Para-aortic Node Involvement Research Articles

The ability to evaluate prognostic variables on frozen section in hysterectomies performed for endometrial carcinoma

The purpose of this study was to evaluate the ability of the pathologist to assess intraoperatively the hysterectomy specimen in patients with endometrial carcinoma. The past few years have seen the definition of prognostic variables that predict the ultimate outcome of patients with endometrial carcinoma. As a result, the International Federation of Gynecology and Obstetrics (FIGO) revised the staging system to take into account such prognostic factors as grade, depth of myometrial penetration by tumor, cervical involvement, adnexal metastasis, peritoneal cytology, and involvement of pelvic and para-aortic lymph nodes. The need for node evaluation has led to considerable controversy as to whether all hysterectomies for Stage I disease should be performed by gynecologic oncologists. To help predict which patients will need node sampling, several published studies have shown that determination of depth of myometrial penetration can be accomplished by gross evaluation of the uterine specimen, and even more accurately on frozen section. These studies recorded excellent results, but were limited to evaluation by pathologists with specific expertise in gynecologic pathology. The current study evaluated the ability to assess tumor grade, depth of invasion, and presence of cervical invasion by intra-operative evaluation of sixty hysterectomy specimens from patients with clinical Stage I disease. The gross and frozen section reports used for this study were produced by anatomic pathologists ranging in experience level from lecturer to professor, with varying levels of experience in gynecologic pathology. Our results indicate that the level of experience of the pathologist does not affect the ability to accurately assess the specimen for the parameters described. This, in turn, allows the surgeon to correctly determine the need for lymph node sampling in 94% of cases.

Three-dimensional treatment planning for para-aortic node irradiation in patients with cervical cancer

Three-dimensional treatment planning has been used by four cooperating centers to prepare and analyze multiple treatment plans on two cervix cancer patients. One patient had biopsy-proven and CT-demonstrable metastasis to the para-aortic nodes, while the other was at high risk for metastatic involvement of para-aortic nodes. Volume dose distributions were analyzed, and an attempt was made to define the role of 3-D treatment planning to the para-aortic region, where moderate to high doses (50–66 Gy) are required to sterilize microscopic and gross metastasis. Plans were prepared using the 3-D capabilities for tailoring fields to the target volumes, but using standard field arrangements (3-D standard), and with full utilization of the 3-D capabilities (3-D unconstrained). In some but not all 3-D unconstrained plans, higher doses were delivered to the large nodal volume and to the volume containing gross nodal disease than in plans analyzed but not prepared with full 3-D capability (3-D standard). The small bowel was the major dose limiting organ. Its tolerance would have been exceeded in all plans which prescribed 66 Gy to the gross nodal mass, although some reduction in small bowel near-maximum dose was achieved in the 3-D unconstrained plans. All plans were able to limit doses to other normal organs to tolerance levels or less, with significant reductions seen in doses to spinal cord, kidneys, and large bowel in the 3-D unconstrained plans, as compared to the 3-D standard plans. A high probability of small bowel injury was detected in one of four 3-D standard plans prescribed to receive 50 Gy to the large para-aortic nodal volume; the small bowel dose was reduced to an acceptable level in the corresponding 3-D unconstrained plan. An optimum beam energy for treating this site was not identified, with plans using 4, 6, 10, 15, 18, and 25 MV photons all being equally acceptable. Attempts to deliver moderate or high doses (50–66 Gy) to this region should be made only after careful analysis of the plan with techniques similar to those employed in this study.

