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Biomedical subjects

L D Sullivan

Publications and source records attributed to L D Sullivan.

At least 19 recordsLinked to original sources
PubMed2000

Long-term neoadjuvant hormone therapy prior to radical prostatectomy: evaluation of risk for biochemical recurrence at 5-year follow-up.

OBJECTIVES: To assess the effects of 8 months of neoadjuvant therapy on pathologic stage and biochemical recurrence rates. METHODS: One hundred fifty-six men with clinically localized prostate cancer were treated with neoadjuvant combined androgen withdrawal therapy for 8 months prior to radical prostatectomy. Preoperative clinical stage, Gleason score, and serum prostate-specific antigen (PSA) levels were compared with treatment outcome (pathologic stage and PSA recurrence). RESULTS: PSA at diagnosis was 10 microg/L or higher in 36% with a mean of 11.5 microg/L. Clinical stage was T1c in 18%, T2 in 74%, and T3a in 8%. Gleason score was 6 or lower in 76% and 7 or higher in 24%. Pathologic stage was T0 in 13%, T2 in 66%, T3 (specimen confined) in 13%, T3 (margin positive) in 6%, and TxN+ in 2%. Incidence of positive margins increased with clinical stage T3a versus organ-confined disease (25% versus 4%, P <0.05), pretreatment Gleason scores 7 or higher versus Gleason scores 6 or lower (11% versus 4%, P = NS), and pretreatment PSA levels higher than 10 microg/L compared with PSA levels lower than 10 microg/L (15% versus 0%, P <0.01). Overall PSA recurrence rate was 12.2% after a mean postoperative follow-up of 54 months. Risk of PSA recurrence increased with clinical stage (25% T3 versus 11% organ confined, P <0.01), pretreatment PSA (7% if PSA lower than 10 microg/L versus 21% if 10 microg/L or higher, P <0.02), Gleason score (9% if 6 or lower versus 22% if 7 or higher, P <0.02), and pathologic stage (6% of pT2, 24% of pT3M-, and 56% of pT3M+, P <0.01). PSA recurrences occurred in 6% of patients with no adverse preoperative risk factors, 12% with any one of the high-risk factors, and 29% with any two of the high-risk factors. CONCLUSIONS: Risk of PSA recurrence after 8 months of neoadjuvant therapy is low after 5 years of follow-up and remains proportional to the presence of adverse preoperative risk factors. Prospective randomized studies are required to determine whether longer duration of neoadjuvant therapy reduces the risk of biochemical recurrence after radical prostatectomy.

Adult↗
PubMed2000

A comparison of the relative merits of radical perineal and radical retropubic prostatectomy.

OBJECTIVE: To compare the outcome, advantages and disadvantages of retropubic and perineal approach to radical prostatectomy, as performed by one surgeon. PATIENTS AND METHODS: This unrandomized study included 138 patients who underwent either radical retropubic (RRP) or radical perineal prostatectomy (RPP), based on the specific conditions or the patient's choice; 79 patients (mean age 64.6 years) underwent RPP and 59 (mean age 61.7 years) RRP. Outcome measures included estimated blood loss, the incidence of blood transfusions, positive margins and complications, operative duration, analgesic use, days in hospital and quality of life. RESULTS: There was no difference in operative duration, and the incidence of positive margins or complications between the groups. The mean estimated blood loss in the RPP and RRP groups was 415 and 1,138 mL, respectively. The RPP group stayed a mean of 2.2 days less in hospital and took 2.8 days less to regain a full diet than the RRP group; the RPP group needed 1.7 days before using oral analgesics and the RRP group 3.8 days. Of patients in both groups, 85% were pad-free at one year and their overall quality of life was similar. CONCLUSIONS: The results of RRP and RPP are comparable; the advantages of the perineal approach include minimal blood loss, low-intensity postoperative nursing care, low analgesic use and earlier discharge from hospital.

Aged↗
PubMed1998

Pseudoacids. II. 2-Acylbenzoic acid derivatives.

