Clinical Stage B2 Research Articles

Neoadjuvant hormonal therapy prior to radical prostatectomy: evaluation of pathological downstaging and biochemical relapse.

The effect of neoadjuvant hormonal therapy (NHT) prior to radical prostatectomy (RP) on pathological downstaging of prostate cancer and biochemical relapse of serum prostate specific antigen (PSA) level was evaluated. Twenty selected patients with prostate cancer, who were treated with hormonal therapy and demonstrated biochemical downstaging by reduction of PSA prior to RP and bilateral pelvic node dissection at the Tohsei National Hospital between January 1997 and August 2001, are reported on. The complete RP specimens of these 20 men were used for accurate evaluation of the pathological stage. All 20 patients received NHT; ten patients were treated with leuprolide plus flutamide and 10 received leuprolide plus chlormadinone acetate (CMA). Decreases in serum PSA values were demonstrated from a pre-hormonal average of 49.7 ng/ml to an average of 0.52 ng/ml after NHT. Of the three clinical stages, A2-C, for cancer patients, two of the 20 patients had stage A2, two had stage B1, nine had stage B2, and seven had stage C. Of the 20 patients with biochemical downstaging, two had pathological stage B1, seven had pathological stage B2, eight had pathological stage C, and three had positive pelvic lymph nodes. Ten (50%) of the 20 patients were reported to have positive surgical margins. Seminal vesical extension was observed in two cases, and penetration was not observed. Positive nodes were identified in three (15%) patients. Among the seven clinical stage C patients, one had pathological stage B1 disease and two had pathological stage B2. Four of nine patients with clinical stage B2 prostatic cancer had pathological stage C disease. The actuarial incidence of a rising PSA at 3 years for the leuprolide plus CMA group was 28.9% compared with 37.5%for the group receiving leuprolide plus flutamide. The cases of biochemical relapse did not necessarily indicate a high stage and had no tendency to be high for baseline PSA level, positive margin rates or Gleason scores. A significant decrease in the rate of penetration could be observed after NHT, though it was not so effective for pathological downstaging, and changes in the preoperative PSA level did not predict those patients who might have a favorable result.

SILDENAFIL CITRATE AFTER RADICAL RETROPUBIC PROSTATECTOMY

Erectile dysfunction continues to be a significant problem for men after radical retropubic prostatectomy despite nerve sparing techniques. Sildenafil citrate (Viagra) has proved effective for erectile dysfunction in many men. We determine the efficacy of sildenafil in men with erectile dysfunction after radical retropubic prostatectomy and examine variables that may impact the response to treatment. A total of 84 men were prescribed sildenafil after radical retropubic prostatectomy and asked to complete a series of questionnaires, including the International Index of Erectile Function (IIEF), on erectile function before and after sildenafil administration. The importance of factors, such as patient age, time since surgery, degree of cavernous nerve sparing, preoperative prostate specific antigen, Gleason score, clinical and pathological stage, and baseline postoperative erectile function, was examined. Of the 84 patients 45 (53%) had improved erections and 34 (40%) had improved ability for intercourse while taking sildenafil. Mean IIEF score for the erectile function domain increased from 9 to 14 (p <0.001). Orgasmic function (p = 0.004) and intercourse satisfaction (p = 0.009) also significantly improved. The degree of nerve sparing and baseline postoperative erectile dysfunction had a significant impact on the ability of sildenafil to improve erectile function (p = 0.010 and p <0.001, respectively) and total IIEF questionnaire responses (p = 0.031 and p <0.001, respectively). Age and pathological stage also appeared to have a significant effect. Sildenafil improved erectile function and the ability to have intercourse in more than half of men after radical retropubic prostatectomy. Baseline postoperative erectile function, which is dependent on the degree of nerve sparing technique, significantly impacts the likelihood that patients will respond to sildenafil.