Patterns of pelvic and paraaortic lymph node involvement in ovarian cancer

One hundred eighty patients with ovarian cancer underwent complete pelvic lymphadenectomy ( n = 75) or pelvic and paraaortic lymphadenectomy ( n = 105). Twenty-one patients underwent a preoperative biopsy of the scalene lymph nodes. The incidence of positive lymph nodes was 24% in stage I ( n = 37), 50% in stage II ( n = 14), 74% in stage III ( n = 114), and 73% in stage IV ( n = 15). Of the 105 patients who underwent pelvic and paraaortic lymphadenectomy, 13 (12%) had positive pelvic and negative paraaortic nodes and 10 (9%) had positive paraaortic and negative pelvic nodes. Positive scalene nodes were found in four patients (19%) later shown to have stage IV disease. One hundred forty patients were studied for number of involved nodes and node groups, size of nodal metastases, residual tumor, and survival. Of the 81 patients with positive nodes, most had only one or two positive node groups or one to three positive individual nodes. A few patients had seven to eight involved node groups with up to 44 positive nodes. Greater numbers of positive nodes were found in stage III than stage IV. The size of the largest nodal metastasis was not related to the clinical stage or survival, but did correlate with the number of positive nodes. Stage III patients with no residual tumor had a significantly lower rate of lymph node involvement than those with tumor residual ( P < 0.01). Actuarial 5-year survival rates of patients with stage III disease and no, one, or more than one positive nodes were 69, 58, and 28%, respectively.

Effect of Paraaortic Lymphadenectomy on 5‐Year Survival in Early Stage Cervical Cancer

This study includes 278 patients with Stages 1 and 2 cervical cancer subjected to type 3 hysterectomy and lymphadenectomy. The incidence of lymph node metastasis and effect of paraaortic lymphadenectomy on 5-year survival were evaluated. The overall incidences of pelvic and paraaortic lymph node involvement were 24.1% and 8.0%, respectively. The overall 5-year survival rate was 83.8%. The 5-year survival of patients subjected to both pelvic and paraaortic lymphadenectomy was found to be 84.6%; the figure was 80.9% for patients subjected to only pelvic lymphadenectomy. No statistical difference in survival was found between patients with and without paraaortic lymphadenectomy.

Ovarian serous borderline tumors with stromal microinvasion: A report of 21 cases

The clinicopathologic features of 21 cases of otherwise typical serous borderline tumors that contained small foci of stromal invasion were reviewed. The mean age of the patients was 43 years and six of them were pregnant at the time of diagnosis. Nineteen tumors were stage I, one was stage III (para-aortic lymph node involvement) and one was stage IV (parenchymal liver metastasis). The tumor invaded the stroma predominantly as individual cells or nests or clusters of cells with abundant eosinophilic cytoplasm (17 cases), as small confluent nests with a cribriform pattern (two cases) and as rounded aggregates of papillae (two cases). Seven women were treated with bilateral salpingo-oophorectomy and hysterectomy; 13 had less than bilateral oophorectomy. Of the 17 patients for whom followup data were available, 16 were without evidence of disease 1 to 11 (mean, 5.2) years postoperatively, and one patient had a serous borderline tumor with microinvasion in a conserved contralateral ovary 2.8 years postoperatively, but was well 6 months after a partial oophorectomy. These data suggest that serous borderline tumors with microinvasion have a prognosis similar to that of the usual serous borderline tumor, and that conservation of the contralateral ovary and uterus may be acceptable therapy in young women who wish to preserve their fertility.

Testicular seminoma. Results of the Yale University experience, 1964-1984.