Structures of derivatives of cyclic o-acylbenzoic acids, including the chloride, endo- and exocyclic amides, esters and anhydrides, are examined. 3-Chloro-1(3H)-isobenzofuranone (1), orthorhombic, Pbca, a = 11.616 (5), b = 8.120 (3), c = 15.640 (9) A; 3-methoxy-3-phenyl-1(3H)-isobenzofuranone (3), orthorhombic, P2(1)2(1)2(1), a = 6.923 (2), b = 8.291 (4), c = 21.551 (8) A; 3-hydroxy-3-phenyl-N-propyl-1(3H)-isoindolone (4), orthorhombic, P2(1)2(1)2(1), a = 8.662 (4), b = 9.551 (7), c = 17.649 (14) A; 3-(N-morpholino)-1(3H)-isobenzofuranone (5), triclinic, P1, a = 6.172 (4), b = 11.163 (7), c = 17.33 (2) A, alpha = 105.91 (6), beta = 99.85 (6), gamma = 97.57 (5) degrees; 3-(2'-benzoylbenzoyloxy)-3-phenyl-1(3H)-isobenzofuranone (7), triclinic, P1, a = 9.694 (3), b = 10.505 (4), c = 11.163 (4) A, alpha = 80.58 (3), beta = 80.41 (3), gamma = 76.49 (3) degrees; bis[1(3H)-isobenzofuranone-3-yl]ether (8), monoclinic, I2/a, a = 15.31 (2), b = 6.111 (12), c = 28.30 (5) A, beta = 101.61 (12) degrees. An open oxoacid tertiary amide is also described: N-morpholino 2'-benzoylbenzamide (6): monoclinic, P2(1)/c, a = 6.844 (4), b = 15.696 (8), c = 14.154 (7) A, beta = 99.43 (4). Pseudoacid derivatives form planar isobenzofuran and isoindole rings, and the former aldehyde/ketone carbon-heteroatom endocyclic and exocyclic bond distances show bond length variations which correlate with the relative basicities of the attached groups. Structures of both endocyclic and exocyclic nitrogen pseudoamides are reported as well as examples of the normal-pseudoanhydride and the dipseudoanhydride.

Acylation↗
PubMed1998

Transurethral electrovaporization of the prostate versus transurethral prostatic resection: a comparison of postoperative hemorrhage.

OBJECTIVES: To determine the acute and delayed hemorrhage rate of transurethral electrovaporization of the prostate (TEVP) versus standard transurethral resection of the prostate (TURP). METHODS: A retrospective review of 524 consecutive patients who underwent TURP and 302 consecutive patients who underwent TEVP was conducted. The indications for both procedures were identical and based on history, physical examination, American Urological Association symptom score, and uroflowmetry. Parameters of evaluation included the incidence of both initial and delayed hemorrhages, the time until a delayed bleed occurred, blood transfusion rates, and the average length of stay in hospital after a bleed. RESULTS: The overall hemorrhage rate for TURP and TEVP was 4.8% and 4.0%, respectively. In the TURP group, there was a 1.1% incidence of acute bleeds and 3.6% incidence of delayed bleeds. For the TEVP group, 0.3% had an acute hemorrhage, and 3.6% were readmitted for clot retention. The average length of time from original discharge to readmission was 12.9 days for the TURP group with a mean repeat stay of 5.7 days. For the TEVP group, the average interval to readmission was 15.4 days with a stay of 3.1 days. CONCLUSIONS: The overall rate of hemorrhage for the TEVP group was slightly lower than for the TURP group due to fewer acute bleeds. However, the incidence of delayed bleeds and clot retention between the two was identical at 3.6%. Because of improved hemostasis intraoperatively with similar functional results in the long term as shown by other investigators, we foresee TEVP continuing as a viable alternative to TURP.

Acute Disease↗
PubMed1998

Retroperitoneal lymphadenectomy for post-chemotherapy residual masses: is a modified dissection and resection of residual masses sufficient?

OBJECTIVE: To determine if post-chemotherapy retroperitoneal lymphadenectomy for residual masses can be limited to resection of the residual masses and a modified template dissection, without loss of therapeutic efficacy. PATIENTS AND METHODS: Between 1985 and 1995, 50 patients underwent one of three types of retroperitoneal lymphadenectomy for a residual mass after cisplatin-based chemotherapy for stages II and III testicular non-seminomatous germ cell tumour. The pre-operative imaging, operative record and pathology reports were reviewed to determine the location of the residual masses and whether tumour, defined as teratoma or viable carcinoma, was within the boundaries of the modified template and/or residual masses. The median (range) follow-up was 56 (1-140) months. RESULTS: Of 39 patients undergoing a bilateral dissection, one (2.6%) with a left testicular cancer had teratoma identified outside the boundaries of the modified template and the residual masses. The nine patients who underwent resection of residual masses and a modified-template dissection were relapse-free at a median follow-up of 55 months. One of two patients undergoing resection of residual mass alone had two recurrences arising from incomplete resection. Four of eight patients undergoing a modified dissection retained ejaculation, compared with seven of 25 (28%) undergoing a non-nerve sparing bilateral dissection. CONCLUSION: This retrospective study suggests that in patients whose tumour markers become normal and have a residual mass after chemotherapy, residual masses can be resected with a modified-template dissection with no significant risk of leaving tumour in the retroperitoneum.