Treatment of A2-B2 prostatic cancer: results of a hormonoradiotherapy combination in the PSA era

Prospective analysis of results of combined neoadjuvant hormonetherapy and external beam radiation therapy in A2-B2 prostate adenocarcinoma. Between 1986 and 1994, 36 patients with clinical stage A2 (five patients), B1 (12 patients) and B2 (19 patients) N0 adenocarcinoma of the prostate declined for radical surgery, underwent a brief neoadjuvant hormonal therapy before external beam radiotherapy at our radiation therapy department. They all had a PSA determination before the combined treatment and no evidence of local extension or metastatic spread. They were followed clinically and with serial PSA levels for a median time of 58 months. Relapse was defined by a PSA level > or = 2.5 ng/mL. Median pre-treatment PSA level was 16.5 ng/mL; 16 patients had less than 15 ng/mL. Combined treatment was very well tolerated. After 3 months of neoadjuvant hormonetherapy, digital rectal examination was normalized in 27 cases with a PSA value < or = 1 ng/mL in 23. Only four tumors have relapsed (one local failure, two metastases and one PSA failure). The single factor that predicted biochemical relapse was pre-treatment PSA level: the 5-year actuarial rate of PSA failure when PSA level < 15 ng/mL was 0% and 27.5% if it was > or = 15 ng/mL (p = 0.05). During follow-up, only two patients suffered grade 2 rectitis and seven complained a total impotency. This limited study advocates hormonal neoadjuvant therapy and radiotherapy association in intracapsular prostatic carcinoma in patients declined for surgery or when pre-treatment PSA is above 15 ng/mL, with mild acute and late toxicity.

Adjunctive value of cell proliferation but not of apoptosis to interpret pathologic effects on prostatic cancer after neoadjuvant endocrine therapy.

The current histological evaluation of the effects of endocrine therapy has difficulty in distinguishing pathologic degeneration caused by androgen ablation from residual poorly differentiated tumor. Therefore, we examined the changes in cell proliferation and apoptosis before and after endocrine therapy and analyzed whether they correlated with pathologic effects and histological differentiation. Between January 1986 and December 1995, 52 patients with clinical stage B2 and C prostate cancer underwent radical prostatectomy after neoadjuvant endocrine therapy (median duration 3.8 months). Proliferative and apoptotic activities of pretreatment biopsy specimens and radical prostatectomy specimens were analyzed with MIB-1 monoclonal antibody and in situ end-labeling of fragmented DNA. The mean proliferative index (PI) of radical prostatectomy specimens was significantly lower than that of biopsy specimens (P = 0.000003) and the decrease in PI after endocrine therapy was significantly related to histological differentiation (P = 0.014). There was a weak relationship between the decrease in PI after endocrine therapy and pathologic effects (P = 0.054), while in pathologically effective cases (Grades 2 and 3), three out of 16 (19%) showed a < 50% decrease in PI after endocrine therapy, and may be regarded as having poorly differentiated tumors. The mean apoptotic index (AI) of prostatectomy specimens tended to be higher than that of biopsy specimens (P = 0.054). The increase in AI after endocrine therapy was not related to histological differentiation and pathologic effects. Pathologic effects caused by endocrine therapy may be in part misled by routine histopathologic staining and the change in PI may help in recognizing the pathologic effects of endocrine therapy and have adjunctive value for the interpretation of the effects of endocrine therapy.

RECOVERY OF SPONTANEOUS ERECTILE FUNCTION AFTER NERVE-SPARING RADICAL RETROPUBIC PROSTATECTOMY WITH AND WITHOUT EARLY INTRACAVERNOUS INJECTIONS OF ALPROSTADIL: RESULTS OF A PROSPECTIVE, RANDOMIZED TRIAL

