 15 patients died of disease (all with local recurrence), and one has been living with disease (local recurrence). Eight (53%) of 15 patients have been living free of disease 12+ to 53+ months. The results suggest that many patients with fixed postirradiation anorectal tumors may be salvaged by aggressive surgery.

Multiparameter Evaluation of the Expression In Situ of Normal and Tumor-Associated Antigens in Human Colorectal Carcinoma<xref ref-type="fn" rid="FN1">2</xref>

The immunoreactivity of a panel of monoclonal antibodies (MoAb) was studied in a series of patients with colorectal carcinomas to test the association of antigen expression with other parameters such as histopathologic stage, differentiation, and clinical outcome. Low-level binding to normal tissue and high-level binding to malignant tissue were observed with MoAb defining, respectively, a gastrointestinal cancer antigen (GICA), Leb (distal colon only), A, H type 2 antigen, X-like antigen, and the 200-kilodalton (Kd) protein of carcinoembryonic antigen (CEA). The degree of histologic differentiation correlated with the expression of Lea antigen, A, and Y haptens, whereas a progressive loss of these antigens coincided with loss of differentiation. Two undifferentiated carcinomas expressed only two, H type 2 antigen and a highly glycosylated protein of 20-50 Kd, of the 14 antigens investigated. An interesting, but not significant, association between Leb antigen expression and more extensive disease was found: Whereas 71% of Dukes C tumors were positive for Leb, only 48% of patients with Dukes A and B2 tumors showed the presence of Leb antigen. On the other hand, the presence of B72.3-defined antigen is significantly associated with an earlier stage of disease. Chi-square tests to assess the association of antigen positivity with disease recurrence indicated a significant binding association with tumor recurrence over a broad range of percent positive cells for two MoAb defining different determinants of GICA. Similar associations, but over a narrow range of positive cells, were found for H type 2 antigen and the 200-Kd protein of CEA.

Prognostic Factors in Localized Prostatic Carcinoma

Serial histological sections were performed in 54 radical prostatectomy specimens in an attempt to identify prognostic factors responsible for dissemination of prostatic cancer. Factors considered in the study included clinical versus pathological staging, histological grading of the biopsy specimen compared to the final pathological result, intraprostatic tumor distribution and deoxyribonucleic acid analysis of the tumor by flow cytometry in the last 33 cases. In patients with clinical stages A2 and Bl disease pathological findings were in accord in 78 per cent (11 of 14). However, only 3 of 40 patients with clinical stage B2 tumor had pathological stage B2 disease. Histologically, 72 per cent of the tumors were bilateral. Microscopic involvement of the capsule per se did not appear to influence lymph node invasion, since only 1 of 27 patients with microscopic capsular involvement had pelvic lymph node raetastasis. However, 9 of 13 patients with seminal vesicle involvement had pelvic lymph node metastasis. The addition of flow cytometry to the Gleason score improves the predictive value of histological grade in higher stage lesions.

Absence of a relationship of size of primary colon carcinoma with metastasis and survival.

This retrospective study analysed the relationship of tumor size to regional and systemic metastasis and to survival according to stage of disease. Colon cancers (391 cases) that were treated surgically at M. D. Anderson Hospital from 1955 to 1975 were reviewed. Staging of disease was based on the Astler-Coller modification of Dukes' staging classification. The mean diameters (cm +/- s.e.m.) of Dukes' B1, B2, C2 and D tumors were 4.47 +/- 0.34 (n = 46), 6.61 +/- 0.29 (n = 147), 5.39 +/- 0.23 (n = 71) and 5.78 +/- 0.24 (n = 120), respectively. The mean diameter of Dukes' B2 tumors was significantly greater than C2 (P less than 0.001) and D (P less than 0.05) tumors. Within stage B and C, size of the primary tumor showed no relationship to five year adjusted survival. Our findings suggest that colon carcinoma metastasis and survival are independent of tumor size. Because tumor burden does not account for distant disease, specific tumor cell phenotypes and biological processes are probably more important in determining metastatic disease.