Adolescent↗
PubMed1998

An evaluation of quality of life in patients with continent urinary diversions after cystectomy.

OBJECTIVE: To determine the long-term results and assess the quality of life in patients with continent urinary diversions after cystectomy. PATIENTS AND METHODS: Eighty-six consecutive patients who received a continent urinary diversion from 1988 to 1994 at the Vancouver Hospital and Health Sciences Center were evaluated. The evaluation comprised a review of their hospital charts and clinic visits at 3 months and then yearly. Quality of life issues were assessed using a postal questionnaire pertaining to the patient's urinary symptoms. activity level and overall well-being while living with a continent urinary diversion. Two separate questionnaires were sent, addressing heterotopic or orthotopic diversions. RESULTS: There was an acceptable rate of complications, with stone formation and urinary tract infection as the most common morbidities. Continence was rated as good in most patients, with no patient reporting complete incontinence. Undesirable urinary symptoms occurred less often than 20% of the time in most patients. Although there was a significant effect on sex life, the overall quality of life appeared to be very good, as 70% of the patients had no limitations to their activities. CONCLUSIONS: The techniques currently evolved for urinary diversion produce good long-term results and quality of life. These diversions should be considered in a well selected patient population.

Adult↗
PubMed1997

A metastatic and androgen-sensitive human prostate cancer model using intraprostatic inoculation of LNCaP cells in SCID mice.

Several metastasizing murine and human animal models for prostate cancer are available. However, these models are androgen-independent and lack differentiated features such as androgen receptor and androgen-regulated gene expression like prostate-specific antigen (PSA). The objective of this study was to develop a metastasizing prostate cancer model with differentiated features using the human LNCaP cell line. Athymic and SCID mice were injected either s.c. or intraprostatically with 1 x 10(6) LNCaP cells. Changes in serum and tumor PSA mRNA levels were determined before and after castration to assess time to androgen-independent progression. Local tumor and metastatic growth was assessed at sacrifice after 12 weeks. Reverse transcription-PCR (RT-PCR) was used to detect circulating LNCaP cells. LNCaP tumor incidence after s.c. injection was 100% (65 of 65) in SCID mice and 80% in athymic mice. No lymph node or distant metastases were observed with s.c. tumors, and RT-PCR for PSA transcripts was negative. Primary tumor incidence after intraprostatic injection was 89% (39 of 44) in SCID mice and 60% in athymic mice. In 10 SCID mice with primary tumors followed for 12 weeks, retroperitoneal or mediastinal lymph node metastases were found in 100%, and microscopic pulmonary metastases were identified in 40%. RT-PCR for PSA transcripts was positive in 3 of 10 mice tested. Serum PSA levels in mice with s.c. and intraprostatic tumors decreased by 65% to nadir levels at 7 and 4 days after castration, respectively. Serum PSA and LNCaP tumor PSA mRNA levels increased to precastration levels earlier in SCID mice with intraprostatic tumors compared to those with s.c. tumors. Intraprostatic injection of LNCaP cells in SCID mice provides a useful animal model to investigate mechanisms of metastasis and to evaluate therapies targeted toward inhibiting the metastatic cascade.

Animals↗
PubMed1997

Early experience with high-intensity focused ultrasound for the treatment of benign prostatic hypertrophy.

