Biomedical subjects
Publications and source records attributed to D F Paulson.
Patients with margin positive disease after radical prostatectomy are prognostically disadvantaged. The question of postoperative adjunctive radiotherapy in these patients is controversial. A retrospective study suggested that adjunctive radiation therapy reduced the local recurrence rate but did not alter survival.
The pathologic material and medical records of 76 patients with primary upper urinary tract carcinomas were reviewed to identify the role of grade and stage in predicting survival; to determine any differences in survival between ureteral and renal pelvic carcinoma; to understand the role of local therapy in low grade, low stage tumors; and to establish the usefulness of adjuvant therapies in metastatic disease. Kaplan-Meier survival curves with Cox-Mantel analysis for statistical significance revealed both grade and stage to be excellent predictors of survival. No differences in survival were noted between renal pelvic and ureteral carcinomas for equivalent stage tumors. For low grade, low stage tumors, although there was an increased risk of local recurrence with local therapy, there were no differences in survival between patients treated with local therapy or radical surgery. Finally, cisplatin-based chemotherapy seemed to improve survival in patients with metastatic disease.
A total of 441 stage T1-2N0M0 and 11 stage T1-2N0M0 cancer patients with an elevated acid phosphatase level only, and 18 stage T1-2N+M0 cancer patients underwent radical prostatectomy. Analysis of the 441 stage T1-2N0M0 cancer patients demonstrated that failure and survival were a function of the disease being organ-confined, specimen-confined or margin-positive, with 10-year failure rates of 12, 30 and 60%, respectively. Of the patients with positive margins 44 were and 79 were not irradiated postoperatively. Postoperative radiation produced no survival advantage. No difference in interval to failure or of survival could be identified between 105 patients whose disease was diagnosed by transurethral resection and 328 who had a palpable abnormality. Eleven patients had negative bone and node findings but they had an elevated acid phosphatase level. All 8 patients not treated with immediate androgen deprivation failed within 36 months.
In an effort to determine the impact of a delayed diagnosis in testicular cancer the records of 148 patients with a known interval of delay were reviewed. The over-all mean symptomatic interval of this population was 21.1 weeks and did not change significantly during an 18-year review period. An increased symptomatic interval correlated with an increased presenting stage of disease for nonseminoma and a delay of greater than 16 weeks strongly (p equals 0.002) lowered survival for these patients during the study interval. However, the symptomatic interval was not significantly associated with stage for seminoma patients nor did the symptomatic interval influence survival for these patients. Further analysis of the nonseminoma patients revealed that delay strongly affected survival (p equals 0.001) in the pre-cisplatin era (1970 to 1978) but it was less pronounced (p equals 0.262) in the cisplatin era (1979 to 1987). Despite an attenuation of the effect of delay in the current era of effective chemotherapy, deaths still occur due to delay in diagnosis and programs to lessen delay, such as testicular self-examination, and patient and physician education, are strongly encouraged.
A group of 159 patients previously reported as having margins positive for disease after radical prostatectomy with or without adjunctive postoperative radiation was reanalyzed to determine whether the reported benefit did indeed exist. Upon re-examination of the 159 patients 15 were identified who did not receive radical prostatectomy but who were analyzed as if they had received this therapy. An updated review of the total pool of 159 patients with analysis as to failure, death of any cause or death of prostatic cancer demonstrated no benefit of postoperative radiation therapy for margin positive disease. Exclusion of patients who did not receive radical prostatectomy and analysis as described also failed to identify any benefit of postoperative adjunctive radiation therapy.
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A case of prostate cancer in which the parotid gland was the sole site of metastatic disease is presented. Special immunohistochemical stains of the excisional biopsy allowed for rapid, accurate diagnosis and appropriately directed successful therapy.