Eighty-three testicular seminoma patients were treated with radiation therapy from 1964 through 1984. Seventy-nine (95%) of the 83 patients had early disease that included 61 Stage I, 15 Stage IIA (pelvic or paraaortic lymph node involvement less than or equal to 5 cm), and 3 Stage IIB (pelvic or paraaortic lymph node involvement greater than 5 cm) patients. The 15-year actuarial survival for this group of Stage I and II patients was 95% (+/- 5%). Stage I patients were treated with a mean paraaortic/pelvic dose of 2924 cGy and only one patient developed recurrent disease. This recurrence was at the margin of the radiation field and probably represents a marginal miss. The Stage IIA patients were treated with slightly higher doses (mean, 3335 cGY) to the paraaortic/pelvic region and there were no recurrences. The three Stage IIB patients received tumor doses of 3245 cGy, 4090 cGy, and 4500 cGy, respectively, and there were no recurrences. Low dose prophylactic mediastinal and supraclavicular irradiation (mean, 2320 cGy) was used in 17 (94%) of the 18 Stage II patients and there were no mediastinal or supraclavicular recurrences. Four patients presented with advanced disease (one Stage III, three Stage IV) and the only disease-free survivor was treated with cisplatinum-based combination chemotherapy and radiation therapy. Three patients developed minor complications from the radiation therapy: one patient had persistent scrotal and leg edema and two patients treated with prophylactic mediastinal irradiation had chronic low leukocyte counts. Two of the 79 Stage I and II patients developed a second malignancy: one had bronchogenic carcinoma at the margin of a mediastinal field, and one had diffuse histiocytic lymphoma both in and out of the radiation therapy fields. The 15-year actuarial probability of developing a second malignancy was 3.3%. Radiation therapy after operation is a successful treatment option for most patients with Stage I and II seminoma.

Concurrent Radiation Therapy, cis-Platinum, and Mitomycin C in Patients with Poor Prognosis Cancer of the Cervix

Nineteen patients with poor prognosis squamous cell cancer of the cervix were treated with concurrent radiation therapy (RT) and chemotherapy between February 1986 and July 1988. Treatment consisted of intravenous Mitomycin C 10 mg/m2 on days 1 and 43 and cis-platinum 50 mg/m2 on days 1, 22, and 43. All patients received external RT (5,000 cGy in 28 fractions) and brachytherapy (6,000 cGy to point A.) Additionally, patients with paraaortic lymph node involvement received 4,000 cGy paraaortic RT. The toxicity of this regimen was assessed using Southwest Oncology Group criteria. Toxicity was acceptable and did not significantly delay RT. In addition, complete pelvic response was noted in 18 of 19 (95%) patients within month of completion of therapy and maintained despite distant metastases. At the time of this report, 14 of the 19 patients are alive 9-22 months after initiation of treatment. Chemotherapy with cis-platinum and Mitomycin C concurrently with RT is feasible in patients with locally advanced cervical cancer. Further follow-up of our patients is required to determine whether this regimen will have a favorable impact on survival.

1 The spread of ovarian cancer

Spreading intra-abdominally, ovarian cancer reaches the upper abdomen relatively quickly. Metastases result from the implantation of cells from the primary tumour or, perhaps, may arise de novo from the peritoneal epithelium. The tumour also spreads via the lymphatics directly to the pelvic nodes, directly to the para-aortic nodes, or directly to both. Pelvic nodes were positive in 57.9% of patients of all stages. The highest incidence, 70.4%, was found in Stage III. The percentage of positive para-aortic nodes was lower, namely 50.9% overall incidence and 67.6% in Stage III. Concerning the concomitant involvement of pelvic and para-aortic nodes, 40.4% of patients with positive pelvic nodes also had positive para-aortic nodes. Of patients with negative pelvic nodes, 36.8% also had negative para-aortic nodes. Of all patients, 12.3% had positive pelvic nodes and negative para-aortic nodes. Conversely, 10.5% of all patients had positive para-aortic nodes and negative pelvic nodes. There is a significant association between the involvement of the diaphragm and that of the pelvic and para-aortic nodes. Of those patients with tumour deposits on the diaphragm, 84.4% also had positive retroperitoneal nodes. Conversely, 55.9% of patients with positive nodes also had tumour deposits on the diaphragm. This means that ovarian cancer spreads almost simultaneously in two ways: intra-abdominally and retroperitoneally. Surgical treatment must address both modes.

