Long-term biochemical disease-free and cancer-specific survival following anatomic radical retropubic prostatectomy. The 15-year Johns Hopkins experience.

In a large series of 2404 men with a mean follow-up of 6.3 plus or minus 4.2 years (range, 1-17) after anatomic RRP for clinically localized prostate cancer, 412 men (17%) have recurred. A detectable PSA was the only evidence of recurrence in 9.7%, whereas 1.7% and 5.8% had local recurrence and distant metastasis, respectively. The overall actuarial 5-, 10-, and 15-year recurrence-free survival rates for these men were 84%, 74%, and 66%, respectively. As demonstrated in the authors' previous reports, the actuarial likelihood of a postoperative recurrence increased with advancing clinical stage, Gleason-score, preoperative PSA level, and pathologic stage. Subdivision of men with Gleason 7 tumors resulted in better stratification. There was a similar actuarial likelihood of postoperative recurrence for men with Gleason 4 + 3 and Gleason score 8 to 10 disease. The actuarial rate of recurrence of tumor for men with Gleason 3 + 4 disease was statistically different from the rate for men with Gleason score 6 or Gleason 4 + 3 disease. The overall actuarial metastasis-free survival rates at 5, 10, and 15 years were 96%, 90%, and 82%, respectively. The overall actuarial cancer-specific survival rates at 5, 10, and 15 years were 99%, 96%, and 90%, respectively. This study provides long-term outcome of patients with clinically localized cancer who underwent RRP between 1982 and 1999. Recognizing that this long-term study includes many patients with more advanced disease diagnosed before the PSA era, caution must be exercised in comparing these results with the outcomes for cohorts of patients treated since 1989. Anatomic RRP is an effective way to manage clinically localized prostate cancer. Excellent long-term results can be obtained with RRP for early stage disease. The proportion of men with early stage prostate cancer will continue to increase with wide use of serum PSA testing and digital rectal examination.

Isolated local recurrence is rare after radical prostatectomy in men with Gleason 7 prostate cancer and positive surgical margins: therapeutic implications.

PURPOSE: We determined whether the high biochemical failure rate in men with Gleason score 7 disease and positive surgical margins after radical retropubic prostatectomy is secondary to distant metastasis or to local tumor recurrence that could be eliminated by immediate adjuvant radiation therapy. MATERIALS AND METHODS: Between 1982 and 1997, 112 men with Gleason score 7 disease and positive surgical margins but no seminal vesicle or lymph node involvement underwent radical retropubic prostatectomy without immediate adjuvant radiation or hormonal therapy. Median followup was 8 years (range 1 to 16) and 45 men (40%) were followed 10 years or more. Kaplan-Meier actuarial survival estimates were used to determine the actuarial 5 and 10-year post-prostatectomy, and 5-year post-radiation recurrence rates. RESULTS: The actuarial 5 and 10-year post-prostatectomy biochemical, local and distant recurrence rates were 40% and 52%, 6% and 6%, and 7% and 16%, respectively. For 20 men who received radiation therapy for isolated prostate specific antigen elevation actuarial 5-year post-radiation biochemical recurrence-free rate was 34%. For 5 men who received radiation therapy for local recurrence actuarial 5-year post-radiation biochemical recurrence-free rate was 20%. CONCLUSIONS: Isolated clinical local recurrence is rare during long-term followup of men with Gleason score 7 disease and positive surgical margins at radical prostatectomy. Radiation therapy given at prostate specific antigen elevation poorly controlled the disease. Because patients with biochemical failure rarely had local recurrence at long-term followup, they most likely harbored subclinical distant metastasis. These data suggest that immediate adjuvant radiation therapy will not have a major impact on outcome because most men with Gleason score 7 disease and positive surgical margins in whom treatment fails most likely had distant metastasis at surgery. To improve the outcome in cases of Gleason score 7 disease and positive surgical margins a systemic approach to adjuvant therapy is necessary.

Evaluation and treatment of men with biochemical prostate-specific antigen recurrence following definitive therapy for clinically localized prostate cancer.

