C. Eugene Carlton

Prognostic significance of lymph nodal metastases in prostate cancer

Pelvic lymph node metastases indicate a poor prognosis for patients with clinically localized prostate cancer but the significance of minimal nodal metastases still is debated. We determined the progression and cancer specific survival rates based on the extent of nodal metastases in 511 patients followed for a mean of 8.6 years (range 2.5 to 17.5 years) after bilateral pelvic lymph node dissection and irradiation therapy. The patients were divided into 4 groups based on the extent of nodal metastases: NO--negative nodes (359 patients), N1--a single microscopic positive node (37), N2--multiple microscopic positive nodes (86) and N3--grossly positive or juxtaregional nodes (29). The risks of distant metastases and of dying of prostate cancer were much greater in the 152 patients with positive nodes (N+) than in those with negative nodes (p less than 0.00005). The risk of metastatic disease at 10 years was only 31 +/- 7 per cent for the NO patients compared to 83 +/- 7 per cent for the N+ patients, and the risk of dying of prostate cancer was only 17 +/- 6 per cent at 10 years for the NO group and 57 +/- 11 per cent for the N+ patients. Patients with a single microscopic node (N1) had a pattern of progression and cancer specific mortality rate similar to patients with more extensive nodal metastases and markedly worse than patients with negative nodes. The risk of distant metastases was 80 +/- 15 per cent at 10 years for the N1 group, 84 +/- 11 per cent for the N2 group and 88 +/- 13 per cent for the N3 group, while the risk of dying of prostate cancer at 10 years was 40 +/- 19, 66 +/- 15 and 58 +/- 24 per cent, respectively. The finding of a single pelvic lymph node containing microscopic metastatic disease markedly worsened the prognosis of our patients with prostate cancer. Once prostate cancer is found within the pelvic lymph nodes the patient has systemic disease unlikely to be controlled by pelvic lymph node dissection and radiotherapy.

The Prognostic Significance of Post-Irradiation Biopsy Results in Patients with Prostatic Cancer

To evaluate the prognostic significance of post-irradiation biopsy results in patients with prostatic cancer, we reviewed the records of 803 patients who had been treated with pelvic lymph node dissection, radioactive gold seed implantation and external beam irradiation. Of the patients 124 had 1 or more biopsies within 6 to 36 months after completion of radiotherapy when there was no evidence of local or distant recurrence of tumor. Patients were followed for a mean of 64 months (range 14 to 175 months) and received no other therapy before relapse. Over-all, 43 of these patients (35 per cent) had a positive biopsy result. The incidence of positive biopsy results correlated directly with the initial stage of the tumor, ranging from 22 per cent of stage B1N to 50 per cent of stage C1 lesions. However, biopsy results did not correlate with the grade of the tumor. Local recurrence and distant metastases were much more common among patients with a positive biopsy result (p equals 0.0006). Local recurrence developed in 58 per cent of the patients with a positive biopsy by 5 years and in 82 per cent by 10 years. Of those in whom all biopsies were negative only 18 per cent had local recurrence by 5 years and 32 per cent by 10 years. Biopsy results retained their prognostic significance even among the more favorable subset of patients whose pelvic lymph nodes were negative initially and those with a normal prostatic examination at biopsy. These results indicate that a post-irradiation prostate biopsy 6 to 36 months after completion of treatment can be used to determine the efficacy of a particular radiotherapeutic regimen as well as the success or failure of radiotherapy in an individual patient.

The frequency and morbidity of local tumor recurrence after definitive radiotherapy for stage C prostate cancer.

Radiotherapy is reported to provide good control of locally advanced prostate cancer. However, few long-term studies have assessed the morbidity related to local tumor recurrence in patients treated with radiotherapy alone (without hormonal manipulation). To determine the frequency and severity of morbidity related to local recurrence we reviewed the course of all patients with clinical stage C prostate cancer treated at our institution between 1966 and 1979 with bilateral pelvic lymph node dissection, radioactive gold seed implantation and external beam irradiation therapy to the prostate. Of the 121 patients 60% died and the 40% still alive at the time of review were followed for a mean of 8.1 years (range 3.3 to 14.8 years). Over-all, 64 patients (53%) had local recurrence, which was defined as a clinical event causing signs or symptoms and was proved by biopsy. On an actuarial basis the risk of local recurrence was 43 +/- 10% (mean +/- 2 standard errors) at 5 years and 74 +/- 11% at 10 years. Any symptomatic episode requiring active intervention or causing morbidity was denoted an adverse event. There were 162 adverse events among the 73 patients (2.2 adverse events per patient): 69% of these were severe (requiring surgical intervention) and 55% were chronic (more than 3 months in duration). The most common cause of an adverse event was bladder outlet obstruction requiring transurethral resection of the prostate (44 patients); 16 patients (13%) became incontinent. Hydronephrosis developed in 24 patients (20%). Local recurrence after definitive radiotherapy for our patients with stage C prostate cancer was common and was associated with serious morbidity, frequently requiring surgical intervention. Radiotherapy alone may not be sufficient to provide long-term local control of stage C prostate cancer.