OBJECTIVE: To evaluate the safety and effectiveness of high-intensity focused ultrasound (HIFU) in patients with benign prostatic hypertrophy (BPH). PATIENTS AND METHODS: The study comprised 25 patients (mean age 67 years: range 47-84) with BPH treated using the Sonoblate HIFU device. Patients were evaluated before and after one treatment of HIFU using the American Urological Association (AUA) symptom score, peak urinary flow rate (Qmax) and a quality-of-life (QOL) score, and any complications were noted. RESULTS: Five patients with large glands were withdrawn because the failure rate was high in these patients. The remaining 20 patients showed a mean improvements in the AUA symptom score (20.25 to 9.56), Qmax (9.2 to 13.7 mL/s) and QOL score (4.75 to 2.50). There were no major complications. CONCLUSIONS: HIFU is safe, produces minimal side-effects or complications and relieves the symptoms of prostatism.

Aged↗
PubMed1997

Neoadjuvant androgen deprivation therapy before radical prostatectomy: who is unlikely to benefit?

OBJECTIVE: To determine which patients undergoing radical prostatectomy for localized cancer are unlikely to benefit from neoadjuvant androgen withdrawal therapy. PATIENTS AND METHODS: Over a 5-year period, 173 patients underwent radical retropubic prostatectomy: 87 patients received no pre-operative androgen withdrawal therapy, for whom the clinical stages were T1b (17 patients), T1c (3), T2a (31) and T2b/c (36). Pre-operative prostate biopsies contained well-differentiated cancer in 43 and moderately differentiated cancer in 44 patients. Serum prostate-specific antigen (PSA) ranged from 0.4 ng/mL to 110.1 ng/mL (median 5.0). The presence of extracapsular disease, positive surgical margins and seminal vesicle involvement were correlated with pre-operative PSA, PSA density (PSAD), the natural logarithm of PSA [In(PSA)], biopsy grade, clinical stage, and sparing of neurovascular bundles. RESULTS: Patients with a PSA < or = 4.0 ng/mL had a rate of extracapsular disease and positive margins of 8.3% and none had seminal vesicle invasion; corresponding rates for patients with a PSA > 4.0 ng/mL were 57%, 51% and 12%, respectively. Multivariate analysis revealed In(PSA) to be the best predictor of extracapsular disease (P < < 0.001), margin positivity (P < < 0.001) and seminal vesicle invasion (P = 0.0019). CONCLUSIONS: These results suggest that in patients who have clinically localized, well or moderately differentiated prostate cancer, a PSA < or = 4.0 ng/mL is predictive for organ-confined disease. This group is unlikely to benefit from neoadjuvant androgen deprivation. Ln(PSA) may be able to improve the accuracy of mathematical multivariate models predicting the presence of extracapsular disease or margin positivity, but this will require verification in larger population-based studies.

Aged↗
PubMed1997

Neoadjuvant androgen withdrawal therapy decreases local recurrence rates following tumor excision in the Shionogi tumor model.

PURPOSE: The role of neoadjuvant androgen withdrawal before radical prostatectomy continues to be defined and remains investigational. It is unknown whether decreases in positive margin rates will translate into lower biochemical and local recurrence rates until long-term followup is available. We determined whether local recurrence rates after tumor excision were less with neoadjuvant compared to adjuvant androgen ablation in the Shionogi tumor model. Androgen withdrawal in this model triggers apoptosis and complete tumor regression but rapidly growing androgen independent tumors inevitably recur after 1 month. Conceptually, the ideal time for excision is after maximal castration induced tumor involution but before outgrowth of androgen resistant clones. MATERIALS AND METHODS: Shionogi tumors were allowed to grow to 1 to 2 gm. before mice were randomly assigned to group 1-tumor excision with wide margins and castration at tumor recurrence and group 2-neoadjuvant castration for 10 days followed by wide excision of the regressed tumor. RESULTS: Tumors recurred locally in 87% of group 1 mice after a median of 17 days (range 6 to 24) and all regressed completely with adjuvant castration. However, androgen independent tumors recurred in 92% of mice after a median of 36 days. In group 2 androgen independent disease recurred in 44% of mice after a median of 40 days. Tumor-free survival was significantly greater in group 2 than in group 1 (56 versus 20%, respectively, p <0.05). Inked surgical resection margins were positive in two-thirds of group 1 and one-third of group 2 mice. CONCLUSIONS: Neoadjuvant androgen withdrawal decreases local recurrence and positive margin rates by 50% after tumor excision in the Shionogi tumor model. Although this model cannot address the issue of effect of neoadjuvant therapy on subclinical metastases, extrapolation of these results to the clinical disease suggests that neoadjuvant therapy may help to decrease not only the positive margin rates but also the subsequent risk of local recurrence following radical prostatectomy.