Early detection and monitoring by serum prostate-specific antigen (PSA) measurement has increased the number of men presenting with potentially curable prostate cancer. Most will choose radical prostatectomy or some form of radiation therapy for treatment, but some will have evidence of biochemical disease recurrence following therapy, shown by a rising PSA level without other clinical evidence of disease. Radical prostatectomy involves the removal of all prostate tissue, causing the serum PSA to decline to undetectable levels within four to six weeks following surgery; a subsequent rise in the serum PSA to a detectable level indicates disease recurrence. Patients should be evaluated to assess whether rising PSA levels indicate local recurrence or early metastatic disease. The advantages of salvage radiation, endocrine therapy, and other treatment modalities in local disease recurrence must be weighed against potential side effects and the resulting decrease in quality of life. Radiation therapy does not immediately eradicate all PSA-producing cells; therefore the persistence of a detectable PSA does not necessarily imply residual cancer, but rising PSA levels indicate treatment failure. Salvage surgery can be performed after radiotherapy for the purpose of removing all viable cancer cells, but should be weighed against a higher incidence of surgical complications; cryoablation offers a less invasive therapeutic modality.

What does prostate-specific antigen recurrence mean?

The return of the prostate-specific antigen (PSA) to a detectable serum level (PSA recurrence) is usually the first sign of recurrent disease after radical prostatectomy. PSA recurrence generally occurs in men who are otherwise asymptomatic and may occur as late as 5 to 10 years after surgery. Men in this situation want to know what this means regarding the likelihood of clinical disease recurrence and, ultimately, survival. An evaluation for recurrent disease is warranted but generally does not reveal objective signs of clinical disease in the majority of men. Although select men may benefit from salvage local therapy, a PSA recurrence is most often an early sign of distant disease present since the time of surgery. The decision whether or not to initiate systemic therapy in these men is difficult and controversial. Fortunately, recent developments in determining the significance of a PSA recurrence may help the patient and his physician to make a more informed decision regarding treatment options.

Nuclear shape and nuclear matrix protein composition in prostate and seminal vesicles.

OBJECTIVES: The nucleus controls cell function and behavior. The nuclear matrix determines internal nuclear changes. Two-dimensional gel electrophoresis is the reference standard for the analysis of nuclear matrix protein (NMP) composition. Differences in NMP composition should therefore be reflected by changes in nuclear shape. We investigated the differences in NMP composition and nuclear morphometry of the prostate and seminal vesicles. Both tissues are androgen-dependent sex accessory organs with completely different biologic behavior. METHODS: High-resolution two-dimensional gel electrophoresis and silver staining were used to evaluate NMP composition from histologically normal prostate and seminal vesicle epithelial cells. Nuclear morphometry, performed using a computer-assisted image analysis system, described the distribution, variability, and extremes of nuclear shape. RESULTS: NMP composition analysis demonstrated that both tissues have a similar NMP composition, and tissue-specific NMPs that were consistently present in all specimens of each tissue could not be demonstrated. Nuclear morphometry showed a significantly greater heterogeneity in nuclear shape in the seminal vesicles than in the prostate. CONCLUSIONS: The striking similarity of the NMP composition demonstrates the close biologic relationship between prostate and seminal vesicle tissue. The similar NMP composition does not correlate with the marked alterations in nuclear shape and structure between these tissues. Therefore, nuclear morphometry may depict differences in the functional state of a similar set of NMPs, shown by two-dimensional gel electrophoresis, which may be responsible for the different biologic behavior of these tissues.

Digital rectal examination and imaging studies are unnecessary in men with undetectable prostate specific antigen following radical prostatectomy.