This study was aimed at assessing prospectively the effect of postoperative intracavernous injections of alprostadil on the recovery of spontaneous erectile function after nerve-sparing radical retropubic prostatectomy. A total of 30 potent patients with clinically localized prostate cancer (clinical stage B1 or B2, Gleason sum 7 or greater, prostatic specific antigen less than 20 ng./ml.) underwent nerve-sparing radical retropubic prostatectomy and was subsequently randomized to alprostadil injections 3 times per week for 12 weeks (group 1, 15 patients) or observation without any erectogenic treatment (group 2, 15 patients). Patients were assessed at the 6-month followup by sexual history, physical examination, color Doppler sonography of the cavernous arteries and polisomnographic recording of nocturnal erections. In group 1, 12 patients (80%) completed the entire treatment schedule and were evaluated at the long-term followup. Eight patients in this group (67%) reported the recovery of spontaneous erection sufficient for satisfactory sexual intercourse, compared with 3 patients (20%) in group 2. The difference between the 2 groups was statistically significant (p <0.01). In group 1, all but 1 patient reporting normal postoperative erections also showed normal erections at nocturnal testing, whereas color Doppler sonography demonstrated normal penile hemodynamics in all of them. In these patients, failures were the result of cavernous veno-occlusive dysfunction (2 cases, 17%) and cavernous nerve injury (2 cases, 17%). In group 2, patients with normal erections showed both normal nocturnal testing and penile hemodynamics, whereas failures were the result of cavernous veno-occlusive dysfunction (8 cases, 53%), cavernous arterial insufficiency (2 cases, 13%) or cavernous nerve injury (3 cases, 20%). Complications in patients treated with alprostadil injections accounted for 2 cases (13%) of a penile nodule and 1 further case (6%) of prolonged penile erection. Complications were not seen in group 2 patients. Early postoperative administration of alprostadil injections significantly increases the recovery rate of spontaneous erections after nerve-sparing radical retropubic prostatectomy. It is our belief that programmed vasoactive injections improve cavernous oxygenation, thereby limiting the development of hypoxia-induced tissue damage. The potential complications related to the use of intracavernous injections must be clearly explained to patients.

Randomized Prospective Study Comparing Radical Prostatectomy Alone Versus Radical Prostatectomy Preceded by Androgen Blockage in Clinical Stage B2 (T2bNxM0) Prostate Cancer

Nonrandomized clinical trials have suggested that preoperative androgen deprivation can decrease the likelihood of positive surgical margins in patients with clinically localized prostate cancer. A multicenter prospective randomized trial compared radical prostatectomy alone to radical prostatectomy after 3 months of leuprolide acetate depot and flutamide in patients with stage cT2bNxM0 prostate cancer and a serum prostate specific antigen level less than 50 ng./ml.We randomized 149 patients to undergo androgen deprivation and 138 to undergo lymphadenectomy with (137) or without (1) prostatectomy. Of the 154 patients randomized to the surgery alone group 144 underwent pelvic node dissection with (138) or without (6) prostatectomy.There was no statistically significant difference between the 2 groups in operating time, blood loss, need for transfusion, postoperative morbidity or length of hospital stay. There were 4 rectal and 2 ureteral injuries in the surgery alone group and none in the pretreatment group (p < 0.05). Patients who received androgen deprivation preoperatively had a significantly lower rate of capsule penetration (47% versus 78%, p < 0.001), positive surgical margins (18% versus 48%, p < 0.001) and tumor at the urethral margin (6% versus 17%, p < 0.01).Long-term followup data will be needed to determine whether there will be a lower incidence of biochemical relapse as determined by prostate specific antigen, local recurrence or metastasis, with an improvement in patient survival.

Randomized Prospective Study Comparing Radical Prostatectomy Alone Versus Radical Prostatectomy Preceded by Androgen Blockage in Clinical Stage B2 (T2bNxM0) Prostate Cancer

Purpose Nonrandomized clinical trials have suggested that preoperative androgen deprivation can decrease the likelihood of positive surgical margins in patients with clinically localized prostate cancer. A multicenter prospective randomized trial compared radical prostatectomy alone to radical prostatectomy after 3 months of leuprolide acetate depot and flutamide in patients with stage cT2bNxM0 prostate cancer and a serum prostate specific antigen level less than 50 ng./ml. Materials and Methods We randomized 149 patients to undergo androgen deprivation and 138 to undergo lymphadenectomy with (137) or without (1) prostatectomy. Of the 154 patients randomized to the surgery alone group 144 underwent pelvic node dissection with (138) or without (6) prostatectomy. Results There was no statistically significant difference between the 2 groups in operating time, blood loss, need for transfusion, postoperative morbidity or length of hospital stay. There were 4 rectal and 2 ureteral injuries in the surgery alone group and none in the pretreatment group (p less than 0.05). Patients who received androgen deprivation preoperatively had a significantly lower rate of capsule penetration (47 percent versus 78 percent, p less than 0.001), positive surgical margins (18 percent versus 48 percent, p less than 0.001) and tumor at the urethral margin (6 percent versus 17 percent, p less than 0.01). Conclusions Long-term followup data will be needed to determine whether there will be a lower incidence of biochemical relapse as determined by prostate specific antigen, local recurrence or metastasis, with an improvement in patient survival.

