Evaluation and management of prostate-specific antigen recurrence after radical prostatectomy for localized prostate cancer

A radical prostatectomy has been established as one of the standardmanagement options for localized prostate cancer. However, asubstantial proportion of patients who undergo a radical prostatectomydevelop prostate-specific antigen (PSA) recurrence which iscommonly defined as a PSA cut-off point value of 0.2 ng/ml.Although the management of PSA recurrence after radical prostatectomymay depend on the site of recurrence, it is quite difficultto identify the recurrent lesion accurately based on the currentlyavailable imaging technology. Patients who have surgical margininvolvement or a Gleason score 7 based on the radical prostatectomyspecimens, who do not have nodal or seminal vesicle involvement,and who develop a PSA recurrence >1–2 years after surgerywith a doubling time of >1 year, and whose pre-treatmentPSA is <1.0–1.5 ng/ml are considered to benefit fromlocal treatment with at least 64 Gy of salvage radiotherapy.Patients with different characteristics are considered to havedistant metastases or both local lesions and distant metastases,and thus may be candidates for hormonal manipulation ratherthan radiotherapy. Since local recurrent lesions are consideredto be quite small at the early stage of PSA recurrence, hormonalmanipulation may be sufficient to prevent disease progressioninstead of radiotherapy. However, the optimal type and timingof hormonal manipulation remain to be elucidated. As a result,no consensus regarding the treatment for PSA recurrence afterradical prostatectomy has yet been reached.     

Prostate cancer-specific mortality after radical prostatectomy or external beam radiation therapy in men with 1 or more high-risk factors

BACKGROUND: Estimates of prostate cancer-specific mortality (PCSM) were determined after radical prostatectomy (RP) or radiation therapy (RT) in men with >or=1 high-risk factors. METHODS: The study cohort comprised 948 men who underwent RP (N = 660) or RT (N = 288) for localized prostate cancer between 1988 and 2004 and had at least 1 of the following high-risk factors: a prostate-specific antigen (PSA) velocity >2 ng/mL/year during the year before diagnosis, a biopsy Gleason score of >or=7, a PSA level of >or=10 ng/mL, or clinical category T2b or high disease. Grays regression was used to evaluate whether the number and type of high-risk factors were associated with time to PCSM. RESULTS: Multiple determinants of high risk were found to be significantly associated with a shorter time to PCSM after RP (P < .001) or RT (P 2 ng/mL/year was associated with an increased risk of PCSM after RP (hazards ratio [HR] of 7.3; 95% confidence interval [95% CI], 1.0-59 [P = .05]) or RT (HR of 12.1; 95% CI, 1.4-105 [P = .02]) when compared with men with any other single high-risk factor. CONCLUSIONS: Men with a PSA velocity >2 ng/mL/year had a significantly higher risk of PCSM compared with men who had any other single high-risk factor. These men should be considered for randomized trials evaluating the impact on PCSM from adding systemic agents to standards of care for men with high-risk PC.     

Patient selection, cancer control, and complications after salvage local therapy for postradiation prostate-specific antigen failure: a systematic review of the literature

Among men who experience prostate-specific antigen (PSA) failure after external beam radiation or brachytherapy (RT), many will harbor occult micrometastases; however, a significant minority will have a true local-only failure and, thus, potentially may benefit from a salvage local therapy. Those most likely to have a local-only failure initially have low-risk disease (PSA < 10 ng/mL, Gleason score < or =6, clinical T1c or T2a tumor status), pretreatment PSA velocity < 2.0 ng/mL per year at the time of initial presentation, interval to PSA failure > 3 years, PSA doubling time > 12 months, negative bone scan and pelvic imaging, and positive rebiopsy. In addition, men with presalvage PSA levels > 10 ng/mL, presalvage T3/T4 disease, or presalvage Gleason scores > or =7 on a rebiopsy sample without significant RT effects are unlikely to be cured by salvage local therapy. Based on a review of all series of post-RT salvage prostatectomy, cryosurgery, and brachytherapy published in English since 1990, morbidity can be substantial. Although urinary incontinence appeared to be greater after salvage prostatectomy (41%) or cryosurgery (36%) than after brachytherapy (6%), patients who received salvage brachytherapy faced a 17% risk of grade 3 or 4 genitourinary complications and a fistula risk that averaged 3.4% across all series. From this review, the authors concluded that prospective randomized studies are needed to determine the relative efficacy of the 3 major local salvage modalities and that additional research is needed to identify factors associated with an increased risk of significant complications to improve patient selection and to augment the benefit/risk ratio associated with attempts to cure local-only recurrences after radiation therapy.     