PURPOSE: We determine the probability of local or distant recurrence following radical prostatectomy in men with an undetectable prostate specific antigen (PSA) level. MATERIALS AND METHODS: The clinical course of 1,916 consecutive men followed during a 14-year period after radical prostatectomy was reviewed. Average followup plus or minus standard deviation is 5.5+/-3.5 years, and 326 men (17%) have been followed for more than 10 years. In total this population of men has been followed for 10,540 patient-years. RESULTS: Of 1,916 men 56 (2.9%) had local recurrence an average of 6.1+/-2.7 years (range 1 to 12) after surgery. No man had local recurrence with an undetectable serum PSA. Mean serum PSA at the time of local recurrence was 5.8 ng./ml. Of the 56 men 13 (25%) who had local disease recurrence had an undetectable serum PSA at 5 years of followup but had progression to biochemical and local disease recurrence later. Of 1,916 men 118 had distant metastases with a mean serum PSA of 28.6 ng./ml. No man has had distant metastasis with an undetectable serum PSA. CONCLUSIONS: Disease can recur after radical prostatectomy even after an extended biochemical disease-free interval. None of the 1,916 men followed for an average of greater than 5 years after surgery had local recurrence or distant metastasis with an undetectable serum PSA. Based on these observations, we recommend no further evaluation, that is digital rectal examination or imaging studies, in men with an undetectable PSA following radical prostatectomy.

Natural history of progression after PSA elevation following radical prostatectomy.

CONTEXT: In men who develop an elevated serum prostate-specific antigen level (PSA) after having undergone a radical prostatectomy, the natural history of progression to distant metastases and death due to prostate cancer is unknown. OBJECTIVE: To characterize the time course of disease progression in men with biochemical recurrence after radical prostatectomy. DESIGN: A retrospective review of a large surgical series with median (SD) follow-up of 5.3 (3.7) years (range, 0.5-15 years) between April 1982 and April 1997. SETTING: An urban academic tertiary referral institution. PATIENTS: A total of 1997 men undergoing radical prostatectomy, by a single surgeon, for clinically localized prostate cancer. None received neoadjuvant therapy, and none had received adjuvant hormonal therapy prior to documented distant metastases. MAIN OUTCOME MEASURES: After surgery, men were followed up with PSA assays and digital rectal examinations every 3 months for the first year, semiannually for the second year, and annually thereafter. A detectable serum PSA level of at least 0.2 ng/mL was evidence of biochemical recurrence. Distant metastases were diagnosed by radionuclide bone scan, chest radiograph, or other body imaging, which was performed at the time of biochemical recurrence and annually thereafter. RESULTS: The actuarial metastasis-free survival for all 1997 men was 82% (95% confidence interval, 76%-88%) at 15 years after surgery. Of the 1997 men, 315 (15%) developed biochemical PSA level elevation. Eleven of these underwent early hormone therapy after the recurrence and are not included in the study. Of the remaining 304 men, 103 (34%) developed metastatic disease within the study period. The median actuarial time to metastases was 8 years from the time of PSA level elevation. In survival analysis, time to biochemical progression (P<.001), Gleason score (P<.001), and PSA doubling time (P<.001) were predictive of the probability and time to the development of metastatic disease. An algorithm combining these parameters was constructed to stratify men into risk groups. Once men developed metastatic disease, the median actuarial time to death was 5 years. The time interval from surgery to the appearance of metastatic disease was predictive of time until death (P<.02). CONCLUSIONS: Several clinical parameters help predict the outcomes of men with PSA elevation after radical prostatectomy. These data may be useful in the design of clinical trials, the identification of men for enrollment into experimental protocols, and counseling men regarding the timing of administration of adjuvant therapies.

Excision of the neurovascular bundle at radical prostatectomy in cases with perineural invasion on needle biopsy.

