Health-related quality of life following salvage radical prostatectomy for recurrent prostate cancer after radiotherapy or focal therapy

Salvage radical prostatectomy (sRP) is an established treatment option for patients with recurrent prostate cancer following primary treatment of the prostate, by radiotherapy (RT) or focal therapy (FT). Salvage RP provides sufficient long-term cancer control regardless of the primary treatment modality, with 5-year cancer-specific survival rates up to 95% [1, 2]. Yet only few patients with local prostate cancer recurrence after non-surgical primary treatment will receive sRP [3]. This might be due to inherent technical challenges, considerably high complication rates and poor functional results, with earlier studies reporting urinary incontinence rates up to 90% following sRP [4]. More recent studies however have reported better functional results for patients treated with sRP with continence rates up to 90% [5, 6]. In direct comparison of functional results depending on primary treatment modality, higher continence rates following sRP are reported after focal therapy [7].

However, evidence on patient-reported outcome measures (PROMs) following sRP is scarce, with unknown impact of the primary treatment modality on health-related quality of life (HRQOL). With growing recognition of the guiding role of patients’ perspectives, HRQOL has gained importance in clinical decision making [8]. Therefore, driven by this paucity of data we conducted this first comparative analysis of PROMS from a contemporary sRP cohort. We hereby aimed to assess the impact of primary treatment modality on long-term HRQOL-outcomes following sRP.

The current study provides novel comparative PROM-based data on HRQOL following sRP after primary treatment with RT or FT. We found HRQOL of patients with recurrent PCa to be significantly impacted by sRP independent of the primary treatment. In line, we observed functional outcomes to be deteriorated, however cancer progression was prevented in more than 60% of all patients over a period of 5 years. These results have to be discussed in light of treatment alternatives regarding the best trade-off between HRQOL and oncological safety.

Salvage radical prostatectomy remains a challenging treatment option for radio-recurrent prostate cancer following non-surgical primary treatment. Blunt preparations, especially of posterior planes close to the rectal wall and of the neurovascular bundle are complicated due to fibrosis following radiation or focal therapy [3], with potentially negative impact on urinary continence an erectile function. To date, evidence on functional outcome following sRP remain scarce, as randomized trials are not performed in this particular area. Furthermore, HRQOL data were not included in previous studies based on cancer registries or multicenter studies [15]. Therefore, data from large prospectively maintained institutional databases is urgently required to fill this knowledge gap. Due to the scarcity of data and challenge of the procedure, sRP might be underused in daily practice. In order to counsel patients appropriately, alternative treatment options and their impact on HRQOL as well as oncological outcome have to be analyzed.

Early commencement of androgen deprivation therapy (ADT) is the standard treatment of recurrent prostate cancer [16]. ADT is known to cause toxicity, such as hot flushes, erectile dysfunction, fatigue, and gynecomastia [17]. HRQOL is thereby negatively impact by ADT [18]. In addition, especially increase of cardiovascular risk has become a concern in recent years [19]. Therefore, attempts are undertaken to avoid or shorten time of ADT exposure [20, 21]. In the setting of local recurrence, this implicates a thorough analysis of treatment alternatives and their impact on HRQOL and oncological outcomes.

Prior studies focused on the comparison of sRP to patients after primary treatment with RP. In a small case series including 13 sRP-patients after primary treatment with HIFU, Spitznagel et al. found functional outcomes to be comparable to those after RP as primary treatment. Complication rates however were more frequent after sRP [22]. In line, Nathan et al. reveal similar continence rate with 78.8% 2 years after sRP and 84.3% 2 years after RP in propensity score-matched patient cohorts [23]. Interestingly, functional outcomes for sRP were previously reported to be superior after FT compared to RT with continence rates of 77.3% versus 39.2% [7]. Our current study adds valuable insights into long-term follow-up of functional outcomes and HRQOL based on PROMs for patients who underwent sRP. Noteworthy in our study, patients already reported impaired functional data at baseline prior sRP, as 16–20% of all patients present with mild or no erectile dysfunction and only 66.7–87.5% revealed urinary continence. This rate of preoperative incontinence and erectile dysfunction in our cohort is significantly higher than the expected rate especially after FT [24]. Our study cohort might represent complex cases treated at a large referral center. Regardless of primary treatment patients reported similar erectile function with mild erectile dysfunction in 10–14.3% of all patients and a sustained continence in 48.4–52.9% of all patients.

With comparable functional outcome for both primary treatment modalities, the assessment of endpoints such as HRQOL becomes crucial for guidance of therapy. Our results revealed HRQOL to be significantly affected by salvage surgical treatment. Only about 50% of all patients in our study presented with “good general HRQOL”, defined as aGHS of ≥ 70. HRQOL remains good (GHS ≥ 70) in about 25% of all patients in long-term follow-up after salvage prostatectomy. Decline in HRQOL is markedly higher than in patients undergoing RP for primary PCa. Here, experience from our center revealed a decline of HRQOL at 3 months after the procedure but return to baseline values in the long-term follow-up [25]. HRQOL-outcomes for sRP were independent of the primary treatment in our study. This finding is especially interesting, as patients who had undergone FT that had opted for a therapy with the aim to conserve erectile function and continence [26]. Therefore, they might present with different attitude toward worsening of HRQOL or are more sensitive to changes through functional outcomes.

Regarding oncological outcome our study revealed comparable BCR-free survival rates for each primary treatment modality with a 5-year BRFS of 60% for RT and 68% for FT. In line with our findings, 5-year BCRF of 47–82% across several studies were reported in a systematic review [4]. Similar results are seen in systematic review on patients after focal therapy and sRP with a 2-year BCR-free probability of 77% [27].

This study is limited by the retrospective study design and by potential selection bias as therapy recommendation has been performed on a single-patient basis. However, as outlined in the discussion section, other study types are difficult to conduct in this setting. The retrospective single-center design focuses on open surgery and low rates of nerve-sparing might also limits the comparability in terms of functional outcomes compared to other cohorts.

sRP impacts HRQOL in patients with PCa after RT and FT alike. Oncological outcomes are excellent in light of the treatment situation. As treatment alternatives including early commencement of androgen deprivation therapy are impacting HRQOL but with another profile, exploring precise patient´s preference is paramount.