Significance of para-aortic node irradiation in the treatment of cervical cancer

In 1980, we introduced para-aortic node irradiation as a part of our treatment of cervical cancer. Eighty-six patients with cervical cancer were selected for such treatment, based on histologic or radiologic criteria for lymph node involvement. We delivered 45 Gy to the para-aortic nodes in 5 weeks. Comparison studies on the prognosis and on the incidence of side effects with and without para-aortic node irradiation were carried out on a total of 783 patients who had invasive cervical cancer and were treated from 1975 to 1984. For patients in stages Ib and II who met, or before 1980 would have met, our criteria there was no significant difference in survival for those in stage Ib, but in stage II the para-aortic node irradiation group did significantly better (P less than 0.01). For the entire series of patients, for all stages from Ib to IV, the prognosis for the group treated after the introduction of para-aortic node irradiation was superior, with a statistically significant difference from the prognosis for patients treated before the introduction of this mode (Ib, P less than 0.05; II, P less than 0.01; III, P less than 0.01; IV, P less than 0.05). None of the patients had severe complications after para-aortic node irradiation. We conclude that, by irradiating the para-aortic nodes, we can improve the prognosis of cervical cancer patients who may have para-aortic node involvement, a situation which formerly was considered hopeless.

Combined Chemotherapy and Radiation Therapy for Advanced Carcinoma of the Cervix

Ten patients with advanced squamous cell carcinoma of the uterine cervix received induction chemotherapy with cis-platinum, mitomycin-C, vincristine, and bleomycin (BOMP) over a 5 week period, followed by radiotherapy with concomitant weekly cisplatinum. Two patients were FIGO stage I-B barrel-shaped, five were stage II-B, and three were III-B. All patients responded to induction chemotherapy with five complete and five partial responses. At the completion of radiation therapy, nine patients had negative biopsies. One patient never reached a complete response and died of distant metastasis. Another underwent total exenteration for a central recurrence and was found to have microscopic paraaortic lymph node involvement. A third recurred in the parametrium. Two patients with barrel-shaped tumors underwent extrafascial hysterectomies; both had negative specimens and tolerated surgery well. Although follow-up is short, this new approach for advanced carcinoma of the cervix yielded excellent results and was well tolerated.

Extended-field radiation therapy for prostatic carcinoma with para-aortic lymph node metastasis.

The finding of involvement of para-aortic lymph nodes in patients with adenocarcinoma of the prostate has been considered so ominous that further therapy has often only been palliative. What is the proportion of patients with carcinoma of the prostate with regional metastasis limited to the infra-diaphragmatic lymph nodes who might be cured or at least offered long-term progression-free survival by aggressive treatment? From June 1970 through March 1983, 114 patients were treated with curative intent for adenocarcinoma of the prostate, clinical Stage III, at the Medical College of Wisconsin Affiliated Hospitals. Twenty-three of these patients had evidence of metastasis to the para-aortic lymph nodes. These patients were treated aggressively with external radiation therapy to the entire pelvis and para-aortic region. The median dose to the prostate was 70 Gy, the pelvis 54 Gy, and the para-aortic region 50 Gy. The median period of observation after treatment was 53.5 months. The actuarial survival was 90% at 5 years and progression-free survival was 73% at 5 years. The rate of major complications was 4.3%. Although the number of patients is small, the data suggest that extended field radiation therapy can result in prolonged progression-free survival and perhaps cure many patients with juxtaregional dissemination of adenocarcinoma of the prostate.

Para-aortic node biopsy in cervical and endometrial cancers: Does it affect survival?

Two hundred ten patients with endometrial and cervical carcinoma had para-aortic node biopsies. Nineteen of the 210 patients (9.0%) had positive para-aortic nodes. These 19 patients received pelvic irradiation, and 18 patients received para-aortic irradiation. The incidence of para-aortic nodal involvement in cervical carcinoma was directly related to the stage of the disease. Eleven of the 12 patients with cervical carcinoma and positive para-aortic nodes received both pelvic and para-aortic irradiation. Three of these patients are alive without disease, resulting in a survival rate of 25%. These patients are surviving for 16, 30, and 41 months. The incidence of positive para-aortic nodes in endometrial adenocarcinoma was related to the uterine length and the histologic grade. The survival rate for patients with endometrial adenocarcinoma and positive para-aortic nodes in this study was 57.1%. Four patients have survived for 1, 30, 60, and 71 months. There were no surgical deaths or radiation therapy complications directly attributable to para-aortic biopsy or irradiation.