OBJECTIVES: To assess, in a group of patients who had undergone radical prostatectomy and who were likely to have extraprostatic extension of their tumors based on the previous finding of perineural invasion on needle biopsy, how effective excision of the neurovascular bundle was in reducing the number of positive margins and increasing the potential cure rate. METHODS: Eighty radical prostatectomy cases from our institution that had perineural invasion on prostate needle biopsy were retrospectively studied to determine the presence and location of extraprostatic extension, positive margins, and seminal vesicle or lymph node involvement, whether the neurovascular bundle had been excised, and whether tumor was present in the bundle region. RESULTS: In 14 (17.5%) of 80 cases, excising the neurovascular bundle led to a situation in which there was tumor in the neurovascular bundle, all the surgical margins of resection were negative for tumor, and there was no seminal vesicle or lymph node involvement. The remaining cases were equally divided between (a) less aggressive tumors that were organ-confined or had only focal extraprostatic extension with no tumor in the neurovascular bundle and (b) more aggressive tumors that had positive margins or involvement of the seminal vesicles or lymph nodes. Within the latter group, however, there were 9 patients (11.3% of all 80 cases) with negative seminal vesicles and lymph nodes in whom excision of the neurovascular bundle at least reduced the extent of positive margins. Most of the positive margins in patients with tumor in the neurovascular bundle occurred outside the bundle region, and in this study, none of the cases with positive surgical margins were the sole result of failure to excise the neurovascular bundle. CONCLUSIONS: When perineural invasion is seen on needle biopsy, the morbidity of resecting one or both neurovascular bundles, which in some cases could turn out to be unnecessary, must be weighed against the benefit of reducing the incidence of positive margins (17.5% of our cases) or decreasing the extent of positive margins (11.3% of our cases).

Nuclear morphometry adds significant prognostic information to stage and grade for renal cell carcinoma.

OBJECTIVES: Identification of patients with a high probability of recurrence after nephrectomy for renal cell carcinoma (RCC) is required for adjuvant studies of new therapies. Nuclear morphometry predicts prognosis for prostate, bladder, and Wilms' tumors and in RCC according to previous small pilot studies. METHODS: To validate this finding, we studied an additional 101 patients who underwent nephrectomy for Stage pT1 to pT3 RCC at our institution from 1977 to 1993 for whom data regarding recurrence or disease-free survival of greater than 60 months were available. Patient records and pathology specimens were reviewed. Of the 101 patients, 66 (65%) did not experience recurrence with greater than 60 months of follow-up, and 35 (35%) had RCC recurrence with a median time to recurrence of 17 months. Nuclear shape descriptors were tested as predictors of disease recurrence after accounting for stage and grade in proportional hazards regression models. RESULTS: Range of ellipticity (hazards ratio 3.39, P = 0.014) was confirmed to be a significant predictor of recurrence. A prognostic model using stage, grade, and range of ellipticity identified three distinct groups: low, moderate, and high recurrence risk groups, with recurrence rates of 4%, 37%, and 63%, respectively, at 5 years of follow-up. Morphometry significantly (P = 0.018) improved prognostication on the basis of stage and grade alone in this multivariate model. CONCLUSIONS: Nuclear morphometry is valid and accurate in predicting relapse in early-stage RCC. The model can select patients with RCC for adjuvant therapies.

Frequent occurrence of metastatic disease in patients with renal cell carcinoma and intrahepatic or supradiaphragmatic intracaval extension treated with surgery: an outcome analysis.

OBJECTIVES: Previous reports indicate that up to 10% of patients with localized renal cell carcinoma have direct intracaval neoplastic extension. Many patients with locally confined tumors and small intracaval tumor extensions can be surgically cured. Few studies have documented long-term survival after radical surgery for renal cell carcinoma involving higher vena caval tumor extension. We report the follow-up of 34 consecutive patients undergoing radical nephrectomy and intrahepatic or supradiaphragmatic intracaval thrombectomy for renal cell carcinoma. METHODS: From October 1982 through January 1993, 34 consecutive patients with a mean age of 60 years were identified as having clinical Stage T3 renal cell carcinoma (mean diameter 9.5+/-4.0 cm) with intrahepatic (41%) or supradiaphragmatic (59%) intracaval neoplastic extension. Patients underwent radical nephrectomy with intrahepatic caval thrombectomy (38%) or supradiaphragmatic caval thrombectomy using cardiac bypass with hypothermia and circulatory arrest (62%). Clinical outcome was assessed during a mean follow-up of 30 months (range 1 to 182). RESULTS: A total of 24 (71%) of 34 tumors demonstrated capsular penetration, and 22 (65%) of 34 had significant perinephric extension into Gerota's fascia by pathologic analysis. Metastatic disease was identified in 35% of patients either at the time of surgery or by pathologic analysis. Using Kaplan-Meier actuarial analysis, the likelihood of survival for all 34 consecutive patients after surgery was 68% (95% confidence interval [CI] 49% to 81%) at 1 year, 32% (95% CI 18% to 48%) at 2 years, 14% (95% CI 5% to 28%) at 5 years, and 9% (95% CI 2% to 24%) at 10 years. Neither capsular penetration, perinephric extension, the level of intracaval extension of tumor, nor the use of cardiopulmonary bypass significantly affected survival. CONCLUSIONS: In patients with renal cell carcinoma and intrahepatic or supradiaphragmatic intracaval extension of tumor, the presence of metastases is a frequent occurrence and, if present, greatly diminishes survival. Improvements in the preoperative detection of occult metastases are needed if surgery alone is to improve survival.