Adult primary pure teratoma of the testis. The Indiana experience

Pure testicular teratoma in adults is a relatively rare malignant tumor with the ability to invade and metastasize. Pure teratoma generally is believed to be less aggressive and less likely to progress, to present in lower stages, and to have better survival rates then other forms of germ cell tumor. Consequently, clinical stage A patients with pure testicular teratoma commonly have been considered to be managed best by surveillance. A computerized database search identified 41 patients presenting to Indian University with pure teratoma in the orchiectomy specimen. These patients were further subdivided into four groups based on clinical stage, as follows: Group I, 18 patients with clinical Stage A disease; Group II, 4 patients with clinical Stages A-B1 disease based on questionable computed tomography findings; Group III, 3 patients with clinical Stage B1 disease; Group IV, 16 patients with advanced stage (B3-C) disease. The experience with these patients was reviewed. The overall risk of lymph node metastasis in retroperitoneal lymph node dissection (RPLND) and the risk of relapse after RPLND for patients with low stage pure testicular teratoma (groups I-III) were 40 and 16%, respectively. In patients with clinical Stage A teratoma, the risk of retroperitoneal metastasis in RPLND was 16.7% and the relapse rate was 11.1%. In addition, nearly 37% of referred patients with pure teratoma presented with advanced disease. These data provide additional confirmation of the metastatic potential of pure testicular teratoma. The proper management of the adult clinical stage A patient with primary pure teratoma of the testis should not necessarily differ from the management of any other histologic type of nonseminomatous testicular tumor. Accordingly, histologic diagnosis of pure teratoma should not mandate surveillance. Instead, patients must be given adequate information regarding management options, as are all other patients presenting with clinical Stage A nonseminoma.

Phase II trial of hormonal cytoreduction with megestrol and diethylstilbestrol in conjunction with radiotherapy for carcinoma of the prostate: Outcome results of RTOG 83-07

Purpose : RTOG 83-07 is a Phase II randomized protocol designed to compare the efficacy and toxicity of Megestrol vs. Diethylstilbestrol (DES) used as cytoreductive agents prior to and during radiotherapy. The end points of this study include tumor clearance rate, effect on serum testosterone, loco-regional control, disease-free interval, and survival. Methods and Materials : Eligible patients were those with confirmed locally advanced adenocarcinoma, clinical Stage B2 (T2B) and C (T3) without regional lymph node involvement, or with lymph node involvement limited to the pelvis. Patients were stratified by clinical stage, hisotological grade, and nodal status, and were randomized to receive either Megestrol40 mg three times per day by mouth, or Diethylstilbestrol 1 mg three times per day by mouth. The drugs were started 2 months prior to initiation of radiotherapy and were continued throughout the radiotherapy course. Radiotherapy consisted of 44–46 Gy, 1.8–2 Gy per day to the regional lymphatics, followed by a boost to the prostate consisting of 20–25 Gy, 1.8–2 Gy per day, to a total of 65–70 Gy. Serum testosterone levels were recorded throughout the treatment course. Tumor response was assessed clinically and radiographically (CT scan). From March 1983 through June 1986 a total of 203 patients were accessioned to the study; 198 were analyzable. Results : Correlation of the incidence of drug-related toxicity and treatment arm assignment revealed a significantly higher incidence of complications in teh diethylstilbestrol (DES) arm. The most prominent were the differences in the incidence of gynecomastia (55% vs. 7%) and fluid retention (21% vs. 6%). The incidence of thromboembolic phenomena was comparable (8% vs. 5% in the Megestrol arm). Patients on the DES arm demonstrated a significantly greater median decrease in testosterone level. Correlation of the treatment arm assignment and the rate of tumor regression and the incidence of complete response revealed no significant difference between the arms. At 7 years, 16% of patients on the Megace arm and 21% of patients on the DES arm manifested evidence of local failure. Conclusion : The results of the study indicate comparable efficacy (using tumor clearance as an end point) of DES and Megestrol. Although DES appears more effective in suppressing testosterone, it is also associated with a higher incidence of drug-related toxicity.

