Long-term outcome following three-dimensional conformal/intensity-modulated external-beam radiotherapy for clinical stage T3 prostate cancer

OBJECTIVE: To report the long-term tumor control and survival outcomes after conformal external-beam radiotherapy for patients with clinical stage T3 prostate cancer. METHODS: Between 1988 and 2000, 296 patients with clinical stage T3 prostate cancer were treated with three-dimensional conformal radiotherapy and intensity-modulated radiotherapy. Of these, 130 patients (44%) had stage T3a (extracapsular extension without seminal vesicle involvement [SVI]) and 166 patients (56%) had stage T3b disease (SVI). Prior to radiotherapy, 189 patients (43%) were treated with short-course androgen-deprivation therapy (ADT). The median follow-up time was 8 yr. RESULTS: The 5- and 10-yr prostate-specific antigen (PSA) relapse-free survival (PRFS) outcomes for stage T3a tumors were 69% and 44%, respectively. The corresponding PRFS outcomes for T3b tumors were 49% and 32% (p=0.005). Despite the presence of locally advanced disease, the 5- and 10-yr local progression-free survival (LPFS) outcomes for all patients were 87% and 83%. Among patients who received > or =8100 cGy and ADT, the 5- and 10-yr local control rates were 96% and 88%. The 5- and 10-yr distant metastases-free survival (DMFS) outcomes for stage T3a tumors were 85% and 73%. The corresponding DMFS outcomes for T3b tumors were 49% and 32% (p=0.005). Multivariate analysis demonstrated that ADT conferred a 7-fold risk reduction for local failure. Pretreatment PSA levels and the presence of SVI on clinical staging were important predictors of distant metastases. CONCLUSIONS: Conformal radiotherapy for T3 prostate cancer is associated with excellent tumor control and survival outcomes. These results are at least comparable to reported outcomes from surgical series for T3 disease and substantiate the role of radiotherapy as the standard management option for locally advanced stage prostate cancer.     

Salvage surgery following radical radiotherapy for adenocarcinoma of the prostate

The development and proliferation of modern radiotherapy techniques, and their application in the 1970s to the treatment of localized adenocarcinoma of the prostate have led to substantial improvement in therapy of this disease. However, treatment failures occur. Among these patients is a small subset who have local recurrence of disease confirmed by biopsy without evidence of metastatic disease, and who still are relatively young and healthy. We report on 7 patients who satisfy these criteria. All 7 patients underwent a salvage operation with removal of the prostate gland following attempted curative radiotherapy: 3 underwent cystoprostatectomy and urinary diversion, and 4 underwent radical prostatectomy. Operating times averaged 4.9 hours and average blood transfusion was 5.3 units. Postoperative hospital stay averaged 13 days. Significant morbidity included 2 patients with rectal lacerations (1 of whom suffered a rectourethroperineal fistula that closed spontaneously), 2 with temporary urinary incontinence, and 1 with idiopathic thrombocytopenia and pseudomembranous colitis. As illustrated by these patients salvage surgery is difficult and there is substantial morbidity. However, this treatment option with its potential for cure can be offered to patients as a reasonable and rational approach to the problem.     

Clinical stage T1c prostate cancer: pathologic outcomes following radical prostatectomy in black and white men

BACKGROUND: The incidence of prostate cancer in black men is 50% to 70% higher than among age-matched white men. Black men have a twofold higher mortality rate and overall tend to have higher serum prostate-specific antigen (PSA) levels than white men. To determine whether racial differences exist in men whose prostate cancer was diagnosed based solely on an elevated serum PSA level, we compared clinical and pathologic features in black and white men undergoing radical prostatectomy (RP) for clinical stage T1c prostate cancer. METHODS: We used a prospectively collected database to identify all men undergoing RP for clinical T1c prostate cancer between July 1995 and October 2000. A total of 129 consecutive men (56 black men and 73 white men) were compared for age at diagnosis, serum PSA level, biopsy Gleason score, pathologic stage, RP specimen Gleason score, incidence of lymph node metastasis, and incidence of positive surgical margins. RESULTS: Statistically significant differences were not found by race in patients' ages, serum PSA levels, biopsy Gleason score, pathologic stage, incidence of lymph node metastases, or incidence of positive surgical margins. The RP specimen Gleason score was more heterogeneous in black men than white men (P=0.02). CONCLUSIONS: Racial differences in the incidence and mortality rate of prostate cancer are well known, but differences in the clinical and pathologic features between black and white men with prostate cancer identified solely based on an elevated serum PSA level with negative results on digital rectal examination (clinical stage T1c ) have been poorly studied. Our results suggest that men with clinical stage T1c prostate cancer have similar clinical and pathologic findings regardless of race. These results suggest that early-detection programs using serum PSA testing for prostate cancer in black men potentially can result in improvements in prostate cancer outcomes in this high-risk group.     