Comparison of radical prostatectomy and iodine 125 interstitial radiotherapy for the treatment of clinically localized prostate cancer: a 7-year biochemical (PSA) progression analysis.

OBJECTIVES: To evaluate the relative efficacy of brachytherapy to radical prostatectomy, we compared biochemical progression rates from a published series of men who underwent iodine 125 (125I) interstitial radiotherapy for localized prostate cancer to a similar group of men who underwent anatomic radical prostatectomy using appropriate end points. METHODS: Seventy-six men who underwent anatomic radical prostatectomy between 1988 and 1990 were carefully matched for Gleason score and clinical stage to a recently reported contemporary series of patients treated at another institution with 125I brachytherapy without adjuvant treatment. The definition of biochemical progression was a serum PSA level greater than 0.2 ng/mL after anatomic radical prostatectomy and greater than 0.5 ng/mL for brachytherapy-treated patients. RESULTS: The 7-year actuarial PSA progression-free survival following anatomic radical prostatectomy was 97.8% (95% confidence interval [CI], 85.6% to 99.7%) for this group of men selected to match the brachytherapy group, compared to 79% (95% CI not published) for men treated with 125I interstitial radiotherapy. CONCLUSIONS: Using comparative end points for biochemical-free progression, failure rates may be higher following 125I interstitial radiotherapy compared to anatomic radical prostatectomy. These data provide a better comparison of biochemical progression than previously published studies and emphasize the need for caution in interpreting the relative efficacy of brachytherapy in controlling localized prostate cancer.

Disease progression following radical prostatectomy in men with Gleason score 7 tumor.

PURPOSE: The long-term prognosis of men with Gleason score 7 adenocarcinoma of the prostate is uncertain. MATERIALS AND METHODS: We studied 488 men whose radical prostatectomy specimen showed Gleason score 7 tumor without involvement of the seminal vesicles or lymph nodes. Of the 400 men without progression 318 had been followed for 2 years or more and 93 for 7 years or more. RESULTS: Cases of organ confined disease and negative margins regardless of extent of extraprostatic extension had roughly similar and better prognoses than cases of focal and established extraprostatic extension with positive margins. The greater influence of margin status on progression (p <0.0001) compared to extent of extraprostatic extension (p = 0.023) was evidenced in the multivariate analysis. Of 30 men with established extraprostatic extension and positive margins 6 (20%) had progression to distant metastases, which was similar to 14 of 58 (24%) without established extraprostatic extension and positive margins. There was no difference in response to radiotherapy between men with established extraprostatic extension and positive margins compared to the other cases. CONCLUSIONS: Margins status greatly influences the risk of progression in men with Gleason score 7 tumors. Among men with Gleason score 7 tumors, except for those with established extraprostatic extension and positive margins, more than 50% appear to be cured at long-term followup. Because of the high risk of progression in patients with positive margins, clinical studies of adjuvant therapy in this population appear warranted.

Automated image analysis system for detecting boundaries of live prostate cancer cells.