Indications for laparoscopic pelvic lymph node dissection in the staging of prostate cancer.

Laparoscopic pelvic lymph node dissection is increasing in popularity, in the absence of validated surgical indications. This retrospective study was performed to identify those patients who would benefit from laparoscopic pelvic lymphadenectomy. The case notes of 50 patients who underwent bilateral open pelvic lymphadenectomy with frozen section examination were reviewed. The patients were staged clinically as having A2 (16), B1 (20) and B2 (14) prostate cancer. Except for the two patients who had macroscopically involved pelvic lymph nodes at operation, all proceeded to total prostatectomy. Six patients were found to have positive pelvic nodes. Of the six, four patients were clinical stage B2, one was B1 and one was A2. The Gleason score of two of these six patients was greater than seven. The prostate specific antigen (PSA) levels correlated more with high tumour volume (i.e. grade C) rather than with D1 disease. Frozen section at the time of lymphadenectomy had a false negative rate of 2 of 6. We conclude that laparoscopic pelvic lymph node dissections (LPLND) should be performed where there is a high likelihood of nodal disease, viz. bulky tumours, poorly differentiated histology and a high PSA reading. We consider that such selective use of LPLND optimizes its diagnostic utility while minimizing its unnecessary application.

Hormonal pretreatment does not affect the final pathologic stage in locally advanced prostate cancer

Abstract Objective To determine the effect of hormonal deprivation on final pathologic stage in locally advanced prostate cancer. Methods We studied 34 patients with clinical stage B2 or C prostate cancer whounderwent androgen deprivation therapy before radical prostatectomy at the University of Colorado Health Sciences Center. Staging was primarily based on digital rectal examination, transrectal ultrasound (TRUS), radionucleotide bone scan, computed tomography (CT scan) of the pelvis, transrectal coil magnetic resonance imaging (MRI), and measurement of serum prostate-specific antigen (PSA). The majority of patients underwent laparoscopic lymph node dissection and 5 patients with positive nodes were excluded. Five patients were treated with oral flutamide (250 mg three times daily), the other patients received a combination of the depot luteinizing hormone-releasing hormone analog leuprolide (7.5 mg) and flutamide (250 mg three times daily). Treatment duration was 4 months. PSA measurement was repeated every 4 weeks and TRUS as well as endorectal MRI was repeated prior to surgery. Results Although serum PSA levels dropped significantly by 98% from a mean of 37.4to 0.9 ng/mL (mean ± SD), volume reduction of 50% occurred, and histopathologic changes as an effect of androgen deprivation could be observed in all patients; all but 1 patient had pathologic stage C disease. Conclusion We conclude that the value, if any, of such an approach is limited regarding the final pathologic stage. However, since 14 of 18 patients had an undetectable serum PSA after a mean follow-up of 15 months, the long-term effect of this concept warrants further study.

Laparoscopic staging of prostatic carcinoma.

Current treatment of prostate cancer is highly controversial, however accurate assessment of pelvic lymph node status is important to determine early in the course of therapy if adjuvant hormonal ablation is necessary. Indications for laparoscopic assessment of pelvic lymph nodes are now better defined and the technique requires a high degree of technical skill and expertise. A series of 50 patients who underwent laparoscopic pelvic lymphadenectomy is presented. A greater than 40% chance of node positivity was found in a group of patients who had either a clinical stage B2, C, DO, or a prostate-specific antigen level greater than 40 ng/dl, or a total Gleason score of 7, 8, 9, or 10. Laparoscopic pelvic lymphadenectomy remains the current method to accurately stage lymph node involvement in prostate carcinoma.

Linear regressive analysis using prostate-specific antigen doubling time for predicting tumor biology and clinical outcome in prostate cancer.