Of 244 patients with testis cancer seen between January 1970 and December 1987 (mean followup 70 months) 88 (36.1%) experienced 1 or more early complications (within 1 year), while 16 (6.6%) had a late (greater than 1 year) complication. Chemotherapy-related complications occurred in 55 of 141 patients (39%), including 6 (4.3%) treatment-related deaths. Chemotherapy-related complications were correlated to the initial extent of disease (p equals 0.021) and to more than 4 cycles of cisplatin-based therapy (p equals 0.001). Retroperitoneal lymphadenectomy-related complications occurred in 48 of 148 patients (32.4%) without surgical mortality and were not statistically increased in those performed after chemotherapy. Kidney loss occurred in 6 patients (4.1%) after retroperitoneal lymphadenectomy. Nine of 110 patients (8.2%) treated with radiotherapy experienced an early therapy-related complication, while late complications included 3 gastrointestinal strictures requiring surgical intervention 8 to 10 years after radiotherapy. Only 1 secondary malignancy (other than contralateral testis cancer) was discovered in this review. Initial extent of disease was the best predictor for over-all complication rate and higher over-all complications were noted in the cisplatin era (1979 to 1987) but these associations were not necessarily present for complication rates of individual therapies.
A series of 145 patients with T1-2NOMO prostatic carcinoma underwent radical prostatectomy. Specimens were analysed by Gleason sum and categorised according to whether the disease was organ-confined, specimen-confined or margin-positive. The failure of treatment was indicated by elevation of acid phosphatase, by the appearance of biopsy proven local disease or distant nodal disease, or by parenchymal or nodal disease by any imaging modality. Analysis of the data demonstrated that the outcome of surgical intervention was related to the anatomical extent of disease. The Gleason sum was related to the extent of disease and predicted the probability of disease outside the organ of origin.
A total of 76 patients (18 with stage A1 and 58 with stage A2 cancer) underwent radical perineal prostatectomy. No perioperative deaths occurred and no patient suffered rectal injury or was incontinent postoperatively. Five patients (3 with stage A1 and 2 with stage A2 disease) had negative surgical specimens, while 6 (4 with stage A1 and 2 with stage A2 cancer) had a single microscopic focus in the radical prostatectomy specimen. Outcome was assessed by first evidence of disease recurrence as a function of the Gleason sum and the local anatomical extent of disease. Of 41 patients 4 (9.7 per cent) with organ-confined disease failed at 2.5, 2.6, 4.3 and 11.9 years. None of 11 patients with specimen-confined disease failed, and 6 of 24 (25 per cent) with positive margins failed at 0.9, 1.2, 2.1, 3.1, 3.2 and 8.0 years. Radiation after an operation for margin-positive disease did not seem to alter the incidence of failure. The distribution frequency of the Gleason sum was noted to shift to a higher total sum as the extent of local disease increased. Kaplan-Meier analysis of the failure rate of patients with organ-confined and organ-nonconfined disease with a Gleason sum of 7 or less versus greater than 7 demonstrated an advantage for those with a sum of 7 or less (p less than or equal to 0.018).
Flow cytometry was used to evaluate 88 deparaffinized radical prostatectomy specimens to compare deoxyribonucleic acid ploidy in prostatic adenocarcinoma as a predictor of disease progression with other well documented predictors of clinical recurrence. Aneuploidy, Gleason grade and seminal vesicle involvement were nonindependent variables, and all correlated to statistical significance with disease recurrence. The incidence of aneuploidy in the total population was 51 of 88 (58 per cent). Aneuploidy was found in 25 of 28 primary tumors (89 per cent) from patients who subsequently had recurrent disease. Aneuploidy was noted in 40 of 59 specimens (68 per cent) exhibiting seminal vesicle involvement, compared to 11 of 29 (38 per cent) without seminal vesicle involvement (p less than 0.01). The probability of an interval free of disease of 60 months was calculated by Kaplan-Meier analysis to be 85 per cent in diploid specimens compared to 9 per cent in aneuploid specimens (p less than 0.001), and 87 per cent in the absence of seminal vesicle involvement compared to 28 per cent in the presence of seminal vesicle involvement (p less than 0.003). The probability of remaining free of disease in patients exhibiting concomitant diploidy and seminal vesicle involvement (17) was 73 per cent compared to 8 per cent in those with aneuploid specimens and seminal vesicle involvement (p less than 0.004). The incidence of recurrence in patients with Gleason sums of 7 or less was 22 per cent compared to 62 per cent in patients with Gleason sums of greater than 7. There was a 29 per cent incidence of recurrence in intermediate grade tumors (Gleason sum 5 to 7) but only 5 per cent of the patients with intermediate grade diploid tumors had recurrent disease. In conclusion, the recognition of a deoxyribonucleic acid aneuploid stem line in a primary prostatic adenocarcinoma is correlated statistically with a greater likelihood of seminal vesicle invasion and subsequent development of recurrent disease. The markedly increased probability of remaining free of disease in diploid patients, even in the presence of seminal vesicle involvement, suggests that routine flow cytometric analysis in prostatic adenocarcinoma would significantly enhance prognostic stratification.
