Long-term survival after radical prostatectomy versus external-beam radiotherapy for patients with high-risk prostate cancer

BACKGROUND:

The long‐term survival of patients with high‐risk prostate cancer was compared after radical prostatectomy (RRP) and after external beam radiation therapy (EBRT) with or without adjuvant androgen‐deprivation therapy (ADT).

METHODS:

In total, 1238 patients underwent RRP, and 609 patients received with EBRT (344 received EBRT plus ADT, and 265 received EBRT alone) between 1988 and 2004 who had a pretreatment prostate‐specific antigen (PSA) level ≥ 20 ng/mL, a biopsy Gleason score between 8 and 10, or clinical tumor classification ≥ T3. The median follow‐up was 10.2 years, 6.0 years, and 7.2 years after RRP, EBRT plus ADT, and EBRT alone, respectively. The impact of treatment modality on systemic progression, cancer‐specific survival, and overall survival was evaluated using multivariate Cox proportional hazard regression analysis and a competing risk‐regression model.

RESULTS:

The 10‐year cancer‐specific survival rate was 92%, 92%, and 88% after RRP, EBRT plus ADT, and EBRT alone, respectively (P = .06). After adjustment for case mix, no significant differences in the risks of systemic progression (hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.51‐1.18; P = .23) or prostate cancer death (HR, 1.14; 95% CI, 0.68‐1.91; P = .61) were observed between patients who received EBRT plus ADT and patients who underwent RRP. The risk of all‐cause mortality, however, was greater after EBRT plus ADT than after RRP (HR, 1.60; 95% CI, 1.25‐2.05; P = .0002).

CONCLUSIONS:

RRP alone and EBRT plus ADT provided similar long‐term cancer control for patients with high‐risk prostate cancer. The authors concluded that continued investigation into the differing impact of treatments on quality‐of‐life and noncancer mortality will be necessary to determine the optimal management approach for these patients. Cancer 2011. © 2011 American Cancer Society.     

Combining a recombinant cancer vaccine with standard definitive radiotherapy in patients with localized prostate cancer.

PURPOSE: Many patients with clinically localized prostate cancer develop biochemical failure despite excellent local therapy perhaps due to occult metastatic disease. One potential solution is the utilization of a well-tolerated systemic therapy (e.g., vaccine) in concert with local therapy. EXPERIMENTAL DESIGN: We present a randomized phase II clinical trial designed to determine if a poxviral vaccine encoding prostate-specific antigen (PSA) can induce a PSA-specific T-cell response when combined with radiotherapy in patients with clinically localized prostate cancer. Thirty patients were randomized in a 2:1 ratio into vaccine plus radiotherapy or radiotherapy-only arms. Those patients in the combination arm received a "priming" vaccine with recombinant vaccinia (rV) PSA plus r V containing the T-cell costimulatory molecule B7.1 (rV-B7.1) followed by monthly booster vaccines with recombinant fowlpox PSA. The vaccines were given with local granulocyte-macrophage colony-stimulating factor and low-dose systemic interleukin-2. Standard external beam radiation therapy was given between the fourth and the sixth vaccinations. RESULTS: Seventeen of 19 patients in the combination arm completed all eight vaccinations and 13 of these 17 patients had increases in PSA-specific T cells of at least 3-fold versus no detectable increases in the radiotherapy-only arm (P < 0.0005). There was also evidence of de novo generation of T cells to well-described prostate-associated antigens not found in the vaccine, providing indirect evidence of immune-mediated tumor killing. The vaccine was well tolerated. CONCLUSION: This vaccine regimen can be safely given in patients undergoing radiation therapy for localized prostate cancer, with the majority of patients generating a PSA-specific cellular immune response to vaccine.     

Neoadjuvant docetaxel before radical prostatectomy in patients with high-risk localized prostate cancer.

