Effect of neoadjuvant hormonal therapy on prostatic intraepithelial neoplasia and its prognostic significance.

PURPOSE: We studied the effect of neoadjuvant hormonal therapy on prostatic intraepithelial neoplasia in patients undergoing radical prostatectomy and assessed the effect of prostatic intraepithelial neoplasia on disease recurrence as measured by serum prostate specific antigen (PSA). MATERIALS AND METHODS: A total of 278 patients with clinically localized prostate cancer were included in phase II and III studies evaluating radical prostatectomy alone versus radical prostatectomy following neoadjuvant hormonal therapy at Memorial Sloan-Kettering Cancer Center between October 1991 and August 1996. Patient data related to prostatic intraepithelial neoplasia were analyzed. RESULTS: Of 275 evaluable patients 145 (52.7%) had prostatic intraepithelial neoplasia. Of 50 patients treated with neoadjuvant hormonal therapy (hormone group) 22 (44%) had a lower incidence of prostatic intraepithelial neoplasia compared to 69 of 80 controls (86.3%) (chi-square test p<0.0001). Of 262 patients (95.3%) with followup PSA 44 (16.8%) had PSA recurrence at a median followup of 32 months, with a median time to recurrence of 30 months. PSA recurrence was noted in 23 of 145 patients with compared to 21 of 130 without prostatic intraepithelial neoplasia (chi-square test p = 0.95), and did not significantly differ between the hormone group (25 of 142, 17.6%) and controls (19 of 130, 14.6%) (chi-square test p = 0.45). CONCLUSIONS: While patients treated with neoadjuvant hormonal therapy had significantly lower incidence of prostatic intraepithelial neoplasia, neither prostatic intraepithelial neoplasia nor neoadjuvant hormonal therapy significantly affected PSA recurrence at a median followup of 32 months.

Prostate specific antigen doubling time after radical prostatectomy: effect of neoadjuvant androgen deprivation therapy.

PURPOSE: We determined the predictors of prostate specific antigen (PSA) doubling time in patients with relapse after radical prostatectomy as well as whether PSA doubling time is shorter in those treated versus not treated with neoadjuvant androgen deprivation therapy. MATERIALS AND METHODS: We calculated PSA doubling time in 204 patients with PSA relapse after radical prostatectomy who were or were not treated with neoadjuvant androgen deprivation therapy. Analysis of covariance was used to determine the effect of clinical and pathological parameters on PSA doubling time, and the proportion of variability explained by these parameters. RESULTS: Clinical stage, and combined clinical stage and margin status, clinical stage and androgen deprivation therapy status, androgen deprivation therapy status and time to PSA relapse, and androgen deprivation therapy status and pretreatment PSA were significant predictors of PSA doubling time. Any variable or combination of variables explained up to only 21% of PSA doubling time variability. When stratified by pretreatment PSA, clinical stage and biopsy grade, the difference in doubling times in patients treated with or without neoadjuvant androgen deprivation therapy was significant only for 4.1 to 10 ng./ml. PSA. In this group mean doubling time plus or minus standard deviation in patients receiving neoadjuvant androgen deprivation therapy and those treated only with radical prostatectomy was 7.6+/-1.0 and 15.4+/-2.6 months, respectively. CONCLUSIONS: Our study indicates that it is difficult to predict PSA doubling time in an individual. The small proportion of variability in PSA doubling time explained by the interaction of androgen deprivation therapy status and other variables indicates that these factors are not clinically significant.

Neoadjuvant Hormone Therapy Before Radical Prostatectomy: Update on the Memorial Sloan-Kettering Cancer Center Trials.