The Risk of Dying of Prostate Cancer in Patients with Clinically Localized Disease

From 1966 to 1979, 360 patients with clinical stages A2, B and C1 prostate cancer underwent staging pelvic lymphadenectomy, and completed a course of combined interstitial radioactive gold seeds and external beam radiotherapy. All patients had a normal serum prostatic acid phosphatase level and a bone scan negative for metastases. All patients were followed until death or for a mean of 7.3 years (range 1.2 to 18.25 years) for those alive at analysis. To determine the risk of dying of prostate cancer we reviewed the records of the 142 patients (39%) who died. At analysis 21% of the patients had died of prostate cancer and 17% of other known causes. The cause of death could not be determined in 4 patients (1%). Cardiovascular disease accounted for a fifth of all deaths. The actuarial risk of death of prostate cancer for all patients was 8 +/- 3% (+/- 2 standard errors) at 5 years and 30 +/- 7% at 10 years. The risk of death of all causes was 16 +/- 4% at 5 years and 46 +/- 7% at 10 years. An increased risk of cancer death was associated with established risk factors, including advanced local disease, poorly differentiated histology, pelvic nodal metastases and distant recurrence. We also noted a substantial risk of cancer death in patients who had local tumor recurrence. While previous studies have reported a relatively low incidence of cancer deaths (4 to 17%) in patients initially diagnosed with localized disease, our data suggest that prostate cancer is the major cause of mortality in such patients. Aggressive curative therapy, regardless of treatment modality, should be considered for localized prostate cancer in men with a life expectancy of 10 or more years.

Incidental Carcinoma of the Prostate at the Time of Transurethral Resection: Importance of Evaluating Every Chip

Incidental adenocarcinoma of the prostate has been divided into stage A1--less than 3 foci of well differentiated adenocarcinoma present and stage A2--3 or more foci of poorly differentiated tumor present. The clinical significance of these 2 stages has been well documented, with stage A1 lesions causing no increased mortality, while up to 30 per cent of patients with clinical stage A2 disease will have positive pelvic lymph nodes at exploration and, thus, will have surgical stage D1 tumor. Most pathology laboratories submit only a fraction of the transurethral resection chips for permanent blocks. In an effort to evaluate the over-all incidence and distribution of stages A1 and A2 lesions were began a prospective study in 1978 whereby all prostatic chips were submitted for permanent sections. A review of 500 consecutive cases of transurethral resection for clinically benign prostates before 1978 revealed 43 cases of adenocarcinoma: 10 (23 per cent) stage A1 and 33 (77 per cent) stage A2. A review of a similar series of 500 consecutive patients since 1978 revealed 71 cases of adenocarcinoma: 17 (24 per cent) clinical stage A1 and 54 (76 per cent) clinical stage A2. Thus, we found that since 178 incidental adenocarcinoma of the prostate has increased by 65 per cent and the distribution of stages A1 and A2 lesions has remained unchanged, 76 per cent of these lesions being clinical stage A2 with its much greater clinical significance. Evaluation of every chip does make a clinically significant difference in the subsequent management of patients with incidental adenocarcinoma of the prostate.

The risk of distant metastases after transurethral resection of the prostate versus needle biopsy in patients with localized prostate cancer.

Although transurethral resection of the prostate provides an effective treatment for obstructive voiding symptoms associated with prostate cancer, there is growing concern about the possible role of transurethral resection in the dissemination of this malignancy. To determine the effect of transurethral resection on the rate of development of distant metastasis, we analyzed a large series of patients (379) treated at our institution with definitive radiotherapy for localized prostate cancer that was diagnosed by either needle biopsy or transurethral prostatic resection. In our series the presence of lymph node metastasis was documented by pelvic lymph node dissection in all patients. An initial univariate analysis suggested that patients diagnosed by transurethral resection had distant metastases significantly more rapidly than patients diagnosed by needle biopsy. However, transurethral resection usually was performed because of the presence of obstructive voiding symptoms and such patients were much more likely to have positive lymph node dissections than patients without obstructive voiding symptoms. A proportional hazards regression analysis showed that nodal status and the degree of obstructive voiding symptoms at diagnosis were independent and powerful predictors of the interval to distant metastases, along with stage and grade. The type of initial biopsy (transurethral prostatic resection versus needle biopsy) had no independent prognostic significance in this analysis. Among patients who had substantial obstructive voiding symptoms there was no significant difference in interval to distant metastases between the transurethral prostatic resection and needle biopsy groups. We conclude that the apparent adverse effect of transurethral prostatic resection results from the poor prognosis of tumors causing obstructive voiding symptoms rather than as a direct result of the resection itself.

Duplication of penis

Abstract Duplication of the penis is a very uncommon congenital anomaly. It may occur alone, but the more striking examples are usually associated with anomalies of the remainder of the genito-urinary tract and lower gastrointestinal tract. The extent of the anomaly ranges from a partial duplication of the glans to two separate penes located at some distance from each other. An illustrated classification is presented. The cause is unknown but is best explained by an early disturbance in the embryologic development of the hindgut and ventral abdomen. Treatment must be individualized and consists of various procedures to restore normal appearance and function. A case is reported and the literature reviewed.