PURPOSE: To determine the clinical, pathologic, and molecular effects of neoadjuvant docetaxel chemotherapy in high-risk localized prostate cancer. EXPERIMENTAL DESIGN: Patients with biopsy Gleason scores of 8 to 10, serum prostate-specific antigen levels >20 ng/mL, and/or clinical stage T3 disease received weekly docetaxel (36 mg/m2) for 6 months, followed by radical prostatectomy, and were monitored with weekly visits, serum prostate-specific antigen measurements, and endorectal magnetic resonance imaging (MRI). Frozen tumor specimens were collected for microarray analysis. RESULTS: The 19 patients enrolled received 82% of the planned chemotherapy. Toxicity was mild to moderate; fatigue and taste disturbance were common. Prostate-specific antigen declines of >50% were seen in 11 of 19 patients (58%; 95% confidence interval, 33-80%) and endorectal MRI showed maximum tumor volume reduction of at least 25% in 13 of 19 patients (68%; 95% confidence interval, 47-85%) and at least 50% in 4 patients (21%; 95% confidence interval, 6-46%). Sixteen patients completed chemotherapy and had radical prostatectomy; none achieved pathologic complete response. Microarray analysis identified coordinate up-regulation of genes involved in androgen metabolism associated with docetaxel therapy. Specifically, RNA expression for genes that decrease cellular levels of bioactive androgens was coordinately increased in response to chemotherapy. CONCLUSIONS: Neoadjuvant docetaxel administered for 6 months before radical prostatectomy is feasible, well tolerated, and often results in prostate-specific antigen declines of >50% and decreased tumor volume on endorectal MRI. No pathologic complete responses were observed. Altered androgen metabolism may partially account for the noted declines in prostate-specific antigen and be a mechanism for chemotherapy resistance.     

Health-related quality-of-life effects of radical prostatectomy and primary radiotherapy for screen-detected or clinically diagnosed localized prostate cancer.

PURPOSE: The current study was undertaken within the framework of a screening trial to compare the health-related quality-of-life (HRQOL) outcomes of two primary treatment modalities for localized prostate cancer: radical prostatectomy and external-beam radiotherapy. PATIENTS AND METHODS: We conducted a prospective longitudinal cohort study among 278 patients with early screen-detected (59%) or clinically diagnosed (41%) prostate cancer using both generic and disease-specific HRQOL measures (SF-36, UCLA Prostate Cancer Index [urinary and bowel modules] and items relating to sexual functioning) at three points in time: t1 (baseline), t2 (6 months later), and t3 (12 months after t1). RESULTS: Questionnaires were completed by 88% to 93% of all initially enrolled patients. Patients referred for primary radiotherapy were significantly older than prostatectomy patients (63 v 68 years, P <.01). Analyses (adjusted for age and pretreatment level of functioning) revealed poorer levels of generic HRQOL after radiotherapy. Prostatectomy patients reported significantly higher (P <.01) posttreatment incidences of urinary incontinence (39% to 49%) and erectile dysfunction (80% to 91%) than radiotherapy patients (respectively, 6% to 7% and 41% to 55%). Bowel problems (urgency) affected 30% to 35% of the radiotherapy group versus 6% to 7% of the prostatectomy group (P <.01). Patients with screen-detected and clinically diagnosed cancer reported similar posttreatment HRQOL. CONCLUSION: Prostatectomy and radiotherapy differed in the type of HRQOL impairment. Because the HRQOL effects may be valued differently at the individual level, patients should be made fully aware of the potential benefits and adverse consequences of therapies for early prostate cancer. Differences in posttreatment HRQOL were not related to the method of cancer detection.     

10-year survival and quality of life in patients with high-risk pN0 prostate cancer following definitive radiotherapy

PURPOSE: To evaluate long-term overall survival (OS), cancer-specific survival (CSS), clinical progression-free survival (cPFS), and health-related quality of life (HRQoL) following definitive radiotherapy (RT) given to T(1-4p)N(0)M(0) prostate cancer patients provided by a single institution between 1989 and 1996. METHODS AND MATERIALS: We assessed outcome among 203 patients who had completed three-dimensional conformal RT (66 Gy) without hormone treatment and in whom staging by lymphadenectomy had been performed. OS was compared with an age-matched control group from the general population. A cross-sectional, self-report survey of HRQoL was performed among surviving patients. RESULTS: Median observation time was 10 years (range, 1-16 years). Eighty-one percent had high-risk tumors defined as T(3-4) or Gleason score (GS) > or =7B (4+3). Among these, 10-year OS, CSS, and cPFS rates were 52%, 66%, and 39%, respectively. The corresponding fractions in low-risk patients (T(1-2) and GS < or =7A [3+4]) were 79%, 95%, and 73%, respectively. Both CSS and cPFS were predicted by GS and T-classification; OS was associated with GS only. High-risk, but not low-risk, patients had reduced OS compared with the general population (p < 0.0005). When pelvis-related side effects were included in multivariate analyzes together with physical function and pain, sexual, urinary, and bowel function were not independently associated with self-reported global quality of life. CONCLUSIONS: Despite surgically proven (p)N(0), RT with dosage <70 Gy as monotherapy does not give satisfactory CSS rates after 10 years in patients with T(3-4) or GS > or =7B.     