This study was undertaken to calculate the prostate-specific antigen doubling time (PSA-DT) of prostate cancers recurrent after external beam radiation therapy and to investigate if a correlation exists between the PSA-DT and the clinical behavior of prostate cancer as a possible reflection of the tumor doubling time. Twenty-two patients treated with external beam radiation between October 1985 and October 1990 for clinical stages B1, B2, and C (T2a, T2b, T3) prostate cancer experienced PSA elevation as their only sign of failure. Serial PSA determinations are available before initiation of any secondary treatment and these have been used to calculate PSA-DT. The results of this study reveal that the PSA-DT is a constant (r > or = 0.98). Mathematically, this means the PSA value is growing exponentially and may represent tumor growth in the exponential phase. Second, the PSA-DT was found to be linearly correlated (r = 0.86) with the interval to clinical relapse after PSA failure. Graphically, the slope of this correlation is equal to the number of PSA-DT (4.5 with 95% confidence interval [3.6]) required before clinical disease manifests after PSA failure. Using this relationship, one can delineate those patients with aggressive tumor biology (PSA-DT < 3.8 months) who require immediate therapeutic intervention versus a relatively indolent tumor biology (PSA-DT > or = 3.8 months) who can be spared the morbidity and expense of androgen deprivation therapy until clinical recurrence manifests. Furthermore, in the pretreatment setting, observation rather than treatment may be indicated for patients with PSA-DT for 18 months or more, because the disease may not become clinically apparent during the patient's lifetime. PSA-DT after radiation therapy may reflect the tumor doubling time and has implications in the posttherapy setting regarding the optimal time of intervention with androgen deprivation and in the pretreatment setting regarding the necessity for treatment rather than observation.

Neoadjuvant Hormonal Deprivation in Patients with Locally Advanced Prostate Cancer

A total of 22 patients with locally advanced prostate cancer (stage B2 to C) was entered into a protocol for 3 months of preoperative hormonal deprivation. Of the patients 8 were judged to have clinical stage B2 and 14 to have stage C disease. The protocol regimen consisted of daily administration of flutamide (250mg. orally 3 times per day) and leuprolide injection (7.5mg. intramuscularly) every month. Patients with objective evidence of downstaging by prostate specific antigen (PSA) levels and transrectal ultrasound were offered surgical therapy.Of the 22 patients 20 have completed the protocol and are evaluable, and 2 of them did not show significant downstaging and elected radiotherapy. Preoperative hormonal therapy produced an average 33% downsizing of the prostate gland as determined by transrectal ultrasound volumetrics. Decreases in serum PSA values were demonstrated from a pre-hormonal average of 30 μg./l. (range 0.7 to 97.7) to an average of 0.53 μg./l. (range 0.2 to 5.7) after hormonal therapy. Of the 18 patients who underwent an operation after demonstrating significant downsizing 7 had pathologically confirmed stage B disease, 7 had stage C cancer and 4 had positive pelvic lymph nodes. Of the 8 clinical stage B2 cancer patients 4 had pathological stage B2 disease following the protocol. Of the 12 clinical stage C cancer patients 3 had pathological stage B disease, 4 had positive pelvic lymph nodes and the remainder had pathological stage C cancer. Thus, only 3 of 20 patients (15%) demonstrated pathological downstaging from the clinical stage. Downsizing the prostate volume and PSA changes with hormonal therapy were not predictive of patient outcome either alone or in combination.Preoperative hormonal therapy did not appear to facilitate the surgical procedure. Patients completing neoadjuvant hormonal therapy had an average estimated blood loss of 1,238ml. and an average operating time of 183 minutes. A group of 20 consecutive patients with stage B2 prostate cancer who underwent radical prostatectomy without preoperative hormone therapy had an average estimated blood loss of 1,296ml. and an average operating time of 171 minutes.