Animals↗
PubMed1996

Teratoma in primary testis tumor reduces complete response rates in the retroperitoneum after primary chemotherapy. The case for primary retroperitoneal lymph node dissection of stage IIb germ cell tumors with teratomatous elements.

BACKGROUND: Recent advances in the therapy of advanced testicular nonseminomatous germ cell tumors (NSGCT) have resulted in increased attention to avoiding double therapy in cases where single modality therapy will suffice. METHODS: Over an 8-year period, 104 patients with Stage II and III testicular NSGCT received primary chemotherapy. Seventy-nine patients had retroperitoneal lymph nodal metastases, 33 of whom had a radiologic complete response, 43 a radiologic incomplete response, and 3 were not re-evaluated after induction chemotherapy. Thirty-nine patients underwent retroperitoneal lymph node dissection (RPLND). The radiologic and pathologic response of the nodes to primary chemotherapy was correlated with tumor burden (lymph node metastasis size < or = 2 cm, 2.1-5 cm, 5.1-10 cm, and >10 cm), primary tumor pathology, and prechemotherapy marker levels. RESULTS: Larger initial lymph node size, metastases size, the presence of teratoma in the primary tumor, and prechemotherapy alpha-fetoprotein (alpha-FP) > 80 mg/L and beta-HCG (bHCG) 10000 IU/L were found to correlate significantly with an incomplete radiologic response. Lymph node metastases size was the only independent prognostic factor on multivariable logistic regression analysis. Prechemotherapy alpha-FP > 80 mg/L and beta-HCG > 10000 IU/L were associated with the presence of teratoma or carcinoma in the retroperitoneal nodes. The presence of teratoma in the primary tumor is associated with a higher incomplete response rate and residual teratoma in the retroperitoneal lymph nodes after primary chemotherapy. CONCLUSIONS: Predictors of need for postchemotherapy RPLND include large lymph node metastasis size and presence of teratomatous elements in the primary tumor. To reduce the need for and morbidity of double therapy, patients with low volume clinical Stage II, NSGCT and teratomatous elements in the primary tumor are arguably better served by primary RPLND.

Adolescent↗
PubMed1996

Intermittent androgen suppression delays progression to androgen-independent regulation of prostate-specific antigen gene in the LNCaP prostate tumour model.

In most patients with prostate cancer, continuous androgen suppression (CAS) therapy causes tumour regression and an accompanying decrease in serum prostate specific antigen (PSA). However, with tumour progression, regulation of both tumour growth and PSA gene expression becomes androgen-independent. Because androgen resistance develops, in part, from adaptive cell survival mechanisms activated by androgen withdrawal, we hypothesize that intermittent re-exposure to androgens may prolong time to androgen-independent progression. The objective of this study was to determine whether intermittent androgen suppression (IAS) could delay the onset of androgen-independent PSA gene regulation in LNCaP prostate tumour model when compared to CAS. Five or six cycles of IAS were possible before progression developed. IAS prolonged time to androgen-independent PSA gene regulation from an average of 26 days in CAS to 77 days in IAS. Serum PSA increased above pre-castrate levels in all mice treated with CAS by 28 days post-castration, but remained below pre-castrate levels in 75% of IAS-treated mice by 60 days post-castration. By 15 weeks post-castration, serum PSA levels increased 7-fold above pre-castrate levels in CAS-treated mice compared to 1.9-fold increase in IAS-treated mice. PSA mRNA expression levels highly correlated with serum PSA levels in both groups. Maintenance of androgen dependency through IAS may be due to androgen-induced differentiation and/or down-regulation of androgen-suppressed gene expression.

Androgens↗
PubMed1996

Low-dose cyproterone acetate plus mini-dose diethylstilbestrol--a protocol for reversible medical castration.