Operable Prostatic Carcinoma: Correlations Among Clinical Stage, Pathological Stage, Gleason Histological Score and Early Disease-Free Survival

We investigated the relationships among clinical and pathological stages, Gleason histological score and early disease-free survival of 75 patients with localized prostatic carcinoma treated by radical prostatectomy. Carcinoma was confined histologically to the prostate in 81 per cent of the patients with clinical stage A2, 79 per cent with B1N, 38 per cent with B1 and 0 per cent with B2 tumors. The Gleason score correlated directly with clinical and pathological stages, estimated extent of intraprostatic tumor and invasive capacity of the primary tumor. Of the tumors with a Gleason score of 8 or more 81 per cent extended beyond the prostatic capsule. Of 12 patients who suffered distant metastases 9 had tumors that extended beyond the prostatic capsule and 5 had tumors with Gleason scores of 8 or more.

Failure patterns following curative resection of colonic carcinoma.

To identify patterns of failure following curative resection of colonic (nonrectal) carcinoma, the medical records of 533 patients undergoing resection with curative intent were reviewed. The overall local failure rate was 19% (102/533 patients) with 32 patients having local failure alone and 70 patients having concurrent local failure and distant metastases. The incidence of local failure rose with advancing stage of disease. Tumors staged B3, C2, and C3 had local failure rates in excess of 30%. Local failures occurred predominantly in tumor bed and adjoining structures (82%) and not by regional nodal failure (18%). One hundred thirty-one patients (25%) developed distant metastases. One hundred ten patients (84%) failed in the abdomen-liver, peritoneal seeding, para-aortic, or portahepatic lymph nodes. Patients with Stage B3, C2, and C3 tumors were found to have abdominal failure rates (excluding local failure) of greater than 20%. The highest failure rates in the liver were in Stage C2 and C3 patients in which the subsequent development of liver metastases was 29% and 31%, respectively. In Stage C3, peritoneal seeding and abdominal lymph node failure occurred in 18% and 14% of the patients, respectively.

Changing Concepts in the Treatment of Nonseminomatous Germ Cell Tumors of the Testis

The development of effective chemotherapy for advanced nonseminomatous germ cell tumors of the testis has changed dramatically the outlook for this once uniformly fatal disease. We reviewed our experience with changing modalities of therapy during a 7-year period in the treatment of 152 patients with all stages of testis tumor. Survival rates have increased from 84 per cent for patients with stage A, B1 or B2 tumors treated with sandwich irradiation therapy and retroperitoneal lymph node dissection to 100 per cent for patients with node dissection with or without chemotherapy. Survival rates continuously free of disease for patients with advanced (stage B3 or C) disease have increased from 53 per cent in 1975 to 1977 to 82 per cent by the addition of platinum-based polychemotherapy and judicious lymphadenectomy. A unified plan of management for patients with low stage and advanced stage nonseminomatous testicular tumors has evolved.

Pelvic Lymph Node Metastasis from Prostatic Cancer: Influence of Tumor Grade and Stage in 452 Consecutive Patients

During the last decade 452 patients have undergone pelvic lymphadenectomy as a staging procedure for apparently localized prostatic cancer. Of these patients 105 (23 per cent) had pelvic node metastasis. Node involvement occurred in no patient with a stage A1, 24 per cent with stage A2, 12 per cent with stage B1, 28 per cent with stage B2 and 53 per cent with stage C tumor. Correlation with tumor grade revealed nodal metastasis in 10 per cent of the patients with well differentiated tumors, 24 per cent with moderately differentiated lesions and 54 per cent with poorly differentiated tumors. The incidence of positive nodes is low enough to preclude lymphadenectomy in patients with stage A1 (0 per cent) and well differentiated stage B1 tumors (4 per cent), and high enough to assume metastatic disease without lymphadenectomy in those with poorly differentiated stage C tumors (93 per cent). All other patients with apparently localized prostatic cancer should undergo a staging pelvic node dissection before definitive treatment.