Comparing radical prostatectomy and brachytherapy for localized prostate cancer

Radical prostatectomy and ultrasound-guided transperineal brachytherapy are both commonly used for the treatment of localized prostate cancer. No randomized trials are available to compare these modalities. Therefore, the physician must rely on institutional reports of results to determine which therapy is most effective. While some investigators have concluded that both therapies are effective, others have concluded that radical prostatectomy should remain the gold standard for the treatment of this disease. This article reviews the major series available for both treatments and discusses the major controversies involved in making these comparisons. The data indicate that for low-risk disease, both treatments are effective, controlling disease in over 80% of the cases, with no evidence to support the use of one treatment over the other. Similarly, for intermediate-risk disease, the conclusion that one treatment is superior to the other cannot be drawn. Brachytherapy should be performed in conjunction with external-beam radiation therapy in this group of patients. For patients with high-risk disease, neither treatment consistently achieves biochemical control rates above 50%. Although radical prostatectomy and/or brachytherapy may play a role in the care of high-risk patients in the future, external-beam radiation therapy in combination with androgen deprivation has the best track record to date.     

Effect of combined treatment with salvage radiotherapy plus androgen suppression on quality of life in patients with recurrent prostate cancer after radical prostatectomy

PURPOSE: To examine the effect of salvage radiotherapy (RT) plus 2-year androgen suppression (AS) on quality of life (QOL). METHODS AND MATERIALS: A total of 74 patients with biopsy-proven local recurrence or PSA relapse after radical prostatectomy were treated with salvage RT plus 2-year AS, as per a phase II study. Quality of life was prospectively assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30-Item Version 3.0 with the added prostate cancer-specific module at baseline and predefined follow-up visits. RESULTS: Patients experienced a significant increase in bowel dysfunction (23%) by the end of RT (p < 0.0001). This bowel dysfunction improved after RT but remained slightly elevated (5-10%) throughout the 2-year AS period. This extent of residual bowel dysfunction would be considered of minimal clinical importance. A similar, but less pronounced, pattern of change did occur for urinary dysfunction. Erectile function showed no change during RT, but had an abrupt decline (10%) with initiation of AS that was of moderate clinical significance (p < 0.01). None of the other QOL domains demonstrated a persistent, significant change from baseline that would be considered of major clinical significance. CONCLUSION: The combined treatment with salvage RT plus 2-year AS had relatively minor long-term effects on QOL.     

Comparison of biochemical disease-free survival of patients with localized carcinoma of the prostate undergoing radical prostatectomy, transperineal ultrasound-guided radioactive seed implantation, or definitive external beam irradiation

PURPOSE: This retrospective study compares the long-term biochemical disease-free survival for patients undergoing radical prostatectomy, transperineal ultrasound-guided (125)Iodine implantation, or external beam irradiation alone in a tertiary referral community-based hospital. METHODS AND MATERIALS: Five hundred forty patients were available for evaluation, which included: external beam, 132; (125)I, 186; and radical prostatectomy, 222. For the 318 patients referred to the Department of Radiation Oncology, those with T3 disease underwent external beam irradiation while patients with T1 or T2 underwent (125) 0.2 ng/mL or if they had three consecutive increases in their PSA or an increase in their postoperative PSA warranting intervention with androgen ablation or external beam irradiation to the pelvis. RESULTS: Patients were stratified by pretreatment risk groups predicting for post-treatment PSA recurrence. Patients were considered to be at a low or intermediate risk for recurrence if their clinical stage was T1c, T2a, T2b, pretreatment PSA level was 20, or Gleason score was >/= 7. For 132 patients undergoing external beam irradiation, 28 of 37 low or intermediate risk obtained a 1 year nadir PSA of < 1 (76%) while 40% of high risk patients obtained nadir < 1. Of 186 patients undergoing (125)I, 112 of 147 low or intermediate risk (76%) obtained a nadir PSA < 1. Twenty of 39 (51%) high risk obtained a nadir PSA < 1. Of the 222 patients undergoing prostatectomy, 83 of 88 (94%) low or intermediate risk had undetectable levels of PSA at 1 year. One hundred seventeen of 134 (86%) were high risk and had undetectable levels of PSA at 1 year. The biochemical disease-free survival for patients with low or intermediate risk at 5 years is approximately 70% with no significant difference between those patients treated with radical prostatectomy, external beam, or (125)I. For those patients with high risk factors for recurrence, there is no significant difference between ultrasound-guided implant or external beam, but there is a significant improvement in biochemical disease-free survival with radical prostatectomy. CONCLUSION: For patients with low or intermediate risk disease, external beam, ultrasound-guided (125)I, or a radical prostatectomy give comparable long-term biochemical disease-free survival. For patients with high risk disease, a radical prostatectomy provides a significantly improved biochemical disease-free survival. Our current protocols utilize androgen ablation in combination with conformal three-dimensional external beam irradiation or androgen ablation in conjunction with external beam irradiation and (103)Pd seed implantation for patients at high risk for extra capsular disease. It is too early to determine if this combination therapy will give results comparable to radical prostatectomy. For patients who obtain a 1 year nadir PSA of < 1, the biochemical disease-free survival is durable with little risk of subsequent recurrence.     