Preservation of Ejaculation Through a Modified Retroperitoneal Lymph Node Dissection in Low Stage Testis Cancer

We studied ejaculatory function in 47 patients who underwent modified retroperitoneal lymph node dissection for nonseminomatous germ cell tumors of the testis from 1983 to 1989. Our goal was to assess the effectiveness of a modified node dissection in preserving ejaculatory function while eliminating the risk of retroperitoneal recurrence. There were 13 left and 34 right tumors. Of the patients 45 had clinical stage A cancer, and 2 had clinical stage B2 disease and received preoperative chemotherapy. The template method of dissection was used, which spares the preaortic area below the inferior mesenteric artery, including the sacral promontory. Average operating time was 3hours 40 minutes. There was no operative mortality. Spontaneous recovery of ejaculation occurred in 38 patients (81%), more commonly with right (88%) than with left dissections (62%). The mean interval to recovery of ejaculation was 5 months (92% within 12 months). Five patients (10%) had recurrence, with a mean followup of 28 months. All recurrences were in the lungs 4 to 8 months after retroperitoneal lymph node dissection, and all patients were salvaged with chemotherapy and are disease-free. We confirmed that a modified template-type retroperitoneal lymph node dissection can be accomplished safely with preservation of ejaculation in more than 80% of the patients without increasing the risk of local recurrence.

Preoperative Androgen Deprivation Therapy: Artificial Lowering of Serum Prostate Specific Antigen without Downstaging the Tumor

We studied 22 patients with clinical stage B2 (T2c) or C (T3) prostate cancer who underwent androgen deprivation therapy before radical prostatectomy as part of a downstaging protocol (group 1). The concentration of serum prostate specific antigen (PSA) was determined before and at the conclusion of androgen deprivation therapy, just before the operation. For each group 1 patient a match patient who had not received preoperative endocrine therapy (group 2) was chosen. The age of the group 2 patients was similar to that of the group 1 patients. The clinical stage of disease and pretreatment tumor grade in group 2 were identical to the stage and grade in group 1, and the serum PSA value in group 2 was similar to that of group 1 before initiation of androgen deprivation therapy. In group 1 the median serum PSA concentration was 14.8ng./ml. (range 3.1 to 99) before endocrine therapy and 0.2ng./ml. (range 0.1 to 3.4) after hormonal treatment. Group 2 had a median level of 13.3ng./ml. (range 3.4 to 100). The median decrease in the serum PSA concentration for group 1 as a result of androgen deprivation therapy was 98.5%. The radical prostatectomy specimens from these 2 groups of similar patients had no difference with regard to maximal tumor dimension, pathological stage and deoxyribonucleic acid ploidy status. These findings indicate that serum PSA becomes an unreliable indicator of disease status after initiating preoperative androgen deprivation therapy and that preoperative androgen deprivation therapy has little or no benefit for decreasing the extent of tumor or pathological stage. The concept of downstaging is misleading and must be examined in a randomized clinical trial.

Ability of preoperative serum prostatespecific antigen value to predict pathologic stage and DNA ploidy Influence of clinical stage and tumor grade

Although the preoperative serum prostate-specific antigen (PSA) concentration has been demonstrated to be directly proportional to pathologic stage, it has been found to be unreliable for predicting final pathologic stage on an individual basis. Statistical analysis was thus performed to determine whether combining various preoperative parameters could enhance the predictive power of PSA. Multivariate logistic regression analysis revealed that, indeed, local clinical stage (determined by digital rectal examination) and tumor grade (determined from the biopsy specimen) significantly enhanced the predictive power of PSA ( P < 0.0001 and < 0.0001, respectively). These preoperative parameters were thus all combined into a model from which probability plots were generated. These probability plots allow the practicing urologist to estimate preoperatively for an individual patient the probability of a given pathologic stage and DNA ploidy status. For example, the predicted probability of organ-confined disease for a patient with a PSA value of 10 ng/mL, when used alone, is 53 percent. However, the predicted probability of organ-confined disease for a patient with a PSA value of 10 ng/mL, clinical Stage B2, and high-tumor grade is only 30 percent. Thus, the findings of this investigation allow the physician maximal use of the preoperative variables to discuss more accurately with the patient what might be expected at the time of operation and to plan more precisely the surgical procedure that will possibly ensure complete removal of the prostate cancer with the least compromise to normal physiologic function (continence and potency).