Metastatic patterns of prostatic cancer. Correlation between sites and number of organs involved.

Prostatic cancer in 1885 autopsy cases was classified according to the number of organs involved in metastasis, and a comparison was made concerning the frequency of metastasis to the various organs. The frequencies of metastasis to the lungs and para-aortic lymph nodes were low in cases with single-organ involvement (4.6% and 2.3%, respectively), but increased rectilinearly in accordance with the number of organs involved and became high in cases with metastasis to three or more organs (49.1% and 21.8% in total, respectively). On the other hand, the frequencies of local extension to the bladder and invasion of the pelvic lymph nodes were high even in cases with single-organ involvement (34.5% and 9.2%, respectively) and were not significantly changed regardless of the number of organs involved. No significant correlation was seen between pelvic and para-aortic lymph node involvement. In cases with single-organ involvement, metastasis to the lumbar spine occurred frequently, but those to the ribs, sternum, and ilium occurred less frequently. There may be multiple metastases in cases with metastases to the para-aortic lymph nodes, sternum, and ilium. The number of metastatically involved organs is useful in analyzing the mode of metastasis.

COMPUTED TOMOGRAPHY IN INVASIVE CARCINOMA OF THE CERVIX: AN APPRAISAL

The clinical staging, computed tomographic scans, and surgical findings in 42 patients with cervical carcinoma were compared prospectively to determine the accuracy and clinical utility of computed tomography in demonstrating extent of disease and involvement of paraaortic lymph nodes. Computed tomography was of limited value in stage IB and IIB tumors, but was comparable in accuracy to clinical examination in the assessment of IIB disease. Computed tomography was of value in radiation therapy and may detect unsuspected bony metastases (stage IVB). Retroperitoneal adenopathy can be detected by computed tomography with an overall accuracy of 83% and a specificity of 86%. Computed tomography is an important adjunct in determining tumor extent in more advanced disease (stages IIIB and IVB) and in detecting paraaortic adenopathy.

Survival, prognostic factors, and relapse patterns in uterine cervical carcinoma.

Between 1965 and 1979, 295 evaluable patients were treated with radiotherapy and/or surgery for invasive cervical carcinoma at the Stanford University Medical Center. The records of these patients were analyzed retrospectively with regard to survival, possible prognostic factors of freedom-from-relapse, and relapse patterns. Survival for the entire population at 5 years was 67%, with a median follow-up of 5 years. Five-year freedom-from-relapse (FFR) rates for stages I-IV were 88%, 61%, 33%, and 11%, respectively. Eighty-eight percent of all relapses occurred within 5 years. Several possible prognostic factors of FFR--including stage, histology, tumor differentiation, lymphangiogram status, treatment modality, age, presence of cervical stump, and initial serum hemoglobin value--were evaluated with a multivariate analysis. Stage was the best predictor of FFR, and lymphangiogram (LAG) status was the next most important covariate: 13 of 19 patients who showed involvement of paraaortic nodes on LAG relapsed within 1 year. There was no difference in survival or FFR between adenocarcinoma or squamous cell histologies. FFR in stage IB patients was independent of treatment modality; i.e., radiotherapy alone, surgery alone, or combined therapy. Initial serum hemoglobin (less than 12 vs. greater than 12) was not predictive of FFR or survival. Stage for stage, patients over 57 years of age tended to have better FFR than younger patients. The majority of relapses occurred centrally or at the pelvic sidewalls (58%), and future attempts to improve local control rates will rely more heavily on the individualized use of interstitial template applicators.

An evaluation of the computed tomographic scanner for the staging of carcinoma of the cervix.