Long-term oncologic results of salvage radical prostatectomy for locally recurrent prostate cancer after radiotherapy

PURPOSE: Salvage radical prostatectomy (RP) may potentially cure patients who have isolated local prostate cancer recurrence after radiotherapy (RT). We report the long-term cancer control associated with salvage RP in a consecutive cohort of patients and identify the variables associated with disease progression and cancer survival. METHODS AND MATERIALS: A total of 100 consecutive patients underwent salvage RP with curative intent for biopsy-confirmed, locally recurrent, prostate cancer after RT. Disease progression after salvage RP was defined as a prostate-specific antigen (PSA) level of > or =0.2 ng/mL or by initiation of androgen deprivation therapy. Cancer-specific mortality was defined as active clinical disease progression despite castration. Cox regression analysis was used to evaluate these endpoints. The median follow-up from RT was 10 years (range, 3-27 years) and from salvage RP was 5 years (range, 1-20 years). RESULTS: Overall, the 5-year progression-free probability was 55% (95% confidence interval, 46-64%), and the median progression-free interval was 6.4 years. The preoperative PSA level was the only significant pretreatment predictor of disease progression in the multivariate analysis (p = 0.01). The 5-year progression-free probability for patients with a preoperative PSA level of <4, 4-10, and >10 ng/mL was 86%, 55%, and 37%, respectively. The 10-year and 15-year cancer-specific mortality after salvage RP was 27% and 40%, respectively. The median time from disease progression to cancer-specific death was 10.3 years (95% confidence interval, 7.6-12.9). After multivariate analysis, the preoperative serum PSA level and seminal vesicle or lymph node status correlated independently with disease progression. CONCLUSIONS: Greater preoperative PSA levels are associated with disease progression and cancer-specific death. Long-term control of locally recurrent prostate cancer after definitive RT is possible when salvage RP is performed early in the course of recurrent disease.     

Salvage radiotherapy in patients with persisting prostate-specific antigen after radical prostatectomy for prostate cancer

Salvage radiotherapy in patients with persisting prostate-specific antigen (PSA) after radical prostatectomy for prostate cancer offers an approach to reduce local recurrence rates and to improve the rate of biochemical freedom from relapse. 30-70% of these patients experience a decrease in their PSA to an undetectable range; in about 40-50% of these patients, PSA remains stable after 5 years. Therefore, radiation therapy offers these patients an ultimate chance of cure. The pre-irradiation PSA value is of particular importance. The PSA level should not exceed 2 ng/ml because otherwise the rate of distant metastases increases significantly. Serious side effects are apparently low, thus confirming the suitability of this therapeutic approach.     

Cardiopulmonary morbidity and quality of life in non-small cell lung cancer patients treated with or without postoperative radiotherapy

Aim

To prospectively assess the cardiopulmonary morbidity and quality of life in patients with non-small cell lung cancer (NSCLC) treated with postoperative radiotherapy (PORT) in comparison to those not receiving PORT.

Materials and methods

From 2003 to 2007, 291 patients entered the study; 171 pN2 patients received 3D-planned PORT (PORT group), 120 pN1 patients (non-PORT group) did not. One month after surgery, all patients completed EORTC QLQ C-30 questionnaire and had pulmonary function tests (PFT); cardiopulmonary symptoms were assessed by modified LENT-SOM scale. Two years later, disease-free patients repeated the same examinations. The differences between baseline values and values recorded at two years in QLQ, LENT-SOM and the PFT of the two groups were compared.