OBJECTIVES: To determine whether a low dose of cyproterone acetate (CPA) (50 mg twice a day) with minidose diethylstilbesterol (DES) is efficacious in rapidly reducing and maintaining serum testosterone at less than 10% of pretreatment level and whether the effect is reversible upon cessation of therapy. METHODS: Data were collected prospectively on 62 subjects, aged 50 to 90 years (mean 69) with histologically confirmed prostate cancer and normal serum testosterone levels. Treatment was initiated with CPA 50 mg twice a day plus DES 0.11 mg once a day, both administered orally, and continued or 6 months unless discontinued for reasons unrelated to the study. Subsequent management was at the discretion of the investigator/managing physician. Treatment was discontinued with determination of at least one follow-up testosterone level in 28 patients. RESULTS: Mean pretreatment testosterone level was 13.8 nmol/L (range 4.5 to 46.6, median 14.0, 95% confidence interval [CI] 12.0 to 15.0). Testosterone dropped to a mean of 0.6 nmol/L (range 0.1 to 2.2, median 0.5, 95% CI 0.4 to 0.6) by first follow-up (usually 1 month) in all patients (P <0.001) and remained at this level as long as treatment continued. Testosterone normalized in all subjects whose treatment was discontinued. Side effects were minimal. CONCLUSIONS: An oral dosage of CPA of 50 mg twice a day in combination with a mini-dose of DES results in rapid and reversible reduction in serum testosterone to castrate levels. This regimen minimizes morbidity and monetary costs of therapy and allows the implementation of novel treatment approaches such as intermittent or neoadjuvant withdrawal therapy.

Aged↗
PubMed1996

Ability of serum prostate-specific antigen levels to predict normal bone scans in patients with newly diagnosed prostate cancer.

OBJECTIVES: To determine whether pretreatment serum prostate-specific antigen (PSA) levels in newly diagnosed prostate cancer patients can identify a group with a low probability of osseous metastasis and safely eliminate the need for a bone scan as a routine part of the staging evaluation. METHODS: We retrospectively reviewed 683 patients with prostate cancer between 1990 and 1993. Patients with prior therapy or serum PSA levels obtained longer than 3 months prior to bone scan were excluded. Bone scans were reviewed by two nuclear medicine physicians with a third deciding equivocal cases. RESULTS: Only 6% of 490 evaluable patients had a positive bone scan on initial evaluation. Scans were positive in 0 of 290 (0%) with PSA levels below 10 micrograms/L, 4 of 88 (4.5%) with PSA levels between 10 and 20 micrograms/L, and 24 of 112 (21%) with PSA levels above 20 micrograms/L. Although the risk of a positive bone scan increased with increasing PSA levels, PSA is a poor positive predictor of positive bone scans. The risk of a positive bone scan was 8% (5 of 64 patients) when PSA was between 20 and 50 micrograms/L, and increased to 40% (19 of 48 patients) for PSA levels greater than 50 micrograms/L. In contrast, serum PSA levels below 10 micrograms/L are strong negative predictors of positive bone scans, with no positive scans in 290 patients with PSA levels below 10 micrograms/L. Although the risk of a positive bone scan increased with increasing stage and grade, tumor stage and grade were poor negative predictors of positive bone scans. Up to 4% of patients with clinically confined or well-differentiated to moderately differentiated tumors had positive scans. Scans were positive in 12% of poorly differentiated tumors, but all these patients had PSA levels above 10 micrograms/L. CONCLUSIONS: Our data support the elimination of routine bone scintigraphy in patients with newly diagnosed prostate cancer and PSA levels below 10 micrograms/L. Bone scans are indicated when PSA levels are above 10 micrograms/L, or with T3 or poorly differentiated disease.

Adult↗
PubMed1996

Improved local control of invasive bladder cancer by concurrent cisplatin and preoperative or definitive radiation. The National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: A prospective randomized trial was conducted to determine whether the addition of concurrent cisplatin to preoperative or definitive radiation therapy in patients with muscle-invasive bladder cancer improved local control or survival. PATIENTS AND METHODS: Ninety-nine eligible patients with T2 to T4b transitional cell bladder cancer participated, 64% with cT3b or cT4. Patients and their physicians selected either definitive radiotherapy or precystectomy radiotherapy; patients were then randomly allocated to receive intravenous cisplatin 100 mg/m2 at 2-week intervals for three cycles concurrent with pelvic radiation, or to receive radiation without chemotherapy. Patients were stratified by clinical tumor stage and by radiation plan. The median follow-up duration is 6.5 years. RESULTS: The occurrence of distant metastases was the same in both study arms. However, 25 of 48 control patients have had a first recurrence in the pelvis, compared with 15 of 51 cisplatin-treated patients (P = .036). The pelvic relapse rate in the two groups was significantly reduced by concurrent cisplatin (P = .038, log-rank test) and this effect was preserved in a stepwise Cox regression model of prognostic factors (hazards ratio, 0.50; 90% confidence interval [CI], 0.29 to 0.86; P = .036). The hazard reduction was similar for both radiation plans. Pretreatment leukocytosis and high clinical stage were independent adverse factors in a Cox model of overall survival, but the effect of cisplatin was not significant. CONCLUSION: Concurrent cisplatin may improve pelvic control of locally advanced bladder cancer with preoperative or definitive radiation, but has not been shown to improve overall survival. The use of concurrent cisplatin had no detectable effect on distant metastases.