Despite the clear indications for an inguinal approach, reports indicate that up to 53 per cent of all testicular tumors are diagnosed or initially treated in a manner inconsistent with the classical radical orchiectomy. Of 462 evaluable patients from the Testicular Cancer Intergroup Study 47 (10.2 per cent) had undergone a nonclassical orchiectomy as the initial surgical management. This group was analyzed separately to determine the prognostic significance of needle aspiration, open biopsy, a scrotal approach and tumor contamination. Within this group of patients, those who received no adjuvant chemotherapy exhibited no increase in local or distant recurrence. While the recurrence rate similarly was not adversely affected by even gross tumor contamination, this subset underwent significantly more aggressive local surgical salvage (p less than 0.01), with scrotectomy procedures found to be of probable therapeutic value. While not to be condoned, we conclude that deviations from the classical orchiectomy, when followed by appropriate surgical management and close observation, can be of little clinical impact.
In the early 1970s, a multicentered cooperative group effort was established by urologists and oncologists to examine the relative disease control provided by surgery, radiation therapy, or observation for patients with localized or regional disease. The data derived from this trial were controversial because they 1) did not support previous concepts regarding the relative impact of treatment and 2) raised provocative questions as to the interpretation of previous institutional reports that promoted a single treatment modality. The data from the randomized trial demonstrated that: 1) bipedal lymphangiography could not demonstrate accurately the presence or absence of microscopic involvement of pelvic lymphatic structures, 2) treatment selection should be based on the anatomic distribution of disease; 3) a clinician's use of first appearance of local or distant disease in a patient who was supposedly disease free after receiving the chosen therapy served as an accurate way to define the impact of the initial treatment; 4) radical surgery was more effective than radiation therapy in controlling disease that was clinically confined to the primary organ of origin; and 5) the apparent disease control produced by radiation on large-volume, localized disease might only reflect the natural history of the disease.
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Between 1979 and 1984, 195 evaluable patients were entered in an international multicenter study comparing two regimens for patients with completely resected pathological Stage II testicular cancer (that is, with positive retroperitoneal lymph nodes). All patients had undergone orchiectomy and dissection of the retroperitoneal lymph nodes. They were randomly assigned to be treated with two cycles of immediate adjuvant cisplatin-based chemotherapy or to be observed monthly with treatment at relapse. The median follow-up period was four years. Of the 97 patients assigned to adjuvant chemotherapy, 6 (6 percent) had a recurrence; however, only 1 had received adjuvant chemotherapy before the recurrence. Three died (one of testicular cancer), and 94 of the 97 survived. Of the 98 patients who were observed, 48 (49 percent) had a relapse. However, almost all patients with relapses were effectively treated, and 93 of the 98 are alive and disease-free; 3 have died of testicular cancer. No identifiable factors were strongly associated with the risk of relapse. We conclude that two courses of cisplatin-based adjuvant chemotherapy will almost always prevent relapse in pathological Stage II testicular cancer treated with orchiectomy and retroperitoneal-lymph-node dissection. However, when surgery, follow-up, and chemotherapy are optimal, observation with chemotherapy only for relapse will lead to equivalent cure rates.