Results

In the whole cohort, the rate of non-cancer related deaths was 5.3% and 5.0% in PORT and non-PORT group, respectively. Ninety-five patients (47 - PORT group, 48 - non-PORT group) were included into the final analysis. The differences in the QLQ and cardiopulmonary function (LENT/SOM, PFT) between both groups were insignificant. The forced expiratory volume in one second was on average 12.2% and 1.3% better in the PORT and the non-PORT group, respectively, p = 0.2.

Conclusions

Our findings support the hypothesis about insignificant morbidity of 3D-planned PORT.     

Adjuvant and salvage radiotherapy after radical prostatectomy for prostate cancer

PURPOSE: The optimal role of radiotherapy (RT) to the prostate bed after radical prostatectomy (RP) is the subject of much debate. In this study, the results of adjuvant RT (ART) and salvage RT (SRT) were compared. METHODS AND MATERIALS: A total of 146 lymph node-negative patients were treated postoperatively after RP with RT to the prostate bed between 1987 and 1998. Of these, 75 patients had an undetectable prostate-specific antigen (PSA) level and were treated with ART for adverse pathologic features only to a median dose of 60 Gy (range 51-70). A positive margin was identified in 96%, and two of the three with negative margins had seminal vesicle involvement (SVI). SRT was administered for either a persistently detectable PSA level after RP (n = 27) or for a delayed rise in PSA (n = 44) to a median dose of 70 Gy (range 60-78). Adjuvant androgen ablation was given to 37 patients; 2 who had received ART and 35 had who received SRT. The median duration of androgen ablation was 24 months. The primary end point was freedom from biochemical failure (bNED), which was considered to be an undetectable PSA level. The median follow-up was 53 months for all patients: 68 months for the ART patients and 35 months for the SRT patients. RESULTS: For the ART group, 8 patients subsequently developed a rising PSA level. The 5-year bNED rate was 88%. SVI was the strongest predictor of outcome, with a 5-year bNED rate of 94% for those without SVI and 65% for those with SVI (p = 0.0002). SVI was the only significant factor in Cox proportional hazards regression analysis in the ART cohort. For the SRT group, 20 patients developed a rising PSA level after RT. The 5-year bNED rate was 66% for all SRT patients, and 43% and 78% in those with a persistently detectable PSA and those with a delayed rise in PSA, respectively. In the Cox proportional hazards regression analysis, this subdivision of SRT was statistically significant. Moreover, when the Cox model included all patients and variables, the timing of RT (ART vs. SRT) was an independent correlate of bNED, as was androgen ablation. CONCLUSION: For RP patients with high-risk pathologic features, the timing of postoperative RT and the PSA status after RP were strong determinants of outcome. Because of the potential confounding factors, direct comparisons of ART and SRT are problematic; however, ART is extremely effective and offers the surest approach for maintaining biochemical control.     

Long-term results of radical prostatectomy in clinically localized prostate cancer: experience at the Johns Hopkins Hospital

The objectives of our retrospective long-term analysis of radical prostatectomy at The Johns Hopkins Hospital are to determine the efficacy of radical prostatectomy and the optimal statistical method for ascertaining survival following therapeutic intervention for men with clinically localized prostate cancer. The duration of survival and the cause of death were ascertained for 57 men with clinical stage B1 prostate cancer who had radical prostatectomies at The Johns Hopkins Hospital between 1951 and 1963. The absence of metastatic disease was determined by radiographic survey of the bones only. The survival curve determined by the direct method was virtually identical to the projected survival curve for a 62-year-old man in 1960. The cause-specific actuarial survival analysis indicated that only 14% of the men with stage B1 disease and a 15-year life expectancy will develop metastatic prostate cancer following radical prostatectomy. The cause-specific survival curve plateaued after 10 years, which indicated that the majority of men surviving 10 years free of disease are cured of the disease. Survival analysis was also determined by the direct method for 48 men with clinical stage B2 prostate cancer who had undergone radical prostatectomy between 1951 and 1963. Overall, the survival rates for these men were considerably lower than those for similarly treated men with clinical stage B1 disease. The survival curves following radical prostatectomy for men with stage B1 disease and clinical stage B2 disease pathologically confined to the prostate were similar. Radical prostatectomy for stage B1 disease was performed with minimal morbidity, and potency was preserved in most patients with the use of nerve-sparing modifications.(ABSTRACT TRUNCATED AT 250 WORDS)