Bilateral pelvic lymphadenectomy and radical retropubic prostatectomy for stage C adenocarcinoma of prostate

A series of 105 patients with surgical Stage C adenocarcinoma of the prostate underwent pelvic lymphadenectomy and radical retropubic prostatectomy and were followed up from one and one-half to fifteen years; 33 (31%) of the 105 had clinical Stage C disease. Of the 105 patients, 92 were at risk for greater than or equal to two years, 42 for greater than or equal to five years, and 12 for greater than or equal to ten years. Survival and disease progression were related to tumor grade (Mayo grades 1 through 4) and tumor bulk (less than 3, 3 to 10, greater than 10 cm3) but not to seminal vesicle involvement. Twenty-seven patients received adjuvant treatment (orchiectomy, DES, radiation, or combinations of these); it was administered to patients with higher tumor grades, larger tumor bulk, and/or residual cancer. Overall actuarial survival at five and ten years was 85 per cent and 72 per cent, respectively; five-year nonprogression rate was 64 per cent. Local recurrence was noted in only 8 patients (7.6%). Radical surgical treatment for nonbulky Stage C disease of the prostate is associated with favorable survival results and good local control. Adjuvant treatment may favorably affect disease outcome. Clinical seminal vesicle involvement with negative urethrocystoscopy should not necessarily deter the surgeon from planning radical prostatectomy. Prospective adjuvant treatment protocols need to be developed to identify the value of adjuvant hormone and/or radiation therapy.     

Long-term outcome following radical prostatectomy in men with clinical stage T3 prostate cancer

PURPOSE: We evaluated patients at our institution who underwent radical prostatectomy for clinical stage T3 prostate cancer to determine their long-term clinical outcomes. MATERIALS AND METHODS: We reviewed our prospective surgical database and identified 176 men who underwent radical retropubic prostatectomy for clinical stage T3 prostate cancer from 1983 to 2003. Clinical and pathological data were reviewed and evaluated in a Cox proportional hazards model to determine preoperative predictors of biochemical recurrence. Clinical progression following biochemical recurrence was evaluated and clinical failure was defined as the development of clinical metastases or progression to hormone refractory prostate cancer. RESULTS: Of the 176 patients with cT3 prostate cancer 64 (36%) received neoadjuvant hormonal therapy. At a mean followup of 6.4 years 84 (48%) patients had disease recurrence with a median time to biochemical recurrence of 4.6 years. The actuarial 10-year probability of freedom from recurrence was 44%. On multivariate analysis biopsy Gleason score, pretreatment serum prostate specific antigen and year of surgery were independent predictors of biochemical recurrence. Neoadjuvant hormonal therapy was not a significant predictor of biochemical recurrence. Following biochemical recurrence clinical failure developed in 30 of 84 (36%) men with a median time of 11 years. Overall the 5, 10 and 15-year probabilities of death from prostate cancer were 6%, 15% and 24%, respectively. CONCLUSIONS: More than half (52%) of our patients remained free of disease recurrence following radical prostatectomy. In our series neoadjuvant hormonal therapy offered no advantage with respect to disease recurrence. Radical prostatectomy remains an integral component in the treatment of select patients with clinical stage T3 prostate cancer.     