Bladder cancer in men and women treated by radiation therapy and/or radical cystectomy

Four-hundred fifty-one patients with bladder cancer, 348 men and 103 women, were treated by radiation therapy and/or radical cystectomy during the last two decades at Memorial Sloan-Kettering Cancer Center. Radical cystectomy alone was the treatment in 98 men and 39 women. Radical radiation therapy to an average tumor dose of 6,000 rad in six weeks was given to 79 men and 30 women ± one year before salvage cystectomy was done for recurrent or persistent tumors. Planned preoperative irradiation was delivered to the true pelvis either 4,000 rad in four weeks in 95 men and 24 women or 2,000 rad in one week in 76 men and 10 women ± six weeks and two days, respectively, before radical cystectomy. Over-all survival and recurrence results in both sexes were similar; 40 per cent of men and 36 per cent of women were alive at five years without recurrence, 45 per cent of men and 48 per cent of women died in five or more years with local and/or distant recurrences, and 21 per cent of men and 15 per cent of women died before five years from causes other than cancer recurrence. Higher five-year survival for high clinical stage B 2 to D 1 tumors was noted similarly in the irradiated men (30 per cent) and women (37 per cent) than in the cystectomy alone patients (19 per cent in men and 4 per cent in women). Similar survival rates (52 to 57 per cent) were observed in men and women with low clinical stage O to B1 tumors treated with or without irradiation.

Differences in Pathological Characteristics and Prognosis of Clinical A2 Prostatic Cancer from A1 and B Disease

A retrospective study was done of 53 cases of clinical stages A1 to B2 prostatic carcinomas staged by pelvic lymphadenectomy. The study compared the histologic differentiation, degree of lymphocytic infiltration, incidence of lymph node metastases and type of cellular response of clinical stage A2 to stages A1 and B disease. The available data pertaining to the incidence and survival of patients with stage A2 prostatic carcinoma were analyzed.Our study indicates that 1 of every 3 unsuspected carcinomas is of clinical stage A2. The stage A2 tumors are diffused, with a higher degree of undifferentiation and a higher incidence of lymph node metastases than tumors classified clinically as stages A1 and B1. Also the survival of patients with clinical stage A2 tumors is lower than the survival of patients with clinical stage B1 disease. Clinical stage A2 tumors are more advanced biologically than clinical stage B1 tumors.

Bladder cancer: results of radiation therapy in 384 patients.

Between 1957 and 1972, 384 patients with bladder cancers were treated initially with megavoltage radiation therapy. Actuarial five-year survival ranged from 35 to 42% for Stages A and B1 tumors, and was 35, 22 and 7%, respectively, for Stages B2, C and D carcinomas. Approximately 30-40% of deeply invasive tumors confined to the bladder can be controlled with radiation therapy alone, directed solely to the bladder itself.

The Present Status of Radical Prostatectomy for Stages A and B Prostatic Cancer

The natural history of prostatic cancer is incompletely understood. Small cancers may have a very slow or rapid growthrate, and the majority are differentiated. Cells may leave the prostate by blood or lymph without penetrating capsule or invading the seminal vesicles. The predication of latency or of biologic activity in any givne case is impossible. Stage A cancer should be separated into A1 (focal) and A2 (diffuse). Stage A1 cancer that is low grade is best lfet alone. Stage A2 cancer and high grade cancer probably should be treated by megavoltage radiation. Stage B includes many cancers that are microscopically stage C. If this stage is separated into clinical stage B1 (tumors grossly involving less than one lobe), and B2 (tumors involving one lobe or more) the underestimation of microscopic extent in B1 will be less than in 10 per cent of the cases. In clinical stage B2 cancer, 50 per cent are microscopically stage C. Radical prostatectomy for cure should be limited to clinical B1 cases without distant spread. It is not a cure-all, but it provides the best 15-year survival rate more completely, more quickly, less expensively, and with fewer discomforts than other methods. The alternative options are no treatment, endocrine treatment, and radiation. The first is risky in many instances and may allow an ac-ive cancer to get out of control. The second rarely destroys all of the cells in the total cell population and gives one a false sense of security. The last should be reserved for cases well beyond stage B1, but without distant metastases, where its usefulness exceeds that of radical excision.