Influence of body mass index on prostate-specific antigen failure after androgen suppression and radiation therapy for localized prostate cancer

BACKGROUND: Increasing body mass index (BMI) is associated with shorter time to prostate-specific antigen (PSA) failure after radical prostatectomy. Whether BMI is associated with time to PSA failure was investigated in men treated with androgen suppression therapy (AST) and radiation therapy (RT) for clinically localized prostate cancer. METHODS: The observational prospective cohort study consisted of 102 men with clinically localized prostate cancer who received 70 Gy RT with 6 months of AST on a single arm of a randomized trial between December 1995 and April 2001. Height and weight data were available at baseline for 99 (97%) of the men, from which BMI was calculated. Adjusting for age (continuous) and known prognostic factors including PSA level (continuous), Gleason score, and T-category, Cox regression analyses were performed to analyze whether BMI (continuous) was associated with time to PSA failure (PSA >1.0 ng/mL and increasing >0.2 ng/mL on 2 consecutive visits). RESULTS: Median age and median BMI (interquartile range [IQR]) at baseline was 72 (69.1-74.7) years and 27.4 (24.8-30.7) kg/m,(2) respectively. In addition to an increasing PSA level (P = .006) and Gleason 8-10 cancer (P = .024), after a median follow-up (IQR) of 6.9 (5.6-8.5) years, an increasing BMI was also significantly associated with a shorter time to PSA failure (adjusted hazard ratio [HR]: 1.10; 95% confidence interval [CI]: 1.01-1.19; P = .026) after RT and AST. CONCLUSIONS: After adjusting for known prognostic factors, baseline BMI is significantly associated with time to PSA failure after RT and AST for men with clinically localized prostate cancer. Further study is warranted to assess the impact of an increasing BMI after AST administration on PSA failure, prostate cancer-specific, and all-cause mortality.     

Salvage laparoscopic surgery in advanced prostate cancer: is it possible or beneficial?

Purpose: The surgical management of recurrent urological cancer continues to evolve. This review focuses on the role laparoscopic surgical techniques have within recurrent prostate treatments. Methods: A literature search from 1990 to 2007 was conducted using the PubMed database to determine the role of laparoscopic salvage surgery for prostate cancers. In all articles studied, we evaluated: estimated blood loss; transfusion rates; hemoglobin level; serum and drain fluid creatinine levels; bowel injury; hospital stay and complication rates. Results: Laparoscopic surgery is used regularly for the treatment of urological cancers; however, its role in treating radiorecurrent or chemoradiorecurrent cancer is unknown. Adjuvant chemo-radiotherapy, other experimental localized therapies (cryotherapy) or hormonal therapy are known to affect the operative field, causing greater morbidity in open surgery. Relative survival rates were lowest among patients who received no treatment and highest among patients who underwent surgical procedures. Conclusions: Although associated with significant morbidity, salvage prostatectomy remains a viable form of therapy. Laparoscopic salvage radical prostatectomy for recurrent cancer is feasible with no more morbidity than an open procedure, with promising short-term oncologic and functional outcomes. Long-term data will ultimately confirm the viability of the laparoscopic approach most probably in a multicenter setting.     

Long-term outcomes of radical prostatectomy with multimodal adjuvant therapy in men with a preoperative serum prostate-specific antigen level > or =50 ng/mL

BACKGROUND.

The authors evaluated the long‐term outcomes of men with prostate cancer and very high (≥50 ng/mL) preoperative serum prostate‐specific antigen (PSA) values that were treated with radical prostatectomy.

METHODS.

This study included 236 men with preoperative serum PSA values ≥50ng/mL who underwent radical retropubic prostatectomy between 1987 and 2004. For comparison, the study cohort was divided into 2 groups: patients with PSA levels between 50 and 99 ng/mL and patients with PSA levels ≥100 ng/mL. Biochemical recurrence was defined as a single postoperative serum PSA value of 0.4 ng/mL or greater. Systemic disease progression was defined as the development of a local recurrence or systemic metastases, and any death resulting from prostate cancer or its treatment was defined as a cancer‐specific mortality.

RESULTS.

Biochemical recurrence‐free survival rates in the groups of patients with a PSA level 50 to 99 ng/mL and ≥100 ng/mL were 43% and 36% at 10 years, respectively. Systemic progression‐free survival rates in the PSA 50 to 99 ng/mL and PSA ≥100 ng/mL groups were 83% and 74% at 10 years, respectively. Estimated overall cancer‐specific survival was 87% at 10 years.

CONCLUSIONS.

Patients with prostate cancer and a serum PSA level ≥50 ng/mL have very high‐risk prostate cancer that carries a high likelihood of being pathologically advanced. Although the probability of realizing long‐term survival in these high‐risk patients is less than in patients with more favorable disease, 10‐year survival outcomes remain excellent and argue for aggressive management of these cases. Cancer 2008. © 2008 American Cancer Society.     