Image analysis provides a powerful tool for quantifying cell motility and has been used to correlate motility with metastatic potential in an animal model of prostate cancer. However, widespread use of this image analysis method has been limited because earlier methods of quantitative analysis required time-intensive and subjective manual tracing of cell contours. In this report, we describe a fully automated image segmentation algorithm for detection and morphometric description of prostatic cells. The segmentation system was tested on prostate cell images generated from Hoffman modulation contrast microscopy (47 cells at 64 time points = 3,008 images) and differential interference contrast microscopy (29 cells at 64 times points plus 1 cell at 62 time points = 1,918 images). Morphometric measurements were derived from computer-determined cell boundaries and compared with the same measurements derived from manually traced cell boundaries. Final correlation coefficients for area and perimeter measurements for Hoffman and differential interference contrast microscopy were (0.76, 0.62) and (0.93, 0.93), respectively. Results with our differential interference contrast images demonstrate that our segmentation algorithm reliably and efficiently replaces the need for manually traced cell boundaries in addition to eliminating intraobserver variation. Our automated segmentation process will have immediate utility in our motility analysis system that relates cell motility with metastatic potential of prostate cancer.

Prostate-specific antigen after anatomic radical retropubic prostatectomy. Patterns of recurrence and cancer control.

In a series of 1623 men with a follow-up of 5 +/- 3 years (range 1-13) after anatomic RRP for clinically localized prostate cancer, 17% (276/1623) have shown recurrence. A detectable PSA was the only evidence of recurrence in 7.9%, whereas 2.5% have recurred locally and 5.4% have developed distant metastases. The overall actuarial progression-free rate for these men at 10 years was 68%. Actuarial rates at 10 years were 18% for development of an isolated PSA recurrence, 8% for local recurrence, and 9% for distant recurrence. The actuarial likelihood of a postoperative recurrence increased with increasing clinical stage, Gleason score, preoperative PSA level, and pathologic stage. Although not shown in our previous report, the actuarial rate of recurrence of tumors with a Gleason score of 7 was statistically different from that of tumors of higher Gleason score (8-10). As well, men with preoperative PSA levels of 10.1 to 20 ng/mL experienced recurrence at a significantly lower rate than did men with preoperative PSA levels greater than 20 ng/mL. By using a combination of Gleason score, pathologic stage, and surgical margin status, we demonstrated that the presence of a positive surgical margin did not dramatically affect recurrence in tumors of Gleason scores 2 to 6 with capsular penetration. Surgical margin status was important in high-grade tumors with capsular penetration. In fact, tumors with capsular penetration, Gleason score of at least 7, and a positive surgical margin behaved similarly to tumors with invasion of the seminal vesicles. Preservation of potency did not adversely influence cancer control. The Gleason score, presence or absence of seminal vesicle or lymph node involvement, and the timing of PSA recurrence are all important variables in predicting eventual local versus distant failure associated with an isolated rise in serum PSA. Overall actuarial cause-specific survival at 5 and 10 years was 99% and 93%. Although there was no difference in survival among men grouped by TNM stage or preoperative PSA, advancing histologic grade and pathologic stage did have an effect on actuarial cause-specific survival. Men undergoing RRP for clinically localized prostate cancer showed a 16% actuarial rate of development of metastatic disease at 10 years. This is considerably better than conservative therapy and justifies RRP as the treatment of choice for men with clinically localized disease who are otherwise healthy and have a greater than 10-year life expectancy.

Radical prostatectomy as treatment for prostate-specific antigen-detected stage T1c prostate cancer.

The use of serum prostate-specific antigen (PSA) measurement as a method for early detection of prostate cancer has increased the detection of clinically and pathologically localized prostate cancer. Clinical stage T1c was introduced to describe cancers discovered on prostate biopsy as a result of an abnormal serum PSA level without a palpable prostatic abnormality on digital rectal examination. The majority of men with stage T1c tumors have significant disease warranting treatment. We report the results of anatomic radical retropubic prostatectomy as therapy for PSA-detected stage T1c prostate cancer in 340 men treated at a single institution. In all, 17 men (5%) have had a recurrence with 2.3 +/- 1.2 years of follow-up, 15 of whom have experienced an isolated biochemical PSA recurrence only. The overall actuarial biochemical PSA recurrence-free rate at 6 years is 87%, with pathologic stage being the best single indicator of the likelihood of progression. Although a longer period of follow-up is needed, this interim report suggests that these men can be cured by surgery at rates equal to or better than those of previously reported radical prostatectomy series.