Optimal timing of early versus delayed adjuvant radiotherapy following radical prostatectomy for locally advanced prostate cancer

ObjectivesAlthough post–radical prostatectomy (RP) adjuvant radiation therapy (ART) benefits disease that is staged as pT3 or higher, the optimal ART timing remains unknown. Our objective is to characterize the outcomes and optimal timing of early vs. delayed ART.Materials and methodsFrom the Surveillance, Epidemiology and End Results-Medicare data from 1995 to 2007, we identified 963 men with pT3N0 disease receiving early (<4 mo after RP, n = 419) vs. delayed (4–12 mo after RP, n = 544) ART after RP. Utilizing propensity score methods, we compared overall mortality, prostate cancer–specific mortality (PCSM), bone-related events (BRE), salvage hormonal therapy utilization, and intervention for urethral stricture. We then used the maximal statistic approach to determine at what time post-RP ART had the most significant effect on outcomes of interest in men with pT3N0 disease.ResultsWhen compared with delayed ART in men with pT3 disease, early ART was associated with improved PCSM (0.47 vs. 1.02 events per 100 person-years; P = 0.038) and less salvage hormonal therapy (2.88 vs. 4.59 events per 100 person-years; P = 0.001). Delaying ART beyond 5 months is associated with worse PCSM (hazard ratio [HR] 2.3; P = 0.020), beyond 3 months is associated with more BRE (HR 1.6; P = 0.025), and beyond 4 months is associated higher rates of salvage hormonal therapy (HR 1.6; P = 0.002). ART performed after 9 months was associated with fewer urethral strictures (HR 0.6; P = 0.042).ConclusionInitiating ART less than 5 months after RP for pT3 is associated with improved PCSM. Early ART is also associated with fewer BRE and less use of salvage hormonal therapy if administered earlier than 3 and 4 months after RP, respectively. However, ART administered later than 9 months after RP is associated with fewer urethral strictures. Our population-based findings complement randomized trials designed with fixed ART timing.     

Comparison of surgery alone with surgery and adjuvant radiotherapy for pT3N0 prostate cancer

OBJECTIVE: To compare the outcome between patients with pT3N0 adenocarcinoma of the prostate treated with radical prostatectomy (RP) and those receiving RP followed by a planned course of postoperative radiation therapy (RT). PATIENTS AND METHODS: During a period of 22 years 622 patients with pT3N0 prostate cancer were treated in one medical centre by RP. Of these, 199 (32%) were treated with surgery alone while 423 (68%) received planned postoperative pelvic RT (median 48 Gy). Patients were selected for RT by having a higher incidence of adverse prognostic factors than those undergoing RP alone. These prognostic factors included pathological stage (P = 0.001) preoperative prostate specific antigen (PSA) level (P < 0.001) and Gleason score (P = 0.18). The patients' median age was 66 years; the median follow-up was 6.1 years for all patients, 7 years for RP + RT and 5 years for the RP-alone. RESULTS: The 5- and 10-year actuarial survival was 92% and 73%, respectively, for RP + RT patients, and nearly identical for those in the RP-alone group (P = 0.73). The 5- and 10-year disease-free survival (DFS; PSA < 0.05 ng/mL) was 69% and 51%, respectively, for the former, and 71% and 60%, respectively, for the latter group. There was no significant difference in DFS between the treatment groups by pathological stage and Gleason score (P = 0.77). Likewise, there was no significant difference in mean and median time to relapse. A preoperative PSA level of < 10 vs 10-25 vs > 25 ng/mL did not influence overall survival but a PSA of > 25 ng/mL was predictive of DFS (P = 0.02). In a multivariate analysis the Gleason score was the most important predictor for overall survival and DFS (P < 0.001), while pathological stage was predictive of clinical recurrence and DFS (P < 0.001). After controlling for pathological stage and Gleason score, RP + RT patients were predicted to recur at 92% of the rate of RP-alone patients (P = 0.65). In all, 43 (10%) patients developed a clinical recurrence in the RP + RT group, including 30 (7%) patients with distant metastases alone, 13 (3%) with local recurrence, with an additional 88 (21%) who had PSA recurrence (PSA > 0.05 ng/mL). This compared with 13 (6.5%) patients with clinical recurrence, including seven (3.5%) with local recurrence and 23 (11.6%) with PSA > 0.05 ng/mL in the RP-alone group. Postoperative RT was well tolerated and did not add to the incidence of surgical complications. CONCLUSION: We propose that postoperative RT, as described here, helped to reduce the incidence of local recurrence and improved DFS to equal that of a lower-risk group of patients treated with RP alone. A randomized comparison is needed to define the role of adjuvant RT in patients with pT3N0 disease.     