We report here the latest follow-up of the Phase II and III trials evaluating pathologic results and relapse-free survival, as judged by serum prostate specific antigen (PSA), in patients with localized prostate cancer who had radical prostatectomy performed at the Memorial Sloan-Kettering Center (MSKCC) either with or without neoadjuvant hormone therapy (NHT). Pelvic lymphadenectomy (PLND), radical prostatectomy, or both with or without NHT was performed in 141 patients enrolled in a Phase II trial comparing patients receiving NHT with concurrent controls and 140 patients in a randomized Phase III trial. In the Phase II study, there was a significant difference in the pathologic results, with only 35 (49%) of the 72 patients in the control group having organ-confined margin-negative disease compared with 48 (70%) of the 69 patients in the NHT arm (P = 0.0057; chi(2) test). With a median follow-up of 57 months, there was no significant difference in the PSA relapse rates in the two arms (P = 0.92; log-rank test). In the Phase III study, 39 (59%) of the 66 patients in the control arm had organ-confined margin-negative disease compared with 52 (70%) of the 74 patients in the NHT arm (P = 0.17; chi(2) test). However, the positive-margin rate was significantly lower in the NHT arm (19%) than in the control arm (37%) (P = 0.023; chi(2) test). With a median follow-up of 35 months, there was no significant difference in the PSA relapse rates in the two arms (P = 0.73; log-rank test). Thus, although NHT improves the pathologic results, further follow-up is necessary to determine if this marked reduction in the positive-margin rate will translate into improved disease-free survival.

Site specific predictors of positive margins at radical prostatectomy: an argument for risk based modification of technique.

PURPOSE: We identify patients at high risk for positive bladder neck, apical or posterior margins who may benefit from technical modifications, such as excision of the bladder neck or wide excision of the neurovascular bundles. MATERIALS AND METHODS: We studied 242 patients with clinically localized prostate cancer undergoing radical prostatectomy with or without neoadjuvant androgen deprivation therapy between June 1992 and August 1997 who had a sextant biopsy available for review. Multivariate logistic regression analysis was used to develop models for prediction of positive bladder neck, apical, and right and left posterior margins based on clinical parameters. From these models patients at low and high risk for positive margins were identified. RESULTS: The incidence of positive margins was 36% with 69% solitary sites. Patients with a prostate specific antigen of greater than 10 ng./ml. had a higher incidence (16%) of positive bladder neck margins. Patients with 3 or more positive cores who did not receive neoadjuvant androgen deprivation therapy had a higher incidence (24%) of positive apical margins. A nomogram incorporating pretreatment serum prostate specific antigen, number of ipsilateral positive cores and whether androgen deprivation therapy was used identified patients at high risk for positive posterior margins. CONCLUSIONS: The nomograms presented identify patients at high risk for positive margins at various sites who may benefit from modification of surgical technique based on risk.

Clustering of colorectal cancer in families of probands under 40 years of age.

UNLABELLED: Although sporadic colorectal cancer (CRC) is relatively uncommon in the young, it may constitute an elevated genetic risk for CRC in these individuals. PURPOSE: This study was designed to determine extent of colorectal cancer in families of probands under 40 years of age. METHODS: Medical records of all consecutive patients, 40 years of age or younger at the time of CRC surgery, during the time period 1986 to 1994 were examined. Cases of familial adenomatous polyposis and ulcerative colitis were excluded. Via interviews of surviving probands or nearest relatives, dates of birth and death, causes of death, and diagnosis of cancer were recorded on all first-degree relatives (parents, siblings, and offspring), second-degree relatives (grandparents, aunts, and uncles), and any other relatives. RESULTS: A total of 128 patients, 40 years of age or less at time of CRC resection, were identified. Of these, 45 probands/families were reached by phone, and 45 detailed family histories were obtained. Age range of these 45 probands was 19 to 40 (mean, 33.1) years. In 25 families there was no history of CRC in first-degree, second-degree, or third-degree relatives. Eight of 45 probands (17.8 percent) had at least one first-degree relative with CRC, and three of these eight families fulfilled the Amsterdam criteria for hereditary nonpolyposis colorectal cancer (HNPCC). In all three families, inheritance of CRC appeared to segregate with the maternal side of the family. In addition, 5 of 43 non-HNPCC probands had at least one first-degree, second-degree, or third-degree relative less than 40 years of age, at time of CRC diagnosis. CONCLUSION: Ascertainment of a detailed family history in early age of onset CRC patients identifies frequent familial clustering of CRC and HNPCC in 17.8 percent of cases.