Adult↗
PubMed1996

Biochemical and pathological effects of 8 months of neoadjuvant androgen withdrawal therapy before radical prostatectomy in patients with clinically confined prostate cancer.

PURPOSE: A prospective, nonrandomized trial was initiated to determine the duration of neoadjuvant therapy required for prostate specific antigen (PSA) to reach its nadir, evaluate the ability of an ultrasensitive assay to measure decreases in PSA less than 0.2 microgram./l., and characterize the effects of 8 months of neoadjuvant therapy on pathological stage, positive margin rates, proliferation and tumor marker immuno-staining. MATERIALS AND METHODS: We evaluated 50 patients with clinically localized prostate cancer treated by 8 months of reversible androgen ablation before radical prostatectomy. Serum PSA and testosterone levels were measured monthly. RESULTS: Serum PSA decreased by 84% after 1 month and by a further 52% between 3 and 8 months. Using an ultrasensitive assay, serum PSA decreased to undetectable levels (less than 0.1 microgram./l.) or reached its nadir in 22% of the cases after 3 months, 42% after 5 months and 84% after 8 months. Overall, the positive margin rate was 4%. Of the cases 68% were organ-confined and 24% were specimen-confined. The positive margin rate was not increased after reevaluation with cytokeratin, PSA and prostatic acid phosphatase immuno-staining but of 4 cases initially staged as P0 on hematoxylin and eosin evaluation 2 had microscopic foci of cancer with prostatic acid phosphatase staining. Immuno-staining with the proliferation markers proliferation cell nuclear antigen and Ki-67 showed decreased staining in surgical specimens relative to pretreatment needle biopsy specimens, which suggests that outgrowth of androgen independent clones does not develop during prolonged neoadjuvant therapy. CONCLUSIONS: Eight months of neoadjuvant androgen withdrawal therapy results in low positive margin rates and PSA nadir levels. The initial rapid decrease in PSA results from cessation of androgen regulated PSA synthesis and apoptosis, while the ongoing slower decrease reflects decreasing tumor volume.

Androgen Antagonists↗
PubMed1996

Postoperative radiotherapy for stage pT3 carcinoma of the prostate: improved local control.

PURPOSE: We determined whether radiotherapy after radical prostatectomy leads to improved results in patients with stage pT3 carcinoma of the prostate. MATERIALS AND METHODS: In a prospective nonrandomized study of 203 patients with clinical stage T2 prostate cancer treated with radical prostatectomy 88 underwent surgery alone, 89 received early postoperative radiotherapy generally because of pathological stage T3 disease and 26 received delayed radiotherapy for local recurrence. The disease was stage pT3N0/X in 135 patients. RESULTS: For patients with pathological stage T3 cancer actuarial local recurrence rates were significantly decreased in the early postoperative radiotherapy group compared to the surgery only group (p = 0.005), while actuarial metastatic rates (p = 0.6) and cause specific survival rates (p = 0.04) were not significantly different. Multivariate analysis for all patients in both groups identified adverse features of increased postoperative prostate specific antigen levels, seminal vesicle involvement, lack of postoperative radiotherapy and positive lymph nodes. Late toxicity was severe (Radiation Therapy Oncology Group grade 3 or 4) in 13 surgery only and 17 early postoperative radiotherapy group patients. Of those who were potent postoperatively the incidence of impotence in the early postoperative radiotherapy group was 89% compared to 59% in the surgery only group (p = 0.003). For patients treated with delayed radiation for clinical local recurrence the actuarial local control rate was 54% after 10 years. CONCLUSIONS: Local radiotherapy appears to improve local control of stage pT3 cancer but has no impact on overall survival.

Actuarial Analysis↗