Salvage Radical Prostatectomy for Radio-Recurrent Prostate Cancer: An Updated Systematic Review of Oncologic,Histopathologic and Functional Outcomes and Predictors of Good Response

A valid treatment option for recurrence after definite radiotherapy (RT) for localized prostate cancer (PC) is salvage radical prostatectomy (SRP). However, data on SRP are scarce, possibly resulting in an underutilization. A systematic review was performed using MEDLINE (Pubmed), Embase, and Web of Science databases including studies published between January 1980 and April 2020. Overall, 23 English language articles including a total number of 2323 patients were selected according to PRISMA criteria. The overall median follow-up was 37.5 months (IQR 35.5–52.5). Biochemical-recurrence (BCR)-free probability ranged from 34% to 83% at five years, respectively, and from 31% to 37% at 10 years. Cancer specific survival (CSS) and overall survival (OS) ranged from 88.7% to 98% and 64% to 95% at five years and from 72% to 83% and 65% to 72% at 10 years, respectively. Positive surgical margins ranged from 14% to 45.8% and pathologic organ-confined disease was reported from 20% to 57%. The rate of pathologic > T2-disease ranged from 37% to 80% and pN1 disease differed between 0% to 78.4%. Pre-SRP PSA, pre-SRP Gleason Score (GS), pathologic stage after SRP, and pathologic lymph node involvement seemed to be the strongest prognostic factors for good outcomes. SRP provides accurate histopathological and functional outcomes, as well as durable cancer control. Careful patient counseling in a shared decision-making process is recommended.     

FROGG high‐risk prostate cancer workshop: Patterns of practice and literature review. Part II post‐radical prostatectomy

Australian and New Zealand radiation oncologists with an interest in uro‐oncology were invited to undertake a pattern of practice survey dealing with issues encountered in the management of high‐risk prostate cancer in the post‐prostatectomy setting. Responses from practitioners revealed a lack of consensus regarding the optimal timing of radiation therapy, the use of whole pelvic radiation therapy and the use of androgen deprivation therapy. A review of the literature outlining the current body of knowledge and the clinical studies that will inform future practice is presented.     

Management of prostate cancer recurrences after radiation therapy-brachytherapy as a salvage option

Depending on initial prognostic factors, an estimated 10%-60% of men who undergo definitive radiation therapy for prostate cancer may experience a biochemical recurrence. Even though hormonal therapy is standard for metastatic recurrences, no consensus exists on optimal salvage therapy for those recurrences thought confined to the prostate. Salvage treatment options for these local recurrences have historically been limited to salvage prostatectomy, hormonal therapy, or cryotherapy. Salvage prostate brachytherapy, however, uses a widely available technique and may provide another option for attaining disease control in patients with localized failures, although only about 110 cases have been reported in the literature. In this report, the authors have described their own series of salvage brachytherapy cases as well as presented a review of other such series reported in the literature. In addition, the authors included a comprehensive review of published experiences with surgery and cryotherapy as salvage options. It appears that salvage brachytherapy, when combined with careful patient selection, is at least as effective as other salvage options with comparable or potentially fewer treatment-related side effects.     

Predictor of response to salvage radiotherapy in patients with PSA recurrence after radical prostatectomy: the usefulness of PSA doubling time

BACKGROUND: We assessed predictors of response to salvage radiotherapy (sRT) in patients with prostate-specific antigen (PSA) recurrence after radical prostatectomy. METHODS: A total of 21 patients receiving sRT for PSA recurrence without systemic progression after radical prostatectomy had medical records available for retrospective review. We defined sRT as external beam radiotherapy for patients with a continuous increase in PSA level > or =0.2 ng/ml after radical prostatectomy. Response was defined as achievement of a PSA nadir of < or =0.1 ng/ml. Various pre-treatment parameters were evaluated retrospectively. RESULTS: The median follow-up period after sRT was 38 months. Of the 21 patients, 15 were good responders (71%). The only predictive factor was PSA doubling time (PSADT). Age and PSA level at diagnosis, Gleason score and surgical margin status were not significant predictors of response. The median PSADT in responders was 6.2 months versus 1.9 months in non-responders (P = 0.019). The patients with a PSADT of > or =5 months were all responders. CONCLUSION: PSADT appears to be a good predictor of response to sRT. sRT was especially effective when PSADT was > or =5 months.     

Effect of exogenous testosterone replacement on prostate-specific antigen and prostate-specific membrane antigen levels in hypogonadal men

Previous studies have suggested that serum prostate-specific antigen (PSA) levels are under androgenic influence, especially in patients with adenocarcinoma of the prostate. PSMA (prostate-specific membrane antigen) is thought to reflect hormonal or clonal resistance or an independence with respect to testosterone regulation. The influence of testosterone on serum PSA expression in normal men is not clear. We studied the effect of exogenous testosterone administration on the serum levels of PSA and PSMA in hypogonadal men. Serial serum PSA, serum PSMA by Western blot, and serum total testosterone levels were obtained at intervals of every 2–4 weeks in 10 hypogonadal men undergoing treatment with exogenous testosterone, delivered as testosterone enanthate injection or by testosterone patch. Linear and quadratic orthogonal polynomial scores were calculated for PSMA, PSA, and testosterone. A 2-tailed, paired t-test failed to demonstrate a significant correlation between serum PSA (linear P = 0.432, quadratic P = 0.290) or PSMA (linear P = 0.162, quadratic P = 0.973) and serum testosterone levels. This study suggests that in hypogonadal men, neither PSMA nor PSA expression is testosterone-dependent.     

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.