Clinical results of radical surgery for prostate cancer

We reported the clinical results of radical surgeries for 44 patients with prostate cancer performed between November 1984 and December 1992. The patients were aged from 57 to 79-year-old (mean 67.2) and classified as clinical stage A2 (6 cases), B1 (7), B2 (12), C (16) and D1 (3) respectively. Radical prostatectomy was performed in 42 cases and radical cystoprostatectomy with urinary diversion in 2 patients, and thirty-nine of 44 cases underwent endocrine or chemoendocrine therapies prior to the surgeries. In all patients with stage A2-B1, the operations were curative, on the other hand, more than 80% of clinical stage B2 patients had pT3 tumors and 33.3% of them had lymph node involvements. With regard to stage C patients, the incidence of lymph node metastasis and positive margin was more frequent. Postoperative adjuvant therapies were added to the patients with pT3,4 tumors and nodal involvements. Patients without residual tumors (n = 20) remained disease-free for 8-89 months (mean 32.8). Of 24 patients who had incomplete resection of tumors, 2 died of other diseases, other 2 were alive recurrent and 20 were alive free from disease for 3-99 months (mean 33.8). The surgical indication for low-stage (A2-B2) prostate cancer has been widely accepted, however that for high-stage cancer (C,D1) has remained controversial. It was our belief that radical surgeries for high-stage cancer could become a potentially curative therapeutic modality in combination with pre- and post-operative adjuvant therapies.

Clinical stage B o or T1c prostate cancer: Nonpalpable disease identified by elevated serum prostate-specific antigen concentration

A retrospective study was performed to evaluate the clinical and pathologic characteristics of 60 patients with a palpably benign prostate gland, but with biopsy-proved prostate cancer. All patients underwent prostate biopsy because of elevated serum prostate-specific antigen (PSA) concentration, and subsequently underwent radical retropubic prostatectomy (RRP). Similar analysis was performed for a randomly selected group of 60 clinical Stage BI prostate cancers from the same period (control cohort). Patients with nonpalpable prostate cancers had a higher preoperative PSA level as compared with the clinical Stage BI group (median value: 12.3 ng/mL versus 4.6 ng/mL, p < 0.001). There was no significant difference between the two groups with regard to clinical parameters (voiding symptoms, hematuria, age). The nonpalpable prostate cancers exhibited a significant tumor volume (mean: 7.4 cc; range: 0.3–56 cc), and 18 (30 %) demonstrated capsular perforation to involve the periprostatic tissues. Of these, three (5 %) had seminal vesicle invasion, and one (2 %) had pelvic lymph node involvement. There was no difference between these pathologic characteristics and those of the clinical Stage B1 prostate cancers. These findings suggest that nonpalpable prostate cancers identified by an elevated serum PSA level can be of clinical significance and warrant therapeutic consideration. Although nonpalpable, these cancers are peripherally located and were clinically suspected prior to biopsy. Therefore, we propose that these cancers be classified as clinical Stage B o in the Whitmore-Jewett staging system; in the new TNM staging system, they are designated as clinical Stage T1c.

Staging laparoscopic pelvic lymph node dissection. Experience and indications.

Laparoscopic pelvic lymph node dissection has proven to be a reliable, less-invasive method for staging prostate cancer. Presently, no clear indications for its performance prior to radical retropubic prostatectomy are available. With the purpose of identifying clinical parameters by which to better select patients who would benefit from laparoscopic pelvic lymph node dissection, we chose to perform the procedure only in patients considered at high risk for nodal metastasis: clinical stages B2 or C, poorly differentiated tumors, and/or a serum prostatic-specific antigen level of more than 20 ng/dL. We compared the results with those of patients not meeting such parameters. Of 80 men receiving treatment for clinically localized disease, 30 (38%) fulfilled one or more of the criteria. When considering the individual clinical parameters, clinical stage was predictive of nodal involvement in five (26%) of 19 patients, grade was predictive in three (37.5%) of eight patients, and prostatic-specific antigen level was predictive in six (40%) of 15 patients. Statistical analysis confirmed that the prostatic-specific antigen level was the single best predictor of nodal involvement. However, better predictive values were obtained when the different criteria were combined. Nodal involvement was predicted most consistently by a combination of clinical stage and prostatic-specific antigen level.