Patterns of recurrence following pelvic exenteration and external radiotherapy for locally advanced primary rectal adenocarcinoma

Background: Local recurrence remains the main site of failure after pelvic exenteration for locally advanced primary rectal adenocarcinoma. This is a report on the patterns of recurrence in a group of such patients treated with pelvic exenteration and radiotherapy. Methods: Between 1980 and 1992, we treated 49 patients. Thirty-one received preoperative radiotherapy (pre-RT), 4,500 cGy. Six weeks later, we performed posterior pelvic exenteration (PPE) in 21 patients, and total pelvic exenteration (TPE) in 10. Nine patients received postoperative radiotherapy (post-RT), 5,000 cGy after a PPE. Nine patients had surgery only, PPE (n=7) and TPE (n=2). Results: Surgical mortality occurred in 16% of those patients who received pre-RT. The median follow-up was 52 months. Recurrences occurred in 23% of those patients who received pre-RT (local, one; local/distant, one; distant, four); in 88% of those patients treated with surgery only (local/distant, four; distant, four); and in 11% of those treated with post-RT (distant, one). The 5-year survival for patients who received radiotherapy was 66 versus 44% for those treated with surgery only. Conclusion: Local control of locally advanced primary rectal adenocarcinoma requiring a pelvic exenteration is improved by the addition of radiotherapy. When recurrences do occur they are predominantly at extrapelvic sites.Results of this study were presented at The 48th Annual Cancer Symposium of the Society of Surgical Oncology, Boston, Massachusetts, March 23–26, 1995.     

Bladder cancer risk following primary and adjuvant external beam radiation for prostate cancer

PURPOSE: Increased rates of secondary bladder malignancies have been reported after external beam radiation therapy (EBRT) for gynecological malignancies with relative risks of 2 to 4. This study was designed to determine if there was an increase in bladder cancer after EBRT for prostate cancer. MATERIALS AND METHODS: We retrospectively reviewed the Mayo Clinic Cancer Registry for patients who received EBRT for prostate cancer (1980 to 1998). Patients diagnosed with bladder cancer were identified. Comparative incidence rates were obtained from the national Surveillance, Epidemiology and End Results database. Subset analysis included patients treated with adjuvant radiation and those residing locally. Medical histories of patients with bladder cancer were reviewed. RESULTS: A total of 1,743 patients received EBRT for prostate cancer at our institution. In more than 12,353 man-years of followup no increase in bladder cancer risk was encountered. Subset analysis of men who received adjuvant radiation demonstrated that the relative risk of bladder cancer was increased but was not statistically significant. When the analysis was restricted to patients residing in the local area, the number of patients in whom subsequent bladder cancer developed was similar to Surveillance, Epidemiology and End Results rates. However, in the adjuvant radiation subset there was a statistically significant increase in subsequent bladder cancer. Patients in whom bladder cancer develops after EBRT often present with low grade disease but many have recurrence and progression. CONCLUSIONS: This retrospective review suggests there is not evidence of increased risk of bladder cancer after radiation therapy, assuming unbiased followup and complete ascertainment of cases. The natural history of bladder cancer in this population does not seem to be altered by a history of radiation.     

Long-term results of adjuvant hormonal therapy plus radiotherapy following radical prostatectomy for patients with pT3N0 or pT3N1 prostate cancer