Partial nephrectomy: technique, complications and pathological findings.

PURPOSE: We evaluate whether partial nephrectomy can be performed safely and efficaciously for renal tumors. MATERIALS AND METHODS: The results of 67 partial nephrectomies performed between 1977 and 1994 for renal cell carcinoma (51), oncocytoma (9), angiomyolipoma (3), transitional cell carcinoma (3) and other nonneoplastic lesions (2) were analyzed retrospectively in detail. RESULTS: Diminished complication rates were noted after 1988, and were attributed to improvements in surgical technique and an increased incidence of smaller, serendipitously discovered tumors. Although 35.5% of the patients had preoperative renal impairment (mean serum creatinine 2.1 mg./dl.), there were minimal changes in renal function and no patient required acute hemodialysis following partial nephrectomy. Among 42 patients with clinical stage T1 to T2 renal cell carcinoma undergoing partial nephrectomy local recurrence was identified in 8.3% of those with primary neoplasms. All 6 patients with local recurrence had negative surgical margins, recurrence often, distant from the operative site and multifocal disease, implicating multicentricity as the etiology of local recurrence. Five patients (83.3%) with local recurrence were alive and asymptomatic at a mean of 138 months after partial nephrectomy. Since capsular penetration was identified in 5 of 27 renal cell carcinomas (18.5%) with a diameter of 3.5 cm. or less, aggressive surgical resection with adequate tumor-free parenchymal and perinephric margins is necessary even for small lesions. CONCLUSIONS: With improved surgical techniques, including regional hypothermia, intraoperative sonography, meticulous dissection and injection of the collecting system with methylene blue, partial nephrectomy is safe and effective in properly selected patients.

Radical surgery for renal-cell carcinoma: caval neoplastic excision, adrenalectomy, lymphadenectomy, adjacent organ resection.

A radical nephrectomy typically includes early ligation of the renal vessels, excision of the kidney and perinephric tissue, a regional lymphatenectomy, and an adrenalectomy. More controversial may be excision of supradiaphragmatic caval neoplastic extension and adjacent organ resection. Although survival is low in these unfavorable groups of patients, some patients may benefit from the extensive local resection of tumor, including adrenalectomy, lymphatenectomy, caval resection, and resection of adjacent organs.

Evaluation of serum prostate-specific antigen velocity after radical prostatectomy to distinguish local recurrence from distant metastases.

OBJECTIVE: Serum prostate-specific antigen (PSA) values are most useful for prediction of disease recurrence after surgery. It is unknown whether a detectable PSA level after surgery indicates a local recurrence potentially benefiting from pelvic irradiation or distant metastases requiring hormonal treatment. METHODS: We analyzed postoperative rate of change of serum PSA levels as a predictor of local versus distant disease recurrence after radical prostatectomy. Between 1982 and 1991, 1,058 men underwent radical prostatectomy for localized prostate cancer and follow-up consisted of determining serum PSA levels and digital rectal examinations. Clinical follow-up of 542 men for four or more years and 78 men for eight or more years yielded ten-year actuarial disease recurrence rates of 4 percent for local recurrence, 8 percent for distant metastases, and 23 percent for an isolated elevation of serum PSA level only. Fifty-one patients with isolated elevations of PSA levels only were followed expectantly until they were diagnosed with either local or distant metastases. RESULTS: A linear mixed effects regression analysis was used to model these data. Using these models, the time to a serum PSA level of 0.5 ng/mL, the PSA level one year following surgery, pathologic stage, Gleason sum, and the rate of change of PSA (PSA velocity [PSAV]) were tested as predictors of local versus distant metastases. A combination of PSAV, pathologic stage, and Gleason grade best distinguished local from distant metastases. CONCLUSIONS: These data suggest that PSAV in men with an isolated elevation of PSA levels following radical prostatectomy might aid in clinical decision making.