Twenty patients with invasive carcinoma of the cervix (FIGO stages IB-IV) were staged by routine pelvic examination, intravenous urography, chemistry studies, and barium enema. All patients received a CT scan of the abdomen and pelvis followed by pelvic examination under anesthesia (EUA). CT agreed with EUA staging in 13 of 20 patients (65%). All patients had surgical para-aortic lymph node sampling. The sensitivity of CT for para-aortic lymph node involvement was 67% and the specificity was 92%. CT scanning is equal to other clinical staging procedures for carcinoma of the cervix. It offers the advantages of being noninvasive and visualizing tumor for the construction of radiation portals. CT is useful in the detection of para-aortic lymphadenopathy; however, the presence of normal sized or enlarged nodes makes pathologic examination, either by needle aspiration or surgery, necessary.

Endometrial cancer: Evaluation of spread and follow-up in one hundred eighty-nine patients with Stage I or Stage II disease

A retrospective study was undertaken of 189 patients with Stage I or Stage II endometrial cancer in whom selective lymphadenectomy had been performed between the years 1974 and 1981. Pelvic and para-aortic nodal involvement increased with increasing stage, grade, and depth of myometrial invasion. The incidences of pelvic and para-aortic node metastases in Stage I were 1.4% and 3.8%, respectively, while 17.6% of Stage II patients had para-aortic metastases. Mortality was significantly greater for Stage I adenosquamous carcinoma (10.5%) and papillary serous adenocarcinoma (37.5%) than for Stage I adenocarcinoma (2.2%). In Stage I, grade 3 nonrandomized cases of endometrial cancer, no significant difference in survival or morbidity occurred between those patients treated with external radiation and those who were not. Intraperitoneal or adnexal spread occurred in 12 of the 189 patients, and lymph nodes were diseased in two of these. Sixteen of 17 recurrences developed at extrapelvic sites, indicating the need for effective systemic chemotherapy in high-risk patients. The overall 5-year survival rates for Stage I and II patients were 88.0% and 83.3%, respectively.

Carcinoma of the cervix metastatic to the liver presenting with obstructive jaundice

A patient with obstructive jaundice secondary to cervical carcinoma metastatic to the liver without paraaortic lymph node involvement is presented.

Non-Hodgkin lymphoma of the testis.

Sixteen patients (median age 67 yrs.) with non-Hodgkin lymphoma of the testis were studied. Twelve of these patients had disease that was classified as local (Stages IE and IIE). Eight patients had diffuse histiocytic lymphoma, 6 had diffuse poorly differentiated lymphocytic lymphoma, 1 had both lymphoma and seminoma, and 1 had nodular poorly differentiated lymphocytic lymphoma. The overall median survival was 9.5 months. Para-aortic nodal involvement was the factor that had the strongest prognostic influence with the management methods used. Median survival without para-aortic nodal involvement was 57+ months, but with such involvement it was 6 months (p = 0.002). There is a high probability of generalized disease if lymphoma can be detected in the para-aortic nodes. For patients with Stages IE and IIE disease, radical radiation therapy is the preferred treatment. For those with disseminated disease, chemotherapy, with irradiation reserved for symptomatic and bulky localized deposits, is the recommended method of management.

Carcinoma of the endometrium.

Controversy continues as to how and when radiation therapy can best be combined with surgery in order to improve treatment results in patients, with endometrial cancer. Various prognostic factors--tumor grade, depth of myometrial invasion, size of the uterine cavity, and the presence of nodal or parametrial spread--must all be considered when planning therapy. Well-differentiated Stage IA endometrial cancers hav an excellent prognosis when treated by surgery alone. Evidence suggests, however, that all other Stage I tumors benefit from combined radiation and surgical treatment. Patients with advanced stages of disease are candidates for combined surgery and radiation or radiation alone, owing to the high frequency of pelvic node involvement. Areas of active investigation include the addition of systemic therapy in patients with Stage III disease and the evaluation of extended field radiation in patients with histologically confirmed high pelvic or paraaortic nodal involvement.