BACKGROUND: The objective of the present study was to evaluate the efficacy of adjuvant androgen suppression in conjunction with external beam irradiation after radical prostatectomy in patients with pathologically confirmed extraprostatic disease. METHODS: Between July 1988 and October 1999, 38 patients with pT3N0 or pT3N1 prostate cancer received adjuvant hormonal therapy and external beam irradiation following radical retropubic prostatectomy and pelvic lymphadenectomy. Administration of luteinizing hormone-releasing hormone analog or castration were initiated as an adjuvant androgen suppression within 4 weeks after surgery, whereas pelvic irradiation was performed at a median dose of 50 G within 3 months after surgery. The prognostic advantage of this combined adjuvant therapy was analyzed. RESULTS: During the median observation period of 92 months, biochemical recurrence occurred in four of the 38 patients and five patients died. Of these five patients, only one died of prostate cancer progression. The 10-year biochemical recurrence-free, cancer-specific and overall survival rates of the 38 patients were 86.7%, 90.9% and 78.7%, respectively. Among several factors examined, only tumor grade was significantly associated with biochemical recurrence-free survival in these patients; however, there were no factors that were independent predictors for biochemical recurrence, based on multivariate analysis. Furthermore, biochemical recurrence-free survival in the 38 patients was significantly superior to that in 54 patients with locally advanced disease who did not receive any postoperative therapies until biochemical recurrence; however, there was no significant difference in cancer-specific and overall survival between these two groups. CONCLUSION: Despite retrospective analysis with a relatively small number of patients, results of the present study suggest favorable effects of the combined adjuvant treatments with androgen ablation and pelvic irradiation on cancer control for patients with pT3N0 or pT3N1 disease. However, considering the absence of a significant difference in cancer-specific and overall survival between patients with and without adjuvant treatments, it might not be necessary to routinely perform combined hormonal and radiation therapies in an adjuvant setting for pT3N0 or pT3N1 prostate cancer.     

Malignancy grade and clinical stage T0-T3 in prostate cancer

The frequency of malignancy grade I-III (grading system according to B?cking and Sommerkamp, 1980) and of clinical stages T0-T3 in 393 unselected prostatic carcinomas (227 punch biopsies and 166 transurethral resections) were investigated over a period of 2 years. G III carcinomas were represented most frequently in the whole material (54%) as well as in punch biopsies (62%). G I carcinomas with a favorable prognosis make up 20% of the tumors in the whole material and only 10% in punch biopsies. In contrast, 54.9% of incidental carcinomas (T0) are G I tumors, 18.6% G III carcinomas with an unfavorable prognosis. The advanced clinical stages T2 and T3 predominate in the whole material with 62.4%, compared to stages T0 and T1 comprising 37.6%. Malignancy grade and clinical stage are clearly correlated in the whole material. In incidental carcinoma, there is also a correlation between malignancy grade and histologic extension. The percentage of higher malignancy grades G II and G III increases with age. This is true for incidental carcinoma as well. The findings emphasize the prognostic significance of the grading system.     

Treatment-related toxicity and symptom-related bother following postoperative radiotherapy for prostate cancer

Introduction:

Patients have reported late effects and symptom-related bother following postoperative radiotherapy for prostate cancer.

Methods:

Patients treated with postoperative radiotherapy were surveyed at a median 56 months after radiotherapy using the Prostate Cancer Radiation Therapy instrument. A retrospective review was undertaken to obtain Radiation Therapy Oncology Group-Late Effects Normal Tissue (RTOG-LENT) toxicity scores at baseline and during follow-up.

Results:

Survey response was 64.5%. Median prostate bed radiation dose was 66 Gy given at a median 14 months after surgery. Adjuvant hormone therapy was given for 2 to 3 years to 40 patients; 22 received salvage therapy.PCRT impairment subscales were reported as mild for gastrointestinal dysfunction, moderate for genitourinary dysfunction and marked for sexual dysfunction. The use of one or more incontinence pads daily was reported by 25.6% and was similar to 23% use reported at baseline. Frequent or worse urinary frequency or hematuria was reported by 4.8%, and by 8.4% of respondents for bowel dysfunction. Moderate to severe disruption from bowel and bladder dysfunction was reported by up to 5.4% and 2.4% of respondents, respectively.Erectile function was described as poor to none in 88.3% of respondents, and dissatisfaction with sexual functioning was reported by 42.7%. Counselling or treatment was offered to 59% of those followed.

Conclusion:

Combined surgery and postoperative radiotherapy are associated with low and moderate rates of bowel and bladder dysfunction respectively, with low reported bother. High levels of sexual dysfunction and bother are seen following combined therapy. More effective pre- and post-treatment counselling are required, along with research into more effective prevention and treatment strategies.